Safety assessment of green tea based beverages and dried green tea extracts as nutritional supplements.

PubMed

Dekant, Wolfgang; Fujii, Kenkichi; Shibata, Eiichiro; Morita, Osamu; Shimotoyodome, Akira

2017-08-05

The safety of green tea infusions and green tea extract (GTE)-based products is reviewed regarding catechins. Epigallocatechin 3-gallate (EGCG), the major catechin present in green tea, is suspected of being responsible for liver toxicity reported in humans consuming food supplements. Intake of EGCG with green tea infusions and GTE-based beverages is up to about 450mg EGCG/person/day in Europe and higher in Asia. Consumption of green tea is not associated with liver damage in humans, and green tea infusion and GTE-based beverages are considered safe in the range of historical uses. In animal studies, EGCG's potency for liver effects is highly dependent on conditions of administration. Use of NOAELs from bolus administration to derive a tolerable upper intake level applying the margin of safety concept results in acceptable EGCG-doses lower than those from one cup of green tea. NOAELs from toxicity studies applying EGCG with diet/split of the daily dose are a better point of departure for risk characterization. In clinical intervention studies, liver effects were not observed after intakes below 600mg EGCG/person/day. Thus, a tolerable upper intake level of 300mg EGCG/person/day is proposed for food supplements; this gives a twofold safety margin to clinical studies that did not report liver effects and a margin of safety of 100 to the NOAELs in animal studies with dietary administration of green tea catechins. Copyright © 2017 Elsevier B.V. All rights reserved.

Generalized Tumor Dose for Treatment Planning Decision Support

NASA Astrophysics Data System (ADS)

Zuniga, Areli A.

Modern radiation therapy techniques allow for improved target conformity and normal tissue sparing. These highly conformal treatment plans have allowed dose escalation techniques increasing the probability of tumor control. At the same time this conformation has introduced inhomogeneous dose distributions, making delivered dose characterizations more difficult. The concept of equivalent uniform dose (EUD) characterizes a heterogeneous dose distribution within irradiated structures as a single value and has been used in biologically based treatment planning (BBTP); however, there are no substantial validation studies on clinical outcome data supporting EUD's use and therefore has not been widely adopted as decision-making support. These highly conformal treatment plans have also introduced the need for safety margins around the target volume. These margins are designed to minimize geometrical misses, and to compensate for dosimetric and treatment delivery uncertainties. The margin's purpose is to reduce the chance of tumor recurrence. This dissertation introduces a new EUD formulation designed especially for tumor volumes, called generalized Tumor Dose (gTD). It also investigates, as a second objective, margins extensions for potential improvements in local control while maintaining or minimizing toxicity. The suitability of gTD to rank LC was assessed by means of retrospective studies in a head and neck (HN) squamous cell carcinoma (SCC) and non-small cell lung cancer (NSCLC) cohorts. The formulation was optimized based on two datasets (one of each type) and then, model validation was assessed on independent cohorts. The second objective of this dissertation was investigated by ranking the probability of LC of the primary disease adding different margin sizes. In order to do so, an already published EUD formula was used retrospectively in a HN and a NSCLC datasets. Finally, recommendations for the viability to implement this new formulation into a routine treatment planning process as well as the revision of safety margins to improve local tumor control maximizing normal tissue sparing in SCC of the HN and NSCLC are discussed.

Brazed Joints Design and Allowables: Discuss Margins of Safety in Critical Brazed Structures

NASA Technical Reports Server (NTRS)

FLom, Yury

2009-01-01

This slide presentation tutorial discusses margins of safety in critical brazed structures. It reviews: (1) the present situation (2) definition of strength (3) margins of safety (4) design allowables (5) mechanical testing (6) failure criteria (7) design flowchart (8) braze gap (9) residual stresses and (10) delayed failures. This presentation addresses the strength of the brazed joints, the methods of mechanical testing, and our ability to evaluate the margins of safety of the brazed joints as it applies to the design of critical and expensive brazed assemblies.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gougar, Hans

This document outlines the development of a high fidelity, best estimate nuclear power plant severe transient simulation capability that will complement or enhance the integral system codes historically used for licensing and analysis of severe accidents. As with other tools in the Risk Informed Safety Margin Characterization (RISMC) Toolkit, the ultimate user of Enhanced Severe Transient Analysis and Prevention (ESTAP) capability is the plant decision-maker; the deliverable to that customer is a modern, simulation-based safety analysis capability, applicable to a much broader class of safety issues than is traditional Light Water Reactor (LWR) licensing analysis. Currently, the RISMC pathway’s majormore » emphasis is placed on developing RELAP-7, a next-generation safety analysis code, and on showing how to use RELAP-7 to analyze margin from a modern point of view: that is, by characterizing margin in terms of the probabilistic spectra of the “loads” applied to systems, structures, and components (SSCs), and the “capacity” of those SSCs to resist those loads without failing. The first objective of the ESTAP task, and the focus of one task of this effort, is to augment RELAP-7 analyses with user-selected multi-dimensional, multi-phase models of specific plant components to simulate complex phenomena that may lead to, or exacerbate, severe transients and core damage. Such phenomena include: coolant crossflow between PWR assemblies during a severe reactivity transient, stratified single or two-phase coolant flow in primary coolant piping, inhomogeneous mixing of emergency coolant water or boric acid with hot primary coolant, and water hammer. These are well-documented phenomena associated with plant transients but that are generally not captured in system codes. They are, however, generally limited to specific components, structures, and operating conditions. The second ESTAP task is to similarly augment a severe (post-core damage) accident integral analyses code with high fidelity simulations that would allow investigation of multi-dimensional, multi-phase containment phenomena that are only treated approximately in established codes.« less

Flooding Capability for River-based Scenarios

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Curtis L.; Prescott, Steven; Ryan, Emerald

2015-10-01

This report describes the initial investigation into modeling and simulation tools for application of riverine flooding representation as part of the Risk-Informed Safety Margin Characterization (RISMC) Pathway external hazards evaluations. The report provides examples of different flooding conditions and scenarios that could impact river and watershed systems. Both 2D and 3D modeling approaches are described.

Facing the Recession: How Did Safety-Net Hospitals Fare Financially Compared with Their Peers?

PubMed Central

Reiter, Kristin L; Jiang, H Joanna; Wang, Jia

2014-01-01

Objective To examine the effect of the recession on the financial performance of safety-net versus non-safety-net hospitals. Data Sources/Study Setting Agency for Healthcare Research and Quality Hospital Cost and Utilization Project State Inpatient Databases, Medicare Cost Reports, American Hospital Association Annual Survey, InterStudy, and Area Health Resource File. Study Design Retrospective, longitudinal panel of hospitals, 2007–2011. Safety-net hospitals were identified using percentage of patients who were Medicaid or uninsured. Generalized estimating equations were used to estimate average effects of the recession on hospital operating and total margins, revenues and expenses in each year, 2008–2011, comparing safety-net with non-safety-net hospitals. Data Collection/Extraction Methods 1,453 urban, nonfederal, general acute hospitals in 32 states with complete data. Principal Findings Safety-net hospitals, as identified in 2007, had lower operating and total margins. The gap in operating margin between safety-net and non-safety-net hospitals was sustained throughout the recession; however, total margin was more negatively affected for non-safety-net hospitals in 2008. Higher percentages of Medicaid and uninsured patients were associated with lower revenue in private hospitals in all years, and lower revenue and expenses in public hospitals in 2011. Conclusions Safety-net hospitals may not be disproportionately vulnerable to macro-economic fluctuations, but their significantly lower margins leave less financial cushion to weather sustained financial pressure. PMID:25220012

The effects of safety practice, technology adoption, and firm characteristics on motor carrier safety

DOT National Transportation Integrated Search

2004-01-01

The theory of the firm suggests that firms should maximize profit by investing in safety until : marginal cost is equal to the marginal benefit. This paper addresses motor carrier safety from the : perspective of the firm, developing the theoretical ...

Estimation of Inherent Safety Margins in Loaded Commercial Spent Nuclear Fuel Casks

DOE PAGES

Banerjee, Kaushik; Robb, Kevin R.; Radulescu, Georgeta; ...

2016-06-15

We completed a novel assessment to determine the unquantified and uncredited safety margins (i.e., the difference between the licensing basis and as-loaded calculations) available in as-loaded spent nuclear fuel (SNF) casks. This assessment was performed as part of a broader effort to assess issues and uncertainties related to the continued safety of casks during extended storage and transportability following extended storage periods. Detailed analyses crediting the actual as-loaded cask inventory were performed for each of the casks at three decommissioned pressurized water reactor (PWR) sites to determine their characteristics relative to regulatory safety criteria for criticality, thermal, and shielding performance.more » These detailed analyses were performed in an automated fashion by employing a comprehensive and integrated data and analysis tool—Used Nuclear Fuel-Storage, Transportation & Disposal Analysis Resource and Data System (UNF-ST&DARDS). Calculated uncredited criticality margins from 0.07 to almost 0.30 Δk eff were observed; calculated decay heat margins ranged from 4 to almost 22 kW (as of 2014); and significant uncredited transportation dose rate margins were also observed. The results demonstrate that, at least for the casks analyzed here, significant uncredited safety margins are available that could potentially be used to compensate for SNF assembly and canister structural performance related uncertainties associated with long-term storage and subsequent transportation. The results also suggest that these inherent margins associated with how casks are loaded could support future changes in cask licensing to directly or indirectly credit the margins. Work continues to quantify the uncredited safety margins in the SNF casks loaded at other nuclear reactor sites.« less

Modeling of a Flooding Induced Station Blackout for a Pressurized Water Reactor Using the RISMC Toolkit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mandelli, Diego; Prescott, Steven R; Smith, Curtis L

2011-07-01

In the Risk Informed Safety Margin Characterization (RISMC) approach we want to understand not just the frequency of an event like core damage, but how close we are (or are not) to key safety-related events and how might we increase our safety margins. The RISMC Pathway uses the probabilistic margin approach to quantify impacts to reliability and safety by coupling both probabilistic (via stochastic simulation) and mechanistic (via physics models) approaches. This coupling takes place through the interchange of physical parameters and operational or accident scenarios. In this paper we apply the RISMC approach to evaluate the impact of amore » power uprate on a pressurized water reactor (PWR) for a tsunami-induced flooding test case. This analysis is performed using the RISMC toolkit: RELAP-7 and RAVEN codes. RELAP-7 is the new generation of system analysis codes that is responsible for simulating the thermal-hydraulic dynamics of PWR and boiling water reactor systems. RAVEN has two capabilities: to act as a controller of the RELAP-7 simulation (e.g., system activation) and to perform statistical analyses (e.g., run multiple RELAP-7 simulations where sequencing/timing of events have been changed according to a set of stochastic distributions). By using the RISMC toolkit, we can evaluate how power uprate affects the system recovery measures needed to avoid core damage after the PWR lost all available AC power by a tsunami induced flooding. The simulation of the actual flooding is performed by using a smooth particle hydrodynamics code: NEUTRINO.« less

A method for identifying EMI critical circuits during development of a large C3

NASA Astrophysics Data System (ADS)

Barr, Douglas H.

The circuit analysis methods and process Boeing Aerospace used on a large, ground-based military command, control, and communications (C3) system are described. This analysis was designed to help identify electromagnetic interference (EMI) critical circuits. The methodology used the MIL-E-6051 equipment criticality categories as the basis for defining critical circuits, relational database technology to help sort through and account for all of the approximately 5000 system signal cables, and Macintosh Plus personal computers to predict critical circuits based on safety margin analysis. The EMI circuit analysis process systematically examined all system circuits to identify which ones were likely to be EMI critical. The process used two separate, sequential safety margin analyses to identify critical circuits (conservative safety margin analysis, and detailed safety margin analysis). These analyses used field-to-wire and wire-to-wire coupling models using both worst-case and detailed circuit parameters (physical and electrical) to predict circuit safety margins. This process identified the predicted critical circuits that could then be verified by test.

Safety margins in the implementation of planetary quarantine requirements

NASA Technical Reports Server (NTRS)

Schalkowsky, S.; Jacoby, I.

1972-01-01

The formulation of planetary quarantine requirements, and their implementation as determined by a risk allocation model, is discussed. The model defines control safety margins with particular emphasis on utility in achieving the desired minimization of excessive margins, and their effect on implementation procedures.

Texas curve margin of safety.

DOT National Transportation Integrated Search

2013-01-01

This software can be used to assist with the assessment of margin of safety for a horizontal curve. It is intended for use by engineers and technicians responsible for safety analysis or management of rural highway pavement or traffic control devices...

Time Safety Margin: Theory and Practice

DTIC Science & Technology

2016-09-01

Basic Dive Recovery Terminology The Simplest Definition of TSM: Time Safety Margin is the time to directly travel from the worst-case vector to an...Safety Margin (TSM). TSM is defined as the time in seconds to directly travel from the worst case vector (i.e. worst case combination of parameters...invoked by this AFI, base recovery planning and risk management upon the calculated TSM. TSM is the time in seconds to di- rectly travel from the worst case

Determination of safety margins for whole blood concentrations of alcohol and nineteen drugs in driving under the influence cases.

PubMed

Kristoffersen, Lena; Strand, Dag Helge; Liane, Veronica Horpestad; Vindenes, Vigdis; Tvete, Ingunn Fride; Aldrin, Magne

2016-02-01

Legislative limits for driving under the influence of 20 non-alcohol drugs were introduced in Norway in February 2012. Per se limits corresponding to blood alcohol concentrations (BAC) of 0.2g/kg were established for 20 psychoactive drugs, and limits for graded sanctions corresponding to BACs of 0.5 and 1.2g/kg were determined for 13 of these drugs. This new legislation made it possible for the courts to make sentences based on the analytical results, similar to the situation for alcohol. To ensure that the reported concentration is as least as high as the true concentration, with a 99% safety level, safety margins had to be calculated for each of the substances. Diazepam, tetrahydrocannabinol (THC) and alcohol were used as model substances to establish a new model for estimating the safety margins. The model was compared with a previous used model established several years ago, by a similar yet much simpler model, and they were found to be in agreement. The measurement uncertainties depend on the standard batch used, the work list and the measurements' replicate. A Bayesian modelling approach was used to determine the parameters in the model, using a dataset of 4700 diazepam positive specimens and 5400 THC positive specimens. Different safety margins were considered for low and high concentration levels of diazepam (≤2μM (0.6mg/L) and >2μM) and THC (≤0.01μM (0.003mg/L) and >0.01μM). The safety margins were for diazepam 19.5% (≤2μM) and 34% (>2μM), for THC 19.5% (≤0.01μM) and 24.9% (>0.01μM). Concentration dependent safety margins for BAC were based on a dataset of 29500 alcohol positive specimens, and were in the range 10.4% (0.1g/kg) to 4.0% (4.0g/kg) at a 99% safety level. A simplified approach was used to establish safety margins for the compounds amphetamine, MDMA, methamphetamine, alprazolam, phenazepam, flunitrazepam, clonazepam, nitrazepam, oxazepam, buprenorphine, GHB, methadone, ketamine, cocaine, morphine, zolpidem and zopiclone. The safety margins for these drugs were in the range 34-41%. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Inductionless or limited shock testing is possible in most patients with implantable cardioverter- defibrillators/cardiac resynchronization therapy defibrillators: results of the multicenter ASSURE Study (Arrhythmia Single Shock Defibrillation Threshold Testing Versus Upper Limit of Vulnerability: Risk Reduction Evaluation With Implantable Cardioverter-Defibrillator Implantations).

PubMed

Day, John D; Doshi, Rahul N; Belott, Peter; Birgersdotter-Green, Ulrika; Behboodikhah, Mahnaz; Ott, Peter; Glatter, Kathryn A; Tobias, Serge; Frumin, Howard; Lee, Byron K; Merillat, John; Wiener, Isaac; Wang, Samuel; Grogin, Harlan; Chun, Sung; Patrawalla, Rob; Crandall, Brian; Osborn, Jeffrey S; Weiss, J Peter; Lappe, Donald L; Neuman, Stacey

2007-05-08

Implantable cardioverter-defibrillators and cardiac resynchronization therapy defibrillators have relied on multiple ventricular fibrillation (VF) induction/defibrillation tests at implantation to ensure that the device can reliably sense, detect, and convert VF. The ASSURE Study (Arrhythmia Single Shock Defibrillation Threshold Testing Versus Upper Limit of Vulnerability: Risk Reduction Evaluation With Implantable Cardioverter-Defibrillator Implantations) is the first large, multicenter, prospective trial comparing vulnerability safety margin testing versus defibrillation safety margin testing with a single VF induction/defibrillation. A total of 426 patients receiving an implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator underwent vulnerability safety margin or defibrillation safety margin screening at 14 J in a randomized order. After this, patients underwent confirmatory testing, which required 2 VF conversions without failure at < or = 21 J. Patients who passed their first 14-J and confirmatory tests, irrespective of the results of their second 14-J test, had their devices programmed to a 21-J shock for ventricular tachycardia (VT) or VF > or = 200 bpm and were followed up for 1 year. Of 420 patients who underwent 14-J vulnerability safety margin screening, 322 (76.7%) passed. Of these, 317 (98.4%) also passed 21-J confirmatory tests. Of 416 patients who underwent 14-J defibrillation safety margin screening, 343 (82.5%) passed, and 338 (98.5%) also passed 21-J confirmatory tests. Most clinical VT/VF episodes (32 of 37, or 86%) were terminated by the first shock, with no difference in first shock success. In all observed cases in which the first shock was unsuccessful, subsequent shocks terminated VT/VF without complication. Although spontaneous episodes of fast VT/VF were limited, there was no difference in the odds of first shock efficacy between groups. Screening with vulnerability safety margin or defibrillation safety margin may allow for inductionless or limited shock testing in most patients.

Flexible Control of Safety Margins for Action Based on Environmental Variability.

PubMed

Hadjiosif, Alkis M; Smith, Maurice A

2015-06-17

To reduce the risk of slip, grip force (GF) control includes a safety margin above the force level ordinarily sufficient for the expected load force (LF) dynamics. The current view is that this safety margin is based on the expected LF dynamics, amounting to a static safety factor like that often used in engineering design. More efficient control could be achieved, however, if the motor system reduces the safety margin when LF variability is low and increases it when this variability is high. Here we show that this is indeed the case by demonstrating that the human motor system sizes the GF safety margin in proportion to an internal estimate of LF variability to maintain a fixed statistical confidence against slip. In contrast to current models of GF control that neglect the variability of LF dynamics, we demonstrate that GF is threefold more sensitive to the SD than the expected value of LF dynamics, in line with the maintenance of a 3-sigma confidence level. We then show that a computational model of GF control that includes a variability-driven safety margin predicts highly asymmetric GF adaptation between increases versus decreases in load. We find clear experimental evidence for this asymmetry and show that it explains previously reported differences in how rapidly GFs and manipulatory forces adapt. This model further predicts bizarre nonmonotonic shapes for GF learning curves, which are faithfully borne out in our experimental data. Our findings establish a new role for environmental variability in the control of action. Copyright © 2015 the authors 0270-6474/15/359106-16$15.00/0.

Principles of Safety Pharmacology

PubMed Central

Pugsley, M K; Authier, S; Curtis, M J

2008-01-01

Safety Pharmacology is a rapidly developing discipline that uses the basic principles of pharmacology in a regulatory-driven process to generate data to inform risk/benefit assessment. The aim of Safety Pharmacology is to characterize the pharmacodynamic/pharmacokinetic (PK/PD) relationship of a drug's adverse effects using continuously evolving methodology. Unlike toxicology, Safety Pharmacology includes within its remit a regulatory requirement to predict the risk of rare lethal events. This gives Safety Pharmacology its unique character. The key issues for Safety Pharmacology are detection of an adverse effect liability, projection of the data into safety margin calculation and finally clinical safety monitoring. This article sets out to explain the drivers for Safety Pharmacology so that the wider pharmacology community is better placed to understand the discipline. It concludes with a summary of principles that may help inform future resolution of unmet needs (especially establishing model validation for accurate risk assessment). Subsequent articles in this issue of the journal address specific aspects of Safety Pharmacology to explore the issues of model choice, the burden of proof and to highlight areas of intensive activity (such as testing for drug-induced rare event liability, and the challenge of testing the safety of so-called biologics (antibodies, gene therapy and so on.). PMID:18604233

System Guidelines for EMC Safety-Critical Circuits: Design, Selection, and Margin Demonstration

NASA Technical Reports Server (NTRS)

Lawton, R. M.

1996-01-01

Demonstration of safety margins for critical points (circuits) has traditionally been required since it first became a part of systems-level Electromagnetic Compatibility (EMC) requirements of MIL-E-6051C. The goal of this document is to present cost-effective guidelines for ensuring adequate Electromagnetic Effects (EME) safety margins on spacecraft critical circuits. It is for the use of NASA and other government agencies and their contractors to prevent loss of life, loss of spacecraft, or unacceptable degradation. This document provides practical definition and treatment guidance to contain costs within affordable limits.

Statistical issues in the design, conduct and analysis of two large safety studies.

PubMed

Gaffney, Michael

2016-10-01

The emergence, post approval, of serious medical events, which may be associated with the use of a particular drug or class of drugs, is an important public health and regulatory issue. The best method to address this issue is through a large, rigorously designed safety study. Therefore, it is important to elucidate the statistical issues involved in these large safety studies. Two such studies are PRECISION and EAGLES. PRECISION is the primary focus of this article. PRECISION is a non-inferiority design with a clinically relevant non-inferiority margin. Statistical issues in the design, conduct and analysis of PRECISION are discussed. Quantitative and clinical aspects of the selection of the composite primary endpoint, the determination and role of the non-inferiority margin in a large safety study and the intent-to-treat and modified intent-to-treat analyses in a non-inferiority safety study are shown. Protocol changes that were necessary during the conduct of PRECISION are discussed from a statistical perspective. Issues regarding the complex analysis and interpretation of the results of PRECISION are outlined. EAGLES is presented as a large, rigorously designed safety study when a non-inferiority margin was not able to be determined by a strong clinical/scientific method. In general, when a non-inferiority margin is not able to be determined, the width of the 95% confidence interval is a way to size the study and to assess the cost-benefit of relative trial size. A non-inferiority margin, when able to be determined by a strong scientific method, should be included in a large safety study. Although these studies could not be called "pragmatic," they are examples of best real-world designs to address safety and regulatory concerns. © The Author(s) 2016.

Effect of Smaller Left Ventricular Capture Threshold Safety Margins to Improve Device Longevity in Recipients of Cardiac Resynchronization-Defibrillation Therapy.

PubMed

Steinhaus, Daniel A; Waks, Jonathan W; Collins, Robert; Kleckner, Karen; Kramer, Daniel B; Zimetbaum, Peter J

2015-07-01

Device longevity in cardiac resynchronization therapy (CRT) is affected by the pacing capture threshold (PCT) and programmed pacing amplitude of the left ventricular (LV) pacing lead. The aims of this study were to evaluate the stability of LV pacing thresholds in a nationwide sample of CRT defibrillator recipients and to determine potential longevity improvements associated with a decrease in the LV safety margin while maintaining effective delivery of CRT. CRT defibrillator patients in the Medtronic CareLink database were eligible for inclusion. LV PCT stability was evaluated using ≥2 measurements over a 14-day period. Separately, a random sample of 7,250 patients with programmed right atrial and right ventricular amplitudes ≤2.5 V, LV thresholds ≤ 2.5 V, and LV pacing ≥90% were evaluated to estimate theoretical battery longevity improvement using LV safety margins of 0.5 and 1.5 V. Threshold stability analysis in 43,256 patients demonstrated LV PCT stability of <0.5 V in 77% of patients and <1 V in 95%. Device longevity analysis showed that the use of a 0.5-V safety margin increased average battery longevity by 0.62 years (95% confidence interval 0.61 to 0.63) compared with a safety margin of 1.5 V. Patients with LV PCTs >1 V had the greatest increases in battery life (mean increase 0.86 years, 95% confidence interval 0.85 to 0.87). In conclusion, nearly all CRT defibrillator patients had LV PCT stability <1.0 V. Decreasing the LV safety margin from 1.5 to 0.5 V provided consistent delivery of CRT for most patients and significantly improved battery longevity. Copyright © 2015 Elsevier Inc. All rights reserved.

Biophysics, environmental stochasticity, and the evolution of thermal safety margins in intertidal limpets.

PubMed

Denny, M W; Dowd, W W

2012-03-15

As the air temperature of the Earth rises, ecological relationships within a community might shift, in part due to differences in the thermal physiology of species. Prediction of these shifts - an urgent task for ecologists - will be complicated if thermal tolerance itself can rapidly evolve. Here, we employ a mechanistic approach to predict the potential for rapid evolution of thermal tolerance in the intertidal limpet Lottia gigantea. Using biophysical principles to predict body temperature as a function of the state of the environment, and an environmental bootstrap procedure to predict how the environment fluctuates through time, we create hypothetical time-series of limpet body temperatures, which are in turn used as a test platform for a mechanistic evolutionary model of thermal tolerance. Our simulations suggest that environmentally driven stochastic variation of L. gigantea body temperature results in rapid evolution of a substantial 'safety margin': the average lethal limit is 5-7°C above the average annual maximum temperature. This predicted safety margin approximately matches that found in nature, and once established is sufficient, in our simulations, to allow some limpet populations to survive a drastic, century-long increase in air temperature. By contrast, in the absence of environmental stochasticity, the safety margin is dramatically reduced. We suggest that the risk of exceeding the safety margin, rather than the absolute value of the safety margin, plays an underappreciated role in the evolution of thermal tolerance. Our predictions are based on a simple, hypothetical, allelic model that connects genetics to thermal physiology. To move beyond this simple model - and thereby potentially to predict differential evolution among populations and among species - will require significant advances in our ability to translate the details of thermal histories into physiological and population-genetic consequences.

R&D Plan for RISMC Industry Application #1: ECCS/LOCA Cladding Acceptance Criteria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Szilard, Ronaldo Henriques; Zhang, Hongbin; Epiney, Aaron Simon

The Nuclear Regulatory Commission (NRC) is finalizing a rulemaking change that would revise the requirements in 10 CFR 50.46. In the proposed new rulemaking, designated as 10 CFR 50.46c, the NRC proposes a fuel performance-based equivalent cladding reacted (ECR) criterion as a function of cladding hydrogen content before the accident (pre-transient) in order to include the effects of higher burnup on cladding performance as well as to address other technical issues. A loss of operational margin may result due to the more restrictive cladding embrittlement criteria. Initial and future compliance with the rule may significantly increase vendor workload and licenseemore » costs as a spectrum of fuel rod initial burnup states may need to be analyzed to demonstrate compliance. The Idaho National Laboratory (INL) has initiated a project, as part of the DOE Light Water Reactor Sustainability Program (LWRS), to develop analytical capabilities to support the industry in the transition to the new rule. This project is called the Industry Application 1 (IA1) within the Risk-Informed Safety Margin Characterization (RISMC) Pathway of LWRS. The general idea behind the initiative is the development of an Integrated Evaluation Model (IEM). The motivation is to develop a multiphysics framework to analyze how uncertainties are propagated across the stream of physical disciplines and data involved, as well as how risks are evaluated in a LOCA safety analysis as regulated under 10 CFR 50.46c. This IEM is called LOTUS which stands for LOCA Toolkit for US, and it represents the LWRS Program’s response to the proposed new rule making. The focus of this report is to complete an R&D plan to describe the demonstration of the LOCA/ECCS RISMC Industry Application # 1 using the advanced RISMC Toolkit and methodologies. This report includes the description and development plan for a RISMC LOCA tool that fully couples advanced MOOSE tools already in development in order to characterize and optimize plant safety and operational margins. Advanced MOOSE tools that are needed to complete this integrated evaluation model are: RAVEN, RELAP-7, BISON, and MAMMOTH.« less

Estimation Of TMDLs And Margin Of Safety Under Conditions Of Uncertainty

EPA Science Inventory

In TMDL development, an adequate margin of safety (MOS) is required in the calculation process to provide a cushion needed because of uncertainties in the data and analysis. Current practices, however, rarely factor analysis' uncertainty in TMDL development and the MOS is largel...

System Guidelines for EMC Safety-Critical Circuits: Design, Selection, and Margin Demonstration

NASA Technical Reports Server (NTRS)

Lawton, R. M.

1996-01-01

Demonstration of required safety margins on critical electrical/electronic circuits in large complex systems has become an implementation and cost problem. These margins are the difference between the activation level of the circuit and the electrical noise on the circuit in the actual operating environment. This document discusses the origin of the requirement and gives a detailed process flow for the identification of the system electromagnetic compatibility (EMC) critical circuit list. The process flow discusses the roles of engineering disciplines such as systems engineering, safety, and EMC. Design and analysis guidelines are provided to assist the designer in assuring the system design has a high probability of meeting the margin requirements. Examples of approaches used on actual programs (Skylab and Space Shuttle Solid Rocket Booster) are provided to show how variations of the approach can be used successfully.

Effect of Neutron Absorbers Mixed in or Coating the Fuel of a 1-MWt Lithium-Cooled Space Reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amiri, Benjamin W.; Los Alamos National Laboratory, Los Alamos, NM 87545; Poston, David I.

2005-02-06

The goal of this study was to determine the effect of various neutron poisons (boron, dysprosium, erbium, and gadolinium) on a 1-MWt, lithium-cooled liquid-metal reactor. The isotopes were considered to be in-fuel poisons, as well as poisons coating the fuel. One way to quantify the effectiveness of a poison in meeting accident-condition requirements is by defining the safety margin as the difference between keff at the beginning of life and keff during the accident scenarios. The isotope that showed the most potential in increasing the safety margin for the wet-sand/water case was 157Gd. The safety margin was 10%-20% greater usingmore » 157Gd as an in-fuel poison as opposed to a coating, depending on the poison quantity. However, the most limiting condition (i.e., the accident scenario with the highest keff, thus the lowest safety margin) is when the reactor is submerged in wet sand. None of the isotopes considered significantly affected the safety margin for the dry-sand case. However, the poison isotopes considered may have applicability for meeting the wet-sand/water keff requirements or as burnable poisons in a moderated system. The views expressed in this document are those of the author and do not necessarily reflect agreement by the government.« less

Safety-I, Safety-II and Resilience Engineering.

PubMed

Patterson, Mary; Deutsch, Ellen S

2015-12-01

In the quest to continually improve the health care delivered to patients, it is important to understand "what went wrong," also known as Safety-I, when there are undesired outcomes, but it is also important to understand, and optimize "what went right," also known as Safety-II. The difference between Safety-I and Safety-II are philosophical as well as pragmatic. Improving health care delivery involves understanding that health care delivery is a complex adaptive system; components of that system impact, and are impacted by, the actions of other components of the system. Challenges to optimal care include regular, irregular and unexampled threats. This article addresses the dangers of brittleness and miscalibration, as well as the value of adaptive capacity and margin. These qualities can, respectively, detract from or contribute to the emergence of organizational resilience. Resilience is characterized by the ability to monitor, react, anticipate, and learn. Finally, this article celebrates the importance of humans, who make use of system capabilities and proactively mitigate the effects of system limitations to contribute to successful outcomes. Copyright © 2015 Mosby, Inc. All rights reserved.

Chinese Herbal Therapy for the Treatment of Food Allergy

PubMed Central

Li, Xiu-Min

2014-01-01

Traditional Chinese medicine (TCM) has been widely used in China to treat various diseases for thousands of years. Given its reputed effectiveness, low cost, and favorable safety profile, TCM is attracting great interest in Western societies as a source of therapy for an array of illnesses, including allergies and asthma. Although food allergy has not been described in the TCM literature, a novel treatment for food allergy, named the food allergy herbal formula-2 (FAHF-2), was developed using TCM principles. Using a well-characterized murine model of peanut allergy, FAHF-2 has been shown to be highly effective in providing long-term protection against peanut-induced anaphylaxis, with a high safety margin. Phase 1 human trials have demonstrated the safety of FAHF-2 in food allergic individuals. Currently, a phase 2 trial examining efficacy of FAHF-2 is on-going. Other TCMs also show a potential for treating food allergies in preclinical studies. PMID:22581122

Is it necessary to plan with safety margins for actively scanned proton therapy?

NASA Astrophysics Data System (ADS)

Albertini, F.; Hug, E. B.; Lomax, A. J.

2011-07-01

In radiation therapy, a plan is robust if the calculated and the delivered dose are in agreement, even in the case of different uncertainties. The current practice is to use safety margins, expanding the clinical target volume sufficiently enough to account for treatment uncertainties. This, however, might not be ideal for proton therapy and in particular when using intensity modulated proton therapy (IMPT) plans as degradation in the dose conformity could also be found in the middle of the target resulting from misalignments of highly in-field dose gradients. Single field uniform dose (SFUD) and IMPT plans have been calculated for different anatomical sites and the need for margins has been assessed by analyzing plan robustness to set-up and range uncertainties. We found that the use of safety margins is a good way to improve plan robustness for SFUD and IMPT plans with low in-field dose gradients but not necessarily for highly modulated IMPT plans for which only a marginal improvement in plan robustness could be detected through the definition of a planning target volume.

Thulium fiber laser damage to the ureter

NASA Astrophysics Data System (ADS)

Wilson, Christopher R.; Hardy, Luke A.; Irby, Pierce B.; Fried, Nathaniel M.

2015-07-01

Our laboratory is studying experimental thulium fiber laser (TFL) as a potential alternative lithotripter to the clinical gold standard Holmium:YAG laser. Safety studies characterizing undesirable Holmium laser-induced damage to ureter tissue have been previously reported. Similarly, this study characterizes TFL induced ureter and stone basket damage. A TFL beam with pulse energy of 35 mJ, pulse duration of 500 μs, and pulse rates of 150-500 Hz was delivered through a 100-μm-core, low-OH, silica optical fiber to the porcine ureter wall, in vitro. Ureter perforation times were measured and gross, histological, and optical coherence tomography images of the ablation zone were acquired. TFL operation at 150, 300, and 500 Hz produced mean ureter perforation times of 7.9, 3.8, and 1.8 s, respectively. Collateral damage averaged 510, 370, and 310 μm. TFL mean perforation time exceeded 1 s at each setting, which is a greater safety margin than previously reported during Holmium laser ureter perforation studies.

Grip force regulation during pinch grip lifts under somatosensory guidance: comparison between people with stroke and healthy controls.

PubMed

Blennerhassett, Jannette M; Carey, Leeanne M; Matyas, Thomas A

2006-03-01

To compare the timing and grip force application in a pinch grip task performed under somatosensory guidance in stroke and matched controls and to identify characteristics of impaired grip force regulation after stroke. Matched-pairs control group. University research laboratory. Forty-five people with stroke who could pick up a pen lid using a pinch grip and actively participated in rehabilitation and 45 adults without neurologic conditions or musculoskeletal or skin impairments affecting the hand, matched for age, sex, and hand dominance. Not applicable. Timing and magnitude of grip forces applied during pinch grip lift and hold. Prolonged time to grip and lift objects, and excessive grip force prior to commencing the lift occurred in approximately half of the contralesional (involved) hands of people with stroke. Fluctuating irregular forces and reduced adaptation of the grip safety margin were also observed. Excessive safety margins were not predominant after stroke. Extreme slowing and disorganized sequencing of the grip and lifting forces and difficulty maintaining a stable grip characterized severe dysfunction. Delayed grip formulation and variable grip force application are key characteristics of grip dysfunction after stroke.

Increasing Safety of a Robotic System for Inner Ear Surgery Using Probabilistic Error Modeling Near Vital Anatomy

PubMed Central

Dillon, Neal P.; Siebold, Michael A.; Mitchell, Jason E.; Blachon, Gregoire S.; Balachandran, Ramya; Fitzpatrick, J. Michael; Webster, Robert J.

