Safety analysis of the post-operational phase

International Nuclear Information System (INIS)

Berg, H.P.; Ehrlich, D.

1991-01-01

The safety analysis of normal operation covers an analytical study of the system parts ultimate repository - waste forms of the ultimate repository system under normal and accidental operation. On that basis a requirement concept has been developed which entails reactions on planning and design of the repository, and requirements of waste products, packagings and permissible activities. The procedure for the operational phase is explained giving the Konrad repository project as an example. (DG) [de

Extension of CFD Codes Application to Two-Phase Flow Safety Problems - Phase 3

International Nuclear Information System (INIS)

Bestion, D.; Anglart, H.; Mahaffy, J.; Lucas, D.; Song, C.H.; Scheuerer, M.; Zigh, G.; Andreani, M.; Kasahara, F.; Heitsch, M.; Komen, E.; Moretti, F.; Morii, T.; Muehlbauer, P.; Smith, B.L.; Watanabe, T.

2014-11-01

The Writing Group 3 on the extension of CFD to two-phase flow safety problems was formed following recommendations made at the 'Exploratory Meeting of Experts to Define an Action Plan on the Application of Computational Fluid Dynamics (CFD) Codes to Nuclear Reactor Safety Problems' held in Aix-en-Provence, in May 2002. Extension of CFD codes to two-phase flow is significant potentiality for the improvement of safety investigations, by giving some access to smaller scale flow processes which were not explicitly described by present tools. Using such tools as part of a safety demonstration may bring a better understanding of physical situations, more confidence in the results, and an estimation of safety margins. The increasing computer performance allows a more extensive use of 3D modelling of two-phase Thermal hydraulics with finer nodalization. However, models are not as mature as in single phase flow and a lot of work has still to be done on the physical modelling and numerical schemes in such two-phase CFD tools. The Writing Group listed and classified the NRS problems where extension of CFD to two-phase flow may bring real benefit, and classified different modelling approaches in a first report (Bestion et al., 2006). First ideas were reported about the specification and analysis of needs in terms of validation and verification. It was then suggested to focus further activity on a limited number of NRS issues with a high priority and a reasonable chance to be successful in a reasonable period of time. The WG3-step 2 was decided with the following objectives: - selection of a limited number of NRS issues having a high priority and for which two-phase CFD has a reasonable chance to be successful in a reasonable period of time; - identification of the remaining gaps in the existing approaches using two-phase CFD for each selected NRS issue; - review of the existing data base for validation of two-phase CFD application to the selected NRS problems

Tofacitinib, an oral Janus kinase inhibitor, in patients from Mexico with rheumatoid arthritis: Pooled efficacy and safety analyses from Phase 3 and LTE studies.

Science.gov (United States)

Burgos-Vargas, Ruben; Cardiel, Mario; Xibillé, Daniel; Pacheco-Tena, César; Pascual-Ramos, Virginia; Abud-Mendoza, Carlos; Mahgoub, Ehab; Rahman, Mahboob; Fan, Haiyun; Rojo, Ricardo; García, Erika; Santana, Karina

2017-05-25

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We characterized efficacy and safety of tofacitinib in Mexican patients from RA Phase 3 and long-term extension (LTE) studies. Data from Mexican patients with RA and an inadequate response to disease-modifying antirheumatic drugs (DMARDs) were taken from four Phase 3 studies (pooled across studies) and one open-label LTE study of tofacitinib. Patients received tofacitinib 5 or 10mg twice daily, adalimumab (one Phase 3 study) or placebo (four Phase 3 studies) as monotherapy or in combination with conventional synthetic DMARDs. Efficacy up to Month 12 (Phase 3) and Month 36 (LTE) was assessed by American College of Rheumatology 20/50/70 response rates, Disease Activity Score (erythrocyte sedimentation rate), and Health Assessment Questionnaire-Disability Index. Safety, including incidence rates (IRs; patients with events/100 patient-years) for adverse events (AEs) of special interest, was assessed throughout the studies. 119 and 212 Mexican patients were included in the Phase 3 and LTE analyses, respectively. Tofacitinib-treated patients in Phase 3 had numerically greater improvements in efficacy responses versus placebo at Month 3. Efficacy was sustained in Phase 3 and LTE studies. IRs for AEs of special interest were similar to those with tofacitinib in the global and Latin American RA populations. In Mexican patients from the tofacitinib global RA program, tofacitinib efficacy was demonstrated up to Month 12 in Phase 3 studies and Month 36 in the LTE study, with a safety profile consistent with tofacitinib global population. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Criteria Document for B-plant's Surveillance and Maintenance Phase Safety Basis Document

International Nuclear Information System (INIS)

SCHWEHR, B.A.