2017-01-01

Safe and effective planning for robotic surgery that involves cutting or ablation of tissue must consider all potential sources of error when determining how close the tool may come to vital anatomy. A pre-operative plan that does not adequately consider potential deviations from ideal system behavior may lead to patient injury. Conversely, a plan that is overly conservative may result in ineffective or incomplete performance of the task. Thus, enforcing simple, uniform-thickness safety margins around vital anatomy is insufficient in the presence of spatially varying, anisotropic error. Prior work has used registration error to determine a variable-thickness safety margin around vital structures that must be approached during mastoidectomy but ultimately preserved. In this paper, these methods are extended to incorporate image distortion and physical robot errors, including kinematic errors and deflections of the robot. These additional sources of error are discussed and stochastic models for a bone-attached robot for otologic surgery are developed. An algorithm for generating appropriate safety margins based on a desired probability of preserving the underlying anatomical structure is presented. Simulations are performed on a CT scan of a cadaver head and safety margins are calculated around several critical structures for planning of a robotic mastoidectomy. PMID:29200595

Increasing safety of a robotic system for inner ear surgery using probabilistic error modeling near vital anatomy

NASA Astrophysics Data System (ADS)

Dillon, Neal P.; Siebold, Michael A.; Mitchell, Jason E.; Blachon, Gregoire S.; Balachandran, Ramya; Fitzpatrick, J. Michael; Webster, Robert J.

2016-03-01

Safe and effective planning for robotic surgery that involves cutting or ablation of tissue must consider all potential sources of error when determining how close the tool may come to vital anatomy. A pre-operative plan that does not adequately consider potential deviations from ideal system behavior may lead to patient injury. Conversely, a plan that is overly conservative may result in ineffective or incomplete performance of the task. Thus, enforcing simple, uniform-thickness safety margins around vital anatomy is insufficient in the presence of spatially varying, anisotropic error. Prior work has used registration error to determine a variable-thickness safety margin around vital structures that must be approached during mastoidectomy but ultimately preserved. In this paper, these methods are extended to incorporate image distortion and physical robot errors, including kinematic errors and deflections of the robot. These additional sources of error are discussed and stochastic models for a bone-attached robot for otologic surgery are developed. An algorithm for generating appropriate safety margins based on a desired probability of preserving the underlying anatomical structure is presented. Simulations are performed on a CT scan of a cadaver head and safety margins are calculated around several critical structures for planning of a robotic mastoidectomy.

Comparing the Affordable Care Act's Financial Impact on Safety-Net Hospitals in States That Expanded Medicaid and Those That Did Not.

PubMed

Dobson, Allen; DaVanzo, Joan E; Haught, Randy; Phap-Hoa, Luu

2017-11-01

Safety-net hospitals play a vital role in delivering health care to Medicaid enrollees, the uninsured, and other vulnerable patients. By reducing the number of uninsured Americans, the Affordable Care Act (ACA) was also expected to lower these hospitals’ significant uncompensated care costs and shore up their financial stability. To examine how the ACA’s Medicaid expansion affected the financial status of safety-net hospitals in states that expanded Medicaid and in states that did not. Using Medicare hospital cost reports for federal fiscal years 2012 and 2015, the authors compared changes in Medicaid inpatient days as a percentage of total inpatient days, Medicaid revenues as a percentage of total net patient revenues, uncompensated care costs as a percentage of total operating costs, and hospital operating margins. Medicaid expansion had a significant, favorable financial impact on safety-net hospitals. From 2012 to 2015, safety-net hospitals in expansion states, compared to those in nonexpansion states, experienced larger increases in Medicaid inpatient days and Medicaid revenues as well as reduced uncompensated care costs. These changes improved operating margins for safety-net hospitals in expansion states. Margins for safety-net hospitals in nonexpansion states, meanwhile, declined.

A soft-contact model for computing safety margins in human prehension.

PubMed

Singh, Tarkeshwar; Ambike, Satyajit

2017-10-01

The soft human digit tip forms contact with grasped objects over a finite area and applies a moment about an axis normal to the area. These moments are important for ensuring stability during precision grasping. However, the contribution of these moments to grasp stability is rarely investigated in prehension studies. The more popular hard-contact model assumes that the digits exert a force vector but no free moment on the grasped object. Many sensorimotor studies use this model and show that humans estimate friction coefficients to scale the normal force to grasp objects stably, i.e. the smoother the surface, the tighter the grasp. The difference between the applied normal force and the minimal normal force needed to prevent slipping is called safety margin and this index is widely used as a measure of grasp planning. Here, we define and quantify safety margin using a more realistic contact model that allows digits to apply both forces and moments. Specifically, we adapt a soft-contact model from robotics and demonstrate that the safety margin thus computed is a more accurate and robust index of grasp planning than its hard-contact variant. Previously, we have used the soft-contact model to propose two indices of grasp planning that show how humans account for the shape and inertial properties of an object. A soft-contact based safety margin offers complementary insights by quantifying how humans may account for surface properties of the object and skin tissue during grasp planning and execution. Copyright © 2017 Elsevier B.V. All rights reserved.

Hydraulic safety margins and embolism reversal in stems and leaves: Why are conifers and angiosperms so different?

Treesearch

Daniel M. Johnson; Katherine A. McCulloh; David R. Woodruff; Frederick C. Meinzer

2012-01-01

Angiosperm and coniferous tree species utilize a continuum of hydraulic strategies. Hydraulic safety margins (defined as differences between naturally occurring xylem pressures and pressures that would cause hydraulic dysfunction, or differences between pressures resulting in loss of hydraulic function in adjacent organs (e.g., stems vs. leaves) tend to be much greater...

Derivation of improved load transformation matrices for launchers-spacecraft coupled analysis, and direct computation of margins of safety

NASA Technical Reports Server (NTRS)

Klein, M.; Reynolds, J.; Ricks, E.

1989-01-01

Load and stress recovery from transient dynamic studies are improved upon using an extended acceleration vector in the modal acceleration technique applied to structural analysis. Extension of the normal LTM (load transformation matrices) stress recovery to automatically compute margins of safety is presented with an application to the Hubble space telescope.

Predictors of Payer Mix and Financial Performance Among Safety Net Hospitals Prior to the Affordable Care Act.

PubMed

Sommers, Benjamin D; Stone, Juliana; Kane, Nancy

2016-01-01

The objective of this study was to use audited hospital financial statements to identify predictors of payer mix and financial performance in safety net hospitals prior to the Affordable Care Act. We analyzed the 2010 financial statements of 98 large, urban safety net hospital systems in 34 states, supplemented with data on population demographics, hospital features, and state policies. We used multivariate regression to identify independent predictors of three outcomes: 1) Medicaid-reliant payer mix (hospitals for which at least 25% of hospital days are paid for by Medicaid); 2) safety net revenue-to-cost ratio (Medicaid and Medicare Disproportionate Share Hospital payments and local government transfers, divided by charity care costs and Medicaid payment shortfall); and 3) operating margin. Medicaid-reliant payer mix was positively associated with more inclusive state Medicaid eligibility criteria and more minority patients. More inclusive Medicaid eligibility and higher Medicaid reimbursement rates positively predicted safety net revenue-to-cost ratio. University governance was the strongest positive predictor of operating margin. Safety net hospital financial performance varied considerably. Academic hospitals had higher operating margins, while more generous Medicaid eligibility and reimbursement policies improved hospitals' ability to recoup costs. Institutional and state policies may outweigh patient demographics in the financial health of safety net hospitals. © The Author(s) 2015.

Robust Adaptation? Assessing the sensitivity of safety margins in flood defences to uncertainty in future simulations - a case study from Ireland.

NASA Astrophysics Data System (ADS)

Murphy, Conor; Bastola, Satish; Sweeney, John

2013-04-01

Climate change impact and adaptation assessments have traditionally adopted a 'top-down' scenario based approach, where information from different Global Climate Models (GCMs) and emission scenarios are employed to develop impacts led adaptation strategies. Due to the tradeoffs in the computational cost and need to include a wide range of GCMs for fuller characterization of uncertainties, scenarios are better used for sensitivity testing and adaptation options appraisal. One common approach to adaptation that has been defined as robust is the use of safety margins. In this work the sensitivity of safety margins that have been adopted by the agency responsible for flood risk management in Ireland, to the uncertainty in future projections are examined. The sensitivity of fluvial flood risk to climate change is assessed for four Irish catchments using a large number of GCMs (17) forced with three emissions scenarios (SRES A1B, A2, B1) as input to four hydrological models. Both uncertainty within and between hydrological models is assessed using the GLUE framework. Regionalisation is achieved using a change factor method to infer changes in the parameters of a weather generator using monthly output from the GCMs, while flood frequency analysis is conducted using the method of probability weighted moments to fit the Generalised Extreme Value distribution to ~20,000 annual maxima series. The sensitivity of design margins to the uncertainty space considered is visualised using risk response surfaces. The hydrological sensitivity is measured as the percentage change in flood peak for specified recurrence intervals. Results indicate that there is a considerable residual risk associated with allowances of +20% when uncertainties are accounted for and that the risk of exceedence of design allowances is greatest for more extreme, low frequency events with considerable implication for critical infrastructure, e.g., culverts, bridges, flood defences whose designs are normally associated with such return periods. Sensitivity results show that the impact of climate change is not as great for flood peaks with higher return periods. The average width of the uncertainty range and the size of the range for each catchment reveals that the uncertainties in low frequency events are greater than high frequency events. In addition, the uncertainty interval, estimated as the average width of the uncertainty range of flow for the five return periods, grows wider with a decrease in the runoff coefficient and wetness index of each catchment, both of which tend to increase the nonlinearity in the rainfall response. A key management question that emerges is the acceptability of residual risk where high exposure of vulnerable populations and/or critical infrastructure coincide with high costs of additional capacity in safety margins.

Safety Assessment and Biological Effects of a New Cold Processed SilEmulsion for Dermatological Purpose

PubMed Central

Salgado, Ana; Gonçalves, Lídia; Pinto, Pedro C.; Urbano, Manuela; Ribeiro, Helena M.

2013-01-01

It is of crucial importance to evaluate the safety profile of the ingredients used in dermatological emulsions. A suitable equilibrium between safety and efficacy is a pivotal concern before the marketing of a dermatological product. The aim was to assess the safety and biological effects of a new cold processed silicone-based emulsion (SilEmulsion). The hazard, exposure, and dose-response assessment were used to characterize the risk for each ingredient. EpiSkin assay and human repeat insult patch tests were performed to compare the theoretical safety assessment to in vitro and in vivo data. The efficacy of the SilEmulsion was studied using biophysical measurements in human volunteers during 21 days. According to the safety assessment of the ingredients, 1,5-pentanediol was an ingredient of special concern since its margin of safety was below the threshold of 100 (36.53). EpiSkin assay showed that the tissue viability after the application of the SilEmulsion was 92 ± 6% and, thus considered nonirritant to the skin. The human studies confirmed that the SilEmulsion was not a skin irritant and did not induce any sensitization on the volunteers, being safe for human use. Moreover, biological effects demonstrated that the SilEmulsion increased both the skin hydration and skin surface lipids. PMID:24294598

Safety assessment and biological effects of a new cold processed SilEmulsion for dermatological purpose.

PubMed

Raposo, Sara; Salgado, Ana; Gonçalves, Lídia; Pinto, Pedro C; Urbano, Manuela; Ribeiro, Helena M

2013-01-01

It is of crucial importance to evaluate the safety profile of the ingredients used in dermatological emulsions. A suitable equilibrium between safety and efficacy is a pivotal concern before the marketing of a dermatological product. The aim was to assess the safety and biological effects of a new cold processed silicone-based emulsion (SilEmulsion). The hazard, exposure, and dose-response assessment were used to characterize the risk for each ingredient. EpiSkin assay and human repeat insult patch tests were performed to compare the theoretical safety assessment to in vitro and in vivo data. The efficacy of the SilEmulsion was studied using biophysical measurements in human volunteers during 21 days. According to the safety assessment of the ingredients, 1,5-pentanediol was an ingredient of special concern since its margin of safety was below the threshold of 100 (36.53). EpiSkin assay showed that the tissue viability after the application of the SilEmulsion was 92 ± 6% and, thus considered nonirritant to the skin. The human studies confirmed that the SilEmulsion was not a skin irritant and did not induce any sensitization on the volunteers, being safe for human use. Moreover, biological effects demonstrated that the SilEmulsion increased both the skin hydration and skin surface lipids.

Utilization of cone-beam CT for offline evaluation of target volume coverage during prostate image-guided radiotherapy based on bony anatomy alignment.

PubMed

Paluska, Petr; Hanus, Josef; Sefrova, Jana; Rouskova, Lucie; Grepl, Jakub; Jansa, Jan; Kasaova, Linda; Hodek, Miroslav; Zouhar, Milan; Vosmik, Milan; Petera, Jiri

2012-01-01

To assess target volume coverage during prostate image-guided radiotherapy based on bony anatomy alignment and to assess possibility of safety margin reduction. Implementation of IGRT should influence safety margins. Utilization of cone-beam CT provides current 3D anatomic information directly in irradiation position. Such information enables reconstruction of the actual dose distribution. Seventeen prostate patients were treated with daily bony anatomy image-guidance. Cone-beam CT (CBCT) scans were acquired once a week immediately after bony anatomy alignment. After the prostate, seminal vesicles, rectum and bladder were contoured, the delivered dose distribution was reconstructed. Target dose coverage was evaluated by the proportion of the CTV encompassed by the 95% isodose. Original plans employed a 1 cm safety margin. Alternative plans assuming a smaller 7 mm margin between CTV and PTV were evaluated in the same way. Rectal and bladder volumes were compared with the initial ones. Rectal and bladder volumes irradiated with doses higher than 75 Gy, 70 Gy, 60 Gy, 50 Gy and 40 Gy were analyzed. In 12% of reconstructed plans the prostate coverage was not sufficient. The prostate underdosage was observed in 5 patients. Coverage of seminal vesicles was not satisfactory in 3% of plans. Most of the target underdosage corresponded to excessive rectal or bladder filling. Evaluation of alternative plans assuming a smaller 7 mm margin revealed 22% and 11% of plans where prostate and seminal vesicles coverage, respectively, was compromised. These were distributed over 8 and 7 patients, respectively. Sufficient dose coverage of target volumes was not achieved for all patients. Reducing of safety margin is not acceptable. Initial rectal and bladder volumes cannot be considered representative for subsequent treatment.

RAVEN Theory Manual

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alfonsi, Andrea; Rabiti, Cristian; Mandelli, Diego

2016-06-01

RAVEN is a software framework able to perform parametric and stochastic analysis based on the response of complex system codes. The initial development was aimed at providing dynamic risk analysis capabilities to the thermohydraulic code RELAP-7, currently under development at Idaho National Laboratory (INL). Although the initial goal has been fully accomplished, RAVEN is now a multi-purpose stochastic and uncertainty quantification platform, capable of communicating with any system code. In fact, the provided Application Programming Interfaces (APIs) allow RAVEN to interact with any code as long as all the parameters that need to be perturbed are accessible by input filesmore » or via python interfaces. RAVEN is capable of investigating system response and explore input space using various sampling schemes such as Monte Carlo, grid, or Latin hypercube. However, RAVEN strength lies in its system feature discovery capabilities such as: constructing limit surfaces, separating regions of the input space leading to system failure, and using dynamic supervised learning techniques. The development of RAVEN started in 2012 when, within the Nuclear Energy Advanced Modeling and Simulation (NEAMS) program, the need to provide a modern risk evaluation framework arose. RAVEN’s principal assignment is to provide the necessary software and algorithms in order to employ the concepts developed by the Risk Informed Safety Margin Characterization (RISMC) program. RISMC is one of the pathways defined within the Light Water Reactor Sustainability (LWRS) program. In the RISMC approach, the goal is not just to identify the frequency of an event potentially leading to a system failure, but the proximity (or lack thereof) to key safety-related events. Hence, the approach is interested in identifying and increasing the safety margins related to those events. A safety margin is a numerical value quantifying the probability that a safety metric (e.g. peak pressure in a pipe) is exceeded under certain conditions. Most of the capabilities, implemented having RELAP-7 as a principal focus, are easily deployable to other system codes. For this reason, several side activates have been employed (e.g. RELAP5-3D, any MOOSE-based App, etc.) or are currently ongoing for coupling RAVEN with several different software. The aim of this document is to provide a set of commented examples that can help the user to become familiar with the RAVEN code usage.« less

NASA's Spaceliner Investment Area Technology Activities

NASA Technical Reports Server (NTRS)

Hueter, Uwe; Lyles, Garry M. (Technical Monitor)

2001-01-01

NASA's has established long term goals for access-to-space. The third generation launch systems are to be fully reusable and operational around 2025. The goals for the third generation launch system are to significantly reduce cost and improve safety over current conditions. The Advanced Space Transportation Program Office (ASTP) at the NASA's Marshall Space Flight Center in Huntsville, AL has the agency lead to develop space transportation technologies. Within ASTP, under the Spaceliner Investment Area, third generation technologies are being pursued in the areas of propulsion, airframes, integrated vehicle health management (IVHM), avionics, power, operations, and range. The ASTP program will mature these technologies through both ground and flight system testing. The Spaceliner Investment Area plans to mature vehicle technologies to reduce the implementation risks for future commercially developed reusable launch vehicles (RLV). The plan is to substantially increase the design and operating margins of the third generation RLV (the Space Shuttle is the first generation) by incorporating advanced technologies in propulsion, materials, structures, thermal protection systems, avionics, and power. Advancements in design tools and better characterization of the operational environment will allow improvements in design margins. Improvements in operational efficiencies will be provided through use of advanced integrated health management, operations, and range technologies. The increase in margins will allow components to operate well below their design points resulting in improved component operating life, reliability, and safety which in turn reduces both maintenance and refurbishment costs. These technologies have the potential of enabling horizontal takeoff by reducing the takeoff weight and achieving the goal of airline-like operation. These factors in conjunction with increased flight rates from an expanding market will result in significant improvements in safety and reductions in operational costs of future vehicles. The paper describes current status, future plans and technologies that are being matured by the Spaceliner Investment Area under the Advanced Space Transportation Program Office.

Margins of safety provided by COSHH Essentials and the ILO Chemical Control Toolkit.

PubMed

Jones, Rachael M; Nicas, Mark

2006-03-01

COSHH Essentials, developed by the UK Health and Safety Executive, and the Chemical Control Toolkit (Toolkit) proposed by the International Labor Organization, are 'control banding' approaches to workplace risk management intended for use by proprietors of small and medium-sized businesses. Both systems group chemical substances into hazard bands based on toxicological endpoint and potency. COSSH Essentials uses the European Union's Risk-phrases (R-phrases), whereas the Toolkit uses R-phrases and the Globally Harmonized System (GHS) of Classification and Labeling of Chemicals. Each hazard band is associated with a range of airborne concentrations, termed exposure bands, which are to be attained by the implementation of recommended control technologies. Here we analyze the margin of safety afforded by the systems and, for each hazard band, define the minimal margin as the ratio of the minimum airborne concentration that produced the toxicological endpoint of interest in experimental animals to the maximum concentration in workplace air permitted by the exposure band. We found that the minimal margins were always <100, with some ranging to <1, and inversely related to molecular weight. The Toolkit-GHS system generally produced margins equal to or larger than COSHH Essentials, suggesting that the Toolkit-GHS system is more protective of worker health. Although, these systems predict exposures comparable with current occupational exposure limits, we argue that the minimal margins are better indicators of health protection. Further, given the small margins observed, we feel it is important that revisions of these systems provide the exposure bands to users, so as to permit evaluation of control technology capture efficiency.

Compton Camera and Prompt Gamma Ray Timing: Two Methods for In Vivo Range Assessment in Proton Therapy

PubMed Central

Hueso-González, Fernando; Fiedler, Fine; Golnik, Christian; Kormoll, Thomas; Pausch, Guntram; Petzoldt, Johannes; Römer, Katja E.; Enghardt, Wolfgang

2016-01-01

Proton beams are promising means for treating tumors. Such charged particles stop at a defined depth, where the ionization density is maximum. As the dose deposit beyond this distal edge is very low, proton therapy minimizes the damage to normal tissue compared to photon therapy. Nevertheless, inherent range uncertainties cast doubts on the irradiation of tumors close to organs at risk and lead to the application of conservative safety margins. This constrains significantly the potential benefits of protons over photons. In this context, several research groups are developing experimental tools for range verification based on the detection of prompt gammas, a nuclear by-product of the proton irradiation. At OncoRay and Helmholtz-Zentrum Dresden-Rossendorf, detector components have been characterized in realistic radiation environments as a step toward a clinical Compton camera. On the one hand, corresponding experimental methods and results obtained during the ENTERVISION training network are reviewed. On the other hand, a novel method based on timing spectroscopy has been proposed as an alternative to collimated imaging systems. The first tests of the timing method at a clinical proton accelerator are summarized, its applicability in a clinical environment for challenging the current safety margins is assessed, and the factors limiting its precision are discussed. PMID:27148473

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Curtis L.; Prescott, Steven; Coleman, Justin

This report describes the current progress and status related to the Industry Application #2 focusing on External Hazards. For this industry application within the Light Water Reactor Sustainability (LWRS) Program Risk-Informed Safety Margin Characterization (RISMC) R&D Pathway, we will create the Risk-Informed Margin Management (RIMM) approach to represent meaningful (i.e., realistic facility representation) event scenarios and consequences by using an advanced 3D facility representation that will evaluate external hazards such as flooding and earthquakes in order to identify, model and analyze the appropriate physics that needs to be included to determine plant vulnerabilities related to external events; manage the communicationmore » and interactions between different physics modeling and analysis technologies; and develop the computational infrastructure through tools related to plant representation, scenario depiction, and physics prediction. One of the unique aspects of the RISMC approach is how it couples probabilistic approaches (the scenario) with mechanistic phenomena representation (the physics) through simulation. This simulation-based modeling allows decision makers to focus on a variety of safety, performance, or economic metrics. In this report, we describe the evaluation of various physics toolkits related to flooding representation. Ultimately, we will be coupling the flooding representation with other events such as earthquakes in order to provide coupled physics analysis for scenarios where interactions exist.« less

Nuclear power: Siting and safety

DOE Office of Scientific and Technical Information (OSTI.GOV)

Openshaw, S.

1986-01-01

By 2030, half, or even two-thirds, of all electricity may be generated by nuclear power. Major reactor accidents are still expected to be rare occurrences, but nuclear safety is largely a matter of faith. Terrorist attacks, sabotage, and human error could cause a significant accident. Reactor siting can offer an additional, design-independent margin of safety. Remote geographical sites for new plants would minimize health risks, protect the industry from negative changes in public opinion concerning nuclear energy, and improve long-term public acceptance of nuclear power. U.K. siting practices usually do not consider the contribution to safety that could be obtainedmore » from remote sites. This book discusses the present trends of siting policies of nuclear power and their design-independent margin of safety.« less

Coordination of xylem hydraulics and stomatal regulation in keeping the integrity of xylem water transport in shoots of two compound-leaved tree species.

PubMed

Liu, Yan-Yan; Song, Jia; Wang, Miao; Li, Na; Niu, Cun-Yang; Hao, Guang-You

2015-12-01

Hydraulic segmentation between proximal and distal organs has been hypothesized to be an important protective mechanism for plants to minimize the detrimental effects of drought-induced hydraulic failure. Uncertainties still exist regarding the degree of segmentation and the role of stomatal regulation in keeping hydraulic integrity of organs at different hierarchies. In the present study, we measured hydraulic conductivity and vulnerability in stems, compound leaf petioles and leaflet laminas of Fraxinus mandshurica Rupr. and Juglans mandshurica Maxim. growing in Changbai Mountain of Northeast China to identify the main locality where hydraulic segmentation occurs along the shoot water transport pathway. Stomatal conductance in response to leaf water potential change was also measured to investigate the role of stomatal regulation in avoiding extensive transpiration-induced embolism. No major contrasts were found between stems and compound leaf petioles in either hydraulic conductivity or vulnerability to drought-induced embolism, whereas a large difference in hydraulic vulnerability exists between compound leaf petioles and leaflet laminas. Furthermore, in contrast to the relatively large safety margins in stems (4.13 and 2.04 MPa) and compound leaf petioles (1.33 and 1.93 MPa), leaflet lamina hydraulic systems have substantially smaller or even negative safety margins (-0.17 and 0.47 MPa) in F. mandshurica and J. mandshurica. Under unstressed water conditions, gas exchange may be better optimized by allowing leaflet vascular system function with small safety margins. In the meantime, hydraulic safety of compound leaf petioles and stems are guaranteed by their large safety margins. In facing severe drought stress, larger safety margins in stems than in compound leaf petioles would allow plants to minimize the risk of catastrophic embolism in stems by sacrificing the whole compound leaves. A strong coordination between hydraulic and stomatal regulation appears to play a critical role in balancing the competing efficiency and safety requirements for xylem water transport and use in plants. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Flooding Fragility Experiments and Prediction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Curtis L.; Tahhan, Antonio; Muchmore, Cody

2016-09-01

This report describes the work that has been performed on flooding fragility, both the experimental tests being carried out and the probabilistic fragility predictive models being produced in order to use the text results. Flooding experiments involving full-scale doors have commenced in the Portal Evaluation Tank. The goal of these experiments is to develop a full-scale component flooding experiment protocol and to acquire data that can be used to create Bayesian regression models representing the fragility of these components. This work is in support of the Risk-Informed Safety Margin Characterization (RISMC) Pathway external hazards evaluation research and development.

Developing Probabilistic Safety Performance Margins for Unknown and Underappreciated Risks

NASA Technical Reports Server (NTRS)

Benjamin, Allan; Dezfuli, Homayoon; Everett, Chris

2015-01-01

Probabilistic safety requirements currently formulated or proposed for space systems, nuclear reactor systems, nuclear weapon systems, and other types of systems that have a low-probability potential for high-consequence accidents depend on showing that the probability of such accidents is below a specified safety threshold or goal. Verification of compliance depends heavily upon synthetic modeling techniques such as PRA. To determine whether or not a system meets its probabilistic requirements, it is necessary to consider whether there are significant risks that are not fully considered in the PRA either because they are not known at the time or because their importance is not fully understood. The ultimate objective is to establish a reasonable margin to account for the difference between known risks and actual risks in attempting to validate compliance with a probabilistic safety threshold or goal. In this paper, we examine data accumulated over the past 60 years from the space program, from nuclear reactor experience, from aircraft systems, and from human reliability experience to formulate guidelines for estimating probabilistic margins to account for risks that are initially unknown or underappreciated. The formulation includes a review of the safety literature to identify the principal causes of such risks.

Negative Stress Margins - Are They Real?

NASA Technical Reports Server (NTRS)

Raju, Ivatury S.; Lee, Darlene S.; Mohaghegh, Michael

2011-01-01

Advances in modeling and simulation, new finite element software, modeling engines and powerful computers are providing opportunities to interrogate designs in a very different manner and in a more detailed approach than ever before. Margins of safety are also often evaluated using local stresses for various design concepts and design parameters quickly once analysis models are defined and developed. This paper suggests that not all the negative margins of safety evaluated are real. The structural areas where negative margins are frequently encountered are often near stress concentrations, point loads and load discontinuities, near locations of stress singularities, in areas having large gradients but with insufficient mesh density, in areas with modeling issues and modeling errors, and in areas with connections and interfaces, in two-dimensional (2D) and three-dimensional (3D) transitions, bolts and bolt modeling, and boundary conditions. Now, more than ever, structural analysts need to examine and interrogate their analysis results and perform basic sanity checks to determine if these negative margins are real.

Determining the safety of enzymes used in animal feed.

PubMed

Pariza, Michael W; Cook, Mark

2010-04-01

The purpose of this paper is to provide guidance for evaluating the safety of enzyme preparations used in animal feed. Feed enzymes are typically added to animal feed to increase nutrient bioavailability by acting on feed components prior to or after consumption, i.e., within the gastrointestinal tract. In contrast, food processing enzymes are generally used during processing and then inactivated or removed prior to consumption. The enzymes used in both applications are almost always impure mixtures of active enzyme and other metabolites from the production strain, hence similar safety evaluation procedures for both are warranted. We propose that the primary consideration should be the safety of the production strain and that the decision tree mechanism developed previously for food processing enzymes (Pariza and Johnson, 2001) is appropriate for determining the safety of feed enzymes. Thoroughly characterized non-pathogenic, non-toxigenic microbial strains with a history of safe use in enzyme manufacture are also logical candidates for generating safe strain lineages, from which additional strains may be derived via genetic modification by traditional and non-traditional strategies. For new feed enzyme products derived from a safe strain lineage, it is important to ensure a sufficiently high safety margin for the intended use, and that the product complies with appropriate specifications for chemical and microbial contamination. Copyright 2009 Elsevier Inc. All rights reserved.

Margin of Safety Definition and Examples Used in Safety Basis Documents and the USQ Process

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beaulieu, R. A.

The Nuclear Safety Management final rule, 10 CFR 830, provides an undefined term, margin of safety (MOS). Safe harbors listed in 10 CFR 830, Table 2, such as DOE-STD-3009 use but do not define the term. This lack of definition has created the need for the definition. This paper provides a definition of MOS and documents examples of MOS as applied in a U.S. Department of Energy (DOE) approved safety basis for an existing nuclear facility. If we understand what MOS looks like regarding Technical Safety Requirements (TSR) parameters, then it helps us compare against other parameters that do notmore » involve a MOS. This paper also documents parameters that are not MOS. These criteria could be used to determine if an MOS exists in safety basis documents. This paper helps DOE, including the National Nuclear Security Administration (NNSA) and its contractors responsible for the safety basis improve safety basis documents and the unreviewed safety question (USQ) process with respect to MOS.« less

Prediction of Safety Margin and Optimization of Dosing Protocol for a Novel Antibiotic using Quantitative Systems Pharmacology Modeling.

PubMed

Woodhead, Jeffrey L; Paech, Franziska; Maurer, Martina; Engelhardt, Marc; Schmitt-Hoffmann, Anne H; Spickermann, Jochen; Messner, Simon; Wind, Mathias; Witschi, Anne-Therese; Krähenbühl, Stephan; Siler, Scott Q; Watkins, Paul B; Howell, Brett A

2018-06-07

Elevations of liver enzymes have been observed in clinical trials with BAL30072, a novel antibiotic. In vitro assays have identified potential mechanisms for the observed hepatotoxicity, including electron transport chain (ETC) inhibition and reactive oxygen species (ROS) generation. DILIsym, a quantitative systems pharmacology (QSP) model of drug-induced liver injury, has been used to predict the likelihood that each mechanism explains the observed toxicity. DILIsym was also used to predict the safety margin for a novel BAL30072 dosing scheme; it was predicted to be low. DILIsym was then used to recommend potential modifications to this dosing scheme; weight-adjusted dosing and a requirement to assay plasma alanine aminotransferase (ALT) daily and stop dosing as soon as ALT increases were observed improved the predicted safety margin of BAL30072 and decreased the predicted likelihood of severe injury. This research demonstrates a potential application for QSP modeling in improving the safety profile of candidate drugs. © 2018 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

A theory and model of conflict detection in air traffic control: incorporating environmental constraints.

PubMed

Loft, Shayne; Bolland, Scott; Humphreys, Michael S; Neal, Andrew

2009-06-01

A performance theory for conflict detection in air traffic control is presented that specifies how controllers adapt decisions to compensate for environmental constraints. This theory is then used as a framework for a model that can fit controller intervention decisions. The performance theory proposes that controllers apply safety margins to ensure separation between aircraft. These safety margins are formed through experience and reflect the biasing of decisions to favor safety over accuracy, as well as expectations regarding uncertainty in aircraft trajectory. In 2 experiments, controllers indicated whether they would intervene to ensure separation between pairs of aircraft. The model closely predicted the probability of controller intervention across the geometry of problems and as a function of controller experience. When controller safety margins were manipulated via task instructions, the parameters of the model changed in the predicted direction. The strength of the model over existing and alternative models is that it better captures the uncertainty and decision biases involved in the process of conflict detection. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

Final stress analysis report ultraviolet spectrometer S169

NASA Technical Reports Server (NTRS)

Cooper, S.

1971-01-01

The stress analysis report verifies the structural integrity of the Apollo S-169 UV-spectrometer experiment. The methods by which the various members were analyzed are described. A detailed summary of results for the individual structural elements appears in the form of a table of minimum margins of safety. No negative margins of safety were experienced. It is concluded that the component structure is more than adequate to withstand the environmental load conditions given in the design criteria.

Hydraulic safety margins and air-seeding thresholds in roots, trunks, branches and petioles of four northern hardwood trees.

PubMed

Wason, Jay W; Anstreicher, Katherine S; Stephansky, Nathan; Huggett, Brett A; Brodersen, Craig R

2018-04-16

During drought, xylem sap pressures can approach or exceed critical thresholds where gas embolisms form and propagate through the xylem network, leading to systemic hydraulic dysfunction. The vulnerability segmentation hypothesis (VSH) predicts that low-investment organs (e.g. leaf petioles) should be more vulnerable to embolism spread compared to high-investment, perennial organs (e.g. trunks, stems), as a means of mitigating embolism spread and excessive negative pressures in the perennial organs. We tested this hypothesis by measuring air-seeding thresholds using the single-vessel air-injection method and calculating hydraulic safety margins in four northern hardwood tree species of the northeastern United States, in both saplings and canopy height trees, and at five points along the soil-plant-atmosphere continuum. Acer rubrum was the most resistant to air-seeding and generally supported the VSH. However, Fagus grandifolia, Fraxinus americana and Quercus rubra showed little to no variation in air-seeding thresholds across organ types within each species. Leaf-petiole xylem operated at water potentials close to or exceeding their hydraulic safety margins in all species, whereas roots, trunks and stems of A. rubrum, F. grandifolia and Q. rubra operated within their safety margins, even during the third-driest summer in the last 100 yr. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

Contrasting trait syndromes in angiosperms and conifers are associated with different responses of tree growth to temperature on a large scale.

PubMed

Carnicer, Jofre; Barbeta, Adrià; Sperlich, Dominik; Coll, Marta; Peñuelas, Josep

2013-01-01

Recent large-scale studies of tree growth in the Iberian Peninsula reported contrasting positive and negative effects of temperature in Mediterranean angiosperms and conifers. Here we review the different hypotheses that may explain these trends and propose that the observed contrasting responses of tree growth to temperature in this region could be associated with a continuum of trait differences between angiosperms and conifers. Angiosperm and conifer trees differ in the effects of phenology in their productivity, in their growth allometry, and in their sensitivity to competition. Moreover, angiosperms and conifers significantly differ in hydraulic safety margins, sensitivity of stomatal conductance to vapor-pressure deficit (VPD), xylem recovery capacity or the rate of carbon transfer. These differences could be explained by key features of the xylem such as non-structural carbohydrate content (NSC), wood parenchymal fraction or wood capacitance. We suggest that the reviewed trait differences define two contrasting ecophysiological strategies that may determine qualitatively different growth responses to increased temperature and drought. Improved reciprocal common garden experiments along altitudinal or latitudinal gradients would be key to quantify the relative importance of the different hypotheses reviewed. Finally, we show that warming impacts in this area occur in an ecological context characterized by the advance of forest succession and increased dominance of angiosperm trees over extensive areas. In this context, we examined the empirical relationships between the responses of tree growth to temperature and hydraulic safety margins in angiosperm and coniferous trees. Our findings suggest a future scenario in Mediterranean forests characterized by contrasting demographic responses in conifer and angiosperm trees to both temperature and forest succession, with increased dominance of angiosperm trees, and particularly negative impacts in pines.

Contrasting trait syndromes in angiosperms and conifers are associated with different responses of tree growth to temperature on a large scale

PubMed Central

Carnicer, Jofre; Barbeta, Adrià; Sperlich, Dominik; Coll, Marta; Peñuelas, Josep

2013-01-01

Recent large-scale studies of tree growth in the Iberian Peninsula reported contrasting positive and negative effects of temperature in Mediterranean angiosperms and conifers. Here we review the different hypotheses that may explain these trends and propose that the observed contrasting responses of tree growth to temperature in this region could be associated with a continuum of trait differences between angiosperms and conifers. Angiosperm and conifer trees differ in the effects of phenology in their productivity, in their growth allometry, and in their sensitivity to competition. Moreover, angiosperms and conifers significantly differ in hydraulic safety margins, sensitivity of stomatal conductance to vapor-pressure deficit (VPD), xylem recovery capacity or the rate of carbon transfer. These differences could be explained by key features of the xylem such as non-structural carbohydrate content (NSC), wood parenchymal fraction or wood capacitance. We suggest that the reviewed trait differences define two contrasting ecophysiological strategies that may determine qualitatively different growth responses to increased temperature and drought. Improved reciprocal common garden experiments along altitudinal or latitudinal gradients would be key to quantify the relative importance of the different hypotheses reviewed. Finally, we show that warming impacts in this area occur in an ecological context characterized by the advance of forest succession and increased dominance of angiosperm trees over extensive areas. In this context, we examined the empirical relationships between the responses of tree growth to temperature and hydraulic safety margins in angiosperm and coniferous trees. Our findings suggest a future scenario in Mediterranean forests characterized by contrasting demographic responses in conifer and angiosperm trees to both temperature and forest succession, with increased dominance of angiosperm trees, and particularly negative impacts in pines. PMID:24146668

[JUSTIFICATION OF USING EQUIVALENCE OF THE INDICES OF QUALITY, SAFETY, AND EFFICACY IN DEVELOPING BIOANALOGS].

PubMed

Niyazov, R R; Goryachev, D V; Gavrishina, E V; Romodanovskii, D P; Dranitsyna, M A

2015-01-01

We describe general principles of demonstrating biosimilarity, as well as selecting the biosimilarity margins. Any change in the structure of a biological molecule can modify its functional activity. Therefore, therapeutic equivalence between a biosimilar product and the corresponding reference product cannot be demonstrated using a single criterion. To demonstrate biosimilarity between two medicinal products, their various characteristics have to be evaluated which may, directly or indirectly, justify that clinically significant differences are absent. Insufficient understanding of 6ritical quality attributes brings a risk for the biosimilar product developer. This will either increase the number of non-clinical and clinical tests and trials needed or will result in awareness that the manufacturing process needs to be improved at the late stages of development, after investing significant resources in the development process. At the same time, the specification of the biological medicinal product cannot solely ensure safety and efficacy thereof. Properly characterized and controlled manufacturing process, which ensures consistency in its attributes not adequately controlled in specifications but influencing safety and efficacy profiles and showing their relevance in non-clinical tests and clinical trials, is an additional quality assurance factor. Justification of all development strategy details, including biosimilarity margins, has to be provided each time when the development process is initiated or when proceeding to the next steps. All problems encountered by the developer have to be resolved in close communication with the regulatory authority. In order to increase the quality of investigation and developer's adherence to good practices, clinical trial results should be published in detail.

[Nitrates (V) in drinking water as factor of a health risk for people in Podlaskie Voivodship].

PubMed

Szczerbiński, Robert; Karczewski, Jan; Fiłon, Joanna

2006-01-01

The aim of this article was to evaluate of a health danger and to estimate the risk due to the presence of nitrates (V) in drinking water used by people in Podlaskie Voivodship. For research I used water specimens taken in 14 poviats (smaller administration districts) in Podlaskie Voivodship as part of drinking water quality monitoring in the years 2001-2003. Evaluation of danger of nitrates (V) taken in with drinking water by the population of Podlaskie Voivodship was carried out by comparing ADI (Acceptable Daily Intake) with value of EDI (Evaluated Daily Intake) and TMDI (Theoretical Maximum Daily Intake) Risk was estimated by calculating safety margin between ADI and EDI. On the basis of the obtained results it was stated that on the territory of Podlaskie Voivodship 1.79% of urban population and 4.86% of rural population, was taking in nitrates (V) with water supplied by waterworks in doses below the safety margin. Nitrates (V) from drinking water in doses below the safety margin were taken in by population of 10 poviats, with the highest percentage of the population noted in the poviats of: Grajewo (10.97%), Augustów (10.77%) and Sejny (10.43%). Among the urban population the highest percentage noted in the Poviat of Augustów (9.46%), and among the rural population--in the Poviat of Grajewo (22.46%). The highest percentage of the population (69.97%) in Podlaskie Voivodship consumed nitrates (V) with drinking water supplied by waterworks in the range of the safety margin from 1 to 10, including 78.86% of urban population and 53.3% of rural population. It seems useful to continue the environmental research on the exposure of Podlaskie Voivodship inhabitants to nitrates by correlating the risk expressed by the safety margin with cancer epidemiology.

Margins Associated with Loss of Assured Safety for Systems with Multiple Time-Dependent Failure Modes.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Helton, Jon C.; Brooks, Dusty Marie; Sallaberry, Cedric Jean-Marie.

Representations for margins associated with loss of assured safety (LOAS) for weak link (WL)/strong link (SL) systems involving multiple time-dependent failure modes are developed. The following topics are described: (i) defining properties for WLs and SLs, (ii) background on cumulative distribution functions (CDFs) for link failure time, link property value at link failure, and time at which LOAS occurs, (iii) CDFs for failure time margins defined by (time at which SL system fails) – (time at which WL system fails), (iv) CDFs for SL system property values at LOAS, (v) CDFs for WL/SL property value margins defined by (property valuemore » at which SL system fails) – (property value at which WL system fails), and (vi) CDFs for SL property value margins defined by (property value of failing SL at time of SL system failure) – (property value of this SL at time of WL system failure). Included in this presentation is a demonstration of a verification strategy based on defining and approximating the indicated margin results with (i) procedures based on formal integral representations and associated quadrature approximations and (ii) procedures based on algorithms for sampling-based approximations.« less

Impact of long farm working hours on child safety practices in agricultural settings.

PubMed

Marlenga, Barbara; Pahwa, Punam; Hagel, Louise; Dosman, James; Pickett, William; Brison, Robert J; Crowe, Trever; Koehncke, Niels; Snodgrass, Phyllis; Day, Lesley; Voaklander, Donald

2010-01-01

To characterize working hours of adult farm owner-operators and their spouses by season, and to examine associations between working hours and farm safety practices affecting children. We conducted a secondary analysis of cross-sectional survey data collected as part of an existing study of injury and its determinants. Owner-operators reported a median of 60 to 70 hours of farm work per week during warm weather months, with declines in hours over the winter. Spouses reported similar seasonal patterns, although their median reported hours were much lower. Longer farm working hours by owner-operators were marginally associated with increased exposure of teenagers to farm work hazards. Exposures of young children to worksite hazards rose in association with longer farm working hours by spouses. Exposures of children to farm worksite hazards and demands may be consequences of adult long working hours. © 2010 National Rural Health Association.

Safe insertion of S-2 alar iliac screws: radiological comparison between 2 insertion points using computed tomography and 3D analysis software.

PubMed

Yamada, Kentaro; Abe, Yuichiro; Satoh, Shigenobu

2018-05-01

OBJECTIVE S-2 alar iliac (S2AI) screws are commonly used as anchors for lumbosacral fixation. A serious potential complication of screw insertion is major vascular injury due to anterior or caudal screw deviation. To avoid screw deviation, the pelvic inlet view on intraoperative fluoroscopy images is recommended. However, there has been no detailed investigation of optimal fluoroscopic incline with the pelvic inlet view. The purpose of this study was to investigate the safety margins and to optimize fluoroscopic settings to avoid screw deviation with 2 reported insertion techniques using 3D analysis software and CT. METHODS The study included 50 patients (25 men and 25 women) who underwent abdominal-pelvic CT. With the use of software, the ideal S2AI screws were set from 2 entry points: A) the midpoint between the S-1 dorsal foramen and the S-2 dorsal foramen where they meet the lateral sacral crest, and B) 1 mm inferior and 1 mm lateral to the S-1 dorsal foramen. Anteriorly or caudally deviated screws were defined as deviation of a half thread of the ideal screw by rotation anteriorly or caudally from the entry point. The angular safety margins were compared between the 2 entry points, and patients with small safety margins were investigated. Subsequently, fluoroscopic images were virtualized on ray sum-rendered images. Conditions that provided proper recognition of screw deviation were investigated via lateral and anteroposterior views with the beam tilted caudally. RESULTS The safety margins of S2AI screws were smaller in the anterior direction than in the caudal direction and by entry point A than by entry point B (A: 9.1° ± 1.6° and B: 9.7° ± 1.5° in the anterior direction; A: 10.9° ± 3.8° and B: 13.9° ± 4.1° in the caudal direction). In contrast, patients with a deep-seated L-5 vertebral body tended to have smaller safety margins in the caudal direction. All anteriorly deviated screws were recognized with a 60°-70° inlet view from the S-1 slope. The caudally deviated screws were all recognized on the lateral view, but 31% of screws at entry point A and 21% of screws at entry point B were not recognized on the pelvic inlet view. CONCLUSIONS S2AI screws should be carefully placed to avoid anterior deviation compared with caudal deviation in terms of the safety margin, except in patients with a deep-seated L-5. The difference in safety margins between entry points A and B was negligible. Intraoperative fluoroscopy is recommended with a pelvic inlet view tilted 60°-70° from the S-1 slope to avoid anterior screw deviation. The lateral view is recommended to confirm that the screw is not deviated caudally.

Probabilistic margin evaluation on accidental transients for the ASTRID reactor project

NASA Astrophysics Data System (ADS)

Marquès, Michel

2014-06-01

ASTRID is a technological demonstrator of Sodium cooled Fast Reactor (SFR) under development. The conceptual design studies are being conducted in accordance with the Generation IV reactor objectives, particularly in terms of improving safety. For the hypothetical events, belonging to the accidental category "severe accident prevention situations" having a very low frequency of occurrence, the safety demonstration is no more based on a deterministic demonstration with conservative assumptions on models and parameters but on a "Best-Estimate Plus Uncertainty" (BEPU) approach. This BEPU approach ispresented in this paper for an Unprotected Loss-of-Flow (ULOF) event. The Best-Estimate (BE) analysis of this ULOFt ransient is performed with the CATHARE2 code, which is the French reference system code for SFR applications. The objective of the BEPU analysis is twofold: first evaluate the safety margin to sodium boiling in taking into account the uncertainties on the input parameters of the CATHARE2 code (twenty-two uncertain input parameters have been identified, which can be classified into five groups: reactor power, accident management, pumps characteristics, reactivity coefficients, thermal parameters and head losses); secondly quantify the contribution of each input uncertainty to the overall uncertainty of the safety margins, in order to refocusing R&D efforts on the most influential factors. This paper focuses on the methodological aspects of the evaluation of the safety margin. At least for the preliminary phase of the project (conceptual design), a probabilistic criterion has been fixed in the context of this BEPU analysis; this criterion is the value of the margin to sodium boiling, which has a probability 95% to be exceeded, obtained with a confidence level of 95% (i.e. the M5,95percentile of the margin distribution). This paper presents two methods used to assess this percentile: the Wilks method and the Bootstrap method ; the effectiveness of the two methods is compared on the basis of 500 simulations performed with theCATHARE2 code. We conclude that, with only 100 simulations performed with the CATHARE2 code, which is a number of simulations workable in the conceptual design phase of the ASTRID project where the models and the hypothesis are often modified, it is best in order to evaluate the percentile M5,95 of the margin to sodium boiling to use the bootstrap method, which will provide a slightly conservative result. On the other hand, in order to obtain an accurate estimation of the percentileM5,95, for the safety report for example, it will be necessary to perform at least 300 simulations with the CATHARE2 code. In this case, both methods (Wilks and Bootstrap) would give equivalent results.

Data Analysis Approaches for the Risk-Informed Safety Margins Characterization Toolkit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mandelli, Diego; Alfonsi, Andrea; Maljovec, Daniel P.

2016-09-01

In the past decades, several numerical simulation codes have been employed to simulate accident dynamics (e.g., RELAP5-3D, RELAP-7, MELCOR, MAAP). In order to evaluate the impact of uncertainties into accident dynamics, several stochastic methodologies have been coupled with these codes. These stochastic methods range from classical Monte-Carlo and Latin Hypercube sampling to stochastic polynomial methods. Similar approaches have been introduced into the risk and safety community where stochastic methods (such as RAVEN, ADAPT, MCDET, ADS) have been coupled with safety analysis codes in order to evaluate the safety impact of timing and sequencing of events. These approaches are usually calledmore » Dynamic PRA or simulation-based PRA methods. These uncertainties and safety methods usually generate a large number of simulation runs (database storage may be on the order of gigabytes or higher). The scope of this paper is to present a broad overview of methods and algorithms that can be used to analyze and extract information from large data sets containing time dependent data. In this context, “extracting information” means constructing input-output correlations, finding commonalities, and identifying outliers. Some of the algorithms presented here have been developed or are under development within the RAVEN statistical framework.« less

Exposure to solar radiation drives organismal vulnerability to climate: Evidence from an intertidal limpet.

PubMed

Chapperon, Coraline; Volkenborn, Nils; Clavier, Jacques; Séité, Sarah; Seabra, Rui; Lima, Fernando P

2016-04-01

Understanding the physiological abilities of organisms to cope with heat stress is critical for predictions of species' distributions in response to climate change. We investigated physiological responses (respiration and heart beat rate) of the ectotherm limpet Patella vulgata to heat stress events during emersion and the role of seasonal and microclimatic acclimatization for individual thermal tolerance limits. Individuals were collected from 5 microhabitats characterized by different exposure to solar radiation in the high intertidal zone of a semi-exposed rocky shore in winter and summer of 2014. Upper thermal tolerance limits (heat coma temperatures - HCTs, and heart rate Arrhenius break temperatures - ABTs) were determined for individuals from each microhabitat in both seasons under laboratory conditions. While we found a clear seasonal acclimatization, i.e., higher HCTs and ABTs in summer than in winter, we did not find evidence for microhabitat-specific responses that would suggest microclimatic acclimatization. However, operative limpet temperatures derived from in-situ temperature measurements suggest that individuals from sun exposed microhabitats have a much narrower thermal safety margins than those from less exposed surfaces or within crevices. Microhabitat specific thermal safety margins caused by high thermal heterogeneity at small spatial scales and the lack of short term acclimatization will likely shape small scale distribution patterns of intertidal species in response to the predicted increase in the frequency and intensity of heat waves. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cryptosporidium and Giardia safety margin increase in leafy green vegetables irrigated with treated wastewater.

PubMed

Domenech, Eva; Amorós, Inmaculada; Moreno, Yolanda; Alonso, José L

2018-01-01

The presence of Cryptosporidium and Giardia in waste water is a main concern because water reuse for irrigation can jeopardize human health. Spanish Legislation for water reuse does not oblige to analyze the presence of both pathogens Cryptosporidium and Giardia in reused water for irrigation. Therefore, the objective of this paper is to determine the influence of wastewater treatment in the increase of the consumer safety margin in relation to the presence of Cryptosporidium and Giardia in leafy green vegetables. With this aim in mind, a total of 108 samples from raw (influent) and treated wastewater (effluent) from three wastewater treatment plants in Spain were analysed according to USEPA Method 1623. Effluent results show that Cryptosporidium oocysts average counts ranged from 1.38 to 2.6/L oocysts and Giardia cysts ranged from 0.6 to 1.7/L cysts, which means a removal values of 2.7 log, 2.5 log and 1.8 log for Cryptosporidium oocysts and 1 log, 2 log and 2.2 log for Giardia cysts in the three wastewater treatment plants analysed. In relation to safety margin the highest probability that exposure exceed the dose response was observed for Giardia. In addition, the sensitivity analysis showed that (oo)cysts concentration present in the leafy green vegetables and the human dose-response were the most influential inputs in the safety margin obtained. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

A quantitative comparison of the safety margins in the european indicative occupational exposure limits and the derived no-effect levels for workers under REACH.

PubMed

Schenk, Linda; Johanson, Gunnar

2011-06-01

The new European Union (EU) REACH legislation requires derived no-effect levels (DNELs) to be calculated for substances produced in quantities above 10 tonnes/year. Meanwhile, the setting of occupational exposure limits (OELs) continues both at the member state and the EU levels. According to REACH, indicative OEL values (IOELVs) from the Commission may under some circumstances be used as worker-DNELs. On the other hand, worker-DNELs will be derived for several thousand substances, far more than the approximately 100 substances for which IOELVs have been established. Thus, the procedure to set health-based OELs may become influential on that of DNELs and vice versa. In this study, we compare the safety margins of 88 Scientific Committee on OELs (SCOEL) recommendations with those of the corresponding worker-DNELs, derived according to the default approach as described in the REACH guidance document. Overall, the REACH safety margins were approximately six times higher than those derived from the SCOEL documentation but varied widely with REACH/SCOEL safety margin ratios ranging by two orders of magnitude, from 0.3 to 58 (n = 88). The discrepancies may create confusion in terms of legal compliance, risk management, and risk communication. We also found that the REACH guidance document, although encompassing detailed advice on many issues, including default assessment factors for species and route extrapolation, gives little quantitative guidance on when and how to depart from defaults.

Comparisons of Wilks’ and Monte Carlo Methods in Response to the 10CFR50.46(c) Proposed Rulemaking

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Hongbin; Szilard, Ronaldo; Zou, Ling

The Nuclear Regulatory Commission (NRC) is proposing a new rulemaking on emergency core system/loss-of-coolant accident (LOCA) performance analysis. In the proposed rulemaking, designated as 10CFR50.46(c), the US NRC put forward an equivalent cladding oxidation criterion as a function of cladding pre-transient hydrogen content. The proposed rulemaking imposes more restrictive and burnup-dependent cladding embrittlement criteria; consequently nearly all the fuel rods in a reactor core need to be analyzed under LOCA conditions to demonstrate compliance to the safety limits. New analysis methods are required to provide a thorough characterization of the reactor core in order to identify the locations of themore » limiting rods as well as to quantify the safety margins under LOCA conditions. With the new analysis method presented in this work, the limiting transient case and the limiting rods can be easily identified to quantify the safety margins in response to the proposed new rulemaking. In this work, the best-estimate plus uncertainty (BEPU) analysis capability for large break LOCA with the new cladding embrittlement criteria using the RELAP5-3D code is established and demonstrated with a reduced set of uncertainty parameters. Both the direct Monte Carlo method and the Wilks’ nonparametric statistical method can be used to perform uncertainty quantification. Wilks’ method has become the de-facto industry standard to perform uncertainty quantification in BEPU LOCA analyses. Despite its widespread adoption by the industry, the use of small sample sizes to infer statement of compliance to the existing 10CFR50.46 rule, has been a major cause of unrealized operational margin in today’s BEPU methods. Moreover the debate on the proper interpretation of the Wilks’ theorem in the context of safety analyses is not fully resolved yet, even more than two decades after its introduction in the frame of safety analyses in the nuclear industry. This represents both a regulatory and application risk in rolling out new methods. With the 10CFR50.46(c) proposed rulemaking, the deficiencies of the Wilks’ approach are further exacerbated. The direct Monte Carlo approach offers a robust alternative to perform uncertainty quantification within the context of BEPU analyses. In this work, the Monte Carlo method is compared with the Wilks’ method in response to the NRC 10CFR50.46(c) proposed rulemaking.« less

RAVEN User Manual

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mandelli, Diego; Rabiti, Cristian; Cogliati, Joshua Joseph

2015-10-01

RAVEN is a generic software framework to perform parametric and probabilistic analysis based on the response of complex system codes. The initial development was aimed to provide dynamic risk analysis capabilities to the Thermo-Hydraulic code RELAP-7, currently under development at the Idaho National Laboratory (INL). Although the initial goal has been fully accomplished, RAVEN is now a multi-purpose probabilistic and uncertainty quantification platform, capable to agnostically communicate with any system code. This agnosticism includes providing Application Programming Interfaces (APIs). These APIs are used to allow RAVEN to interact with any code as long as all the parameters that need tomore » be perturbed are accessible by inputs files or via python interfaces. RAVEN is capable of investigating the system response, and investigating the input space using Monte Carlo, Grid, or Latin Hyper Cube sampling schemes, but its strength is focused toward system feature discovery, such as limit surfaces, separating regions of the input space leading to system failure, using dynamic supervised learning techniques. The development of RAVEN has started in 2012, when, within the Nuclear Energy Advanced Modeling and Simulation (NEAMS) program, the need to provide a modern risk evaluation framework became stronger. RAVEN principal assignment is to provide the necessary software and algorithms in order to employ the concept developed by the Risk Informed Safety Margin Characterization (RISMC) program. RISMC is one of the pathways defined within the Light Water Reactor Sustainability (LWRS) program. In the RISMC approach, the goal is not just the individuation of the frequency of an event potentially leading to a system failure, but the closeness (or not) to key safety-related events. Hence, the approach is interested in identifying and increasing the safety margins related to those events. A safety margin is a numerical value quantifying the probability that a safety metric (e.g. for an important process such as peak pressure in a pipe) is exceeded under certain conditions. The initial development of RAVEN has been focused on providing dynamic risk assessment capability to RELAP-7, currently under development at the INL and, likely, future replacement of the RELAP5-3D code. Most the capabilities that have been implemented having RELAP-7 as principal focus are easily deployable for other system codes. For this reason, several side activaties are currently ongoing for coupling RAVEN with software such as RELAP5-3D, etc. The aim of this document is the explanation of the input requirements, focalizing on the input structure.« less

RAVEN User Manual

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mandelli, Diego; Rabiti, Cristian; Cogliati, Joshua Joseph

2016-02-01

RAVEN is a generic software framework to perform parametric and probabilistic analysis based on the response of complex system codes. The initial development was aimed to provide dynamic risk analysis capabilities to the Thermo-Hydraulic code RELAP-7, currently under development at the Idaho National Laboratory (INL). Although the initial goal has been fully accomplished, RAVEN is now a multi-purpose probabilistic and uncertainty quantification platform, capable to agnostically communicate with any system code. This agnosticism includes providing Application Programming Interfaces (APIs). These APIs are used to allow RAVEN to interact with any code as long as all the parameters that need tomore » be perturbed are accessible by input files or via python interfaces. RAVEN is capable of investigating the system response, and investigating the input space using Monte Carlo, Grid, or Latin Hyper Cube sampling schemes, but its strength is focused toward system feature discovery, such as limit surfaces, separating regions of the input space leading to system failure, using dynamic supervised learning techniques. The development of RAVEN started in 2012, when, within the Nuclear Energy Advanced Modeling and Simulation (NEAMS) program, the need to provide a modern risk evaluation framework became stronger. RAVEN principal assignment is to provide the necessary software and algorithms in order to employ the concept developed by the Risk Informed Safety Margin Characterization (RISMC) program. RISMC is one of the pathways defined within the Light Water Reactor Sustainability (LWRS) program. In the RISMC approach, the goal is not just the individuation of the frequency of an event potentially leading to a system failure, but the closeness (or not) to key safety-related events. Hence, the approach is interested in identifying and increasing the safety margins related to those events. A safety margin is a numerical value quantifying the probability that a safety metric (e.g. for an important process such as peak pressure in a pipe) is exceeded under certain conditions. The initial development of RAVEN has been focused on providing dynamic risk assessment capability to RELAP-7, currently under development at the INL and, likely, future replacement of the RELAP5-3D code. Most the capabilities that have been implemented having RELAP-7 as principal focus are easily deployable for other system codes. For this reason, several side activates are currently ongoing for coupling RAVEN with software such as RELAP5-3D, etc. The aim of this document is the explanation of the input requirements, focusing on the input structure.« less

RAVEN User Manual

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mandelli, Diego; Rabiti, Cristian; Cogliati, Joshua Joseph

2017-03-01

RAVEN is a generic software framework to perform parametric and probabilistic analy- sis based on the response of complex system codes. The initial development was aimed to provide dynamic risk analysis capabilities to the Thermo-Hydraulic code RELAP-7, currently under development at the Idaho National Laboratory (INL). Although the initial goal has been fully accomplished, RAVEN is now a multi-purpose probabilistic and uncer- tainty quantification platform, capable to agnostically communicate with any system code. This agnosticism includes providing Application Programming Interfaces (APIs). These APIs are used to allow RAVEN to interact with any code as long as all the parameters thatmore » need to be perturbed are accessible by inputs files or via python interfaces. RAVEN is capable of investigating the system response, and investigating the input space using Monte Carlo, Grid, or Latin Hyper Cube sampling schemes, but its strength is focused to- ward system feature discovery, such as limit surfaces, separating regions of the input space leading to system failure, using dynamic supervised learning techniques. The development of RAVEN has started in 2012, when, within the Nuclear Energy Advanced Modeling and Simulation (NEAMS) program, the need to provide a modern risk evaluation framework became stronger. RAVEN principal assignment is to provide the necessary software and algorithms in order to employ the concept developed by the Risk Informed Safety Margin Characterization (RISMC) program. RISMC is one of the pathways defined within the Light Water Reactor Sustainability (LWRS) program. In the RISMC approach, the goal is not just the individuation of the frequency of an event potentially leading to a system failure, but the closeness (or not) to key safety-related events. Hence, the approach is in- terested in identifying and increasing the safety margins related to those events. A safety margin is a numerical value quantifying the probability that a safety metric (e.g. for an important process such as peak pressure in a pipe) is exceeded under certain conditions. The initial development of RAVEN has been focused on providing dynamic risk assess- ment capability to RELAP-7, currently under develop-ment at the INL and, likely, future replacement of the RELAP5-3D code. Most the capabilities that have been implemented having RELAP-7 as principal focus are easily deployable for other system codes. For this reason, several side activates are currently ongoing for coupling RAVEN with soft- ware such as RELAP5-3D, etc. The aim of this document is the explaination of the input requirements, focalizing on the input structure.« less

Risk-Informed External Hazards Analysis for Seismic and Flooding Phenomena for a Generic PWR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parisi, Carlo; Prescott, Steve; Ma, Zhegang

This report describes the activities performed during the FY2017 for the US-DOE Light Water Reactor Sustainability Risk-Informed Safety Margin Characterization (LWRS-RISMC), Industry Application #2. The scope of Industry Application #2 is to deliver a risk-informed external hazards safety analysis for a representative nuclear power plant. Following the advancements occurred during the previous FYs (toolkits identification, models development), FY2017 focused on: increasing the level of realism of the analysis; improving the tools and the coupling methodologies. In particular the following objectives were achieved: calculation of buildings pounding and their effects on components seismic fragility; development of a SAPHIRE code PRA modelsmore » for 3-loops Westinghouse PWR; set-up of a methodology for performing static-dynamic PRA coupling between SAPHIRE and EMRALD codes; coupling RELAP5-3D/RAVEN for performing Best-Estimate Plus Uncertainty analysis and automatic limit surface search; and execute sample calculations for demonstrating the capabilities of the toolkit in performing a risk-informed external hazards safety analyses.« less

LWRS ATR Irradiation Testing Readiness Status

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kristine Barrett

2012-09-01

The Light Water Reactor Sustainability (LWRS) Program was established by the U.S. Department of Energy Office of Nuclear Energy (DOE-NE) to develop technologies and other solutions that can improve the reliability, sustain the safety, and extend the life of the current reactors. The LWRS Program is divided into four R&D Pathways: (1) Materials Aging and Degradation; (2) Advanced Light Water Reactor Nuclear Fuels; (3) Advanced Instrumentation, Information and Control Systems; and (4) Risk-Informed Safety Margin Characterization. This report describes an irradiation testing readiness analysis in preparation of LWRS experiments for irradiation testing at the Idaho National Laboratory (INL) Advanced Testmore » Reactor (ATR) under Pathway (2). The focus of the Advanced LWR Nuclear Fuels Pathway is to improve the scientific knowledge basis for understanding and predicting fundamental performance of advanced nuclear fuel and cladding in nuclear power plants during both nominal and off-nominal conditions. This information will be applied in the design and development of high-performance, high burn-up fuels with improved safety, cladding integrity, and improved nuclear fuel cycle economics« less

The relationship between safety net activities and hospital financial performance

PubMed Central

2010-01-01

Background During the 1990's hospitals in the U.S were faced with cost containment charges, which may have disproportionately impacted hospitals that serve poor patients. The purposes of this paper are to study the impact of safety net activities on total profit margins and operating expenditures, and to trace these relationships over the 1990s for all U.S urban hospitals, controlling for hospital and market characteristics. Methods The primary data source used for this analysis is the Annual Survey of Hospitals from the American Hospital Association and Medicare Hospital Cost Reports for years 1990-1999. Ordinary least square, hospital fixed effects, and two-stage least square analyses were performed for years 1990-1999. Logged total profit margin and operating expenditure were the dependent variables. The safety net activities are the socioeconomic status of the population in the hospital serving area, and Medicaid intensity. In some specifications, we also included uncompensated care burden. Results We found little evidence of negative effects of safety net activities on total margin. However, hospitals serving a low socioeconomic population had lower expenditure raising concerns for the quality of the services provided. Conclusions Despite potentially negative policy and market changes during the 1990s, safety net activities do not appear to have imperiled the survival of hospitals. There may, however, be concerns about the long-term quality of the services for hospitals serving low socioeconomic population. PMID:20074367

ORNL Evaluation of Electrabel Safety Cases for Doel 3 / Tihange 2: Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bass, Bennett Richard; Dickson, Terry L.; Gorti, Sarma B.

Oak Ridge National Laboratory (ORNL) performed a detailed technical review of the 2015 Electrabel (EBL) Safety Cases prepared for the Belgium reactor pressure vessels (RPVs) at Doel 3 and Tihange 2 (D3/T2). The Federal Agency for Nuclear Control (FANC) in Belgium commissioned ORNL to provide a thorough assessment of the existing safety margins against cracking of the RPVs due to the presence of almost laminar flaws found in each RPV. Initial efforts focused on surveying relevant literature that provided necessary background knowledge on the issues related to the quasilaminar flaws observed in D3/T2 reactors. Next, ORNL proceeded to develop anmore » independent quantitative assessment of the entire flaw population in the two Belgian reactors according to the American Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel Code, Section XI, Appendix G, Fracture Toughness Criteria for Protection Against Failure, New York (1992 and 2004). That screening assessment of all EBL-characterized flaws in D3/T2 used ORNL tools, methodologies, and the ASME Code Case N-848, Alternative Characterization Rules for QuasiLaminar Flaws . Results and conclusions from the ORNL flaw acceptance assessments of D3/T2 were compared with those from the 2015 EBL Safety Cases. Specific findings of the ORNL evaluation of that part of the EBL structural integrity assessment focusing on stability of the flaw population subjected to primary design transients include the following: ORNL s analysis results were similar to those of EBL in that very few characterized flaws were found not compliant with the ASME (1992) acceptance criterion. ORNL s application of the more recent ASME Section XI (2004) produced only four noncompliant flaws, all due to LOCAs. The finding of a greater number of non-compliant flaws in the EBL screening assessment is due principally to a significantly more restrictive (conservative) criterion for flaw size acceptance used by EBL. ORNL s screening assessment results (obtained using an analysis methodology different from that of EBL) are interpreted herein as confirming the EBL screening results for D3/T2. ORNL s independent refined analysis demonstrated the EBL-characterized flaw 1660, which is non-compliant in the ORNL and EBL screening assessment, is rendered compliant when modeled as a more realistic individual quasi-laminar flaw using a 3-D XFEM analysis approach. ORNL s and EBL s refined analyses are in good agreement for the flaw 1660 close to the clad/base metal interface; ORNL is not persuaded that repeating this exercise for more than one non-compliant flaw is necessary to accept the EBL conclusions derived from the aggregate of EBL refined analysis results. ORNL General Conclusions Regarding the Structural Integrity Assessment (SIA) Conducted by EBL for D3/T2 Based on comparative evaluations of ORNL and EBL SIA analyses and on consideration of other results, ORNL is in agreement with the general conclusions reported by Electrabel in their RPV D3/T2 Technical Summary Note of April 14, 2015: More than 99 percent of flaws in D3/T2 meet the defined screening criterion, rendering them benign with respect to initiation in the event of a design transient. Refined analyses of non-compliant flaws from the screening assessment indicate that only 11 of the 16196 detected flaws have a critical reference-temperature material index (designated RTNDT) that implies the possibility of the initiation of cleavage fracture at some future time. For those 11 2 flaws, the calculated margin in RTNDT (a measure of acceptable embrittlement relative to end-ofservice-life conditions) is significant, being greater than 80 C. Fatigue crack growth is not a concern in the flaw-acceptability analyses. Primary stress re-evaluation confirms that the collapse pressure is more than 1.5 times the design pressure in the presence of defects detected in D3/T2. Sufficient conservatisms are built into the input data and into the different steps of the SIA; in some cases, those conservatisms are quantified and imply that additional margins exist in the SIA. Taken as a whole, the foregoing results and conclusions confirm the structural integrity of Doel 3 and Tihange 2 under all design transients with ample margin in the presence of the 16196 detected flaws.« less

Defibrillation threshold testing fails to show clinical benefit during long-term follow-up of patients undergoing cardiac resynchronization therapy defibrillator implantation.

PubMed

Michowitz, Yoav; Lellouche, Nicolas; Contractor, Tahmeed; Bourke, Tara; Wiener, Isaac; Buch, Eric; Boyle, Noel; Bersohn, Malcolm; Shivkumar, Kalyanam

2011-05-01

The utility of defibrillation threshold testing in patients undergoing implantable cardioverter-defibrillator (ICD) implantation is controversial. Higher defibrillation thresholds have been noted in patients undergoing implantation of cardiac resynchronization therapy defibrillators (CRT-D). Since the risks and potential benefits of testing may be higher in this population, we sought to assess the impact of defibrillation safety margin or vulnerability safety margin testing in CRT-D recipients. A total of 256 consecutive subjects who underwent CRT-D implantation between January 2003 and December 2007 were retrospectively reviewed. Subjects were divided into two groups based on whether (n= 204) or not (n= 52) safety margin testing was performed. Patient characteristics, tachyarrhythmia therapies, procedural results, and clinical outcomes were recorded. Baseline characteristics, including heart failure (HF) severity, were comparable between the groups. Four cases of HF exacerbation (2%), including one leading to one death, were recorded in the tested group immediately post-implantation. No complications were observed in the untested group. After a mean follow-up of 32 ± 20 months, the proportion of appropriate shocks in the two groups was similar (31 vs. 25%, P = 0.49). There were three cases of failed appropriate shocks in the tested group, despite adequate safety margins at implantation, whereas no failed shocks were noted in the untested group. Survival was similar in the two groups. Defibrillation efficacy testing during implant of CRT-D was associated with increased morbidity and did not predict the success of future device therapy or improve survival during long-term follow-up.

Manipulation of a fragile object by elderly individuals.