1999-01-01

This document is required by the Project Hanford Managing Contractor (PHMC) procedure, HNF-PRO-705, Safety Basis Planning, Documentation, Review, and Approval. This document specifies the criteria that shall be in the B Plant surveillance and maintenance phase safety basis in order to obtain approval of the DOE-RL. This CD describes the criteria to be addressed in the S and M Phase safety basis for the deactivated Waste Fractionization Facility (B Plant) on the Hanford Site in Washington state. This criteria document describes: the document type and format that will be used for the S and M Phase safety basis, the requirements documents that will be invoked for the document development, the deactivated condition of the B Plant facility, and the scope of issues to be addressed in the S and M Phase safety basis document

A Phase 1 Randomized, Open Label, Rectal Safety, Acceptability, Pharmacokinetic, and Pharmacodynamic Study of Three Formulations of Tenofovir 1% Gel (the CHARM-01 Study.

Directory of Open Access Journals (Sweden)

Ian Mcgowan

Full Text Available The CHARM-01 study characterized the safety, acceptability, pharmacokinetics (PK, and pharmacodynamics (PD of three tenofovir (TFV gels for rectal application. The vaginal formulation (VF gel was previously used in the CAPRISA 004 and VOICE vaginal microbicide Phase 2B trials and the RMP-02/MTN-006 Phase 1 rectal safety study. The reduced glycerin VF (RGVF gel was used in the MTN-007 Phase 1 rectal microbicide trial and is currently being evaluated in the MTN-017 Phase 2 rectal microbicide trial. A third rectal specific formulation (RF gel was also evaluated in the CHARM-01 study.Participants received 4 mL of the three TFV gels in a blinded, crossover design: seven daily doses of RGVF, seven daily doses of RF, and six daily doses of placebo followed by one dose of VF, in a randomized sequence. Safety, acceptability, compartmental PK, and explant PD were monitored throughout the trial.All three gels were found to be safe and acceptable. RF and RGVF PK were not significantly different. Median mucosal mononuclear cell (MMC TFV-DP trended toward higher values for RF compared to RGVF (1136 and 320 fmol/106 cells respectively. Use of each gel in vivo was associated with significant inhibition of ex vivo colorectal tissue HIV infection. There was also a significant negative correlation between the tissue levels of TFV, tissue TFV-DP, MMC TFV-DP, rectal fluid TFV, and explant HIV-1 infection.All three formulations were found to be safe and acceptable. However, the safety profile of the VF gel was only based on exposure to one dose whereas participants received seven doses of the RGVF and RF gels. There was a trend towards higher tissue MMC levels of TFV-DP associated with use of the RF gel. Use of all gels was associated with significant inhibition of ex vivo tissue HIV infection.ClinicalTrials.gov NCT01575405.

Safety of Bifidobacterium animalis subsp. lactis (B. lactis) strain BB-12-supplemented yogurt in healthy adults on antibiotics: a phase I safety study.

Science.gov (United States)

Merenstein, Daniel J; Tan, Tina P; Molokin, Aleksey; Smith, Keisha Herbin; Roberts, Robert F; Shara, Nawar M; Mete, Mihriye; Sanders, Mary Ellen; Solano-Aguilar, Gloria

2015-01-01

Probiotics are live microorganisms that, when administered in sufficient doses, provide health benefits on the host. The United States Food and Drug Administration (FDA) requires phase I safety studies for probiotics when the intended use of the product is as a drug. The purpose of the study was to determine the safety of Bifidobacterium animalis subsp lactis (B. lactis) strain BB-12 (BB-12)-supplemented yogurt when consumed by a generally healthy group of adults who were prescribed a 10-day course of antibiotics for a respiratory infection. Secondary aims were to assess the ability of BB-12 to affect the expression of whole blood immune markers associated with cell activation and inflammatory response. A phase I, double-blinded, randomized controlled study was conducted in compliance with FDA guidelines for an Investigational New Drug (IND). Forty participants were randomly assigned to consume 4 ounces of either BB-12 -supplemented yogurt or non-supplemented control yogurt daily for 10 d. The primary outcome was to assess safety and tolerability, assessed by the number of reported adverse events. A total of 165 non-serious adverse events were reported, with no differences between the control and BB-12 groups. When compared to the control group, B lactis fecal levels were modestly higher in the BB-12-supplemented group. In a small subset of patients, changes in whole blood expression of genes associated with regulation and activation of immune cells were detected in the BB-12-supplemented group. BB-12-supplemented yogurt is safe and well tolerated when consumed by healthy adults concurrently taking antibiotics. This study will form the basis for future randomized clinical trials investigating the potential immunomodulatory effects of BB-12-supplemented yogurt in a variety of disease states.

The modification of main steam safety valves in Qinshan phase Ⅱ expansion project

International Nuclear Information System (INIS)

Chen Haiqiao

2012-01-01

The main steam safety valves of NPP steam system are second- class nuclear safety component. It used to limit the pressure of SG secondary side and main steam system via emitting steam into the environment. At present, the main steam safety valves have mechanical valves and assisted power valves. According to the experience of power plants at home and abroad, including Qinshan Phase Ⅱ unit 1/2 experience feedback, Qinshan Phase Ⅱ expansion project made modification on valve type, setting value and valve body. This paper introduce the characteristics of different safety valve types, the modification of main steam safety valves and the modification analysis on safety issues.security and impact on the other systems in Qinshan Phase Ⅱ expansion project. (author)

Phase II open-label study to assess efficacy and safety of lenalidomide in combination with cetuximab in KRAS-mutant metastatic colorectal cancer.

Directory of Open Access Journals (Sweden)

Salvatore Siena

Full Text Available This study aimed to assess the efficacy and safety of combination treatment with lenalidomide and cetuximab in KRAS-mutant metastatic colorectal cancer patients. This was a phase II multicenter, open-label trial comprising a safety lead-in phase (phase IIa to determine the maximum tolerated dose, and a randomized proof of concept phase (phase IIb to determine the response rate of lenalidomide plus cetuximab combination therapy. Phase IIa treatment comprised oral lenalidomide (starting dose 25 mg/day and intravenous cetuximab (400 mg/m(2 followed by weekly 250 mg/m(2 in 28-day cycles. In phase IIb patients were randomized to either the phase IIa treatment schedule of lenalidomide plus cetuximab combination therapy or lenalidomide 25 mg/day monotherapy. Eight patients were enrolled into phase IIa. One patient developed a dose-limiting toxicity and the maximum tolerated dose of lenalidomide was determined at 25 mg/day. Forty-three patients were enrolled into phase IIb proof of concept. Best response was stable disease in 9 patients and study enrollment was terminated prematurely due to lack of efficacy in both treatment arms and failure to achieve the planned response objective. The majority of adverse events were grade 1 and 2. In both phases, the adverse events most commonly attributed to any study drugs were fatigue, rash and other skin disorders, diarrhea, nausea, and stomatitis. Thirty-nine deaths occurred; none was related to study drug. The combination of lenalidomide and cetuximab appeared to be well tolerated but did not have clinically meaningful activity in KRAS-mutant metastatic colorectal cancer patients.Clinicaltrials.gov NCT01032291.

The safety and pharmacokinetics of a reverse transcriptase inhibitor, 3TC, in patients with HIV infection: a phase I study

NARCIS (Netherlands)

van Leeuwen, R.; Lange, J. M.; Hussey, E. K.; Donn, K. H.; Hall, S. T.; Harker, A. J.; Jonker, P.; Danner, S. A.

1992-01-01

To determine the safety and pharmacokinetics of the nucleoside analogue, 3TC. A Phase I, open-label, single-centre study. Twenty asymptomatic, HIV-infected male patients with CD4 lymphocyte counts < 500 x 10(6)/l who had not received previous antiretroviral therapy completed the study. Each patient

Prediction of two-phase choked-flow through safety valves

International Nuclear Information System (INIS)

Arnulfo, G; Bertani, C; De Salve, M

2014-01-01

Different models of two-phase choked flow through safety valves are applied in order to evaluate their capabilities of prediction in different thermal-hydraulic conditions. Experimental data available in the literature for two-phase fluid and subcooled liquid upstream the safety valve have been compared with the models predictions. Both flashing flows and non-flashing flows of liquid and incondensable gases have been considered. The present paper shows that for flashing flows good predictions are obtained by using the two-phase valve discharge coefficient defined by Lenzing and multiplying it by the critical flow rate in an ideal nozzle evaluated by either Omega Method or the Homogeneous Non-equilibrium Direct Integration. In case of non-flashing flows of water and air, Leung/Darby formulation of the two-phase valve discharge coefficient together with the Omega Method is more suitable to the prediction of flow rate.