PubMed

Gorniak, Stacey L; Zatsiorsky, Vladimir M; Latash, Mark L

2011-08-01

We investigated strategies of healthy elderly participants (74-84 years old) during prehension and transport of an object with varying degrees of fragility. Fragility was specified as the maximal normal force that the object could withstand without collapsing. Specifically, kinetic and kinematic variables as well as and force covariation indices were quantified and compared to those shown by young healthy persons (19-28 years old). We tested three hypotheses related to age-related changes in two safety margins (slip safety margin and crush safety margin) and indices of force covariation. Compared to young controls, elderly individuals exhibited a decrease in object acceleration and an increase in movement time, an increase in grip force production, a decrease in the correlation between grip and load forces, an overall decrease in indices of multi-digit synergies, and lower safety margin indices computed with respect to both dropping and crushing the object. Elderly participants preferred to be at a relatively lower risk of crushing the object even if this led to a higher risk of dropping it. Both groups showed an increase in the index of synergy stabilizing total normal force produced by the four fingers with increased fragility of the object. Age-related changes are viewed as a direct result of physiological changes due to aging, not adaptation to object fragility. Such changes in overall characteristics of prehension likely reflect diminished synergic control by the central nervous system of finger forces with aging. The findings corroborate an earlier hypothesis on an age-related shift from synergic to element-based control.

Ensuring the validity of calculated subcritical limits

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clark, H.K.

1977-01-01

The care taken at the Savannah River Laboratory and Plant to ensure the validity of calculated subcritical limits is described. Close attention is given to ANSI N16.1-1975, ''Validation of Calculational Methods for Nuclear Criticality Safety.'' The computer codes used for criticality safety computations, which are listed and are briefly described, have been placed in the SRL JOSHUA system to facilitate calculation and to reduce input errors. A driver module, KOKO, simplifies and standardizes input and links the codes together in various ways. For any criticality safety evaluation, correlations of the calculational methods are made with experiment to establish bias. Occasionallymore » subcritical experiments are performed expressly to provide benchmarks. Calculated subcritical limits contain an adequate but not excessive margin to allow for uncertainty in the bias. The final step in any criticality safety evaluation is the writing of a report describing the calculations and justifying the margin.« less

Coordination of stem and leaf hydraulic conductance in southern California shrubs: a test of the hydraulic segmentation hypothesis.

PubMed

Pivovaroff, Alexandria L; Sack, Lawren; Santiago, Louis S

2014-08-01

Coordination of water movement among plant organs is important for understanding plant water use strategies. The hydraulic segmentation hypothesis (HSH) proposes that hydraulic conductance in shorter lived, 'expendable' organs such as leaves and longer lived, more 'expensive' organs such as stems may be decoupled, with resistance in leaves acting as a bottleneck or 'safety valve'. We tested the HSH in woody species from a Mediterranean-type ecosystem by measuring leaf hydraulic conductance (Kleaf) and stem hydraulic conductivity (KS). We also investigated whether leaves function as safety valves by relating Kleaf and the hydraulic safety margin (stem water potential minus the water potential at which 50% of conductivity is lost (Ψstem-Ψ50)). We also examined related plant traits including the operating range of water potentials, wood density, leaf mass per area, and leaf area to sapwood area ratio to provide insight into whole-plant water use strategies. For hydrated shoots, Kleaf was negatively correlated with KS , supporting the HSH. Additionally, Kleaf was positively correlated with the hydraulic safety margin and negatively correlated with the leaf area to sapwood area ratio. Consistent with the HSH, our data indicate that leaves may act as control valves for species with high KS , or a low safety margin. This critical role of leaves appears to contribute importantly to plant ecological specialization in a drought-prone environment. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

A Research Roadmap for Computation-Based Human Reliability Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boring, Ronald; Mandelli, Diego; Joe, Jeffrey

2015-08-01

The United States (U.S.) Department of Energy (DOE) is sponsoring research through the Light Water Reactor Sustainability (LWRS) program to extend the life of the currently operating fleet of commercial nuclear power plants. The Risk Informed Safety Margin Characterization (RISMC) research pathway within LWRS looks at ways to maintain and improve the safety margins of these plants. The RISMC pathway includes significant developments in the area of thermalhydraulics code modeling and the development of tools to facilitate dynamic probabilistic risk assessment (PRA). PRA is primarily concerned with the risk of hardware systems at the plant; yet, hardware reliability is oftenmore » secondary in overall risk significance to human errors that can trigger or compound undesirable events at the plant. This report highlights ongoing efforts to develop a computation-based approach to human reliability analysis (HRA). This computation-based approach differs from existing static and dynamic HRA approaches in that it: (i) interfaces with a dynamic computation engine that includes a full scope plant model, and (ii) interfaces with a PRA software toolset. The computation-based HRA approach presented in this report is called the Human Unimodels for Nuclear Technology to Enhance Reliability (HUNTER) and incorporates in a hybrid fashion elements of existing HRA methods to interface with new computational tools developed under the RISMC pathway. The goal of this research effort is to model human performance more accurately than existing approaches, thereby minimizing modeling uncertainty found in current plant risk models.« less

77 FR 69507 - Proposed Model Safety Evaluation for Plant-Specific Adoption of Technical Specifications Task...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-19

..., ``Revise Shutdown Margin Definition To Address Advanced Fuel Designs'' AGENCY: Nuclear Regulatory... Shutdown Margin Definition to Address Advanced Fuel Designs.'' DATES: Comment period expires on December 19... address newer BWR fuel designs, which may be more reactive at shutdown temperatures above 68[emsp14][deg]F...

Lung segment geometry study: simulation of largest possible tumours that fit into bronchopulmonary segments.

PubMed

Welter, S; Stöcker, C; Dicken, V; Kühl, H; Krass, S; Stamatis, G

2012-03-01

Segmental resection in stage I non-small cell lung cancer (NSCLC) has been well described and is considered to have similar survival rates as lobectomy but with increased rates of local tumour recurrence due to inadequate parenchymal margins. In consequence, today segmentectomy is only performed when the tumour is smaller than 2 cm. Three-dimensional reconstructions from 11 thin-slice CT scans of bronchopulmonary segments were generated, and virtual spherical tumours were placed over the segments, respecting all segmental borders. As a next step, virtual parenchymal safety margins of 2 cm and 3 cm were subtracted and the size of the remaining tumour calculated. The maximum tumour diameters with a 30-mm parenchymal safety margin ranged from 26.1 mm in right-sided segments 7 + 8 to 59.8 mm in the left apical segments 1-3. Using a three-dimensional reconstruction of lung CT scans, we demonstrated that segmentectomy or resection of segmental groups should be feasible with adequate margins, even for larger tumours in selected cases. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Incidence of ineffective safety margin testing (<10 J) and efficacy of routine subcutaneous array insertion during implantable cardioverter defibrillator implantation.

PubMed

Ohlow, Marc-Alexander; Roos, Marcus; Lauer, Bernward; Geller, J Christoph

2016-01-01

The purpose of this study was to assess (1) the incidence of safety margin testing <10 J (SMT) and (2) the efficacy/safety of routinely adding a subcutaneous array (SQA) (Medtronic 6996SQ) for these patients. Patients with SMT smaller than a 10-J safety margin from maximum output were considered to have very high readings and underwent SQA insertion. These patients were compared with the rest of the patients who had acceptable SMT (≥10 J). A total of 616 patients underwent ICD implantation during the analysis period. Of those, 16 (2.6%) had SMT <10 J. By univariate analysis, younger age, and non-ischemic cardiomyopathy, were all significant predictors of SMT <10 J (p < 0.05). In all 16 cases, other methods to improve SMT prior to array insertion were attempted but failed for all patients: reversing shock polarity (n = 15), removing the superior vena cava coil (n = 14), reprogramming shock waveform (n = 9), and repositioning right ventricular lead (n = 9). Addition of the SQA successfully increased SMT to within safety margin for all patients (32 ± 2 versus 21 ± 3 J; p < 0.001). Follow-up (mean 48.1 ± 21 months) was available for all patients with SQA, only 2 cases with inappropriate shocks due to atrial fibrillation had to be noted. None of the patients experienced complications due to SQA implantation. SMT <10 J occur in about 2.6% of patients undergoing ICD implantation. SQA insertion corrects this problem without procedural/mid-term complications. Copyright © 2016 Indian Heart Rhythm Society. Production and hosting by Elsevier B.V. All rights reserved.

Safety margins in zircaloy oxidation and embrittlement criteria for emergency core cooling system acceptance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williford, R.E.

1986-09-01

Current emergency core cooling system acceptance criteria for light water reactors specify that, under loss-of-coolant accident (LOCA) conditions, the Baker-Just (BJ) correlation must be used to calculate Zircaloy-steam oxidation, calculated peak cladding temperatures (PCT) must not exceed 1204/sup 0/C, and calculated oxidation must not exceed 17% equivalent cladding reacted (ECR). An appropriately defined minimum margin of safety was estimated for each of these criteria. The currently required BJ oxidation correlation provides margins only over the 1100 to 1500/sup 0/C temperature range at the 95% confidence level. The PCT margins for thermal shock and handling failures are adequate at oxidation temperaturesmore » above 1204/sup 0/C for up to 210 and 160 s, respectively, at the 95% confidence level. The ECR thermal shock and handling margins at the 50 and 95% confidence levels, respectively, range between 2 and 7% ECR for the BJ correlation, but vanish at temperatures above 1100 to 1160/sup 0/C for the best-estimate Cathcart-Pawel correlation. However, use of the Cathcart Pawel correlation for ''design basis'' LOCA calculations can be justified at the 85 to 88% confidence level if cooling rate effects can be neglected.« less

Influence of Passive Stiffness of Hamstrings on Postural Stability

PubMed Central

Kuszewski, Michał; Gnat, Rafał; Sobota, Grzegorz; Myśliwiec, Andrzej

2015-01-01

The aim of the study was to explore whether passive stiffness of the hamstrings influences the strategy of maintaining postural stability. A sample of 50 subjects was selected; the final analyses were based on data of 41 individuals (33 men, 8 women) aged 21 to 29 (mean = 23.3, SD = 1.1) years. A quasi- experimental ex post facto design with repeated measures was used. Categories of independent variables were obtained directly prior to the measurement of the dependent variables. In stage one of the study, passive knee extension was measured in the supine position to assess hamstring stiffness. In stage two, the magnitude of postural sway in antero-posterior direction was measured, while varying the body position on a stabilometric platform, both with and without visual control. The margin of safety was used as a measure of postural control. The magnitude of the margin of safety increased significantly between the open-eye and closed-eye trials. However, although we registered a visible tendency for a larger increase of the margin of safety associated with lower levels of passive hamstrings stiffness, no significant differences were found. Therefore, this study demonstrated that hamstring stiffness did not influence the strategy used to maintain postural stability. PMID:25964809

Influence of passive stiffness of hamstrings on postural stability.

PubMed

Kuszewski, Michał; Gnat, Rafał; Sobota, Grzegorz; Myśliwiec, Andrzej

2015-03-29

The aim of the study was to explore whether passive stiffness of the hamstrings influences the strategy of maintaining postural stability. A sample of 50 subjects was selected; the final analyses were based on data of 41 individuals (33 men, 8 women) aged 21 to 29 (mean = 23.3, SD = 1.1) years. A quasi- experimental ex post facto design with repeated measures was used. Categories of independent variables were obtained directly prior to the measurement of the dependent variables. In stage one of the study, passive knee extension was measured in the supine position to assess hamstring stiffness. In stage two, the magnitude of postural sway in antero-posterior direction was measured, while varying the body position on a stabilometric platform, both with and without visual control. The margin of safety was used as a measure of postural control. The magnitude of the margin of safety increased significantly between the open-eye and closed-eye trials. However, although we registered a visible tendency for a larger increase of the margin of safety associated with lower levels of passive hamstrings stiffness, no significant differences were found. Therefore, this study demonstrated that hamstring stiffness did not influence the strategy used to maintain postural stability.

An empirical assessment of driver motivation and emotional states in perceived safety margins under varied driving conditions.

PubMed

Zhang, Yu; Kaber, David B

2013-01-01

Motivation models in driving behaviour postulate that driver motives and emotional states dictate risk tolerance under various traffic conditions. The present study used time and driver performance-based payment systems to manipulate motivation and risk-taking behaviour. Ten participants drove to a predefined location in a simulated driving environment. Traffic patterns (density and velocity) were manipulated to cause driver behaviour adjustments due to the need to conform with the social norms of the roadway. The driving environment complexity was investigated as a mediating factor in risk tolerance. Results revealed the performance-based payment system to closely relate to risk-taking behaviour as compared with the time-based payment system. Drivers conformed with social norms associated with specific traffic patterns. Higher roadway complexity led to a more conservative safety margins and speeds. This research contributes to the further development of motivational models of driver behaviour. This study provides empirical justification for two motivation factors in driver risk-taking decisions, including compliance with social norm and emotions triggered by incentives. Environment complexity was identified as a mediating factor in motivational behaviour model. This study also recommended safety margin measures sensitive to changes in driver risk tolerance.

Structural characterization of nanoscale intermetallic precipitates in highly neutron irradiated reactor pressure vessel steels

DOE PAGES

Sprouster, D. J.; Sinsheimer, J.; Dooryhee, E.; ...

2015-10-21

Here, massive, thick-walled pressure vessels are permanent nuclear reactor structures that are exposed to a damaging flux of neutrons from the adjacent core. The neutrons cause embrittlement of the vessel steel that increases with dose (fluence or service time), as manifested by an increasing temperature transition from ductile-to-brittle fracture. Moreover, extending reactor life requires demonstrating that large safety margins against brittle fracture are maintained at the higher neutron fluence associated with 60 to 80 years of service. Here synchrotron-based x-ray diffraction and small angle x-ray scattering measurements are used to characterize a new class of highly embrittling nm-scale Mn-Ni-Si precipitatesmore » that develop in the irradiated steels at high fluence. Furthermore, these precipitates can lead to severe embrittlement that is not accounted for in current regulatory models. Application of the complementarity techniques has, for the very first time, successfully characterized the crystal structures of the nanoprecipitates, while also yielding self-consistent compositions, volume fractions and size distributions.« less

Disruption Event Characterization and Forecasting in Tokamaks

NASA Astrophysics Data System (ADS)

Berkery, J. W.; Sabbagh, S. A.; Park, Y. S.; Ahn, J. H.; Jiang, Y.; Riquezes, J. D.; Gerhardt, S. P.; Myers, C. E.

2017-10-01

The Disruption Event Characterization and Forecasting (DECAF) code, being developed to meet the challenging goal of high reliability disruption prediction in tokamaks, automates data analysis to determine chains of events that lead to disruptions and to forecast their evolution. The relative timing of magnetohydrodynamic modes and other events including plasma vertical displacement, loss of boundary control, proximity to density limits, reduction of safety factor, and mismatch of the measured and desired plasma current are considered. NSTX/-U databases are examined with analysis expanding to DIII-D, KSTAR, and TCV. Characterization of tearing modes has determined mode bifurcation frequency and locking points. In an NSTX database exhibiting unstable resistive wall modes (RWM), the RWM event and loss of boundary control event were found in 100%, and the vertical displacement event in over 90% of cases. A reduced kinetic RWM stability physics model is evaluated to determine the proximity of discharges to marginal stability. The model shows high success as a disruption predictor (greater than 85%) with relatively low false positive rate. Supported by US DOE Contracts DE-FG02-99ER54524, DE-AC02-09CH11466, and DE-SC0016614.

Talonavicular joint arthroscopic portals: A cadaveric study of feasibility and safety.

PubMed

Xavier, Gabriel; Oliva, Xavier Martin; Rotinen, Mauri; Monzo, Mariano

2016-09-01

The objectives of the study were to evaluate the safety of hypothetical arthroscopic portals from talonavicular joint and to evaluate their reproducibility and enforceability. 19 cadaveric feet were marked and four arthroscopic portals were made (medial, dorsomedial, dorsolateral and lateral). The specimens were dissected in layers and the distances between neurovascular structures and the trocars were measured. Medial and dorsomedial portals were in average 8.3 and 8.7, respectively, to the saphenous vein and nerve. Dorsolateral portal was in average 8.1mm to the deep peroneal nerve and dorsalis pedis artery, and 9.1mm to the medial dorsal cutaneous branch of the superficial peroneal nerve. Lateral portal was in average 12.3mm to the intermediate dorsal cutaneous branch of the superficial peroneal nerve. Tested portals shown to have a good safety margin for the foot neurovascular deep dorsal structures and an acceptable safety margin for the superficial neurovascular structures. Copyright © 2015 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

Assessment of safety margins in zircaloy oxidation and embrittlement criteria for ECCS acceptance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williford, R.E.

1986-04-01

Current Emergency Core Cooling System (ECCS) Acceptance Criteria for light-water reactors include certain requirements pertaining to calculations of core performance during a Loss of Coolant Accident (LOCA). The Baker-Just correlation must be used to calculate Zircaloy-steam oxidation, calculated peak cladding temperatures (PCT) must not exceed 1204/sup 0/C, and calculated oxidation must not exceed 17% equivalent cladding reacted (17% ECR). The minimum margin of safety was estimated for each of these criteria, based on research performed in the last decade. Margins were defined as the amounts of conservatism over and above the expected extreme values computed from the data base atmore » specified confidence levels. The currently required Baker-Just oxidation correlation provides margins only over the 1100/sup 0/C to 1500/sup 0/C temperature range at the 95% confidence level. The PCT margins for thermal shock and handling failures are adequate at oxidation temperatures above 1204/sup 0/C for 210 and 160 seconds, respectively, at the 95% confidence level. ECR thermal shock and handling margins at the 50% and 95% confidence levels, respectively, range between 2% and 7% ECR for the Baker-Just correlation, but vanish at temperatures between 1100/sup 0/C and 1160/sup 0/C for the best-estimate Cathcart-Pawel correlation. Use of the Cathcart-Pawel correlation for LOCA calculations can be justified at the 85% to 88% confidence level if cooling rate effects can be neglected. 75 refs., 21 figs.« less

Design with brittle materials - An interdisciplinary educational program

NASA Technical Reports Server (NTRS)

Mueller, J. I.; Bollard, R. J. H.; Hartz, B. J.; Kobayashi, A. S.; Love, W. J.; Scott, W. D.; Taggart, R.; Whittemore, O. J.

1980-01-01

A series of interdisciplinary design courses being offered to senior and graduate engineering students at the University of Washington is described. Attention is given to the concepts and some of the details on group design projects that have been undertaken during the past two years. It is noted that ceramic materials normally demonstrate a large scatter in strength properties. As a consequence, when designing with these materials, the conventional 'mil standards' design stresses with acceptable margins of safety cannot by employed and the designer is forced to accept a probable number of failures in structures of a given brittle material. It is this prediction of the probability of failure for structures of given, well-characterized materials that forms the basis for this series of courses.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ramuhalli, Pradeep; Hirt, Evelyn H.; Veeramany, Arun

This research report summaries the development and evaluation of a prototypic enhanced risk monitor (ERM) methodology (framework) that includes alternative risk metrics and uncertainty analysis. This updated ERM methodology accounts for uncertainty in the equipment condition assessment (ECA), the prognostic result, and the probabilistic risk assessment (PRA) model. It is anticipated that the ability to characterize uncertainty in the estimated risk and update the risk estimates in real time based on equipment condition assessment (ECA) will provide a mechanism for optimizing plant performance while staying within specified safety margins. These results (based on impacting active component O&M using real-time equipmentmore » condition information) are a step towards ERMs that, if integrated with AR supervisory plant control systems, can help control O&M costs and improve affordability of advanced reactors.« less

High-temperature oxidation of advanced FeCrNi alloy in steam environments

NASA Astrophysics Data System (ADS)

Elbakhshwan, Mohamed S.; Gill, Simerjeet K.; Rumaiz, Abdul K.; Bai, Jianming; Ghose, Sanjit; Rebak, Raul B.; Ecker, Lynne E.

2017-12-01

Alloys of iron-chromium-nickel are being explored as alternative cladding materials to improve safety margins under severe accident conditions. Our research focuses on non-destructively investigating the oxidation behavior of the FeCrNi alloy "Alloy 33" using synchrotron-based methods. The evolution and structure of oxide layer formed in steam environments were characterized using X-ray diffraction, hard X-ray photoelectron spectroscopy, X-ray fluorescence methods and scanning electron microscopy. Our results demonstrate that a compact and continuous oxide scale was formed consisting of two layers, chromium oxide and spinel phase (FeCr2O4) oxides, wherein the concentration of the FeCr2O4 phase decreased from the surface to the bulk-oxide interface.

Safety assessments of subcutaneous doses of aragonite calcium carbonate nanocrystals in rats

NASA Astrophysics Data System (ADS)

Jaji, Alhaji Zubair; Zakaria, Zuki Abu Bakar; Mahmud, Rozi; Loqman, Mohamad Yusof; Hezmee, Mohamad Noor Mohamad; Abba, Yusuf; Isa, Tijani; Mahmood, Saffanah Khuder

2017-05-01

Calcium carbonate nanoparticles have shown promising potentials in the delivery of drugs and metabolites. There is however, a paucity of information on the safety of their intentional or accidental over exposures to biological systems and general health safety. To this end, this study aims at documenting information on the safety of subcutaneous doses of biogenic nanocrystals of aragonite polymorph of calcium carbonate derived from cockle shells (ANC) in Sprague-Dawley (SD) rats. ANC was synthesized using the top-down method, characterized using the transmission electron microscopy and field emission scanning electron microscope and its acute and repeated dose 28-day trial toxicities were evaluated in SD rats. The results showed that the homogenous 30 ± 5 nm-sized spherical pure aragonite nanocrystals were not associated with mortality in the rats. Severe clinical signs and gross and histopathological lesions, indicating organ toxicities, were recorded in the acute toxicity (29,500 mg/m2) group and the high dose (5900 mg/m2) group of the repeated dose 28-day trial. However, the medium- (590 mg/m2 body weight) and low (59 mg/m2)-dose groups showed moderate to mild lesions. The relatively mild lesions observed in the low toxicity dosage group marked the safety margin of ANC in SD rats. It was concluded from this study that the toxicity of CaCO3 was dependent on the particulate size (30 ± 5 nm) and concentration and the route of administration used.

Characterization of Pharmacologic and Pharmacokinetic Properties of CCX168, a Potent and Selective Orally Administered Complement 5a Receptor Inhibitor, Based on Preclinical Evaluation and Randomized Phase 1 Clinical Study.

PubMed

Bekker, Pirow; Dairaghi, Daniel; Seitz, Lisa; Leleti, Manmohan; Wang, Yu; Ertl, Linda; Baumgart, Trageen; Shugarts, Sarah; Lohr, Lisa; Dang, Ton; Miao, Shichang; Zeng, Yibin; Fan, Pingchen; Zhang, Penglie; Johnson, Daniel; Powers, Jay; Jaen, Juan; Charo, Israel; Schall, Thomas J

2016-01-01

The complement 5a receptor has been an attractive therapeutic target for many autoimmune and inflammatory disorders. However, development of a selective and potent C5aR antagonist has been challenging. Here we describe the characterization of CCX168 (avacopan), an orally administered selective and potent C5aR inhibitor. CCX168 blocked the C5a binding, C5a-mediated migration, calcium mobilization, and CD11b upregulation in U937 cells as well as in freshly isolated human neutrophils. CCX168 retains high potency when present in human blood. A transgenic human C5aR knock-in mouse model allowed comparison of the in vitro and in vivo efficacy of the molecule. CCX168 effectively blocked migration in in vitro and ex vivo chemotaxis assays, and it blocked the C5a-mediated neutrophil vascular endothelial margination. CCX168 was effective in migration and neutrophil margination assays in cynomolgus monkeys. This thorough in vitro and preclinical characterization enabled progression of CCX168 into the clinic and testing of its safety, tolerability, pharmacokinetic, and pharmacodynamic profiles in a Phase 1 clinical trial in 48 healthy volunteers. CCX168 was shown to be well tolerated across a broad dose range (1 to 100 mg) and it showed dose-dependent pharmacokinetics. An oral dose of 30 mg CCX168 given twice daily blocked the C5a-induced upregulation of CD11b in circulating neutrophils by 94% or greater throughout the entire day, demonstrating essentially complete target coverage. This dose regimen is being tested in clinical trials in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Trial Registration ISRCTN registry with trial ID ISRCTN13564773.

Characterization of Pharmacologic and Pharmacokinetic Properties of CCX168, a Potent and Selective Orally Administered Complement 5a Receptor Inhibitor, Based on Preclinical Evaluation and Randomized Phase 1 Clinical Study

PubMed Central

Bekker, Pirow; Dairaghi, Daniel; Seitz, Lisa; Leleti, Manmohan; Wang, Yu; Ertl, Linda; Baumgart, Trageen; Shugarts, Sarah; Lohr, Lisa; Dang, Ton; Miao, Shichang; Zeng, Yibin; Fan, Pingchen; Zhang, Penglie; Johnson, Daniel; Powers, Jay; Jaen, Juan; Charo, Israel; Schall, Thomas J.

2016-01-01

The complement 5a receptor has been an attractive therapeutic target for many autoimmune and inflammatory disorders. However, development of a selective and potent C5aR antagonist has been challenging. Here we describe the characterization of CCX168 (avacopan), an orally administered selective and potent C5aR inhibitor. CCX168 blocked the C5a binding, C5a-mediated migration, calcium mobilization, and CD11b upregulation in U937 cells as well as in freshly isolated human neutrophils. CCX168 retains high potency when present in human blood. A transgenic human C5aR knock-in mouse model allowed comparison of the in vitro and in vivo efficacy of the molecule. CCX168 effectively blocked migration in in vitro and ex vivo chemotaxis assays, and it blocked the C5a-mediated neutrophil vascular endothelial margination. CCX168 was effective in migration and neutrophil margination assays in cynomolgus monkeys. This thorough in vitro and preclinical characterization enabled progression of CCX168 into the clinic and testing of its safety, tolerability, pharmacokinetic, and pharmacodynamic profiles in a Phase 1 clinical trial in 48 healthy volunteers. CCX168 was shown to be well tolerated across a broad dose range (1 to 100 mg) and it showed dose-dependent pharmacokinetics. An oral dose of 30 mg CCX168 given twice daily blocked the C5a-induced upregulation of CD11b in circulating neutrophils by 94% or greater throughout the entire day, demonstrating essentially complete target coverage. This dose regimen is being tested in clinical trials in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Trial Registration ISRCTN registry with trial ID ISRCTN13564773. PMID:27768695

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kristine Barrett; Shannon Bragg-Sitton

The Advanced Light Water Reactor (LWR) Nuclear Fuel Development Research and Development (R&D) Pathway encompasses strategic research focused on improving reactor core economics and safety margins through the development of an advanced fuel cladding system. To achieve significant operating improvements while remaining within safety boundaries, significant steps beyond incremental improvements in the current generation of nuclear fuel are required. Fundamental improvements are required in the areas of nuclear fuel composition, cladding integrity, and the fuel/cladding interaction to allow power uprates and increased fuel burn-up allowance while potentially improving safety margin through the adoption of an “accident tolerant” fuel system thatmore » would offer improved coping time under accident scenarios. With a development time of about 20 – 25 years, advanced fuel designs must be started today and proven in current reactors if future reactor designs are to be able to use them with confidence.« less

A Worst-Case Approach for On-Line Flutter Prediction

NASA Technical Reports Server (NTRS)

Lind, Rick C.; Brenner, Martin J.

1998-01-01

Worst-case flutter margins may be computed for a linear model with respect to a set of uncertainty operators using the structured singular value. This paper considers an on-line implementation to compute these robust margins in a flight test program. Uncertainty descriptions are updated at test points to account for unmodeled time-varying dynamics of the airplane by ensuring the robust model is not invalidated by measured flight data. Robust margins computed with respect to this uncertainty remain conservative to the changing dynamics throughout the flight. A simulation clearly demonstrates this method can improve the efficiency of flight testing by accurately predicting the flutter margin to improve safety while reducing the necessary flight time.

Proof-of-Concept Demonstrations for Computation-Based Human Reliability Analysis. Modeling Operator Performance During Flooding Scenarios

DOE Office of Scientific and Technical Information (OSTI.GOV)

Joe, Jeffrey Clark; Boring, Ronald Laurids; Herberger, Sarah Elizabeth Marie

The United States (U.S.) Department of Energy (DOE) Light Water Reactor Sustainability (LWRS) program has the overall objective to help sustain the existing commercial nuclear power plants (NPPs). To accomplish this program objective, there are multiple LWRS “pathways,” or research and development (R&D) focus areas. One LWRS focus area is called the Risk-Informed Safety Margin and Characterization (RISMC) pathway. Initial efforts under this pathway to combine probabilistic and plant multi-physics models to quantify safety margins and support business decisions also included HRA, but in a somewhat simplified manner. HRA experts at Idaho National Laboratory (INL) have been collaborating with othermore » experts to develop a computational HRA approach, called the Human Unimodel for Nuclear Technology to Enhance Reliability (HUNTER), for inclusion into the RISMC framework. The basic premise of this research is to leverage applicable computational techniques, namely simulation and modeling, to develop and then, using RAVEN as a controller, seamlessly integrate virtual operator models (HUNTER) with 1) the dynamic computational MOOSE runtime environment that includes a full-scope plant model, and 2) the RISMC framework PRA models already in use. The HUNTER computational HRA approach is a hybrid approach that leverages past work from cognitive psychology, human performance modeling, and HRA, but it is also a significant departure from existing static and even dynamic HRA methods. This report is divided into five chapters that cover the development of an external flooding event test case and associated statistical modeling considerations.« less

Geomorphology and Neogene tectonic evolution of the Palomares continental margin (Western Mediterranean)

NASA Astrophysics Data System (ADS)

Gómez de la Peña, Laura; Gràcia, Eulàlia; Muñoz, Araceli; Acosta, Juan; Gómez-Ballesteros, María; R. Ranero, César; Uchupi, Elazar

2016-10-01

The Palomares continental margin is located in the southeastern part of Spain. The margin main structure was formed during Miocene times, and it is currently part of the wide deformation zone characterizing the region between the Iberian and African plates, where no well-defined plate boundary occurs. The convergence between these two plates is here accommodated by several structures, including the left lateral strike-slip Palomares Fault. The region is characterized by sparse, low to moderate magnitude (Mw < 5.2) shallow instrumental earthquakes, although large historical events have also occurred. To understand the recent tectonic history of the margin we analyze new high-resolution multibeam bathymetry data and re-processed three multichannel seismic reflection profiles crossing the main structures. The analysis of seafloor morphology and associated subsurface structure provides new insights of the active tectonic features of the area. In contrast to other segments of the southeastern Iberian margin, the Palomares margin contains numerous large and comparatively closely spaced canyons with heads that reach near the coast. The margin relief is also characterized by the presence of three prominent igneous submarine ridges that include the Aguilas, Abubacer and Maimonides highs. Erosive processes evidenced by a number of scars, slope failures, gullies and canyon incisions shape the present-day relief of the Palomares margin. Seismic images reveal the deep structure distinguishing between Miocene structures related to the formation of the margin and currently active features, some of which may reactivate inherited structures. The structure of the margin started with an extensional phase accompanied by volcanic accretion during the Serravallian, followed by a compressional pulse that started during the Latemost Tortonian. Nowadays, tectonic activity offshore is subdued and limited to few, minor faults, in comparison with the activity recorded onshore. The deep Algero-Balearic Basin is affected by surficial processes, associated to halokinesis of Messinian evaporites.

Decoding the Margins: What Can the Fractal Geometry of Basaltic Flow Margins Tell Us?

NASA Astrophysics Data System (ADS)

Schaefer, E. I.; Hamilton, C.; Neish, C.; Beard, S. P.; Bramson, A. M.; Sori, M.; Rader, E. L.

2016-12-01

Studying lava flows on other planetary bodies is essential to characterizing eruption styles and constraining the bodies' thermal evolution. Although planetary basaltic flows are common, many key features are not resolvable in orbital imagery. We are thus developing a technique to characterize basaltic flow type, sub-meter roughness, and sediment mantling from these data. We will present the results from upcoming fieldwork at Craters of the Moon National Monument and Preserve with FINESSE (August) and at Hawai'i Volcanoes National Park (September). We build on earlier work that showed that basaltic flow margins are approximately fractal [Bruno et al., 1992; Gaonac'h et al., 1992] and that their fractal dimensions (D) have distinct `a`ā and pāhoehoe ranges under simple conditions [Bruno et al., 1994]. Using a differential GPS rover, we have recently shown that the margin of Iceland's 2014 Holuhraun flow exhibits near-perfect (R2=0.9998) fractality for ≥24 km across dm to km scales [Schaefer et al., 2016]. This finding suggests that a fractal-based technique has significant potential to characterize flows at sub-resolution scales. We are simultaneously seeking to understand how margin fractality can be modified. A preliminary result for an `a'ā flow in Hawaii's Ka'ū Desert suggests that although aeolian mantling obscures the original flow margin, the apparent margin (i.e., sediment-lava interface) remains fractal [Schaefer et al., 2015]. Further, the apparent margin's D is likely significantly modified from that of the original margin. Other factors that we are exploring include erosion, transitional flow types, and topographic confinement. We will also rigorously test the intriguing possibility that margin D correlates with the sub-meter Hurst exponent H of the flow surface, a common metric of roughness scaling [e.g., Shepard et al., 2001]. This hypothesis is based on geometric arguments [Turcotte, 1997] and is qualitatively consistent with all results so far.

Analysis of a Preloaded Bolted Joint in a Ceramic Composite Combustor

NASA Technical Reports Server (NTRS)

Hissam, D. Andy; Bower, Mark V.

2003-01-01

This paper presents the detailed analysis of a preloaded bolted joint incorporating ceramic materials. The objective of this analysis is to determine the suitability of a joint design for a ceramic combustor. The analysis addresses critical factors in bolted joint design including preload, preload uncertainty, and load factor. The relationship between key joint variables is also investigated. The analysis is based on four key design criteria, each addressing an anticipated failure mode. The criteria are defined in terms of margin of safety, which must be greater than zero for the design criteria to be satisfied. Since the proposed joint has positive margins of safety, the design criteria are satisfied. Therefore, the joint design is acceptable.

Consumer and farmer safety evaluation of application of botanical pesticides in black pepper crop protection.

PubMed

Hernández-Moreno, David; Soffers, Ans E M F; Wiratno; Falke, Hein E; Rietjens, Ivonne M C M; Murk, Albertinka J

2013-06-01

This study presents a consumer and farmer safety evaluation on the use of four botanical pesticides in pepper berry crop protection. The pesticides evaluated include preparations from clove, tuba root, sweet flag and pyrethrum. Their safety evaluation was based on their active ingredients being eugenol, rotenone, β-asarone and pyrethrins, respectively. Botanical pesticides from Acorus calamus are of possible concern because of the genotoxic and carcinogenic ingredient β-asarone although estimated margins of exposure (MOE) for consumers indicate a low priority for risk management. For the other three botanical pesticides the margin of safety (MOS) between established acute reference doses and/or acceptable daily intake values and intake estimates for the consumer, resulting from their use as a botanical pesticide are not of safety concern, with the exception for levels of rotenone upon use of tuba root extracts on stored berries. Used levels of clove and pyrethrum as botanical pesticides in pepper berry crop production is not of safety concern for consumers or farmers, whereas for use of tuba root and sweet flag some risk factors were defined requiring further evaluation and/or risk management. It seems prudent to look for alternatives for use of sweet flag extracts containing β-asarone. Copyright © 2013 Elsevier Ltd. All rights reserved.

White-Tailed Deer Response to Vehicle Approach: Evidence of Unclear and Present Danger

PubMed Central

Blackwell, Bradley F.; Seamans, Thomas W.; DeVault, Travis L.