Occupational Safety. Hand Tools. Pre-Apprenticeship Phase 1 Training.

Science.gov (United States)

Lane Community Coll., Eugene, OR.

This self-paced student training module on safety when using hand tools is one of a number of modules developed for Pre-apprenticeship Phase 1 Training. Purpose of the module is to teach students the correct safety techniques for operating common hand- and arm-powered tools, including selection, maintenance, technique, and uses. The module may…

A Phase Ib open label, randomized, safety study of SANGUINATE™ in patients with sickle cell anemia

Directory of Open Access Journals (Sweden)

Hemant Misra

Full Text Available Abstract Background: Treatment of sickle cell anemia is a challenging task and despite the well understood genetic and biochemical pathway of sickle hemoglobin, current therapy continues to be limited to the symptomatic treatment of pain, supplemental oxygen, antibiotics, red blood cell transfusions and hydroxyurea. SANGUINATE is a carbon monoxide releasing molecule and oxygen transfer agent under clinical development for the treatment of sickle cell anemia and comorbidities. Methods: An open-label randomized Phase Ib study was performed in adult sickle cell anemia patients. Two dose levels of SANGUINATE were compared to hydroxyurea in 24 homozygotes for Hb SS. Twelve subjects received either a low dose (160 mg/kg of SANGUINATE or 15 mg/kg hydroxyurea. Another 12 subjects received either a high dose (320 mg/kg of SANGUINATE or 15 mg/kg hydroxyurea. The primary endpoint was the safety of SANGUINATE versus hydroxyurea in sickle cell anemia patients. Secondary endpoints included determination of the plasma pharmacokinetics and assessment of hematologic measurements. Results: Musculoskeletal related adverse events were the most common. Transient troponin I levels increased in three patients, one of whom had an increase in tricuspid regurgitant velocity; however, no clinical signs were noted. Following an assessment of vital signs, tricuspid regurgitant velocity, electrocardiogram, serum biochemistry, hematology, urinalysis, and analysis of reported adverse events, SANGUINATE was found to be safe in stable sickle cell anemia patients. Conclusions: The clinical trial met its primary objective of demonstrating an acceptable safety profile for SANGUINATE in patients with sickle cell anemia. This trial established the safety of SANGUINATE at both dose levels and permitted its advance to Phase II trials.

Study on Fusion Safety Infrastructure using ISAM

International Nuclear Information System (INIS)

Oh, Kyemin; Kang, Myungsuk; Heo, Gyunyoung; Kim, Hyoungchan

2013-01-01

The regulation of nuclear facilities have checked and managed safety throughout the entire process from design, construction, operation and decommissioning. Also, the same meaning as the regulatory requirements and design requirements, it will be important indicators for detailed design of K-DEMO. K-DEMO has many uncertainties because it is in conceptual design phase. Also, there is no reference material because demonstration scale fusion power plants were not operated yet in overseas. So, hazard that threaten the integrity of K-DEMO have to be defined preferentially to define regulatory or design requirements. This study proposed method that educe regulatory or design requirements and introduce web-based cloud infrastructure to perform renewal and sharing of information related with safety that is required in the study rapidly as a part of the R and D program funded by National Fusion Research Institute of Korea (NFRI). We have been performing QSR and PIRT in accordance with development of fusion DEMO plant, and preparing OPT, PSA and DPA for regulation requirements. This study introduces our recent research activities about ISAM for fusion and CCI built for expert and extant safety related information. Unlike fission, nuclear fusion's safety goal is non-evacuation of the public during an accident. To satisfy this goal not only various safety issues should be analyzed, but safety objectives, regulatory requirements, and design variables should also be established in detailed design phase. The web-based cloud infrastructure proposed in this paper will be able to offer input data of future studies and, it is expected to contribute on general and technical safety principles for national fusion power plant technology plan

Project SAFE. Update of the SFR-1 safety assessment. Phase 1

International Nuclear Information System (INIS)

Andersson, Johan; Riggare, P.; Skagius, K.

1998-10-01

SFR-1 is a facility for disposal of low-level radioactive operational waste from the nuclear power plants in Sweden. Low-level radioactive waste from industry, medicine, and research is also disposed in SFR-1. The facility is situated in bedrock beneath the Baltic Sea, 1 km off the coast near the Forsmark nuclear power plant. SFR-1 was built between the years 1983 and 1988. An assessment of the long-term performance of the facility was included in the vast documentation that was a part of the application for an operational license. The assessment was presented in the form of a final safety report. In the operational licence for SFR-1 it is stated that renewed safety assessments should be carried out at least each ten years. In order to meet this demand SKB has launched a special project, SAFE (Safety Assessment of Final Disposal of Operational Radioactive Waste). The aim of the project is to update the safety analysis and to prepare a safety report that will be presented to the Swedish authorities not later than year 2000. Project SAFE is divided into three phases. The first phase is a prestudy, and the results of the prestudy are given in this report. The aim of the prestudy is to identify issues where additional studies would improve the basis for the updated safety analysis as well as to suggest how these studies should be carried out. The work has been divided into six different topics, namely the inventory, the near field, the far field, the biosphere, radionuclide transport calculations and scenarios. For each topic the former safety reports and regulatory reviews are scrutinised and needs for additional work is identified. The evaluations are given in appendices covering the respective topics. The main report is a summary of the appendices with a more stringent description of the repository system and the processes that are of interest and therefore should be addressed in an updated safety assessment. However, it should be pointed out that one of the

Operational Readiness Verification, Phase 3. A Field Study at a Swedish NPP during a Productive Outage (Safety-train Outage)

International Nuclear Information System (INIS)

Hollnagel, Erik; Gauthereau, Vincent; Persson, Bodil

2004-01-01

This report describes the results from Phase III of a study on Operational Readiness Verification (ORV) that was carried out from December 2002 to November 2003. The work comprised a field study of ORV activities at a Swedish NPP during a planned productive outage [subavstaellning], which allowed empirical work to be conducted in an appropriate environment with good accessibility to technical staff. One conclusion from Phase I of this project was the need to look more closely at the differences between three levels or types of tests that occur in ORV: object (component) test, system level test and (safety) function test, and to analyse the different steps of testing in order to understand the nontrivial relations between tests and safety. A second conclusion was the need to take a closer look at the organisation's ability to improvise in the sense of adjusting pre-defined plans to the actual conditions under which they are to be carried out. Phase II of the project found that although all three types of test occurred, they were rather used according to need rather than to a predefined arrangement or procedure. The complexity of ORV could be understood and described by using the concepts of Community of Practice, embedding, and Efficiency-Thoroughness Trade-Off. In addition, organisation and the different communities of practice improvise by adjusting pre-defined plans or work orders to the existing conditions. Such improvisations take place both on the levels of individual actions, on the level of communities of practice, and on the organisational level. The ability to improvise is practically a necessity for work to be carried out, but is also a potential risk. Phase III of the project studied how tasks are adapted relative to the different types of embedding and the degree of correspondence between nominal and actual ORV. It also looked further at the different Communities of Practice that are part of maintenance and ORV, focusing on the coordination and

A history of studies on safety of irradiated foods

International Nuclear Information System (INIS)

Miyahara, Makoto

2003-01-01

This report explained a history of studies on safety of irradiated foods in the United States. The army of USA had begun an experiment of irradiated foods in 1953. The toxic tests consisted of three phase, the phase I (1954 to 1959), phase II (1956 to 1965) and phase III (1971 to 1978). In the phase I, the short period toxic tests (90days) of 54 kinds of foods were carried out using high and low irradiation. The Swift and Company Laboratories reported detailed animal tests of 2685 albino rat, chickens and human. The animal tests showed many kinds of nutrition disorder, but the human test no problem. On phase II, 22 kinds of foods were tested for long period using rat, dog and mouse. Dog showed many kinds of symptom, for example, low birthrate, short life time, low growth rate, increasing spleen weight and thyroid disease. On phase III, two companies carried out the toxic test and Ralston Purina Company report is only data to be used now. Atomic Energy Commission (AEC) (1960 to 1970), Department of Commerce (1965 to 1976) and Department of Agriculture (1961 to 1966) studied safety of irradiated foods. Food and Drug Administration (FDA) determined that the irradiated foods belonged to under the category of food additive in 1958. FDA tests safety of irradiated foods using the determination tree and permitted many kinds of irradiated foods. (S.Y.)