2014-01-01

The fundamental causes of animal-vehicle collisions are unclear, particularly at the level of animal detection of approaching vehicles and decision-making. Deer-vehicle collisions (DVCs) are especially costly in terms of animal mortality, property damage, and safety. Over one year, we exposed free-ranging white-tailed deer (Odocoileus virginianus) to vehicle approach under low ambient light conditions, from varying start distances, and vehicle speeds from 20 km/h to approximately 90 km/h. We modeled flight response by deer to an approaching vehicle and tested four hypotheses: 1) flight-initiation distance (FID) would correlate positively with start distance (indicating a spatial margin of safety); 2) deer would react to vehicle speed using a temporal margin of safety; 3) individuals reacting at greater FIDs would be more likely to cross the path of the vehicle; and 4) crossings would correlate positively with start distance, approach speed, and distance to concealing/refuge cover. We examined deer responses by quantiles. Median FID was 40% of start distance, irrespective of start distance or approach speed. Converting FID to time-to-collision (TTC), median TTC was 4.6 s, but uncorrelated with start distance or approach speed. The likelihood of deer crossing in front of the vehicle was not associated with greater FIDs or other explanatory variables. Because deer flight response to vehicle approach was highly variable, DVCs should be more likely with increasing vehicle speeds because of lower TTCs for a given distance. For road sections characterized by frequent DVCs, we recommend estimating TTC relative to vehicle speed and candidate line-of-sight distances adjusted downward by (1-P), where P represents our findings for the proportion of start distance by which >75% of deer had initiated flight. Where road design or conservation goals limit effectiveness of line-of-sight maintenance, we suggest incorporation of roadway obstacles that force drivers to slow vehicles, in addition to posting advisory speed limits. PMID:25333922

The risks of radiation

NASA Astrophysics Data System (ADS)

Miettenen, Jorma K.

1988-01-01

The risks of radioactivity are a really complicated matter, yet they are much better known than are the risks relating to thousands of chemical poisons that occur in our environment. The greatest mistakes are probably made in the definition of safety margins. Except for the bombs dropped in Japan and one other case in the Marshall Islands, there has always—luckily—been a wide safety margin between fallout radiation and doses dangerous to health; the margin has actually been about 1000-fold. The Chernobyl dose of 0.5 mGy/year that we received is only 1/1000 of the acute dose of 0.5 Gy which would cause a slight and nonpermanent change in the blood picture. There is no such safety margin with respect to many air pollutants. The safety standards for sulfuric or nitric oxides, ozone and so on, have been set only just below the level that already causes a health hazard, and these standards are exceeded once in a while. Otherwise, traffic would have to be forbidden and many industrial plants, especially power stations using coal, would have to stop working whenever a low-temperature inversion occurred. Environmental radioactivity does not represent a likely health risk in Finland unless a nuclear war breaks out. Air pollutants, on the contrary, are a real and almost daily health risk that should be carefully considered when decisions about our energy production are being made. In spite of what happened at Chernobyl, global consumption of nuclear power will double by the year 2000, since there are about 140 nuclear power plants presently under construction. It is not likely that another catastrophe like Chernobyl will happen, yet nuclear plant accidents are of course possible, even if their likelihood is diminished by improving reactor safety and even if any eventual damage could be expected to be smaller. If a reactor is hooded by a containment structure, no significant release of radioactive materials should be possible even in case of an accident. However, we must be prepared to protect the population with carefully planned civil defense and radiation protection measures.

Invasive vulvar carcinoma and the question of the surgical margin.

PubMed

Palaia, Innocenza; Bellati, Filippo; Calcagno, Marco; Musella, Angela; Perniola, Giorgia; Panici, Pierluigi B

2011-08-01

To assess the discrepancy between width of surgical margin measured with the naked eye/ruler by a surgeon before removing an invasive vulvar carcinoma, and width of margin measured under microscope by pathologist after fixation of the resected lesion with formalin. Potential relationships between discrepancy and disease recurrence were also investigated. This prospective study was conducted with resected lesions from 86 women who underwent surgery for primary/recurrent invasive vulvar carcinoma. After the surgeon removed the lesions surrounded by 1-2-cm margins, the pathologist determined margin width at the 4 cardinal points of 86 lesions (for a total of 344 margin assessments), first macroscopically and then under the microscope. A safety margin of 0.8 cm on microscopic view was achieved in 83% of cases (112 of 135) when the macroscopic measurement was 1cm, in 91% of cases (58 of 64) when it was 1.5 cm, and 98% of cases (105 of 107) when it was 2 cm. There was a small discrepancy between the surgeon's intent and the microscopic margin measurement, mostly related to tissue shrinkage. A 1-cm surgical margin corresponded to a 0.8-cm margin in microscopic view (the "safe margin") in most cases. Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Operating without a Safety Net: Gay Male Adolescents and Emerging Adults' Experiences of Marginalization and Migration, and Implications for Theory of Syndemic Production of Health Disparities

ERIC Educational Resources Information Center

Bruce, Douglas; Harper, Gary W.

2011-01-01

Health disparities among gay men (HIV, substance use, depression) have been described as a mutually occurring "syndemic" that is socially produced through two overarching dynamics: marginalization and migration. Although the syndemic theory proposes a developmental trajectory, it has been largely based on epidemiological studies of adult gay men…

Feminist Heuristics: Transforming the Foundation of Food Quality and Safety Assurance Systems

ERIC Educational Resources Information Center

Kimura, Aya Hirata

2012-01-01

Food safety and quality assurance systems have emerged as a key mechanism of food governance in recent years and are also popular among alternative agrofood movements, such as the organic and fair trade movements. Rural sociologists have identified many problems with existing systems, including corporate cooptation, the marginalization of small…

Indolcarboxamide is a preclinical candidate for treating multidrug-resistant tuberculosis.

PubMed

Rao, Srinivasa P S; Lakshminarayana, Suresh B; Kondreddi, Ravinder R; Herve, Maxime; Camacho, Luis R; Bifani, Pablo; Kalapala, Sarath K; Jiricek, Jan; Ma, Ng L; Tan, Bee H; Ng, Seow H; Nanjundappa, Mahesh; Ravindran, Sindhu; Seah, Peck G; Thayalan, Pamela; Lim, Siao H; Lee, Boon H; Goh, Anne; Barnes, Whitney S; Chen, Zhong; Gagaring, Kerstin; Chatterjee, Arnab K; Pethe, Kevin; Kuhen, Kelli; Walker, John; Feng, Gu; Babu, Sreehari; Zhang, Lijun; Blasco, Francesca; Beer, David; Weaver, Margaret; Dartois, Veronique; Glynne, Richard; Dick, Thomas; Smith, Paul W; Diagana, Thierry T; Manjunatha, Ujjini H

2013-12-04

New chemotherapeutic compounds against multidrug-resistant Mycobacterium tuberculosis (Mtb) are urgently needed to combat drug resistance in tuberculosis (TB). We have identified and characterized the indolcarboxamides as a new class of antitubercular bactericidal agent. Genetic and lipid profiling studies identified the likely molecular target of indolcarboxamides as MmpL3, a transporter of trehalose monomycolate that is essential for mycobacterial cell wall biosynthesis. Two lead candidates, NITD-304 and NITD-349, showed potent activity against both drug-sensitive and multidrug-resistant clinical isolates of Mtb. Promising pharmacokinetic profiles of both compounds after oral dosing in several species enabled further evaluation for efficacy and safety. NITD-304 and NITD-349 were efficacious in treating both acute and chronic Mtb infections in mouse efficacy models. Furthermore, dosing of NITD-304 and NITD-349 for 2 weeks in exploratory rat toxicology studies revealed a promising safety margin. Finally, neither compound inhibited the activity of major cytochrome P-450 enzymes or the hERG (human ether-a-go-go related gene) channel. These results suggest that NITD-304 and NITD-349 should undergo further development as a potential treatment for multidrug-resistant TB.

BWR station blackout: A RISMC analysis using RAVEN and RELAP5-3D

DOE PAGES

Mandelli, D.; Smith, C.; Riley, T.; ...

2016-01-01

The existing fleet of nuclear power plants is in the process of extending its lifetime and increasing the power generated from these plants via power uprates and improved operations. In order to evaluate the impact of these factors on the safety of the plant, the Risk-Informed Safety Margin Characterization (RISMC) project aims to provide insights to decision makers through a series of simulations of the plant dynamics for different initial conditions and accident scenarios. This paper presents a case study in order to show the capabilities of the RISMC methodology to assess impact of power uprate of a Boiling Watermore » Reactor system during a Station Black-Out accident scenario. We employ a system simulator code, RELAP5-3D, coupled with RAVEN which perform the stochastic analysis. Furthermore, our analysis is performed by: 1) sampling values from a set of parameters from the uncertainty space of interest, 2) simulating the system behavior for that specific set of parameter values and 3) analyzing the outcomes from the set of simulation runs.« less

3D Simulation of External Flooding Events for the RISMC Pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prescott, Steven; Mandelli, Diego; Sampath, Ramprasad

2015-09-01

Incorporating 3D simulations as part of the Risk-Informed Safety Margins Characterization (RISMIC) Toolkit allows analysts to obtain a more complete picture of complex system behavior for events including external plant hazards. External events such as flooding have become more important recently – however these can be analyzed with existing and validated simulated physics toolkits. In this report, we describe these approaches specific to flooding-based analysis using an approach called Smoothed Particle Hydrodynamics. The theory, validation, and example applications of the 3D flooding simulation are described. Integrating these 3D simulation methods into computational risk analysis provides a spatial/visual aspect to themore » design, improves the realism of results, and can prove visual understanding to validate the analysis of flooding.« less

High-temperature oxidation of advanced FeCrNi alloy in steam environments

DOE PAGES

Elbakhshwan, Mohamed S.; Gill, Simerjeet K.; Rumaiz, Abdul K.; ...

2017-07-04

Alloys of iron-chromium-nickel are being explored as alternative cladding materials to improve safety margins under severe accident conditions. Here, our research focuses on non-destructively investigating the oxidation behavior of the FeCrNi alloy “Alloy 33” using synchrotron-based methods. The evolution and structure of oxide layer formed in steam environments were characterized using X-ray diffraction, hard X-ray photoelectron spectroscopy, X-ray fluorescence methods and scanning electron microscopy. In conclusion, our results demonstrate that a compact and continuous oxide scale was formed consisting of two layers, chromium oxide and spinel phase (FeCr 2O 4) oxides, wherein the concentration of the FeCr 2O 4 phasemore » decreased from the surface to the bulk-oxide interface.« less

Centrifugal Compressor Surge Margin Improved With Diffuser Hub Surface Air Injection

NASA Technical Reports Server (NTRS)

Skoch, Gary J.

2002-01-01

Aerodynamic stability is an important parameter in the design of compressors for aircraft gas turbine engines. Compression system instabilities can cause compressor surge, which may lead to the loss of an aircraft. As a result, engine designers include a margin of safety between the operating line of the engine and the stability limit line of the compressor. The margin of safety is typically referred to as "surge margin." Achieving the highest possible level of surge margin while meeting design point performance objectives is the goal of the compressor designer. However, performance goals often must be compromised in order to achieve adequate levels of surge margin. Techniques to improve surge margin will permit more aggressive compressor designs. Centrifugal compressor surge margin improvement was demonstrated at the NASA Glenn Research Center by injecting air into the vaned diffuser of a 4:1-pressure-ratio centrifugal compressor. Tests were performed using injector nozzles located on the diffuser hub surface of a vane-island diffuser in the vaneless region between the impeller trailing edge and the diffuser-vane leading edge. The nozzle flow path and discharge shape were designed to produce an air stream that remained tangent to the hub surface as it traveled into the diffuser passage. Injector nozzles were located near the leading edge of 23 of the 24 diffuser vanes. One passage did not contain an injector so that instrumentation located in that passage would be preserved. Several orientations of the injected stream relative to the diffuser vane leading edge were tested over a range of injected flow rates. Only steady flow (nonpulsed) air injection was tested. At 100 percent of the design speed, a 15-percent improvement in the baseline surge margin was achieved with a nozzle orientation that produced a jet that was bisected by the diffuser vane leading edge. Other orientations also improved the baseline surge margin. Tests were conducted at speeds below the design speed, and similar results were obtained. In most cases, the greatest improvement in surge margin occurred at fairly low levels of injected flow rate. Externally supplied injection air was used in these experiments. However, the injected flow rates that provided the greatest benefit could be produced using injection air that is recirculating between the diffuser discharge and nozzles located in the diffuser vaneless region. Future experiments will evaluate the effectiveness of recirculating air injection.

Re-appraisal of the Magma-rich versus Magma-poor Paradigm at Rifted Margins: consequences for breakup processes

NASA Astrophysics Data System (ADS)

Tugend, J.; Gillard, M.; Manatschal, G.; Nirrengarten, M.; Harkin, C. J.; Epin, M. E.; Sauter, D.; Autin, J.; Kusznir, N. J.; McDermott, K.

2017-12-01

Rifted margins are often classified based on their magmatic budget only. Magma-rich margins are commonly considered to have excess decompression melting at lithospheric breakup compared with steady state seafloor spreading while magma-poor margins have suppressed melting. New observations derived from high quality geophysical data sets and drill-hole data have revealed the diversity of rifted margin architecture and variable distribution of magmatism. Recent studies suggest, however, that rifted margins have more complex and polyphase tectono-magmatic evolutions than previously assumed and cannot be characterized based on the observed volume of magma alone. We compare the magmatic budget related to lithospheric breakup along two high-resolution long-offset deep reflection seismic profiles across the SE-Indian (magma-poor) and Uruguayan (magma-rich) rifted margins. Resolving the volume of magmatic additions is difficult. Interpretations are non-unique and several of them appear plausible for each case involving variable magmatic volumes and mechanisms to achieve lithospheric breakup. A supposedly 'magma-poor' rifted margin (SE-India) may show a 'magma-rich' lithospheric breakup whereas a 'magma-rich' rifted margin (Uruguay) does not necessarily show excess magmatism at lithospheric breakup compared with steady-state seafloor spreading. This questions the paradigm that rifted margins can be subdivided in either magma-poor or magma-rich margins. The Uruguayan and other magma-rich rifted margins appear characterized by an early onset of decompression melting relative to crustal breakup. For the converse, where the onset of decompression melting is late compared with the timing of crustal breakup, mantle exhumation can occur (e.g. SE-India). Our work highlights the difficulty in determining a magmatic budget at rifted margins based on seismic reflection data alone, showing the limitations of margin classification based solely on magmatic volumes. The timing of decompression melting onset and melting rates (magmatic processes) relative to crustal thinning (tectonic processes) appear equally, if not more important, than the magmatic budget for unravelling the evolution of rifted margins.

Risk-based Strategy to Determine Testing Requirement for the Removal of Residual Process Reagents as Process-related Impurities in Bioprocesses.

PubMed

Qiu, Jinshu; Li, Kim; Miller, Karen; Raghani, Anil

2015-01-01

The purpose of this article is to recommend a risk-based strategy for determining clearance testing requirements of the process reagents used in manufacturing biopharmaceutical products. The strategy takes account of four risk factors. Firstly, the process reagents are classified into two categories according to their safety profile and history of use: generally recognized as safe (GRAS) and potential safety concern (PSC) reagents. The clearance testing of GRAS reagents can be eliminated because of their safe use historically and process capability to remove these reagents. An estimated safety margin (Se) value, a ratio of the exposure limit to the estimated maximum reagent amount, is then used to evaluate the necessity for testing the PSC reagents at an early development stage. The Se value is calculated from two risk factors, the starting PSC reagent amount per maximum product dose (Me), and the exposure limit (Le). A worst-case scenario is assumed to estimate the Me value, that is common. The PSC reagent of interest is co-purified with the product and no clearance occurs throughout the entire purification process. No clearance testing is required for this PSC reagent if its Se value is ≥1; otherwise clearance testing is needed. Finally, the point of the process reagent introduction to the process is also considered in determining the necessity of the clearance testing for process reagents. How to use the measured safety margin as a criterion for determining PSC reagent testing at process characterization, process validation, and commercial production stages are also described. A large number of process reagents are used in the biopharmaceutical manufacturing to control the process performance. Clearance testing for all of the process reagents will be an enormous analytical task. In this article, a risk-based strategy is described to eliminate unnecessary clearance testing for majority of the process reagents using four risk factors. The risk factors included in the strategy are (i) safety profile of the reagents, (ii) the starting amount of the process reagents used in the manufacturing process, (iii) the maximum dose of the product, and (iv) the point of introduction of the process reagents in the process. The implementation of the risk-based strategy can eliminate clearance testing for approximately 90% of the process reagents used in the manufacturing processes. This science-based strategy allows us to ensure patient safety and meet regulatory agency expectations throughout the product development life cycle. © PDA, Inc. 2015.

Crustal structure and inferred extension mode in the northern margin of the South China Sea

NASA Astrophysics Data System (ADS)

Gao, J.; Wu, S.; McIntosh, K. D.; Mi, L.; Spence, G.

2016-12-01

Combining multi-channel seismic reflection and satellite gravity data, this study has investigated the crustal structure and magmatic activities of the northern South China Sea (SCS) margin. Results show that a broad continent-ocean transition zone (COT) with more than 140 km wide is characterized by extensive igneous intrusion/extrusion and hyper-extended continental crust in the northeastern SCS margin, a broader COT with 220-265 km wide is characterized by crustal thinning, rift depression, structural highs with igneous rock and perhaps a volcanic zone or a zone of tilted fault blocks at the distal edge in the mid-northern SCS margin, and a narrow COT with 65 km wide bounded seawards by a volcanic buried seamount is characterized by extremely hyper-extended continental crust in the northwestern SCS margin, where the remnant crust with less than 3 km thick is bounded by basin-bounding faults corresponding to an aborted rift below the Xisha Trough with a sub-parallel fossil ridge in the adjacent Northwest Sub-basin. Results from gravity modeling and seismic refraction data show that a high velocity layer (HVL) is present in the outer shelf and slope below extended continental crust in the eastern portion of the northern SCS margin and is thickest (up to 10 km) in the Dongsha Uplift where the HVL gradually thins to east and west below the lower slope and finally terminates at the Manila Trench and Baiyun sag of the Pearl River Mouth Basin. The magmatic intrusions/extrusions and HVL may be related to partial melting caused by decompression of passive, upwelling asthenosphere which resulted primarily in post-rifting underplating and magmatic emplacement or modification of the crust. The northern SCS margin is closer to those of the magma-poor margins than those of volcanic margins, but the aborted rift near the northwestern continental margin shows that there may be no obvious detachment fault like that in the Iberia-Newfoundland type margin. The symmetric aborted rift, broad hyper-extended continental crust, locally distributed HVL, and hotter mantle materials indicate that continental crust underwent stretching phase (pure-shear deformation), thinning phase and breakup followed by onset of seafloor spreading and the mantle-lithosphere may break up before crustal-necking in the northern South China Sea margin.

41 CFR 102-80.115 - Is there more than one option for establishing that an equivalent level of safety exists?

Code of Federal Regulations, 2013 CFR

2013-07-01

..., complete sprinkler protection can be expected to prevent flashover in the room of fire origin, limit fire... the times required for egress. If a combination of fire protection systems provides a margin of safety... Contracts and Property Management Federal Property Management Regulations System (Continued) FEDERAL...

41 CFR 102-80.115 - Is there more than one option for establishing that an equivalent level of safety exists?

Code of Federal Regulations, 2012 CFR

2012-01-01

..., complete sprinkler protection can be expected to prevent flashover in the room of fire origin, limit fire... the times required for egress. If a combination of fire protection systems provides a margin of safety... Contracts and Property Management Federal Property Management Regulations System (Continued) FEDERAL...

41 CFR 102-80.115 - Is there more than one option for establishing that an equivalent level of safety exists?

Code of Federal Regulations, 2014 CFR

2014-01-01

..., complete sprinkler protection can be expected to prevent flashover in the room of fire origin, limit fire... the times required for egress. If a combination of fire protection systems provides a margin of safety... Contracts and Property Management Federal Property Management Regulations System (Continued) FEDERAL...

41 CFR 102-80.115 - Is there more than one option for establishing that an equivalent level of safety exists?

Code of Federal Regulations, 2011 CFR

2011-01-01

..., complete sprinkler protection can be expected to prevent flashover in the room of fire origin, limit fire... the times required for egress. If a combination of fire protection systems provides a margin of safety... Contracts and Property Management Federal Property Management Regulations System (Continued) FEDERAL...

Lower Crustal Strength Controls on Melting and Serpentinization at Magma-Poor Margins: Potential Implications for the South Atlantic

NASA Astrophysics Data System (ADS)

Ros, Elena; Pérez-Gussinyé, Marta; Araújo, Mario; Thoaldo Romeiro, Marco; Andrés-Martínez, Miguel; Morgan, Jason P.

2017-12-01

Rifted continental margins may present a predominantly magmatic continent-ocean transition (COT), or one characterized by large exposures of serpentinized mantle. In this study we use numerical modeling to show the importance of the lower crustal strength in controlling the amount and onset of melting and serpentinization during rifting. We propose that the relative timing between both events controls the nature of the COT. Numerical experiments for half-extension velocities <=10 mm/yr suggest there is a genetic link between margin tectonic style and COT nature that strongly depends on the lower crustal strength. Our results imply that very slow extension velocities (< 5 mm/yr) and a strong lower crust lead to margins characterized by large oceanward dipping faults, strong syn-rift subsidence and abrupt crustal tapering beneath the continental shelf. These margins can be either narrow symmetric or asymmetric and present a COT with exhumed serpentinized mantle underlain by some magmatic products. In contrast, a weak lower crust promotes margins with a gentle crustal tapering, small faults dipping both ocean- and landward and small syn-rift subsidence. Their COT is predominantly magmatic at any ultra-slow extension velocity and perhaps underlain by some serpentinized mantle. These margins can also be either symmetric or asymmetric. Our models predict that magmatic underplating mostly underlies the wide margin at weak asymmetric conjugates, whereas the wide margin is mainly underlain by serpentinized mantle at strong asymmetric margins. Based on this conceptual template, we propose different natures for the COTs in the South Atlantic.

Safety and Suitability for Service Assessment Testing for Aircraft Launched Munitions

DTIC Science & Technology

2013-07-01

2013 12 benefits in terms of cost and test efficiency that tend to associate the Analytical S3 Test Approach with complex missile systems and the... systems containing expensive, non-safety related components. c. When using the Analytical S3 Test Approach for aircraft launched bombs, full BTCA is...establish safety margin of the system . Details of the Empirical Test Flow with full and reduced BTCA options are provided in Appendix B, Annexes 3 and

Development, fabrication and test of a high purity silica heat shield

NASA Technical Reports Server (NTRS)

Rusert, E. L.; Drennan, D. N.; Biggs, M. S.

1978-01-01

A highly reflective hyperpure ( 25 ppm ion impurities) slip cast fused silica heat shield material developed for planetary entry probes was successfully scaled up. Process development activities for slip casting large parts included green strength improvements, casting slip preparation, aggregate casting, strength, reflectance, and subscale fabrication. Successful fabrication of a one-half scale Saturn probe (shape and size) heat shield was accomplished while maintaining the silica high purity and reflectance through the scale-up process. However, stress analysis of this original aggregate slip cast material indicated a small margin of safety (MS. = +4%) using a factor of safety of 1.25. An alternate hyperpure material formulation to increase the strength and toughness for a greater safety margin was evaluated. The alternate material incorporates short hyperpure silica fibers into the casting slip. The best formulation evaluated has a 50% by weight fiber addition resulting in an 80% increase in flexural strength and a 170% increase in toughness over the original aggregate slip cast materials with comparable reflectance.

A risk assessment of topical tretinoin as a potential human developmental toxin based on animal and comparative human data.

PubMed

Johnson, E M

1997-03-01

Although topically applied all-trans-retinoic acid (tretinoin) undergoes minimal absorption and adds negligibly to normal endogenous levels, its safety in humans is occasionally questioned because oral ingestion of retinoids at therapeutic levels is known to entail teratogenic risks. To assess the actual potential for developmental toxicity from treatment with topical tretinoin. Risk assessments were conducted on four known human developmental toxicants (valproic acid, methotrexate, thalidomide, and isotretinoin) and a potential developmental toxicant (acetylsalicylic acid). The margin of safety for each chemical was calculated from the ratio of animal no-observed adverse effect levels to human lowest-observed adverse effect levels or estimated exposure doses. The derived safety margin of more than 100 for topical tretinoin (with 2% absorption) contrasted sharply with the near unity values for valproic acid, methotrexate, thalidomide, and isotretinoin and was larger than that for acetylsalicylic acid. These data support other epidemiologic and animal data that topical tretinoin is not a potential human developmental toxicant.

Design and analysis of lifting tool assemblies to lift different engine block

NASA Astrophysics Data System (ADS)

Sawant, Arpana; Deshmukh, Nilaj N.; Chauhan, Santosh; Dabhadkar, Mandar; Deore, Rupali

2017-07-01

Engines block are required to be lifted from one place to another while they are being processed. The human effort required for this purpose is more and also the engine block may get damaged if it is not handled properly. There is a need for designing a proper lifting tool which will be able to conveniently lift the engine block and place it at the desired position without any accident and damage to the engine block. In the present study lifting tool assemblies are designed and analyzed in such way that it may lift different categories of engine blocks. The lifting tool assembly consists of lifting plate, lifting ring, cap screws and washers. A parametric model and assembly of Lifting tool is done in 3D modelling software CREO 2.0 and analysis is carried out in ANSYS Workbench 16.0. A test block of weight equivalent to that of an engine block is considered for the purpose of analysis. In the preliminary study, without washer the stresses obtained on the lifting tool were more than the safety margin. In the present design, washers were used with appropriate dimensions which helps to bring down the stresses on the lifting tool within the safety margin. Analysis is carried out to verify that tool design meets the ASME BTH-1 required safety margin.

Caught in the competitive crossfire: safety-net providers balance margin and mission in a profit-driven health care market.

PubMed

Cunningham, Peter J; Bazzoli, Gloria J; Katz, Aaron

2008-01-01

This paper describes how intensifying competitive pressures in the health system are simultaneously driving increased demand for safety-net care and taxing safety-net providers' ability to maintain the mission of serving all, regardless of ability to pay. Although safety-net providers adapted to previous challenges arising from managed care, health system pressures have been more intense and more generalized across different sectors in recent years than in the past. Providers are adopting some of the same strategies being used in the private sector to attract higher-paying patients and changing their "image" as a safety-net provider.

Characterizing entanglement with global and marginal entropic measures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adesso, Gerardo; Illuminati, Fabrizio; De Siena, Silvio

2003-12-01

We qualify the entanglement of arbitrary mixed states of bipartite quantum systems by comparing global and marginal mixednesses quantified by different entropic measures. For systems of two qubits we discriminate the class of maximally entangled states with fixed marginal mixednesses, and determine an analytical upper bound relating the entanglement of formation to the marginal linear entropies. This result partially generalizes to mixed states the quantification of entanglement with marginal mixednesses holding for pure states. We identify a class of entangled states that, for fixed marginals, are globally more mixed than product states when measured by the linear entropy. Such statesmore » cannot be discriminated by the majorization criterion.« less

Test and model correlation of the atmospheric emission photometric imager fiberglass pedestal

NASA Technical Reports Server (NTRS)

Lee, H. M., III; Barker, L. A.

1990-01-01

The correlation is presented of the static loads testing and finite element modeling for the fiberglass pedestal used on the Atmospheric Emission Photometric Imaging (AEPI) experiment. This payload is to be launched in the space shuttle as part of the ATLAS-1 experiment. Strain gauge data from rosettes around the highly loaded base are compared to the same load case run for the Spacelab 1 testing done in 1981. Correlation of the model and test data was accomplished through comparison of the composite stress invariant using the expected flight loads for the ATLAS-1 mission. Where appropriate, the Tsai-Wu failure criteria was used in the development of the key margins of safety. Margins of safety are all positive for the pedestal and are reported.

DETERMINATION OF THE APPROPRIATE FQPA SAFETY FACTOR(S) IN THE ORGANOPHOSPHOROUS PESTICIDE CUMULATIVE RISK ASSESSMENT: SUSCEPTIBILITY AND SENSITIVITY TO THE COMMON MECHANISM, ACETYLCHOLINESTERASE INHIBITION

EPA Science Inventory

The Food Quality Protection Act of 1996 (FQPA) directs EPA, in setting pesticide tolerances, to use an additional tenfold margin of safety to protect infants and children taking into account the potential for pre- and postnatal toxicity and the completeness of the toxicology and ...

Orion MPCV Touchdown Detection Threshold Development and Testing

NASA Technical Reports Server (NTRS)

Daum, Jared; Gay, Robert

2013-01-01

A robust method of detecting Orion Multi ]Purpose Crew Vehicle (MPCV) splashdown is necessary to ensure crew and hardware safety during descent and after touchdown. The proposed method uses a triple redundant system to inhibit Reaction Control System (RCS) thruster firings, detach parachute risers from the vehicle, and transition to the post ]landing segment of the Flight Software (FSW). The vehicle crew is the prime input for touchdown detection, followed by an autonomous FSW algorithm, and finally a strictly time based backup timer. RCS thrusters must be inhibited before submersion in water to protect against possible damage due to firing these jets under water. In addition, neglecting to declare touchdown will not allow the vehicle to transition to post ]landing activities such as activating the Crew Module Up ]righting System (CMUS), resulting in possible loss of communication and difficult recovery. A previous AIAA paper gAssessment of an Automated Touchdown Detection Algorithm for the Orion Crew Module h concluded that a strictly Inertial Measurement Unit (IMU) based detection method using an acceleration spike algorithm had the highest safety margins and shortest detection times of other methods considered. That study utilized finite element simulations of vehicle splashdown, generated by LS ]DYNA, which were expanded to a larger set of results using a Kriging surface fit. The study also used the Decelerator Systems Simulation (DSS) to generate flight dynamics during vehicle descent under parachutes. Proto ]type IMU and FSW MATLAB models provided the basis for initial algorithm development and testing. This paper documents an in ]depth trade study, using the same dynamics data and MATLAB simulations as the earlier work, to further develop the acceleration detection method. By studying the combined effects of data rate, filtering on the rotational acceleration correction, data persistence limits and values of acceleration thresholds, an optimal configuration was determined. The lever arm calculation, which removes the centripetal acceleration caused by vehicle rotation, requires that the vehicle angular acceleration be derived from vehicle body rates, necessitating the addition of a 2nd order filter to smooth the data. It was determined that using 200 Hz data directly from the vehicle IMU outperforms the 40 Hz FSW data rate. Data persistence counter values and acceleration thresholds were balanced in order to meet desired safety and performance. The algorithm proved to exhibit ample safety margin against early detection while under parachutes, and adequate performance upon vehicle splashdown. Fall times from algorithm initiation were also studied, and a backup timer length was chosen to provide a large safety margin, yet still trigger detection before CMUS inflation. This timer serves as a backup to the primary acceleration detection method. Additionally, these parameters were tested for safety on actual flight test data, demonstrating expected safety margins.

Stratal stacking patterns and tectono-sedimentary evolution of hyperextended magma-poor rifted margins

NASA Astrophysics Data System (ADS)

Ribes, C.; Gillard, M.; Epin, M. E.; Ghienne, J. F.; Manatschal, G.; Karner, G. D.; Johnson, C. A.

2016-12-01

Research on the formation and evolution of deep-water rifted margins has undergone a major paradigm shift in recent years. An increasing number of studies of present-day and fossil rifted margins allow us to identify and characterize the structural architecture of the most distal parts of rifted margins, the so-called hyperextended, magma-poor rifted margins. However, at present, little is known about the depositional environments, sedimentary facies, stacking patterns, subsidence and thermal history within these domains. In this context, characterizing the stratal stacking patterns and understanding their spatial and temporal evolution is a new challenge. The major difficulty comes from the fact that the observed stratigraphic geometries and facies relationships are a result of the complex interplay between sediment supply and available accommodation, which is controlled by not only the regional generation of accommodation, but also by local tectono-magmatic processes. These parameters are poorly constrained or even sufficiently known in these tectonic settings. Indeed, the complex structural evolution of hyperextended magma-poor rifted margins, including the development of poly-phase in-sequence and out of sequence extensional detachment faults and associated mantle exhumation and magmatic activity, can generate complex accommodation patterns over a highly structured top basement. The presentation summarizes early results concerning the controlling parameters on ultra-deep water stratigraphic stacking patterns and to provide a conceptual framework. This observation-driven approach combines fieldwork from fossil Alpine Tethys margins exposed in the Alps and the analysis of seismic reflection data from present-day deep water rifted margins such as the Australian-Antarctic, East India and Iberia-Newfoundland margins.

Prebiotics and probiotics – the importance of branding

PubMed Central

Crittenden, Ross

2012-01-01

The costs of developing a probiotic or prebiotic ingredient have always been substantial. Ingredient characterization, evaluation of technological and physiological properties, and demonstrations of safety and clinical efficacy require expensive research. The demanding regulatory requirements imposed by EFSA raise the bar even higher so that the costs of acquiring the necessary clinical evidence to support labeling of these food ingredients is approaching that of pharmaceuticals. In order to justify investment in such expensive clinical development, companies require certainty that they can gain a return on investment. Patenting can provide some protection but is not always possible to patent ingredients, and the period of protection is limited. All ingredients eventually face the prospect of commoditization once patents expire. Branding strategies offer one means of maintaining adequate product differentiation to protect market share and margins over the long term. PMID:23990815

Prebiotics and probiotics - the importance of branding.

PubMed

Crittenden, Ross

2012-01-01

The costs of developing a probiotic or prebiotic ingredient have always been substantial. Ingredient characterization, evaluation of technological and physiological properties, and demonstrations of safety and clinical efficacy require expensive research. The demanding regulatory requirements imposed by EFSA raise the bar even higher so that the costs of acquiring the necessary clinical evidence to support labeling of these food ingredients is approaching that of pharmaceuticals. In order to justify investment in such expensive clinical development, companies require certainty that they can gain a return on investment. Patenting can provide some protection but is not always possible to patent ingredients, and the period of protection is limited. All ingredients eventually face the prospect of commoditization once patents expire. Branding strategies offer one means of maintaining adequate product differentiation to protect market share and margins over the long term.

Development of future indications for BOTOX.

PubMed

Brin, Mitchell F

2009-10-01

Since the late 1970s, local injections of BoNT have provided clinical benefit for patients with inappropriately contracting muscles with or without pain or sensory disturbance. Marketing authorization for some BoNTs, depending on country, include core indications of dystonia (blepharospasm and cervical dystonia), large muscle spastic disorders (not yet approved in the United States, e.g., adult post-stroke spasticity and equinus foot deformity), hyperhidrosis and aesthetic. Subsequent development has extended to selected conditions characterized by recurrent or chronic pain (migraine headache), and urologic indications (neurogenic/idiopathic overactive bladder; prostate hyperplasia), with multiple additional opportunities available. Portfolio management requires a careful individual opportunity assessment of scientific and technical aspects (basic science foundation, potential to treat unmet medical need, product-specific risk in specific populations, therapeutic margin/safety profile, and probability of successful registration pathway). This article describes ongoing development targets for BOTOX.

Geologic controls on submarine slope failure along the central U.S. Atlantic margin: Insights from the Currituck Slide Complex

USGS Publications Warehouse

Hill, Jenna C.; Brothers, Daniel S.; Craig, Bradley K.; ten Brink, Uri S.; Chaytor, Jason D.; Flores, Claudia

2017-01-01

Multiple styles of failure, ranging from densely spaced, mass transport driven canyons to the large, slab-type slope failure of the Currituck Slide, characterize adjacent sections of the central U.S. Atlantic margin that appear to be defined by variations in geologic framework. Here we use regionally extensive, deep penetration multichannel seismic (MCS) profiles to reconstruct the influence of the antecedent margin physiography on sediment accumulation along the central U.S. Atlantic continental shelf-edge, slope, and uppermost rise from the Miocene to Present. These data are combined with high-resolution sparker MCS reflection profiles and multibeam bathymetry data across the Currituck Slide Complex. Pre-Neogene allostratigraphic horizons beneath the slope are generally characterized by low gradients and convex downslope profiles. This is followed by the development of thick, prograded deltaic clinoforms during the middle Miocene. Along-strike variations in morphology of a regional unconformity at the top of this middle Miocene unit appear to have set the stage for differing styles of mass transport along the margin. Areas north and south of the Currituck Slide are characterized by oblique margin morphology, defined by an angular shelf-edge and a relatively steep (> 8°), concave slope profile. Upper slope sediment bypass, closely spaced submarine canyons, and small, localized landslides confined to canyon heads and sidewalls characterize these sectors of the margin. In contrast, the Currituck region is defined by a sigmoidal geometry, with a rounded shelf-edge rollover and gentler slope gradient (< 6°). Thick (> 800 m), regionally continuous stratified slope deposits suggest the low gradient Currituck region was a primary depocenter for fluvial inputs during multiple sea level lowstands. These results imply that the rounded, gentle slope physiography developed during the middle Miocene allowed for a relatively high rate of subsequent sediment accumulation, thus providing a mechanism for compaction–induced overpressure that preconditioned the Currituck region for failure. Detailed examination of the regional geological framework illustrates the importance of both sediment supply and antecedent slope physiography in the development of large, potentially unstable depocenters along passive margins.

The Continental Margin of East Asia: a collage of multiple plates formed by convergence and extension from multiple directions

NASA Astrophysics Data System (ADS)

Mao, J.; Wang, T.; Ludington, S.; Qiu, Z.; Li, Z.

2017-12-01

East Asia is one of the most complex regions in the world. Its margin was divided into 4 parts: Northeast Asia, North China, South China and Southeast Asia. During the Phanerozoic, continental plates of East Asia have interacted successively with a) the Paleo Tethyan Ocean, b) the Tethyan and Paleo Pacific Oceans and c) the Pacific and Indian. In the Early Mesozoic, the Indosinian orogeny is characterized by the convergence and extension within multiple continental plates, whereas the Late Mesozoic Yanshanian orogeny is characterized by both convergence and compression due to oceanic subduction and by widespread extension. We propose this combination as "East Asia Continental Margin type." Except in Northeast Asia, where Jurassic and Cretaeous accretionary complexes are common, most magmatic rocks are the result of reworking of ancient margins of small continental plates; and oceanic island arc basalts and continental margin arc andesites are largely absent. Because South China is adjacent to the western margin of the Pacific Plate, some effects of its westward subduction must be unavoidable, but juvenile arc-related crust has not been identified. The East Asian Continental Margin is characterized by magmatic rocks that are the result of post-convergent tectonics, which differs markedly from the active continental margins of both South and North America. In summary, the chief characteristics of the East Asian Continental Margin are: 1) In Mesozoic, the periphery of multiple blocks experienced magmatism caused by lithospheric delamination and thinning in response to extension punctuated by shorter periods of convergence. 2) The main mechanism of magma generation was the partial melting of crustal rocks, due to underplating by upwelling mafic magma associated with the collapse of orogenic belts and both extension and compression between small continental blocks. 3) During orogeny, mostly high Sr/Y arc-related granitoids formed, whereas during post-orogenic times, A-type granitoids formed. 4) These dynamics are the result of subduction and extension of the oceanic plates that bordered East Asia. 5) The complex mosaic of geology and geochemistry is the result of compositional variation in the deep lithosphere, as well as variation in the dynamics of oceanic plate movements.

Lower crustal strength controls on melting and type of oceanization at magma-poor margins

NASA Astrophysics Data System (ADS)

Ros, E.; Perez-Gussinye, M.; Araujo, M. N.; Thoaldo Romeiro, M.; Andres-Martinez, M.; Morgan, J. P.

2017-12-01

Geodynamical models have been widely used to explain the variability in the architectonical style of conjugate rifted margins as a combination of lithospheric deformation modes, which are strongly influenced by lower crustal strength. We use 2D numerical models to show that the lower crustal strength also plays a key role on the onset and amount of melting and serpentinization during continental rifting. The relative timing between melting and serpentinization onsets controls whether the continent-ocean transition (COT) of margins will be predominantly magmatic or will mainly consist of exhumed and serpentinized mantle. Based on our results for magma-poor continental rifting, we propose a genetic link between margin architecture and COT styles that can be used as an additional tool to help interpret and understand the processes leading to margin formation. Our results show that strong lower crusts and very slow extension velocities (<5 mm/yr) lead to either symmetric or asymmetric margins with large oceanward dipping faults, strong syn-rift subsidence and abrupt crustal tapering beneath the continental shelf. These margins are characterized by a COT consisting of exhumed and serpentinized mantle and some magmatic products. Weak lower crusts at ultra-slow velocities lead also to either symmetric or asymmetric margins with small faults dipping both ocean- and landward, small syn-rift subsidence and gentle crustal tapering, and present a predominantly magmatic COT, perhaps underlain by some serpentinized mantle. When conjugate margins are asymmetric, if the rheology is relatively strong, serpentinite predominantly underlays the wide margin, whereas if the lower crustal strength is weak, melt preferentially migrates towards the wide margin. Based on the onshore lithospheric structure, extension velocity and margin architecture of the magma-poor section of the South Atlantic, we suggest that the COT of the northern sector, Camamu-Gabon basins, is more likely to consist of exhumed mantle with intruded magmatism, while to the South, the Camamu-Kwanza and North Santos-South Kwanza conjugates, may be better characterized by a predominantly magmatic COT.

Splenic marginal zone lymphoma.

PubMed

Piris, Miguel A; Onaindía, Arantza; Mollejo, Manuela

Splenic marginal zone lymphoma (SMZL) is an indolent small B-cell lymphoma involving the spleen and bone marrow characterized by a micronodular tumoral infiltration that replaces the preexisting lymphoid follicles and shows marginal zone differentiation as a distinctive finding. SMZL cases are characterized by prominent splenomegaly and bone marrow and peripheral blood infiltration. Cells in peripheral blood show a villous cytology. Bone marrow and peripheral blood characteristic features usually allow a diagnosis of SMZL to be performed. Mutational spectrum of SMZL identifies specific findings, such as 7q loss and NOTCH2 and KLF2 mutations, both genes related with marginal zone differentiation. There is a striking clinical variability in SMZL cases, dependent of the tumoral load and performance status. Specific molecular markers such as 7q loss, p53 loss/mutation, NOTCH2 and KLF2 mutations have been found to be associated with the clinical variability. Distinction from Monoclonal B-cell lymphocytosis with marginal zone phenotype is still an open issue that requires identification of precise and specific thresholds with clinical meaning. Copyright © 2016 Elsevier Ltd. All rights reserved.

Characterization of Hypervelocity Metal Fragments for Explosive Initiation

NASA Astrophysics Data System (ADS)

Yeager, John; Bowden, Patrick; Guildenbecher, Daniel; Olles, Joseph

2017-06-01

The off-normal detonation behavior of two plastic-bonded explosive (PBX) formulations was studied using explosively-driven aluminum fragments moving at hypersonic velocity. Witness plate materials, including copper and polycarbonate, were used to characterize the distribution of particles, finding that the aluminum did not fragment homogeneously but rather with larger particles in a ring surrounding finer particles. Digital holography experiments were conducted to measure three-dimensional shape and size of the fastest-moving fragments, which ranged between 100 and 700 microns and traveled between 2 and 3.5 km/s. Crucially, these experiments showed variability in the fragmentation in terms of the number of fragments at the leading edge of the fragment field, indicating that both single and multiple shock impacts could be imparted to the target material. Lower density PBX 9407 (RDX-based) was initiable at up to 4.5 inches, while higher density PBX 9501 (HMX-based) was only initiable at up to 0.25 inches. This type of data is critical for safety experiments and hydrocode simulations to quantify shock-to-detonation transition mechanisms and the associated risk-margins for these materials.

No-Touch Radiofrequency Ablation: A Comparison of Switching Bipolar and Switching Monopolar Ablation in Ex Vivo Bovine Liver

PubMed Central

Chang, Won; Lee, Sang Min; Han, Joon Koo

2017-01-01

Objective To evaluate the feasibility, efficiency, and safety of no-touch switching bipolar (SB) and switching monopolar (SM) radiofrequency ablation (RFA) using ex vivo bovine livers. Materials and Methods A pork loin cube was inserted as a tumor mimicker in the bovine liver block; RFA was performed using the no-touch technique in the SM (group A1; 10 minutes, n = 10, group A2; 15 minutes, n = 10) and SB (group B; 10 minutes, n = 10) modes. The groups were compared based on the creation of confluent necrosis with sufficient safety margins, the dimensions, and distance between the electrode and ablation zone margin (DEM). To evaluate safety, small bowel loops were placed above the liver surface and 30 additional ablations were performed in the same groups. Results Confluent necroses with sufficient safety margins were created in all specimens. SM RFA created significantly larger volumes of ablation compared to SB RFA (all p < 0.001). The DEM of group B was significantly lower than those of groups A1 and A2 (all p < 0.001). Although thermal injury to the small bowel was noted in 90%, 100%, and 30% of the cases in groups A1, A2, and B, respectively, full depth injury was noted only in 60% of group A2 cases. Conclusion The no-touch RFA technique is feasible in both the SB and SM modes; however, SB RFA appears to be more advantageous compared to SM RFA in the creation of an ablation zone while avoiding the unnecessary creation of an adjacent parenchymal ablation zone or adjacent small bowel injuries. PMID:28246508

Medical abortion: understanding perspectives of rural and marginalized women from rural South India.

PubMed

Sri, B Subha; Ravindran, T K Sundari

2012-09-01

To understand how rural and other groups of marginalized women define safe abortion; their perspectives and concerns regarding medical abortion (MA); and what factors affect their access to safe abortion. Focus group discussions were held with various groups of rural and marginalized women in Tamil Nadu to understand their perspectives and concerns on abortion, especially MA. Nearly a decade after mifepristone was approved for abortion in India, most study participants had never heard of MA. When they learned of the method, most preferred it over other methods of abortion. The women also had questions and concerns about the method and recommendations on how services should be provided. Their definition of a "safe abortion" included criteria beyond medical safety. They placed a high priority on "social safety," including confidentiality and privacy. In their view, factors affecting access to safe abortion and choice of provider included cost, assurance of secrecy, promptness of service provision, and absence of provider gatekeeping and provider-imposed conditions for receiving services. Women's preference for MA shows the potential of this technology to address the problem of unsafe abortion in India. Women need better access to information and services to realize this potential, however. Women's preferences regarding information dissemination and service provision need to be taken into account if policies and programs are to be truly responsive to the needs of marginalized women. Copyright © 2012. Published by Elsevier Ireland Ltd.

Real-world effects of using a phone while driving on lateral and longitudinal control of vehicles.

PubMed

Dozza, Marco; Flannagan, Carol A C; Sayer, James R

2015-12-01

Technologies able to augment human communication, such as smartphones, are increasingly present during all daily activities. Their use while driving, in particular, is of great potential concern, because of the high risk that distraction poses during this activity. Current countermeasures to distraction from phone use are considerably different across countries and not always widely accepted/adopted by the drivers. This study utilized naturalistic driving data collected from 108 drivers in the Integrated Vehicle-Based Safety Systems (IVBSS) program in 2009 and 2010 to assess the extent to which using a phone changes lateral or longitudinal control of a vehicle. The IVBSS study included drivers from three age groups: 20–30 (younger), 40–50 (middle-aged), and 60–70 (older). Results from this study show that younger drivers are more likely to use a phone while driving than older and middle-aged drivers. Furthermore, younger drivers exhibited smaller safety margins while using a phone. Nevertheless, younger drivers did not experience more severe lateral/longitudinal threats than older and middle-aged drivers, probably because of faster reaction times. While manipulating the phone (i.e., dialing, texting), drivers exhibited larger lateral safety margins and experienced less severe lateral threats than while conversing on the phone. Finally, longitudinal threats were more critical soon after phone interaction, suggesting that drivers terminate phone interactions when driving becomes more demanding. These findings suggest that drivers are aware of the potential negative effect of phone use on their safety. This awareness guides their decision to engage/disengage in phone use and to increase safety margins (self-regulation). This compensatory behavior may be a natural countermeasure to distraction that is hard to measure in controlled studies. Practical Applications: Intelligent systems able to amplify this natural compensatory behavior may become a widely accepted/adopted countermeasure to the potential distraction from phone operation while driving.

Patient positioning in head and neck cancer : Setup variations and safety margins in helical tomotherapy.

PubMed

Leitzen, Christina; Wilhelm-Buchstab, Timo; Müdder, Thomas; Heimann, Martina; Koch, David; Schmeel, Christopher; Simon, Birgit; Stumpf, Sabina; Vornholt, Susanne; Garbe, Stephan; Röhner, Fred; Schoroth, Felix; Schild, Hans Heinz; Schüller, Heinrich

2018-05-01

To evaluate the interfractional variations of patient positioning during intensity-modulated radiotherapy (IMRT) with helical tomotherapy in head and neck cancer and to calculate the required safety margins (sm) for bony landmarks resulting from the necessary table adjustments. In all, 15 patients with head and neck cancer were irradiated using the Hi-Art II tomotherapy system between April and September 2016. Before therapy sessions, patient position was frequently checked by megavolt computed tomography (MV-CT). Necessary table adjustments (ta) in the right-left (rl), superior-inferior (si) and anterior-posterior (ap) directions were recorded for four anatomical points: second, fourth and sixth cervical vertebral body (CVB), anterior nasal spine (ANS). Based upon these data sm were calculated for non-image-guided radiotherapy, image-guided radiotherapy (IGRT) and image guidance limited to a shortened area (CVB 2). Based upon planning CT the actual treatment required ta from -0.05 ± 1.31 mm for CVB 2 (ap) up to 2.63 ± 2.39 mm for ANS (rl). Considering the performed ta resulting from image control (MV-CT) we detected remaining ta from -0.10 ± 1.09 mm for CVB 4 (rl) up to 1.97 ± 1.64 mm for ANS (si). After theoretical adjustment of patients position to CVB 2 the resulting ta ranged from -0.11 ± 2.44 mm for CVB6 (ap) to 2.37 ± 2.17 mm for ANS (si). These data imply safety margins: uncorrected patient position: 3.63-9.95 mm, corrected positioning based upon the whole target volume (IGRT): 1.85-6.63 mm, corrected positioning based upon CVB 2 (IGRT): 3.13-6.66 mm. The calculated safety margins differ between anatomic regions. Repetitive and frequent image control of patient positioning is necessary that, however, possibly may be focussed on a limited region.

[Soft tissue sarcoma of the upper extremities. Analysis of factors relevant for prognosis in 160 patients].

PubMed

Lehnhardt, M; Hirche, C; Daigeler, A; Goertz, O; Ring, A; Hirsch, T; Drücke, D; Hauser, J; Steinau, H U

2012-02-01

Soft tissue sarcomas (STS) are a rare entity with reduced prognosis due to their aggressive biology. For an optimal treatment of STS identification of independent prognostic factors is crucial in order to reduce tumor-related mortality and recurrence rates. The surgical oncological concept includes wide excisions with resection safety margins >1 cm which enables acceptable functional results and reduced rates of amputation of the lower extremities. In contrast, individual anatomy of the upper extremities, in particular of the hand, leads to an intentional reduction of resection margins in order to preserve the extremity and its function with the main intention of tumor-free resection margins. In this study, the oncological safety and outcome as well as functional results were validated by a retrospective analysis of survival rate, recurrence rate and potential prognostic factors. A total of 160 patients who had been treated for STS of the upper extremities were retrospectively included. Independent prognostic factors were analyzed (primary versus recurrent tumor, tumor size, resection status, grade of malignancy, additional therapy, localization in the upper extremity). Kaplan-Meier analyses for survival rate and local control were calculated. Further outcome measures were functional results validated by the DASH score and rate of amputation. In 130 patients (81%) wide tumor excision (R0) was performed and in 19 patients (12%) an amputation was necessary. The 5-year overall survival rate was 70% and the 5-year survival rate in primary tumors was 81% whereas in recurrences 55% relapsed locally. The 10-year overall survival rate was 45% and the 5-year recurrence rate was 18% for primary STS and 43% for recurrent STS. Variance analysis revealed primary versus recurrent tumor, tumor size, resection status and grade of malignancy as independent prognostic factors. Analysis of functional results showed a median DASH score of 37 (0-100; 0=contralateral extremity). The 5-year survival and local recurrence rates are comparable to STS wide resections with safety margins >1 cm for the lower extremities and the trunk. Analysis of prognostic factors revealed resection status and the tumor-free resection margins to be the main goals in STS resection of upper extremity.

A review of inherent safety characteristics of metal alloy sodium-cooled fast reactor fuel against postulated accidents

DOE PAGES

Sofu, Tanju

2015-04-01

The thermal, mechanical, and neutronic performance of the metal alloy fast reactor fuel design complements the safety advantages of the liquid metal cooling and the pool-type primary system. Together, these features provide large safety margins in both normal operating modes and for a wide range of postulated accidents. In particular, they maximize the measures of safety associated with inherent reactor response to unprotected, double-fault accidents, and to minimize risk to the public and plant investment. High thermal conductivity and high gap conductance play the most significant role in safety advantages of the metallic fuel, resulting in a flatter radial temperaturemore » profile within the pin and much lower normal operation and transient temperatures in comparison to oxide fuel. Despite the big difference in melting point, both oxide and metal fuels have a relatively similar margin to melting during postulated accidents. When the metal fuel cladding fails, it typically occurs below the coolant boiling point and the damaged fuel pins remain coolable. Metal fuel is compatible with sodium coolant, eliminating the potential of energetic fuel--coolant reactions and flow blockages. All these, and the low retained heat leading to a longer grace period for operator action, are significant contributing factors to the inherently benign response of metallic fuel to postulated accidents. This paper summarizes the past analytical and experimental results obtained in past sodium-cooled fast reactor safety programs in the United States, and presents an overview of fuel safety performance as observed in laboratory and in-pile tests.« less

A review of inherent safety characteristics of metal alloy sodium-cooled fast reactor fuel against postulated accidents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sofu, Tanju

2015-04-01

The thermal, mechanical, and neutronic performance of the metal alloy fast reactor fuel design complements the safety advantages of the liquid metal cooling and the pool-type primary system. Together, these features provide large safety margins in both normal operating modes and for a wide range of postulated accidents. In particular, they maximize the measures of safety associated with inherent reactor response to unprotected, double-fault accidents, and to minimize risk to the public and plant investment. High thermal conductivity and high gap conductance play the most significant role in safety advantages of the metallic fuel, resulting in a flatter radial temperaturemore » profile within the pin and much lower normal operation and transient temperatures in comparison to oxide fuel. Despite the big difference in melting point, both oxide and metal fuels have a relatively similar margin to melting during postulated accidents. When the metal fuel cladding fails, it typically occurs below the coolant boiling point and the damaged fuel pins remain cool-able. Metal fuel is compatible with sodium coolant, eliminating the potential of energetic fuel coolant reactions and flow blockages. All these, and the low retained heat leading to a longer grace period for operator action, are significant contributing factors to the inherently benign response of metallic fuel to postulated accidents. This paper summarizes the past analytical and experimental results obtained in past sodium-cooled fast reactor safety programs in the United States, and presents an overview of fuel safety performance as observed in laboratory and in-pile tests.« less

Lunar Reconnaissance Orbiter K-Band (26 GHz) Signal Analysis: Initial Study Results

NASA Astrophysics Data System (ADS)

Morabito, D. D.; Heckman, D.

2017-11-01

Lower frequency telemetry bands are becoming more limited in bandwidth due to increased competition between flight projects and other entities. Higher frequency bands offer significantly more bandwidth and hence the prospect of much higher data rates. Future or prospective flight projects considering higher frequency bands such as Ka-band (32 GHz) for deep-space and K-band (26 GHz) for near-Earth telemetry links are interested in past flight experience with available received data at these frequencies. Given that there is increased degradation due to the atmosphere at these higher frequencies, there is an effort to retrieve flight data of received signal strength to analyze performance under a variety of factors. Such factors include elevation angle, season, and atmospheric conditions. This article reports on the analysis findings of over 10 million observations of received signal strength of the Lunar Reconnaissance Orbiter (LRO) spacecraft collected between 2014 and 2017. We analyzed these data to characterize link performance over a wide range of weather conditions, season, and as a function of elevation angle. Based on this analysis, we have confirmed the safety of using a 3-dB margin for preflight planning purposes. These results suggest that a 3-dB margin with respect to adverse conditions will ensure a 98 to 99 percent data return under 95 percent weather conditions at 26 GHz (K-band), thus confirming expectations from link budget predictions. The results suggest that this margin should be applicable for all elevation angles above 10 deg. Thus, missions that have sufficient power for their desired data rates may opt to use 10 deg as their minimum elevation angle. Limitations of this study include climate variability and the fact that the observations require removal of hotbody noise in order to perform an adequate cumulative distribution function (CDF) analysis, which is planned for a future comprehensive study. Flight projects may use other link margins depending upon available information, uncertainties of non-atmospheric link parameters, and mission phase.

Development of CO2 laser Doppler instrumentation for detection of clear air turbulence, volume 2: Appendices

NASA Technical Reports Server (NTRS)

Harris, C. E.; Jelalian, A. V.

1979-01-01

Analyses of the mounting and mount support systems of the clear air turbulence transmitters verify that satisfactory shock and vibration isolation are attained. The mount support structure conforms to flight crash safety requirements with high margins of safety. Restraint cables reinforce the mounts in the critical loaded forward direction limiting maximum forward system deflection to 1 1/4 inches.

Los Alamos Novel Rocket Design Flight Tested

ScienceCinema

Tappan, Bryce

2018-04-16

Los Alamos National Laboratory scientists recently flight tested a new rocket design that includes a high-energy fuel and a motor design that also delivers a high degree of safety. Researchers will now work to scale-up the design, as well as explore miniaturization of the system, in order to exploit all potential applications that would require high-energy, high-velocity, and correspondingly high safety margins.

Los Alamos Novel Rocket Design Flight Tested

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tappan, Bryce

Los Alamos National Laboratory scientists recently flight tested a new rocket design that includes a high-energy fuel and a motor design that also delivers a high degree of safety. Researchers will now work to scale-up the design, as well as explore miniaturization of the system, in order to exploit all potential applications that would require high-energy, high-velocity, and correspondingly high safety margins.

Structural design/margin assessment

NASA Technical Reports Server (NTRS)

Ryan, R. S.

1993-01-01

Determining structural design inputs and the structural margins following design completion is one of the major activities in space exploration. The end result is a statement of these margins as stability, safety factors on ultimate and yield stresses, fracture limits (fracture control), fatigue lifetime, reuse criteria, operational criteria and procedures, stability factors, deflections, clearance, handling criteria, etc. The process is normally called a load cycle and is time consuming, very complex, and involves much more than structures. The key to successful structural design is the proper implementation of the process. It depends on many factors: leadership and management of the process, adequate analysis and testing tools, data basing, communications, people skills, and training. This process and the various factors involved are discussed.

Protection of Workers and Third Parties during the Construction of Linear Structures

NASA Astrophysics Data System (ADS)

Vlčková, Jitka; Venkrbec, Václav; Henková, Svatava; Chromý, Adam

2017-12-01

The minimization of risk in the workplace through a focus on occupational health and safety (OHS) is one of the primary objectives for every construction project. The most serious accidents in the construction industry occur during work on earthworks and linear structures. The character of such structures places them among those posing the greatest threat to the public (referred to as “third parties”). They can be characterized as large structures whose construction may involve the building site extending in a narrow lane alongside previously constructed objects currently in use by the public. Linear structures are often directly connected to existing objects or buildings, making it impossible to guard the whole construction site. However, many OHS problems related to linear structures can be prevented during the design stage. The aim of this article is to introduce a new methodology which has been implemented into a computer program that deals with safety measures at construction sites where work is performed on linear structures. Based on existing experience with the design of such structures and their execution and supervision by safety coordinators, the basic types of linear structures, their location in the terrain, the conditions present during their execution and other marginal conditions and influences were modelled. Basic safety information has been assigned to this elementary information, which is strictly necessary for the construction process. The safety provisions can be grouped according to type, e.g. technical, organizational and other necessary documentation, or into sets of provisions concerning areas such as construction site safety, transport safety, earthworks safety, etc. The selection of the given provisions takes place using multiple criteria. The aim of creating this program is to provide a practical tool for designers, contractors and construction companies. The model can contribute to the sufficient awareness of these participants about technical and organizational provisions that can help them to meet workplace safety requirements. The software for the selection of safety provisions also contains module that can calculate necessary cost estimates using a calculation formula chosen by the user. All software data conform to European standards harmonized for the Czech Republic.

Characterization of an optimized light source and comparison to pulsed dye laser for superficial and deep vessel clearance.

PubMed

Weiss, Robert A; Ross, E Victor; Tanghetti, Emil A; Vasily, David B; Childs, James J; Smirnov, Mikhail Z; Altshuler, Gregory B

2011-02-01

An arc lamp-based device providing optimized spectrum and pulse shape was characterized and compared with two pulsed dye laser (PDL) systems using a vascular phantom. Safety and effectiveness for facial telangiectasia are presented in clinical case studies. An optimized pulsed light source's (OPL) spectral and power output were characterized and compared with two 595 nm PDL devices. Purpuric threshold fluences were determined for the OPL and PDLs on Fitzpatrick type II normal skin. A vascular phantom comprising blood-filled quartz capillaries beneath porcine skin was treated by the devices at their respective purpuric threshold fluences for 3 ms pulse widths, while vessel temperatures were monitored with an infrared (IR) camera. Patients with Fitzpatrick skin types II-III received a split-face treatment with the OPL and a 595 nm PDL. The OPL provided a dual-band output spectrum from 500 to 670 nm and 850-1,200 nm, pulse widths from 3 to 100 ms, and fluences to 80 J/cm(2). The smooth output power measured during all pulse widths provides unambiguous vessel size selectivity. Percent energy in the near infra-red increased with decreasing output power from 45% to 60% and contributed 15-26% to heating of deep vessels, respectively. At purpuric threshold fluences the ratio of OPL to PDL vessel temperature rise was 1.7-2.8. OPL treatments of facial telangiectasia were well-tolerated by patients demonstrating significant improvements comparable to PDL with no downtime. Intense pulsed light (IPL) and PDL output pulse and spectral profiles are important for selective treatment of vessels in vascular lesions. The OPL's margin between purpuric threshold fluence and treatment fluence for deeper, larger vessels was greater than the corresponding margin with PDLs. The results warrant further comparison studies with IPLs and other PDLs. Copyright © 2011 Wiley-Liss, Inc.

The Study of the Relationship between Probabilistic Design and Axiomatic Design Methodology. Volume 2

NASA Technical Reports Server (NTRS)

Onwubiko, Chin-Yere; Onyebueke, Landon

1996-01-01

The structural design, or the design of machine elements, has been traditionally based on deterministic design methodology. The deterministic method considers all design parameters to be known with certainty. This methodology is, therefore, inadequate to design complex structures that are subjected to a variety of complex, severe loading conditions. A nonlinear behavior that is dependent on stress, stress rate, temperature, number of load cycles, and time is observed on all components subjected to complex conditions. These complex conditions introduce uncertainties; hence, the actual factor of safety margin remains unknown. In the deterministic methodology, the contingency of failure is discounted; hence, there is a use of a high factor of safety. It may be most useful in situations where the design structures are simple. The probabilistic method is concerned with the probability of non-failure performance of structures or machine elements. It is much more useful in situations where the design is characterized by complex geometry, possibility of catastrophic failure, sensitive loads and material properties. Also included: Comparative Study of the use of AGMA Geometry Factors and Probabilistic Design Methodology in the Design of Compact Spur Gear Set.

Genotoxicity testing of a fenugreek extract.

PubMed

Flammang, A M; Cifone, M A; Erexson, G L; Stankowski, L F

2004-11-01

Fenugreek seeds have been used in traditional medicines as a remedy for diabetes. Rich in protein, fenugreek seeds contain the unique major free amino acid 4-hydroxyisoleucine (4-OH-Ile), which has been characterized as one of the active ingredients for blood glucose control. Current use of fenugreek in foodstuff has been limited to its role as a flavoring agent, and not as an ingredient to help mitigate the blood glucose response for people with diabetes. As part of a safety evaluation of novel ingredients for use in blood glucose control, the potential genotoxicity of a fenugreek seed extract (THL), containing a minimum of 40% 4-OH-ILE, was evaluated using the standard battery of tests (reverse mutation assay; mouse lymphoma forward mutation assay; mouse micronucleus assay) recommended by US Food and Drug Administration (FDA) for food ingredients. THL was determined not to be genotoxic under the conditions of the tested genetic toxicity battery. The negative assay results provide support that addition of THL to foodstuffs formulated for people with diabetes is expected to be safe. A wide safety margin is established, as anticipated doses are small compared to the doses administered in the assays.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Curtis; Mandelli, Diego; Prescott, Steven

The existing fleet of nuclear power plants is in the process of extending its lifetime and increasing the power generated from these plants via power uprates. In order to evaluate the impact of these factors on the safety of the plant, the Risk Informed Safety Margin Characterization (RISMC) project aims to provide insight to decision makers through a series of simulations of the plant dynamics for different initial conditions (e.g., probabilistic analysis and uncertainty quantification). This report focuses, in particular, on the application of a RISMC detailed demonstration case study for an emergent issue using the RAVEN and RELAP-7 tools.more » This case study looks at the impact of a couple of challenges to a hypothetical pressurized water reactor, including: (1) a power uprate, (2) a potential loss of off-site power followed by the possible loss of all diesel generators (i.e., a station black-out event), (3) and earthquake induces station-blackout, and (4) a potential earthquake induced tsunami flood. The analysis is performed by using a set of codes: a thermal-hydraulic code (RELAP-7), a flooding simulation tool (NEUTRINO) and a stochastic analysis tool (RAVEN) – these are currently under development at the Idaho National Laboratory.« less

Airframe/TPS Session

NASA Technical Reports Server (NTRS)

Welch, Sharon; Bowles, David

2000-01-01

This viewgraph presentation gives an overview of the second generation Reusable Launch Vehicle (RLV) airframe configuration, including details on the structures and materials, tanks, airframe/cryotank demonstrations, internal assemblies, weight growth and margin, and safety and cost requirements.

Gross mismatch between thermal tolerances and environmental temperatures in a tropical freshwater snail: climate warming and evolutionary implications.

PubMed

Polgar, Gianluca; Khang, Tsung Fei; Chua, Teddy; Marshall, David J

2015-01-01

The relationship between acute thermal tolerance and habitat temperature in ectotherm animals informs about their thermal adaptation and is used to assess thermal safety margins and sensitivity to climate warming. We studied this relationship in an equatorial freshwater snail (Clea nigricans), belonging to a predominantly marine gastropod lineage (Neogastropoda, Buccinidae). We found that tolerance of heating and cooling exceeded average daily maximum and minimum temperatures, by roughly 20°C in each case. Because habitat temperature is generally assumed to be the main selective factor acting on the fundamental thermal niche, the discordance between thermal tolerance and environmental temperature implies trait conservation following 'in situ' environmental change, or following novel colonisation of a thermally less-variable habitat. Whereas heat tolerance could relate to an historical association with the thermally variable and extreme marine intertidal fringe zone, cold tolerance could associate with either an ancestral life at higher latitudes, or represent adaptation to cooler, higher-altitudinal, tropical lotic systems. The broad upper thermal safety margin (difference between heat tolerance and maximum environmental temperature) observed in this snail is grossly incompatible with the very narrow safety margins typically found in most terrestrial tropical ectotherms (insects and lizards), and hence with the emerging prediction that tropical ectotherms, are especially vulnerable to environmental warming. A more comprehensive understanding of climatic vulnerability of animal ectotherms thus requires greater consideration of taxonomic diversity, ecological transition and evolutionary history. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hospital financial performance in the recent recession and implications for institutions that remain financially weak.

PubMed

Bazzoli, Gloria J; Fareed, Naleef; Waters, Teresa M

2014-05-01

The recent recession had a profound effect on all sectors of the US economy, including health care. We examined how private hospitals fared through the recession and considered how changes in their financial health may affect their ability to respond to future industry challenges. We categorized 2,971 private short-term general medical or surgical hospitals (both nonprofit and for-profit) according to their pre-recession financial health and safety-net status, and we examined their operational status changes and operating and total financial margins during 2006-11. We found that hospitals that were financially weak before the recession remained so during and after the recession. The total margins of nonprofit hospitals (both safety-net and other institutions) declined in 2008 but returned to their pre-recession levels by 2011. The recession did not create additional fiscal pressure on hospitals that were previously financially weak or in safety-net roles. However, both groups continue to have notable financial deficiencies that could limit their abilities to meet the growing demands on the industry.

Shuttle Wing Leading Edge Root Cause NDE Team Findings and Implementation of Quantitative Flash Infrared Thermography

NASA Technical Reports Server (NTRS)

Burke, Eric R.

2009-01-01

Comparison metrics can be established to reliably and repeatedly establish the health of the joggle region of the Orbiter Wing Leading Edge reinforced carbon carbon (RCC) panels. Using these metrics can greatly reduced the man hours needed to perform, wing leading edge scanning for service induced damage. These time savings have allowed for more thorough inspections to be preformed in the necessary areas with out affecting orbiter flow schedule. Using specialized local inspections allows for a larger margin of safety by allowing for more complete characterizations of panel defects. The presence of the t-seal during thermographic inspection can have adverse masking affects on ability properly characterize defects that exist in the joggle region of the RCC panels. This masking affect dictates the final specialized inspection should be preformed with the t-seal removed. Removal of the t-seal and use of the higher magnification optics has lead to the most effective and repeatable inspection method for characterizing and tracking defects in the wing leading edge. Through this study some inadequacies in the main health monitoring system for the orbiter wing leading edge have been identified and corrected. The use of metrics and local specialized inspection have lead to a greatly increased reliability and repeatable inspection of the shuttle wing leading edge.

Plutonium Critical Mass Curve Comparison to Mass at Upper Subcritical Limit (USL) Using Whisper

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alwin, Jennifer Louise; Zhang, Ning

Whisper is computational software designed to assist the nuclear criticality safety analyst with validation studies with the MCNP ® Monte Carlo radiation transport package. Standard approaches to validation rely on the selection of benchmarks based upon expert judgment. Whisper uses sensitivity/uncertainty (S/U) methods to select relevant benchmarks to a particular application or set of applications being analyzed. Using these benchmarks, Whisper computes a calculational margin. Whisper attempts to quantify the margin of subcriticality (MOS) from errors in software and uncertainties in nuclear data. The combination of the Whisper-derived calculational margin and MOS comprise the baseline upper subcritical limit (USL), tomore » which an additional margin may be applied by the nuclear criticality safety analyst as appropriate to ensure subcriticality. A series of critical mass curves for plutonium, similar to those found in Figure 31 of LA-10860-MS, have been generated using MCNP6.1.1 and the iterative parameter study software, WORM_Solver. The baseline USL for each of the data points of the curves was then computed using Whisper 1.1. The USL was then used to determine the equivalent mass for plutonium metal-water system. ANSI/ANS-8.1 states that it is acceptable to use handbook data, such as the data directly from the LA-10860-MS, as it is already considered validated (Section 4.3 4) “Use of subcritical limit data provided in ANSI/ANS standards or accepted reference publications does not require further validation.”). This paper attempts to take a novel approach to visualize traditional critical mass curves and allows comparison with the amount of mass for which the k eff is equal to the USL (calculational margin + margin of subcriticality). However, the intent is to plot the critical mass data along with USL, not to suggest that already accepted handbook data should have new and more rigorous requirements for validation.« less

Differential Impact of Close Surgical Margin on Local Recurrence According to Primary Tumor Size in Oral Squamous Cell Carcinoma.

PubMed

Jang, Jeon Yeob; Choi, Nayeon; Ko, Young-Hyeh; Chung, Man Ki; Son, Young-Ik; Baek, Chung-Hwan; Baek, Kwan-Hyuck; Jeong, Han-Sin

2017-06-01

The extent of surgical safety margin (gross tumor border to resection margin) in oral cancer surgery remains unclear, and no study has determined the differential impact of close surgical margin and microscopic extension according to primary tumor size in oral cancers. We retrospectively analyzed the clinical data of 325 patients with surgically treated oral cavity squamous cell carcinomas to determine the effect of a close surgical margin (<5 mm) (cSM 5 ) on local recurrence. In addition, the depth of microscopic tumor infiltration was determined in 90 available surgical specimens. The cSM 5 was not related to the risk of local tumor recurrence in early-stage oral cancer, while it significantly increased the rate of local tumor recurrence in resectable advanced-stage oral cancers (hazard ratio 3.157, 95 % confidence interval 1.050-9.407, p = 0.041). Addition of postoperative adjuvant radiation to early-stage tumors with cSM 5 did not further reduce the local recurrence rate compared to surgery alone. The depth of microscopic tumor extension from the gross tumor border was significantly associated with primary tumor thickness (ρ = 0.390, p < 0.001) and tumor sizes (ρ = 0.308, p = 0.003), which was a median (range) of 0.84 (0.14-2.32) mm in T1, 1.06 (0.20-4.34) mm in T2, and 1.77 (0.13-4.70) mm in T3-4. The cSM 5 was a significant risk factor for local recurrence only in advanced oral cancers, but not in early-stage tumors, where microscopic tumor extension was not beyond 3 mm in T1 tumors. Thus, the extent of surgical safety margin can be redefined according to the primary tumor size.

Earth stewardship on rangelands: Coping with ecological, economic, and political marginality

USDA-ARS?s Scientific Manuscript database

Rangelands encompass 30-40 percent of Earth's land surface and support 1-2 billion people. Their predominant use is extensive livestock production by pastoralists and ranchers. But rangelands are characterized by ecological, economic, and political marginality, and higher-value, more intensive land ...

Nanowire NMOS Logic Inverter Characterization.

PubMed

Hashim, Yasir

2016-06-01

This study is the first to demonstrate characteristics optimization of nanowire N-Channel Metal Oxide Semiconductor (NW-MOS) logic inverter. Noise margins and inflection voltage of transfer characteristics are used as limiting factors in this optimization. A computer-based model used to produce static characteristics of NW-NMOS logic inverter. In this research two circuit configuration of NW-NMOS inverter was studied, in first NW-NMOS circuit, the noise margin for (low input-high output) condition was very low. For second NMOS circuit gives excellent noise margins, and results indicate that optimization depends on applied voltage to the inverter. Increasing gate to source voltage with (2/1) nanowires ratio results better noise margins. Increasing of applied DC load transistor voltage tends to increasing in decreasing noise margins; decreasing this voltage will improve noise margins significantly.

44 CFR 60.22 - Planning considerations for flood-prone areas.

Code of Federal Regulations, 2012 CFR

2012-10-01

... community shall consider— (1) Preservation of the flood-prone areas for open space purposes; (2) Relocation... debris, to provide an added margin of safety against floods having a magnitude greater than the base...

44 CFR 60.22 - Planning considerations for flood-prone areas.

Code of Federal Regulations, 2013 CFR

2013-10-01

... community shall consider— (1) Preservation of the flood-prone areas for open space purposes; (2) Relocation... debris, to provide an added margin of safety against floods having a magnitude greater than the base...

44 CFR 60.22 - Planning considerations for flood-prone areas.

Code of Federal Regulations, 2014 CFR

2014-10-01

... community shall consider— (1) Preservation of the flood-prone areas for open space purposes; (2) Relocation... debris, to provide an added margin of safety against floods having a magnitude greater than the base...

Assessment of the stability of a multimachine power system by the transient energy margin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stanton, S.E.

1982-01-01

This reasearch develops a tool for the direct assessment of the transient stability of a multimachine electric power system that is subject to a large disturbance. The tool is the Transient Energy Margin. The transient of interest is the first swing (or inertial) transient. The Transient Energy Margin is computed by evaluating an energy function using the relevant unstable equilibrium point and the system states at the instant the disturbance is removed. In evaluating the function, a significant portion of the fault kinetic energy is identified as not contributing to system instability. The resulting energy value is a measure ofmore » the margin-of-safety for the disturbed system. A distinction is proposed between assessing system stability and assessing system security. The Transient Energy Margin is used first to assess the stability of the system. This profile ranks various distrubances to display the strengths and weaknesses of the system. A modified Transient Energy Margin is then proposed as an assessment of security; the transient energy margin profile is repeated to evaluate the system response in terms of the local minimum energy conditions approached by the critical trajectories. Both techniques are applied to a practical, 17 generator test system.« less

Comparing vaccines: a systematic review of the use of the non-inferiority margin in vaccine trials.

PubMed

Donken, R; de Melker, H E; Rots, N Y; Berbers, G; Knol, M J

2015-03-17

Non-inferiority (NI) randomized controlled trials (RCTs) aim to demonstrate that a new treatment is no worse than a comparator that has already shown its efficacy over placebo within a pre-specified margin. However, clear guidelines on how the NI margin should be determined are lacking for vaccine trials. A difference (seroprevalence/risk) of 10% or a geometric mean titre/concentration (GMT) ratio of 1.5 or 2.0 in antibody levels is implicitly recommended for vaccine trials. We aimed to explore which NI margins were used in vaccine RCTs and how they were determined. A systematic search for NI vaccine RCTs yielded 177 eligible articles. Data were extracted from these articles using a standardized form and included general characteristics and characteristics specific for NI trials. Relations between the study characteristics and the NI margin used were explored. Among the 143 studies using an NI margin based on difference (n=136 on immunogenicity, n=2 on efficacy and n=5 on safety), 66% used a margin of 10%, 23% used margins lower than 10% (range 1-7.5%) and 11% used margins larger than 10% (range 11.5-25%). Of the 103 studies using a NI margin based on the GMT ratio, 50% used a margin of 0.67/1.5 and 49% used 0.5/2.0. As observed, 85% of the studies did not discuss the method of margin determination; and 19% of the studies lacked a confidence interval or p-value for non-inferiority. Most NI vaccine RCTs used an NI margin of 10% for difference or a GMT ratio of 1.5 or 2.0 without a clear rationale. Most articles presented enough information for the reader to make a judgement about the NI margin used and the conclusions. The reporting on the design, margins used and results of NI vaccine trials could be improved; more explicit guidelines may help to achieve this end. Copyright © 2015 Elsevier Ltd. All rights reserved.

SU-E-T-573: The Robustness of a Combined Margin Recipe for Uncertainties During Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stroom, J; Vieira, S; Greco, C

2014-06-01

Purpose: To investigate the variability of a safety margin recipe that combines CTV and PTV margins quadratically, with several tumor, treatment, and user related factors. Methods: Margin recipes were calculated by monte-carlo simulations in 5 steps. 1. A spherical tumor with or without isotropic microscopic was irradiated with a 5 field dose plan2. PTV: Geometric uncertainties were introduced using systematic (Sgeo) and random (sgeo) standard deviations. CTV: Microscopic disease distribution was modelled by semi-gaussian (Smicro) with varying number of islets (Ni)3. For a specific uncertainty set (Sgeo, sgeo, Smicro(Ni)), margins were varied until pre-defined decrease in TCP or dose coveragemore » was fulfilled. 4. First, margin recipes were calculated for each of the three uncertainties separately. CTV and PTV recipes were then combined quadratically to yield a final recipe M(Sgeo, sgeo, Smicro(Ni)).5. The final M was verified by simultaneous simulations of the uncertainties.Now, M has been calculated for various changing parameters like margin criteria, penumbra steepness, islet radio-sensitivity, dose conformity, and number of fractions. We subsequently investigated A: whether the combined recipe still holds in all these situations, and B: what the margin variation was in all these cases. Results: We found that the accuracy of the combined margin recipes remains on average within 1mm for all situations, confirming the correctness of the quadratic addition. Depending on the specific parameter, margin factors could change such that margins change over 50%. Especially margin recipes based on TCP-criteria are more sensitive to more parameters than those based on purely geometric Dmin-criteria. Interestingly, measures taken to minimize treatment field sizes (by e.g. optimizing dose conformity) are counteracted by the requirement of larger margins to get the same tumor coverage. Conclusion: Margin recipes combining geometric and microscopic uncertainties quadratically are accurate under varying circumstances. However margins can change up to 50% for different situations.« less

Safety of fenbendazole in common peafowl (Pavo cristatus).

PubMed

Umar, Sajid; Abbas, Seema; Khan, Muhammad Irfan; Nisa, Qamarun; Younus, Muhammad; Aqil, Kiran; Qayyum, Rizwan; Yaqoob, Muhammad; Ali, Asif; Yaseen, Muhammad Asif; Shah, Muhammad Ali

2018-01-01

The present study was undertaken to find out the safety levels of fenbendazole in common peafowl. This bird, raised on aviaries and zoos, can be severely parasitized with Ascaridia galli (enteric worms) and Syngamus trachea (gapeworm) along with other parasitic worms. Fenbendazole is a highly effective benzimidazole-class anthelmintic in animals. The objective of this work was to provide target animal safety data in young peafowl and to demonstrate reproductive safety in adult birds. During the experimental study, diets containing fenbendazole at 0, 100, 200 and 300 ppm were fed for 21 days (three times the normal treatment duration). Data for feed consumption, feed conversion rate, and body weights were recorded for each bird in each group. Drug concentrations in different tissues of birds were determined to correlate concentrations with clinical observations, clinical pathology, and histologic findings. There were no morbidities or mortalities after study day 21. Additionally, there were no statistically significant treatment-related differences among above mentioned parameters. Analysis of fenbendazole concentrations in kidney, liver, leg/thigh, and breast muscle and skin with associated fat revealed that, even at the highest dose level used and with no feed withdrawal, fenbendazole concentrations were relatively low in these tissues. These findings indicate that fenbendazole has a relatively wide margin of safety in young peafowl and that the proposed dose of 100 ppm in the feed for 7 consecutive days is well within the margin of safety. In the reproductive safety study, five breeder peafowl farms fed fendbendazole at 100ppm for 7 days and collected data on hatching percentage of peahen eggs before and after treatment. Reproductive performance in peahen was not adversely affected.

Assessment of the Impact of Scheduled Postmarketing Safety Summary Analyses on Regulatory Actions

PubMed Central

Sekine, S; Pinnow, EE; Wu, E; Kurtzig, R; Hall, M; Dal Pan, GJ

2016-01-01

In addition to standard postmarketing drug safety monitoring, Section 915 of the Food and Drug Administration Amendments Act of 2007 (FDAAA) requires the US Food and Drug Administration (FDA) to conduct a summary analysis of adverse event reports to identify risks of a drug or biologic product 18 months after product approval, or after 10,000 patients have used the product, whichever is later. We assessed the extent to which these analyses identified new safety signals and resultant safety-related label changes. Among 458 newly approved products, 300 were the subjects of a scheduled analysis; a new safety signal that resulted in a safety-related label change was found for 11 of these products. Less than 2% of 713 safety-related label changes were based on the scheduled analyses. Our study suggests that the safety summary analyses provide only marginal value over other pharmacovigilance activities. PMID:26853718

Flight-determined stability analysis of multiple-input-multiple-output control systems

NASA Technical Reports Server (NTRS)

Burken, John J.

1992-01-01

Singular value analysis can give conservative stability margin results. Applying structure to the uncertainty can reduce this conservatism. This paper presents flight-determined stability margins for the X-29A lateral-directional, multiloop control system. These margins are compared with the predicted unscaled singular values and scaled structured singular values. The algorithm was further evaluated with flight data by changing the roll-rate-to-aileron command-feedback gain by +/- 20 percent. Minimum eigenvalues of the return difference matrix which bound the singular values are also presented. Extracting multiloop singular values from flight data and analyzing the feedback gain variations validates this technique as a measure of robustness. This analysis can be used for near-real-time flight monitoring and safety testing.

Flight-determined stability analysis of multiple-input-multiple-output control systems

NASA Technical Reports Server (NTRS)

Burken, John J.

1992-01-01

Singular value analysis can give conservative stability margin results. Applying structure to the uncertainty can reduce this conservatism. This paper presents flight-determined stability margins for the X-29A lateral-directional, multiloop control system. These margins are compared with the predicted unscaled singular values and scaled structured singular values. The algorithm was further evaluated with flight data by changing the roll-rate-to-aileron-command-feedback gain by +/- 20 percent. Also presented are the minimum eigenvalues of the return difference matrix which bound the singular values. Extracting multiloop singular values from flight data and analyzing the feedback gain variations validates this technique as a measure of robustness. This analysis can be used for near-real-time flight monitoring and safety testing.

Safety and Tolerability of HSC835 in Patients With Hematological Malignancies

ClinicalTrials.gov

2017-04-03

Acute Myelocytic Leukemia; Acute Lymphocytic Leukemia; Chronic Myelogenous Leukemia; Myelodysplastic Syndrome; Chronic Lymphocytic Leukemia; Marginal Zone Lymphoma; Follicular Lymphomas; Large-cell Lymphoma; Lymphoblastic Lymphoma; Burkitt's Lymphoma; High Grade Lymphomas; Mantle-cell Lymphoma; Lymphoplasmacytic Lymphoma

Towards Biogeochemical Modeling of Anaerobic Oxidation of Methane: Characterization of Microbial Communities in Methane-bearing North American Continental Margin Sediments

NASA Astrophysics Data System (ADS)

Graw, M. F.; Solomon, E. A.; Chrisler, W.; Krause, S.; Treude, T.; Ruppel, C. D.; Pohlman, J.; Colwell, F. S.

2015-12-01

Methane advecting through continental margin sediments may enter the water column and potentially contribute to ocean acidification and increase atmospheric methane concentrations. Anaerobic oxidation of methane (AOM), mediated by syntrophic consortia of anaerobic methanotrophic archaea and sulfate-reducing bacteria (ANME-SRB), consumes nearly all dissolved methane in methane-bearing sediments before it reaches the sediment-water interface. Despite the significant role ANME-SRB play in carbon cycling, our knowledge of these organisms and their surrounding microbial communities is limited. Our objective is to develop a metabolic model of ANME-SRB within methane-bearing sediments and to couple this to a geochemical reaction-transport model for these margins. As a first step towards this goal, we undertook fluorescent microscopic imaging, 16S rRNA gene deep-sequencing, and shotgun metagenomic sequencing of sediments from the US Pacific (Washington) and northern Atlantic margins where ANME-SRB are present. A successful Illumina MiSeq sequencing run yielded 106,257 bacterial and 857,834 archaeal 16S rRNA gene sequences from 12 communities from the Washington Margin using both universal prokaryotic and archaeal-specific primer sets. Fluorescent microscopy confirmed the presence of cells of the ANME-2c lineage in the sequenced communities. Microbial community characterization was coupled with measurements of sediment physical and geochemical properties and, for samples from the US Atlantic margin, 14C-based measurements of AOM rates and 35S-based measurements of sulfate reduction rates. These findings have the potential to increase understanding of ANME-SRB, their surrounding microbial communities, and their role in carbon cycling within continental margins. In addition, they pave the way for future efforts at developing a metabolic model of ANME-SRB and coupling it to geochemical models of the US Washington and Atlantic margins.

Two new species of Haploperla (Plecoptera: Chloroperlidae) from China.

PubMed

Chen, Zhi-Teng; DU, Yu-Zhou

2016-11-23

Two new species of the chloroperline genus Haploperla, H. tuanjiena sp. nov. from Sichuan Province, China and H. datongensis sp. nov. from Qinghai Province, China are described and illustrated. Haploperla tuanjiena is characterized by terga 10 with a medially triangular sclerotized area and the epiproct subtriangular, anterolateral margin sclerotized with apex acute. Haploperla datongensis is characterized by the epiproct tongue-shaped, anterior margin and anteroventrally strongly sclerotized. The new species are compared with similar taxa of the genus. An identification key is provided for the seven known Chinese species of Haploperla.

The influence of novel compliant floors on balance control in elderly women--A biomechanical study.

PubMed

Wright, Alexander D; Laing, Andrew C

2011-07-01

Novel compliant floors aim to decrease the risk for fall-related injury by providing substantial force attenuation during the impact phase of falls. Certain models of compliant flooring have been shown to have limited influence on postural sway and successful completion of dynamic balance tasks. However, the effects of these products on balance recovery mechanisms following an externally induced perturbation have yet to be quantified. We used a floor translation paradigm to induce a balance perturbation to thirteen elderly community-dwelling women. Outcome measures included the displacement rates and margins of safety for both the underfoot centre-of-pressure and whole-body centre-of-mass across two novel compliant floors (SmartCell, SofTile), two basic foam surfaces (Firm-Foam, Soft-Foam) and a standard 'Rigid' floor as a control condition. The centre-of-mass and centre-of-pressure margins of safety, and all centre-of-mass displacement rates, were not significantly lower for the two novel compliant flooring systems compared to the control floor. The centre-of-pressure displacement rates were similar to the control floor for the SmartCell floor condition. The majority of the margin of safety and displacement rate variables for the foam floors were significantly lower than the control condition. This study illustrates that the SmartCell and SofTile novel compliant floors have minimal influences on balance and balance control responses following externally induced perturbations in older community-dwelling women, and supports pilot installations of these floors to inform decisions regarding the development of clinical trials. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

The influence of novel compliant floors on balance control in elderly women—A biomechanical study

PubMed Central

Wright, Alexander D.; Laing, Andrew C.

2012-01-01

Novel compliant floors aim to decrease the risk for fall-related injury by providing substantial force attenuation during the impact phase of falls. Certain models of compliant flooring have been shown to have limited influence on postural sway and successful completion of dynamic balance tasks. However, the effects of these products on balance recovery mechanisms following an externally induced perturbation have yet to be quantified. We used a floor translation paradigm to induce a balance perturbation to thirteen elderly community-dwelling women. Outcome measures included the displacement rates and margins of safety for both the underfoot centre-of-pressure and whole-body centre-of-mass across two novel compliant floors (Smart-Cell, SofTile), two basic foam surfaces (Firm-Foam, Soft-Foam) and a standard ‘Rigid’ floor as a control condition. The centre-of-mass and centre-of-pressure margins of safety, and all centre-of-mass displacement rates, were not significantly lower for the two novel compliant flooring systems compared to the control floor. The centre-of-pressure displacement rates were similar to the control floor for the SmartCell floor condition. The majority of the margin of safety and displacement rate variables for the foam floors were significantly lower than the control condition. This study illustrates that the SmartCell and SofTile novel compliant floors have minimal influences on balance and balance control responses following externally induced perturbations in older community-dwelling women, and supports pilot installations of these floors to inform decisions regarding the development of clinical trials. PMID:21545881

Hydraulic safety margins and embolism reversal in stems and leaves: why are conifers and angiosperms so different?

PubMed

Johnson, Daniel M; McCulloh, Katherine A; Woodruff, David R; Meinzer, Frederick C

2012-10-01

Angiosperm and coniferous tree species utilize a continuum of hydraulic strategies. Hydraulic safety margins (defined as differences between naturally occurring xylem pressures and pressures that would cause hydraulic dysfunction, or differences between pressures resulting in loss of hydraulic function in adjacent organs (e.g., stems vs. leaves) tend to be much greater in conifers than angiosperms and serve to prevent stem embolism. However, conifers tend to experience embolism more frequently in leaves and roots than angiosperms. Embolism repair is thought to occur by active transport of sugars into empty conduits followed by passive water movement. The most likely source of sugar for refilling is from nonstructural carbohydrate depolymerization in nearby parenchyma cells. Compared to angiosperms, conifers tend to have little parenchyma or nonstructural carbohydrates in their wood. The ability to rapidly repair embolisms may rely on having nearby parenchyma cells, which could explain the need for greater safety margins in conifer wood as compared to angiosperms. The frequent embolisms that occur in the distal portions of conifers are readily repaired, perhaps due to the abundant parenchyma in leaves and roots, and these distal tissues may act as hydraulic circuit breakers that prevent tension-induced embolisms in the attached stems. Frequent embolisms in conifer leaves may also be due to weaker stomatal response to changes in ambient humidity. Although there is a continuum of hydraulic strategies among woody plants, there appear to be two distinct 'behaviors' at the extremes: (1) embolism prevention and (2) embolism occurrence and subsequent repair. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Lateral spread of heat during thyroidectomy using different haemostatic devices.

PubMed

Adamczewski, Zbigniew; Król, Aleksander; Kałużna-Markowska, Karolina; Brzeziński, Jan; Lewiński, Andrzej; Dedecjus, Marek

2015-01-01

The presented study is an attempt to comprehensively analyze the lateral spread of heat during thyroidectomy. Obtained results may be valuable in other surgical disciplines in which thermal analysis is difficult or impossible. The aim of the study was to evaluate the temperature distribution in the operating field during thyroidectomy performed with the use of modern haemostatic instruments, and to define the safety margin for the investigated devices. Ninety-three patients were thyroidectomised due to thyroid neoplasm. During all the operations the thermovisual measurements were carried out along with continuous intraoperative neuromonitoring of the recurrent laryngeal nerve (CIONM). Investigated patients were divided into 5 groups, named according to the applied haemostatic technique: LigaSure (N=17); ThermoStapler (N=20); Focus (N=19); SonoSurg (N=17) and Monopolar (N=20). At maximal performance settings, the highest working temperature was observed for the ThermoStapler, while the lowest temperature was recorded for the Monopolar. Safety margin and working time were increased in Focus and SonoSurg, compared to LigaSure and ThermoStapler. The differences in the necrosis thickness were negligible. The largest distance of the midline of the active blade from isotherm of 42ºC observed in the study was 5.51 mm; none of investigated devices used at a bigger distance had influence on the morphology of the electric signal of CIONM. The thermo-visual camera allows non-invasive, safe, and real-time monitoring and analysis of temperature distribution in the operation area during thyroidectomy. Proposed minimal safety margin for the analysed devices is 5.51 mm.

Linking existing in vitro dermal absorption data to physicochemical properties: Contribution to the design of a weight-of-evidence approach for the safety evaluation of cosmetic ingredients with low dermal bioavailability.

PubMed

Ates, Gamze; Steinmetz, Fabian P; Doktorova, Tatyana Yordanova; Madden, Judith C; Rogiers, Vera

2016-04-01

To characterize the risk of cosmetic ingredients when threshold toxicity is assumed, often the "margin of safety" (MoS) is calculated. This uncertainty factor is based on the systemic no observable (adverse) effect level (NO(A)EL) which can be derived from in vivo repeated dose toxicity studies. As in vivo studies for the purpose of the cosmetic legislation are no longer allowed in Europe and a validated in vitro alternative is not yet available, it is no longer possible to derive a NO(A)EL value for a new cosmetic ingredient. Alternatively, cosmetic ingredients with a low dermal bioavailability might not need repeated dose data, as internal exposure will be minimal and systemic toxicity might not be an issue. This study shows the possibility of identifying compounds suspected to have a low dermal bioavailability based on their physicochemical properties (molecular weight, melting point, topological polar surface area and log P) and their in vitro dermal absorption data. Although performed on a limited number of compounds, the study suggests a strategic opportunity to support the safety assessor's reasoning to omit a MoS calculation and to focus more on local toxicity and mutagenicity/genotoxicity for ingredients for which limited systemic exposure is to be expected. Copyright © 2016 Elsevier Inc. All rights reserved.

A tiered asthma hazard characterization and exposure assessment approach for evaluation of consumer product ingredients.

PubMed

Maier, Andrew; Vincent, Melissa J; Parker, Ann; Gadagbui, Bernard K; Jayjock, Michael

2015-12-01

Asthma is a complex syndrome with significant consequences for those affected. The number of individuals affected is growing, although the reasons for the increase are uncertain. Ensuring the effective management of potential exposures follows from substantial evidence that exposure to some chemicals can increase the likelihood of asthma responses. We have developed a safety assessment approach tailored to the screening of asthma risks from residential consumer product ingredients as a proactive risk management tool. Several key features of the proposed approach advance the assessment resources often used for asthma issues. First, a quantitative health benchmark for asthma or related endpoints (irritation and sensitization) is provided that extends qualitative hazard classification methods. Second, a parallel structure is employed to include dose-response methods for asthma endpoints and methods for scenario specific exposure estimation. The two parallel tracks are integrated in a risk characterization step. Third, a tiered assessment structure is provided to accommodate different amounts of data for both the dose-response assessment (i.e., use of existing benchmarks, hazard banding, or the threshold of toxicological concern) and exposure estimation (i.e., use of empirical data, model estimates, or exposure categories). Tools building from traditional methods and resources have been adapted to address specific issues pertinent to asthma toxicology (e.g., mode-of-action and dose-response features) and the nature of residential consumer product use scenarios (e.g., product use patterns and exposure durations). A case study for acetic acid as used in various sentinel products and residential cleaning scenarios was developed to test the safety assessment methodology. In particular, the results were used to refine and verify relationships among tiered approaches such that each lower data tier in the approach provides a similar or greater margin of safety for a given scenario. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

The use of Web-based GIS data technologies in the construction of geoscience instructional materials: examples from the MARGINS Data in the Classroom project

NASA Astrophysics Data System (ADS)

Ryan, J. G.; McIlrath, J. A.

2008-12-01

Web-accessible geospatial information system (GIS) technologies have advanced in concert with an expansion of data resources that can be accessed and used by researchers, educators and students. These resources facilitate the development of data-rich instructional resources and activities that can be used to transition seamlessly into undergraduate research projects. MARGINS Data in the Classroom (http://serc.carleton.edu/ margins/index.html) seeks to engage MARGINS researchers and educators in using the images, datasets, and visualizations produced by NSF-MARGINS Program-funded research and related efforts to create Web-deliverable instructional materials for use in undergraduate-level geoscience courses (MARGINS Mini-Lessons). MARGINS science data is managed by the Marine Geosciences Data System (MGDS), and these and all other MGDS-hosted data can be accessed, manipulated and visualized using GeoMapApp (www.geomapapp.org; Carbotte et al, 2004), a freely available geographic information system focused on the marine environment. Both "packaged" MGDS datasets (i.e., global earthquake foci, volcanoes, bathymetry) and "raw" data (seismic surveys, magnetics, gravity) are accessible via GeoMapApp, with WFS linkages to other resources (geodesy from UNAVCO; seismic profiles from IRIS; geochemical and drillsite data from EarthChem, IODP, and others), permitting the comprehensive characterization of many regions of the ocean basins. Geospatially controlled datasets can be imported into GeoMapApp visualizations, and these visualizations can be exported into Google Earth as .kmz image files. Many of the MARGINS Mini-Lessons thus far produced use (or have studentss use the varied capabilities of GeoMapApp (i.e., constructing topographic profiles, overlaying varied geophysical and bathymetric datasets, characterizing geochemical data). These materials are available for use and testing from the project webpage (http://serc.carleton.edu/margins/). Classroom testing and assessment of the Mini- Lessons begins this Fall.

Sca-1(+) mesenchymal stromal cells inhibit splenic marginal zone B lymphocytes commitment through Caspase-3.

PubMed

Chen, Yaozhen; Yang, Jialei; Zhang, Hui-Jie; Fan, Hong; An, Ning; Xin, Jiajia; Li, Na; Xu, Jinmei; Yin, Wen; Wu, Zhongliang; Hu, Xingbin

2016-05-01

Mesenchymal stromal cells (MSCs) have been characterized as an important component of hematopoietic niche, which are capable of modulating the immune system through interaction with a wide range of immune cells. Marginal zone B cells, one main type of mature B lymphocytes, play a central role in eliciting antibody response against pathogens. However, how MSCs and its subpopulations regulate marginal zone B cells commitment is unknown yet. In this study, we assessed the contribution of Sca-1(+) MSCs on marginal zone B cells commitment. Our results showed that Sca-1(+) MSCs inhibit the commitment of marginal zone B lymphocytes. The inhibition was exerted through lowered Caspase-3 expression. Furthermore, we found marginal zone B lymphocytes in spleen of Caspase-3 knockout mice decreased and Caspase-3 knockout Sca-1(+) MSCs accounted for the MZB lymphocytes decrease. In conclusion, our investigation provided clues about Sca-1(+) MSCs regulation on the commitment of marginal zone B cells through Caspase-3 gene. © 2016 International Federation for Cell Biology.

Thermal-safety margins and the necessity of thermoregulatory behavior across latitude and elevation

PubMed Central

Sunday, Jennifer M.; Bates, Amanda E.; Kearney, Michael R.; Colwell, Robert K.; Dulvy, Nicholas K.; Longino, John T.; Huey, Raymond B.

2014-01-01

Physiological thermal-tolerance limits of terrestrial ectotherms often exceed local air temperatures, implying a high degree of thermal safety (an excess of warm or cold thermal tolerance). However, air temperatures can be very different from the equilibrium body temperature of an individual ectotherm. Here, we compile thermal-tolerance limits of ectotherms across a wide range of latitudes and elevations and compare these thermal limits both to air and to operative body temperatures (theoretically equilibrated body temperatures) of small ectothermic animals during the warmest and coldest times of the year. We show that extreme operative body temperatures in exposed habitats match or exceed the physiological thermal limits of most ectotherms. Therefore, contrary to previous findings using air temperatures, most ectotherms do not have a physiological thermal-safety margin. They must therefore rely on behavior to avoid overheating during the warmest times, especially in the lowland tropics. Likewise, species living at temperate latitudes and in alpine habitats must retreat to avoid lethal cold exposure. Behavioral plasticity of habitat use and the energetic consequences of thermal retreats are therefore critical aspects of species’ vulnerability to climate warming and extreme events. PMID:24616528

Evaluation of Margins of Safety in Brazed Joints

NASA Technical Reports Server (NTRS)

Flom, Yury; Wang, Len; Powell, Mollie M.; Soffa, Matthew A.; Rommel, Monica L.

2009-01-01

One of the essential steps in assuring reliable performance of high cost critical brazed structures is the assessment of the Margin of Safety (MS) of the brazed joints. In many cases the experimental determination of the failure loads by destructive testing of the brazed assembly is not practical and cost prohibitive. In such cases the evaluation of the MS is performed analytically by comparing the maximum design loads with the allowable ones and incorporating various safety or knock down factors imposed by the customer. Unfortunately, an industry standard methodology for the design and analysis of brazed joints has not been developed. This paper provides an example of an approach that was used to analyze an AlBeMet 162 (38%Be-62%Al) structure brazed with the AWS BAlSi-4 (Al-12%Si) filler metal. A practical and conservative interaction equation combining shear and tensile allowables was developed and validated to evaluate an acceptable (safe) combination of tensile and shear stresses acting in the brazed joint. These allowables are obtained from testing of standard tensile and lap shear brazed specimens. The proposed equation enables the assessment of the load carrying capability of complex brazed joints subjected to multi-axial loading.

Using translational medicine to understand clinical differences between botulinum toxin formulations.

PubMed

Aoki, K R; Ranoux, D; Wissel, J

2006-12-01

When using botulinum toxin-based products, the physician must decide the optimal location and dose required to alleviate symptoms and improve the patient's quality of life. To deliver effective treatment, the physician needs to understand the importance of accurate target muscle selection and localization and the implications of each product's migration properties when diluted in different volumes. Pre-clinical mouse models of efficacy and safety have been utilized to compare local and distal muscle relaxation effects following defined intramuscular administration. Data from the model allow the products to be ranked based on their propensity for local efficacy versus their distal migration properties. Using standardized dilutions, the non-parallel dose-response curves for the various formulations demonstrate that they have different efficacy profiles. Distal effects were also noted at different treatment doses, which are reflected in the different safety and/or therapeutic margins. Based on these pre-clinical data, the safety and therapeutic margin rankings are ordered, largest to smallest, as BOTOX, Dysport and Myobloc. The results of subsequent clinical trials are variable and dose comparisons are inconclusive, thus supporting the regulatory position that the dose units of the individual preparations are unique and cannot be simply converted between products.

Thermal-safety margins and the necessity of thermoregulatory behavior across latitude and elevation.

PubMed

Sunday, Jennifer M; Bates, Amanda E; Kearney, Michael R; Colwell, Robert K; Dulvy, Nicholas K; Longino, John T; Huey, Raymond B

2014-04-15

Physiological thermal-tolerance limits of terrestrial ectotherms often exceed local air temperatures, implying a high degree of thermal safety (an excess of warm or cold thermal tolerance). However, air temperatures can be very different from the equilibrium body temperature of an individual ectotherm. Here, we compile thermal-tolerance limits of ectotherms across a wide range of latitudes and elevations and compare these thermal limits both to air and to operative body temperatures (theoretically equilibrated body temperatures) of small ectothermic animals during the warmest and coldest times of the year. We show that extreme operative body temperatures in exposed habitats match or exceed the physiological thermal limits of most ectotherms. Therefore, contrary to previous findings using air temperatures, most ectotherms do not have a physiological thermal-safety margin. They must therefore rely on behavior to avoid overheating during the warmest times, especially in the lowland tropics. Likewise, species living at temperate latitudes and in alpine habitats must retreat to avoid lethal cold exposure. Behavioral plasticity of habitat use and the energetic consequences of thermal retreats are therefore critical aspects of species' vulnerability to climate warming and extreme events.

Tumor response and negative distal resection margins of rectal cancer after hyperthermochemoradiation therapy.

PubMed

Tsutsumi, Soichi; Tabe, Yuichi; Fujii, Takaaki; Yamaguchi, Satoru; Suto, Toshinaga; Yajima, Reina; Morita, Hiroki; Kato, Toshihide; Shioya, Mariko; Saito, Jun-Ichi; Asao, Takayuki; Nakano, Takashi; Kuwano, Hiroyuki

2011-11-01

The safety of regional hyperthermia has been tested in locally advanced rectal cancer. The aim of this study was to assess the effects of shorter distal margins on local control and survival in rectal cancer patients who were treated with preoperative hyperthermochemoradiation therapy (HCRT) and underwent rectal resection by using the total mesorectal excision (TME) method. Ninety-three patients with rectal adenocarcinoma who received neoadjuvant HCRT (total radiation: 50 Gy) were included in this study. Surgery was performed 8 weeks after HCRT, and each resected specimen was evaluated histologically. Length of distal surgical margins, status of circumferential margins, pathological response, and tumor node metastasis stage were examined for their effects on recurrence and survival. Fifty-eight (62.4%) patients had tumor regression, and 20 (21.5%) had a pathological complete response. Distal margin length ranged from 1 to 55 mm (median, 21 mm) and did not correlate with local recurrence (p=0.57) or survival (p=0.75) by univariate analysis. Kaplan-Meier estimates of recurrence-free survival and local recurrence for the <10 mm versus ≥10 mm groups were not significantly different. Positive circumferential margins and failure of tumors to respond were unfavorable factors in survival. Distal resection margins that are shorter than 10 mm but are not positive appear to be equivalent to longer margins in patients who undergo HCRT followed by rectal resection with TME. To improve the down-staging rate, additional studies are needed.

Safety and Suitability for Service Assessment Testing for Surface and Underwater Launched Munitions

DTIC Science & Technology

2014-12-05

test efficiency that tend to associate the Analytical S3 Test Approach with large, complex munition systems and the Empirical S3 Test Approach with...the smaller, less complex munition systems . 8.1 ANALYTICAL S3 TEST APPROACH. The Analytical S3 test approach, as shown in Figure 3, evaluates...assets than the Analytical S3 Test approach to establish the safety margin of the system . This approach is generally applicable to small munitions

10 CFR 72.122 - Overall requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... natural phenomena. (1) Structures, systems, and components important to safety must be designed to... effects of natural phenomena such as earthquakes, tornadoes, lightning, hurricanes, floods, tsunami, and... severe of the natural phenomena reported for the site and surrounding area, with appropriate margins to...

14 CFR 33.62 - Stress analysis.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: AIRCRAFT ENGINES Design and Construction; Turbine Aircraft Engines § 33.62 Stress analysis. A stress analysis must be performed on each turbine engine showing the design safety margin of each turbine...

14 CFR 33.62 - Stress analysis.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: AIRCRAFT ENGINES Design and Construction; Turbine Aircraft Engines § 33.62 Stress analysis. A stress analysis must be performed on each turbine engine showing the design safety margin of each turbine...

Multiphysics Object-Oriented Simulation Environment (MOOSE)

ScienceCinema

None

2017-12-09

Nuclear reactor operators can expand safety margins with more precise information about how materials behave inside operating reactors. INL's new simulation platform makes such studies easier & more informative by letting researchers "plug-n-play" their mathematical models, skipping years of computer code development.

Reliability-based evaluation of bridge components for consistent safety margins.

DOT National Transportation Integrated Search

2010-10-01

The Load and Resistant Factor Design (LRFD) approach is based on the concept of structural reliability. The approach is more : rational than the former design approaches such as Load Factor Design or Allowable Stress Design. The LRFD Specification fo...

Where Do Agricultural Producers Get Safety and Health Information?

PubMed

Chiu, Sophia; Cheyney, Marsha; Ramirez, Marizen; Gerr, Fred

2015-01-01

There is little empirical guidance regarding communication sources and channels used and trusted by agricultural producers. The goal of this study was to characterize frequency of use and levels of trust in agricultural safety and health information sources and channels accessed by agricultural producers. A sample of 195 agricultural producers was surveyed at county fairs in Iowa. Information was collected about the frequency of use and level of trust in 14 information sources and channels. Associations between age, gender, and education level and use and trust of each information source or channel were estimated using logistic regression. The sample consisted of 72% men with a mean age of 50.1 (SD = 15.6) years. Newspaper and magazine articles were the most commonly used agricultural safety and health information source or channel; 77% (n = 140) of respondents reporting using them at least monthly. Among those reporting monthly or more frequent use, 75% reported trusting mostly or completely, compared with 58% using and 49% trusting the Internet. High levels of use and trust of newspaper and magazine articles did not vary significantly by age, gender, or education level. Age in the highest tertile (57-83 years) was marginally associated with lower odds of using, as well as using and trusting, all the information sources and channels studied except for medical clinics (use only: odds ratio [OR], 3.51, 95% confidence interval [CI], 0.79-15.64; use and trust: OR, 5.90, 95% CI, 0.91-38.42). These findings suggest that traditional media may be more effective than digital media for delivering agricultural safety and health information to agricultural producers. Medical clinics may be an untapped venue for communicating with older agricultural producers.

Studies of the pharmacology of 17α-ethynyl-androst-5-ene-3β,7β,17β-triol, a synthetic anti-inflammatory androstene

PubMed Central

Ahlem, Clarence N; Kennedy, Michael R; Page, Theodore M; Reading, Christopher L; White, Steven K; McKenzie, John J; Cole, Phaedra I; Stickney, Dwight R; Frincke, James M

2011-01-01

17α-Ethynyl-androst-5ene-3β, 7β, 17β-triol (HE3286) is an orally bioavailable analogue of androst-5-ene-3β,7β,17β-triol, a non-glucocorticoid anti-inflammatory metabolite of the adrenal steroid, dehydroepiandrosterone. The pharmacology of HE3286 was characterized in preparation for clinical trials in type 2 diabetes mellitus and other diseases of inflammation. Interactions with nuclear hormone receptors and P450 enzymes were measured in vitro. Drug metabolism was studied preclinically in mice, rats, dogs, and monkeys. Neurological and cardiopulmonary safety and dose-ranging and chronic toxicity studies were conducted in rats and dogs in accordance with FDA guidelines. Pharmacokinetics and metabolites were measured in Phase I clinical trials. HE3286 was differentially metabolized between species. HE3286 and metabolites did not bind or transactivate steroid binding nuclear hormone receptors or inhibit P450 enzymes. There were no adverse effects in safety pharmacology and canine toxicology studies. Although HE3286 did not elicit systemic toxicity in rats, mild estrogenic effects were observed, but without apparent association to hormonal changes. Safety margins were greater than 20-fold in rats and dogs with respect to the most commonly used clinical dose of 10 mg/day. The terminal half-life in humans was 8 hours in males and 5.5 hours in females. HE3286 is the first derivative of the DHEA metabolome to undergo a comprehensive pharmacological and safety evaluation. The results of these investigations have shown that HE3286 has a low potential for toxicity and possesses pharmacological properties generally suitable for use in human medicine. The favorable profile of HE3286 warrants further exploration of this new class of anti-inflammatory agents. PMID:21686136

Structural style and tectonic evolution of the easternmost Gulf of Aden conjugate margins (Socotra - Southern Oman)

NASA Astrophysics Data System (ADS)

Nonn, Chloe; Leroy, Sylvie; Castilla, Raymi; de Clarens, Philippe; Lescanne, Marc

2016-04-01

Observations from distal rifted margins in present day magma-poor rifted margins led to the discovery of hyperextended crust and exhumed sub-continental mantle. This finding allowed to better figure out how thinning process are accommodate by tectonic structures, forming various crustal domains, as the deformation localized towards the future area of breakup. However, some of the current challenges are about clarifying how factors as oblique kinematic, pre-existing structures and volcanism can control the 3D geometry and crustal architecture of the passive margins? A key to better understand the rifting evolution in its entirety is to study conjugate margins. The gulf of Aden is a young oceanic basin (with a global trend about N75°E) oblique to the divergence (about 30°N), separating Arabia from Somalia of less than 800 km. Thanks to its immerged margins and its thin post-rift sediment cover, the gulf of Aden basin is a natural laboratory to investigate conjugate margins and strain localisation throughout the rift history. In this contribution, we focus our interest on offshore Socotra Island (Yemen) and its conjugate in Southeastern Oman. This area extends from Socotra-Hadbeen (SHFZ) and the eastern Gulf of Aden fault zones (EGAFZ). In the easternmost part of the gulf of Aden, we provide new insights into crustal deformation and emplacement of the new oceanic crust thanks to bathymetric, magnetic, gravimetric data and single-, multi-channel, high speed seismic reflection data collected during Encens-Sheba (2000), Encens (2006) and the more recent Marges-Aden (2012) cruises respectively. The results obtained after compilation of these data, previous geological (field works) and geophysical (receiver functions, Pn-tomography, magnetic anomalies, heat flow) studies on the focused area, allowed us to provide new structural mapping and stratigraphic correlation between onshore and offshore parts of Socotra and Oman margins. We precisely defined and map crustal domains, syn-tectonic structures and oblique accommodation zones to highlighted asymmetrical margins, characterized by strong lateral variability of crustal domains along and across strike. From external to internal domains of the margins and in between SHFZ and EGAFZ (first-order segment), this study details sharp necking domain and complex transition from hyperextended to oceanic crust characterized by: (i) hyperextended crust affected by volcanic extrusions; (ii) detachment faulting in the distal part of the margins allowing exhumation; (iii) volcanic constructions in the exhumation domain; (iv) a complex proto-oceanic crust. We highlight a significant second-order segmentation characterized by six N20°E trending transfer zones, limiting seven 25 - 60 km length segments and affecting necking domain as well as the ocean-continent transition. Based on interpretative cross-sections and detailed stratigraphic analysis, we discuss the complex temporal and spatial evolution of conjugate margins: (i) the margins segmentation and the relationship with structural inheritance (ii) the set-up of a long-offset detachment fault and the nature of the exhumed basement (iv) the origin and timing of magmatic events and the onset of proto-oceanic crust.

Results of a Demonstration Assessment of Passive System Reliability Utilizing the Reliability Method for Passive Systems (RMPS)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bucknor, Matthew; Grabaskas, David; Brunett, Acacia

2015-04-26

Advanced small modular reactor designs include many advantageous design features such as passively driven safety systems that are arguably more reliable and cost effective relative to conventional active systems. Despite their attractiveness, a reliability assessment of passive systems can be difficult using conventional reliability methods due to the nature of passive systems. Simple deviations in boundary conditions can induce functional failures in a passive system, and intermediate or unexpected operating modes can also occur. As part of an ongoing project, Argonne National Laboratory is investigating various methodologies to address passive system reliability. The Reliability Method for Passive Systems (RMPS), amore » systematic approach for examining reliability, is one technique chosen for this analysis. This methodology is combined with the Risk-Informed Safety Margin Characterization (RISMC) approach to assess the reliability of a passive system and the impact of its associated uncertainties. For this demonstration problem, an integrated plant model of an advanced small modular pool-type sodium fast reactor with a passive reactor cavity cooling system is subjected to a station blackout using RELAP5-3D. This paper discusses important aspects of the reliability assessment, including deployment of the methodology, the uncertainty identification and quantification process, and identification of key risk metrics.« less

Updated evidence-based clinical practice guidelines for the diagnosis and management of melanoma: definitive excision margins for primary cutaneous melanoma.

PubMed

Sladden, Michael J; Nieweg, Omgo E; Howle, Julie; Coventry, Brendon J; Thompson, John F

2018-02-19

Definitive management of primary cutaneous melanoma consists of surgical excision of the melanoma with the aim of curing the patient. The melanoma is widely excised together with a safety margin of surrounding skin and subcutaneous tissue, after the diagnosis and Breslow thickness have been established by histological assessment of the initial excision biopsy specimen. Sentinel lymph node biopsy should be discussed for melanomas ≥ 1 mm thickness (≥ 0.8 mm if other high risk features) in which case lymphoscintigraphy must be performed before wider excision of the primary melanoma site. The 2008 evidence-based clinical practice guidelines for the management of melanoma (http://www.cancer.org.au/content/pdf/HealthProfessionals/ClinicalGuidelines/ClinicalPracticeGuidelines-ManagementofMelanoma.pdf) are currently being revised and updated in a staged process by a multidisciplinary working party established by Cancer Council Australia. The guidelines for definitive excision margins for primary melanomas have been revised as part of this process. Main recommendations: The recommendations for definitive wide local excision of primary cutaneous melanoma are: melanoma in situ: 5-10 mm margins invasive melanoma (pT1) ≤ 1.0 mm thick: 1 cm margins invasive melanoma (pT2) 1.01-2.00 mm thick: 1-2 cm margins invasive melanoma (pT3) 2.01-4.00 mm thick: 1-2 cm margins invasive melanoma (pT4) > 4.0 mm thick: 2 cm margins Changes in management as a result of the guideline: Based on currently available evidence, excision margins for invasive melanoma have been left unchanged compared with the 2008 guidelines. However, melanoma in situ should be excised with 5-10 mm margins, with the aim of achieving complete histological clearance. Minimum clearances from all margins should be assessed and stated. Consideration should be given to further excision if necessary; positive or close histological margins are unacceptable.

Antecedent topography and morphological controls on sediment accumulation and slope stability of the U.S. Atlantic margin

NASA Astrophysics Data System (ADS)

Hill, J. C.; Brothers, D. S.; Ten Brink, U. S.; Andrews, B. D.

2017-12-01

The U.S. Atlantic margin encompasses a wide variety of slope failure processes, ranging from small canyon-confined failures on the upper slope to large, open slope landslides originating in deeper water. Here we used a suite of high-resolution multibeam bathymetry and detailed multichannel seismic data coverage to investigate the relationship between modern seafloor morphology, pre-existing stratigraphy and sediment accumulation patterns. We suggest that a combination of sediment supply and antecedent margin physiography, whereby variations in margin evolution during the Miocene have influenced the modern seafloor morphology, controls both the location of slope sediment accumulation and the style of slope failure. Oversteepened margins with angular shelf breaks and steep upper slopes, referred to as oblique margins, are characterized by downslope mass transport and densely-spaced canyon formation. These margins are most likely the locus of canyon-confined failures and smaller lower slope fan-apron failures (e.g., much of the Mid-Atlantic). Sigmoidal margins with prograded slopes, a rounded shelf edge, and a low gradient slope morphology can support significant sediment accumulation across a broad area, with limited canyon development. These margins are often associated with high sediment supply and are prone to large, upper slope slab-style failures (e.g., the Hudson Apron, southwestern New England, the Currituck and Cape Fear Slide complexes). Areas with morphologies in between these two end members are characterized by limited shelf-edge accommodation space and large-scale lower slope accumulation and onlap, representing transitional stages of equilibrium slope adjustment. Large failures along these intermediate-type margins tend to develop lower on the slope where thick wedges of onlapping sediment are found (e.g., around Washington Canyon, Cape Lookout and southeastern New England). As antecedent topography and sediment loading appear to play an important role in determining the spatial distribution of submarine slope failures, other key processes that contribute to the development of overpressure (e.g., sediment compaction and fluid migration) should be examined with this in mind to improve our understanding of the geologic factors that precondition slopes for failure.

Submarine slumps, slides, and flows dominate sculpting of Beringian Margin, Alaska

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carlson, P.R.; Karl, H.A.; Edwards, B.D.

1990-06-01

The 1,400 km long Beringian margin is characterized by several very large submarine canyons and by a large oceanic plateau at the southern end. GLORIA sidescan-sonar imagery provides a perspective of this margin that is unattainable with conventional acoustic profiles. The broad coverage of GLORIA images emphasizes that, of all the sedimentary processes affecting this vast margin, mass movement is clearly the dominant shaping process. Styles of failure include mud and debris flows, slumps, and massive block slides, some covering areas greater than 1,500 km{sup 2}. GLORIA imagery and seismic-reflection profiles show evidence for a wide variety of slides andmore » slumps in the canyons of the northern margin, Navarin and Pervenets. The 100 km long shelf edge between these two canyons is characterized by a series of scalloped slide scars and incipient scars associated with blocks of sedimentary material, 1 to 2 km across. One of the largest single slide masses is a huge block tens of kilometers wide that occurs on the rise in the central part of the margin beyond the mouth of Zhemchug Canyon. Sliding of this block may have initiated the incision of the world's largest submarine canyon. The removal of this block accelerated headward erosion by retrograde failure until Zhemchug Canyon was cut back to a fault parallel to the shelf edge. Mass movement along the southern margin is widespread at the edges of Umnak Plateau. One mass failure, well-defined by GLORIA, is about 30 km wide and 55 km long. This and other slides along the plateau are associated with diapiric-like structures, suggesting relatively recent tectonism.« less

77 FR 54626 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Approving a...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-05

... Change Relating to Spread Margin Rules August 29, 2012. I. Introduction On May 29, 2012, the Chicago... typically characterized by the simultaneous holding of a long and short option of the same type (put or call... expirations. To be eligible for spread margin treatment, the long option may not expire before the short...

Aviation safety and maintenance under major organizational changes, investigating non-existing accidents.

PubMed

Herrera, Ivonne A; Nordskag, Arve O; Myhre, Grete; Halvorsen, Kåre

2009-11-01

The objective of this paper is to discuss the following questions: Do concurrent organizational changes have a direct impact on aviation maintenance and safety, if so, how can this be measured? These questions were part of the investigation carried out by the Accident Investigation Board, Norway (AIBN). The AIBN investigated whether Norwegian aviation safety had been affected due to major organizational changes between 2000 and 2004. The main concern was the reduction in safety margins and its consequences. This paper presents a summary of the techniques used and explains how they were applied in three airlines and by two offshore helicopter operators. The paper also discusses the development of safety related indicators in the aviation industry. In addition, there is a summary of the lessons learned and safety recommendations. The Norwegian Ministry of Transport has required all players in the aviation industry to follow up the findings and recommendations of the AIBN study.

An assessment and validation study of nuclear reactors for low power space applications

NASA Technical Reports Server (NTRS)

Klein, A. C.; Gedeon, S. R.; Morey, D. C.

1987-01-01

The feasibility and safety of six conceptual small, low power nuclear reactor designs was evaluated. Feasibility evaluations included the determination of sufficient reactivity margins for seven years of full power operation and safe shutdown as well as handling during pre-launch assembly phases. Safety evaluations were concerned with the potential for maintaining subcritical conditions in the event of launch or transportation accidents. These included water immersion accident scenarios both with and without water flooding the core. Results show that most of the concepts can potentially meet the feasibility and safety requirements; however, due to the preliminary nature of the designs considered, more detailed designs will be necessary to enable these concepts to fully meet the safety requirements.

Characterization and Modeling of High Power Microwave Effects in CMOS Microelectronics

DTIC Science & Technology

2010-01-01

margin measurement 28 Any voltage above the line marked VIH is considered a valid logic high on the input of the gate. VIH and VIL are defined...can handle any voltage noise level at the input up to VIL without changing state. The region in between VIL and VIH is considered an invalid logic...29 Table 2.2: Intrinsic device characteristics derived from SPETCRE simulations   VIH  (V)  VIL (V)  High Noise Margin  (V)  Low Noise Margin (V

Flood hazard assessment for french NPPs

NASA Astrophysics Data System (ADS)

Rebour, Vincent; Duluc, Claire-Marie; Guimier, Laurent

2015-04-01

This paper presents the approach for flood hazard assessment for NPP which is on-going in France in the framework of post-Fukushima activities. These activities were initially defined considering both European "stress tests" of NPPs pursuant to the request of the European Council, and the French safety audit of civilian nuclear facilities in the light of the Fukushima Daiichi accident. The main actors in that process are the utility (EDF is, up to date, the unique NPP's operator in France), the regulatory authority (ASN) and its technical support organization (IRSN). This paper was prepared by IRSN, considering official positions of the other main actors in the current review process, it was not officially endorsed by them. In France, flood hazard to be considered for design basis definition (for new NPPs and for existing NPPs in periodic safety reviews conducted every 10 years) was revised before Fukushima-Daichi accident, due to le Blayais NPP December 1999 experience (partial site flooding and loss of some safety classified systems). The paper presents in the first part an overview of the revised guidance for design basis flood. In order to address design extension conditions (conditions that could result from natural events exceeding the design basis events), a set of flooding scenarios have been defined by adding margins on the scenarios that are considered for the design. Due to the diversity of phenomena to be considered for flooding hazard, the margin assessment is specific to each flooding scenario in terms of parameter to be penalized and of degree of variation of this parameter. The general approach to address design extension conditions is presented in the second part of the paper. The next parts present the approach for five flooding scenarios including design basis scenario and additional margin to define design extension scenarios.

Treatment response assessment of radiofrequency ablation for hepatocellular carcinoma: usefulness of virtual CT sonography with magnetic navigation.

PubMed

Minami, Yasunori; Kitai, Satoshi; Kudo, Masatoshi

2012-03-01

Virtual CT sonography using magnetic navigation provides cross sectional images of CT volume data corresponding to the angle of the transducer in the magnetic field in real-time. The purpose of this study was to clarify the value of this virtual CT sonography for treatment response of radiofrequency ablation for hepatocellular carcinoma. Sixty-one patients with 88 HCCs measuring 0.5-1.3 cm (mean±SD, 1.0±0.3 cm) were treated by radiofrequency ablation. For early treatment response, dynamic CT was performed 1-5 days (median, 2 days). We compared early treatment response between axial CT images and multi-angle CT images using virtual CT sonography. Residual tumor stains on axial CT images and multi-angle CT images were detected in 11.4% (10/88) and 13.6% (12/88) after the first session of RFA, respectively (P=0.65). Two patients were diagnosed as showing hyperemia enhancement after the initial radiofrequency ablation on axial CT images and showed local tumor progression shortly because of unnoticed residual tumors. Only virtual CT sonography with magnetic navigation retrospectively showed the residual tumor as circular enhancement. In safety margin analysis, 10 patients were excluded because of residual tumors. The safety margin more than 5 mm by virtual CT sonographic images and transverse CT images were determined in 71.8% (56/78) and 82.1% (64/78), respectively (P=0.13). The safety margin should be overestimated on axial CT images in 8 nodules. Virtual CT sonography with magnetic navigation was useful in evaluating the treatment response of radiofrequency ablation therapy for hepatocellular carcinoma. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Improved safety margin for embryotoxicity in rats for the new endoperoxide artefenomel (OZ439) as compared to artesunate.

PubMed

Clark, Robert L; Edwards, Tammye L; Longo, Monica; Kinney, Joseph; Walker, Don K; Rhodes, Jon; Clode, Sally A; Rückle, Thomas; Wells, Timothy; Andenmatten, Nicole; Huber, Anna Christine

2018-04-17

Combination medicines including an artemisinin are the mainstay of antimalarial therapy. Artemisinins are potent embryotoxicants in animal species due to their trioxane moiety. As part of its development, the new synthetic trioxolane antimalarial artefenomel (OZ439) was tested in rat whole embryo culture and in rat embryo-fetal toxicity studies with dosing throughout organogenesis or with a single dose on Gestational Day (GD) 12. The single-dose studies included groups treated with artesunate to allow a direct comparison of the embryotoxicity of the two antimalarials and included toxicokinetics hematology and histological examination of embryos. In addition, the distribution of artefenomel-related material in plasma was determined after the administration of 14 C-artefenomel. Artefenomel and artesunate showed similar patterns of embryotoxicity including cardiovascular defects and resorption with a steep dose-response. They both also caused a depletion of circulating embryonic erythroblasts both in vitro and in vivo and decreases in maternal reticulocyte count. However, artefenomel was ∼250-fold less potent than the active metabolite of artesunate (dihydroartemisinin) as an embryotoxicant in vitro. The safety margin (based on AUC) for artefenomel administered on GD 12 was approximately 100-fold greater than that for artesunate. Also, unlike artesunate, artefenomel was not a selective developmental toxicant. The lesser embryotoxicity of artefenomel is likely linked to its original design which included two blocking side groups that had been introduced to lower the reactivity with ferrous iron. Our data support the hypothesis that artefenomel's improved safety margin is linked to a lower potential for inhibiting heme biosynthesis in embryonic erythroblasts. © 2017 The Authors. Birth Defects Research Published by Wiley Periodicals, Inc.

Chronic warm exposure impairs growth performance and reduces thermal safety margins in the common triplefin fish (Forsterygion lapillum).

PubMed

McArley, Tristan J; Hickey, Anthony J R; Herbert, Neill A

2017-10-01

Intertidal fish species face gradual chronic changes in temperature and greater extremes of acute thermal exposure through climate-induced warming. As sea temperatures rise, it has been proposed that whole-animal performance will be impaired through oxygen and capacity limited thermal tolerance [OCLTT; reduced aerobic metabolic scope (MS)] and, on acute exposure to high temperatures, thermal safety margins may be reduced because of constrained acclimation capacity of upper thermal limits. Using the New Zealand triplefin fish ( Forsterygion lapillum ), this study addressed how performance in terms of growth and metabolism (MS) and upper thermal tolerance limits would be affected by chronic exposure to elevated temperature. Growth was measured in fish acclimated (12 weeks) to present and predicted future temperatures and metabolic rates were then determined in fish at acclimation temperatures and with acute thermal ramping. In agreement with the OCLTT hypothesis, chronic exposure to elevated temperature significantly reduced growth performance and MS. However, despite the prospect of impaired growth performance under warmer future summertime conditions, an annual growth model revealed that elevated temperatures may only shift the timing of high growth potential and not the overall annual growth rate. While the upper thermal tolerance (i.e. critical thermal maxima) increased with exposure to warmer temperatures and was associated with depressed metabolic rates during acute thermal ramping, upper thermal tolerance did not differ between present and predicted future summertime temperatures. This suggests that warming may progressively decrease thermal safety margins for hardy generalist species and could limit the available habitat range of intertidal populations. © 2017. Published by The Company of Biologists Ltd.

Marginal lung donors: A diminishing margin of safety?

PubMed

Botha, Phil; Fisher, Andrew J; Dark, John H

2006-11-27

Lung donor shortages have resulted in the critical appraisal of cadaveric donor acceptability criteria and the gradual relaxation of once strict guidelines. Many centers have reported their results with these "extended criteria" donors and an increasing number of multicenter registry studies have also been published. The results have been contradictory and leave many questions unanswered. Important new data has however come to light since the last review of the subject by the International Society for Heart and Lung Transplantation Pulmonary Council. We review the current literature focusing on recent developments in the pursuit of an expanded lung donor pool with acceptable outcomes.

Stability evaluation of short-circuiting gas metal arc welding based on ensemble empirical mode decomposition

NASA Astrophysics Data System (ADS)

Huang, Yong; Wang, Kehong; Zhou, Zhilan; Zhou, Xiaoxiao; Fang, Jimi

2017-03-01

The arc of gas metal arc welding (GMAW) contains abundant information about its stability and droplet transition, which can be effectively characterized by extracting the arc electrical signals. In this study, ensemble empirical mode decomposition (EEMD) was used to evaluate the stability of electrical current signals. The welding electrical signals were first decomposed by EEMD, and then transformed to a Hilbert-Huang spectrum and a marginal spectrum. The marginal spectrum is an approximate distribution of amplitude with frequency of signals, and can be described by a marginal index. Analysis of various welding process parameters showed that the marginal index of current signals increased when the welding process was more stable, and vice versa. Thus EEMD combined with the marginal index can effectively uncover the stability and droplet transition of GMAW.

Methodology Development for Passive Component Reliability Modeling in a Multi-Physics Simulation Environment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aldemir, Tunc; Denning, Richard; Catalyurek, Umit

Reduction in safety margin can be expected as passive structures and components undergo degradation with time. Limitations in the traditional probabilistic risk assessment (PRA) methodology constrain its value as an effective tool to address the impact of aging effects on risk and for quantifying the impact of aging management strategies in maintaining safety margins. A methodology has been developed to address multiple aging mechanisms involving large numbers of components (with possibly statistically dependent failures) within the PRA framework in a computationally feasible manner when the sequencing of events is conditioned on the physical conditions predicted in a simulation environment, suchmore » as the New Generation System Code (NGSC) concept. Both epistemic and aleatory uncertainties can be accounted for within the same phenomenological framework and maintenance can be accounted for in a coherent fashion. The framework accommodates the prospective impacts of various intervention strategies such as testing, maintenance, and refurbishment. The methodology is illustrated with several examples.« less

Scaled centrifugal compressor, collector and running gear program

NASA Technical Reports Server (NTRS)

Kenehan, J. G.

1983-01-01

The Scaled Centrifugal Compressor, Collector and Running gear Program was conducted in support of an overall NASA strategy to improve small-compressor performance, durability, and reliability while reducing initial and life-cycle costs. Accordingly, Garrett designed and provided a test rig, gearbox coupling, and facility collector for a new NASA facility, and provided a scaled model of an existing, high-performance impeller for evaluation scaling effects on aerodynamic performance and for obtaining other performance data. Test-rig shafting was designed to operate smoothly throughout a speed range up to 60,000 rpm. Pressurized components were designed to operate at pressures up to 300 psia and at temperatures to 1000 F. Nonrotating components were designed to provide a margin-of-safety of 0.05 or greater; rotating components, for a margin-of-safety based on allowable yield and ultimate strengths. Design activities were supported by complete design analysis, and the finished hardware was subjected to check-runs to confirm proper operation. The test rig will support a wide range of compressor tests and evaluations.

Nozzle extension design status report

NASA Technical Reports Server (NTRS)

Classen, L. B.

1972-01-01

Twenty possible concepts of a possible nozzle/nozzle extension interface were originated. Not all of the concepts were considered worthy of analysis time. Six of them were thermally analyzed and three were stress analyzed. These analyses were done to determine which of the concepts would have the best chance of succeeding, that is, they were a screening process which was to allow rating of one concept against another. This was done because adequate material properties to determine absolute stress levels were not available at the time of the analyses. Through all of the concepts still exhibit some areas of negative margin of safety, concept no. 1 shows good promise that, with slight modifications, it could have all positive margins of safety. Another significant question, regarding these designs, has to do with the Grafoil seals and insulators. Some additional data was just recently received on Grafoil properties, but it was too late to incorporate in the analyses. The new data were not significantly different from the properties which were used.

A predictive index of biomarkers for ictogenesis from tier I safety pharmacology testing that may warrant tier II EEG studies.

PubMed

Gauvin, David V; Zimmermann, Zachary J; Yoder, Joshua; Harter, Marci; Holdsworth, David; Kilgus, Quinn; May, Jonelle; Dalton, Jill; Baird, Theodore J

2018-05-08

Three significant contributions to the field of safety pharmacology were recently published detailing the use of electroencephalography (EEG) by telemetry in a critical role in the successful evaluation of a compound during drug development (1] Authier, Delatte, Kallman, Stevens & Markgraf; JPTM 2016; 81:274-285; 2] Accardi, Pugsley, Forster, Troncy, Huang & Authier; JPTM; 81: 47-59; 3] Bassett, Troncy, Pouliot, Paquette, Ascaha, & Authier; JPTM 2016; 70: 230-240). These authors present a convincing case for monitoring neocortical biopotential waveforms (EEG, ECoG, etc) during preclinical toxicology studies as an opportunity for early identification of a central nervous system (CNS) risk during Investigational New Drug (IND) Enabling Studies. This review is about "ictogenesis" not "epileptogenesis". It is intended to characterize overt behavioral and physiological changes suggestive of drug-induced neurotoxicity/ictogenesis in experimental animals during Tier 1 safety pharmacology testing, prior to first dose administration in man. It is the presence of these predictive or comorbid biomarkers expressed during the requisite conduct of daily clinical or cage side observations, and in early ICH S7A Tier I CNS, pulmonary and cardiovascular safety study designs that should initiate an early conversation regarding Tier II inclusion of EEG monitoring. We conclude that there is no single definitive clinical marker for seizure liability but plasma exposures might add to set proper safety margins when clinical convulsions are observed. Even the observation of a study-related full tonic-clonic convulsion does not establish solid ground to require the financial and temporal investment of a full EEG study under the current regulatory standards. For purposes of this review, we have adopted the FDA term "sponsor" as it refers to any person who takes the responsibility for and initiates a nonclinical investigations of new molecular entities; FDA uses the term "sponsor" primarily in relation to investigational new drug application submissions. Copyright © 2018. Published by Elsevier Inc.

The effect of fault-bend folding on seismic velocity in the marginal ridge of accretionary prisms

USGS Publications Warehouse

Cai, Y.; Wang, Chun-Yong; Hwang, W.-t.; Cochrane, G.R.

1995-01-01

Fluid venting in accretionary prisms, which feeds chemosynthetic biological communities, occurs mostly on the marginal thrust ridge. New seismic data for the marginal ridge of the Cascadia prism show significantly lower velocity than that in the adjacent oceanic basin and place important constraints on the interpretations of why fluid venting occurs mostly on the marginal ridge. We employed a finite-element method to analyze a typical fault-bend folding model to explain the phenomenon. The fault in the model is simulated by contact elements. The elements are characterized not only by finite sliding along a slide line, but also by elastoplastic deformation. We present the results of a stress analysis which show that the marginal ridge is under subhorizontal extension and the frontal thrust is under compression. This state of stress favors the growth of tensile cracks in the marginal ridge, facilitates fluid flow and reduces seismic velocities therein; on the other hand, it may close fluid pathways along the frontal thrust and divert fluid flow to the marginal ridge. ?? 1995 Birkha??user Verlag.

Marginal kidney donor

PubMed Central

Gopalakrishnan, Ganesh; Gourabathini, Siva Prasad

2007-01-01

Renal transplantation is the treatment of choice for a medically eligible patient with end stage renal disease. The number of renal transplants has increased rapidly over the last two decades. However, the demand for organs has increased even more. This disparity between the availability of organs and waitlisted patients for transplants has forced many transplant centers across the world to use marginal kidneys and donors. We performed a Medline search to establish the current status of marginal kidney donors in the world. Transplant programs using marginal deceased renal grafts is well established. The focus is now on efforts to improve their results. Utilization of non-heart-beating donors is still in a plateau phase and comprises a minor percentage of deceased donations. The main concern is primary non-function of the renal graft apart from legal and ethical issues. Transplants with living donors outnumbered cadaveric transplants at many centers in the last decade. There has been an increased use of marginal living kidney donors with some acceptable medical risks. Our primary concern is the safety of the living donor. There is not enough scientific data available to quantify the risks involved for such donation. The definition of marginal living donor is still not clear and there are no uniform recommendations. The decision must be tailored to each donor who in turn should be actively involved at all levels of the decision-making process. In the current circumstances, our responsibility is very crucial in making decisions for either accepting or rejecting a marginal living donor. PMID:19718332

An evaluation of two conducted electrical weapons and two probe designs using a swine comparative cardiac safety model.

PubMed

Dawes, Donald Murray; Ho, Jeffrey D; Moore, Johanna C; Miner, James R

2013-09-01

Despite human laboratory and field studies that have demonstrated a reasonable safety profile for TASER brand conducted electrical weapons (CEW), the results of some swine studies and arrest related deaths temporal to the use of the CEWs continue to raise questions regarding cardiac safety. TASER International, Inc., has released a new CEW, the TASER X2, touted to have a better safety profile than its long-standing predecessor, the TASER X26. We have developed a model to assess the relative cardiac safety of CEWs and used it to compare the TASER X2 and the TASER X26. This safety model was also used to assess the relative safety of an experimental probe design as compared to the standard steel probe. Our results suggest that the TASER X2 has an improved safety margin over the TASER X26. The new probe design also has promise for enhanced cardiac safety, although may have some disadvantages when compared to the existing design which would make field use impractical.

The flammability of lip, face and hair preparations in the presence of 100% oxygen.

DOT National Transportation Integrated Search

1963-11-01

The effects of high concentrations and pressures of oxygen and static sparks upon lip, face and hair preparations were determined because of questions that frequently arise and apprehension that exists. A wide margin of safety was found for their use...

National Defense on the High Frontier.

ERIC Educational Resources Information Center

Graham, Daniel O.

1983-01-01

A new American defense policy based on satellites which can track down and destroy Soviet missiles is less expensive and more workable than is commonly believed. Such a policy would provide a greater margin of safety than the present policy of deterence based on mutually assured destruction. (IS)

Optical characterization of an eddy-induced diatom bloom west of the island of Hawaii

NASA Astrophysics Data System (ADS)

Nencioli, F.; Chang, G.; Twardowski, M.; Dickey, T. D.

2009-08-01

Optical properties are used to characterize the biogeochemistry of cyclonic eddy Opal in the lee of Hawaii. The eddy featured an intense diatom bloom. Our results show that the ratio of chlorophyll concentration to particulate beam attenuation coefficient, [chl]/cp, is not a good indicator of the changes in particle composition through the water column. The ratio is controlled primarily by the variation in chlorophyll concentration per cell with depth (photoadaptation), so that its values increase throughout the Deep Chlorophyll Maximum Layer (DCML). Below the DCML, high values of [chl]/cp suggest that remineralization might be another important controlling factor. On the other hand, the backscattering ratio (particle backscattering to particle scattering ratio, b~bp) clearly indicates a shift from a small phytoplankton to a diatom dominated community. Below an upper layer characterized by constant values, the b~bp ratio showed a rapid decrease to a broad minimum within the DCML. The higher values below the DCML are consistent with enhanced remineralization below the eddy-induced bloom. The DCML was characterized by a layer of "healthy" diatoms underlying a layer of "senescent" diatoms. These two layers are characterized by similar optical properties, indicating some possible limitations in using optical measurements to fully characterize the composition of suspended material in the water column. An inverse relationship between b~bp and [chl]/cp, also reported by others, is observed as deep as the DCML. There, [chl]/cp increases whereas b~bp remains similar to values found in the empty frustule layer. This is a further indication that [chl]/cp might not be a good alternative to the backscattering ratio for investigating changes in particle composition with depth in Case I waters.