Operational Readiness Verification, Phase 3. A Field Study at a Swedish NPP during a Productive Outage (Safety-train Outage)

Energy Technology Data Exchange (ETDEWEB)

Hollnagel, Erik [Linkoeping Univ. (Sweden). Dept. of Computer and Information Science; Gauthereau, Vincent; Persson, Bodil [Linkoeping Univ. (Sweden). Dept. of Industrial Engineering

2004-01-01

This report describes the results from Phase III of a study on Operational Readiness Verification (ORV) that was carried out from December 2002 to November 2003. The work comprised a field study of ORV activities at a Swedish NPP during a planned productive outage, which allowed empirical work to be conducted in an appropriate environment with good accessibility to technical staff. One conclusion from Phase I of this project was the need to look more closely at the differences between three levels or types of tests that occur in ORV: object (component) test, system level test and (safety) function test, and to analyse the different steps of testing in order to understand the nontrivial relations between tests and safety. A second conclusion was the need to take a closer look at the organisation's ability to improvise in the sense of adjusting pre-defined plans to the actual conditions under which they are to be carried out. Phase II of the project found that although all three types of test occurred, they were rather used according to need rather than to a predefined arrangement or procedure. The complexity of ORV could be understood and described by using the concepts of Community of Practice, embedding, and Efficiency-Thoroughness Trade-Off. In addition, organisation and the different communities of practice improvise by adjusting pre-defined plans or work orders to the existing conditions. Such improvisations take place both on the levels of individual actions, on the level of communities of practice, and on the organisational level. The ability to improvise is practically a necessity for work to be carried out, but is also a potential risk. Phase III of the project studied how tasks are adapted relative to the different types of embedding and the degree of correspondence between nominal and actual ORV. It also looked further at the different Communities of Practice that are part of maintenance and ORV, focusing on the coordination and communication between

Phase 2 safety analysis report: National Synchrotron Light Source

International Nuclear Information System (INIS)

Stefan, P.

1989-06-01

The Phase II program was established in order to provide additional space for experiments, and also staging and equipment storage areas. It also provides additional office space and new types of advanced instrumentation for users. This document will deal with the new safety issues resulting from this extensive expansion program, and should be used as a supplement to BNL Report No. 51584 ''National Synchrotron Light Source Safety Analysis Report,'' July 1982 (hereafter referred to as the Phase I SAR). The initial NSLS facility is described in the Phase I SAR. It comprises two electron storage rings, an injection system common to both, experimental beam lines and equipment, and office and support areas, all of which are housed in a 74,000 sq. ft. building. The X-ray Ring provides for 28 primary beam ports and the VUV Ring, 16. Each port is capable of division into 2 or 3 separate beam lines. All ports receive their synchrotron light from conventional bending magnet sources, the magnets being part of the storage ring lattice. 4 refs

Electric capacitance tomography and two-phase flow for the nuclear reactor safety analysis

International Nuclear Information System (INIS)

Lee, Jae Young

2008-01-01

Recently electric capacitance tomography has been developed to be used in the analysis of two-phase flow. Although its electric field is not focused as the hard ray tomography such as the X-ray or gamma ray, its convenience of easy access to the system and easy maintenance due to no requirement of radiation shielding benefits us in its application in the two-phase flow study, one of important area in the nuclear safety analysis. In the present paper, the practical technologies in the electric capacitance tomography are represented in both parts of hardware and software. In the software part, both forward problem and inverse problem are discussed and the method of regularization. In the hardware part, the brief discussion of the electronics circuits is made which provides femto farad resolution with a reasonable speed (150 frame/sec for 16 electrodes). Some representative ideal cases are studied to demonstrate its potential capability for the two-phase flow analysis. Also, some variations of the tomography such as axial tomography, and three dimensional tomography are discussed. It was found that the present ECT is expected to become a useful tool to understand the complicated three dimensional two-phase flow which may be an important feature to be equipped by the safety analysis codes. (author)

Preparation of Phased and Merged Safety Analysis Reports for New DOE Nuclear Facilities

International Nuclear Information System (INIS)

BISHOP, G.E.

2000-01-01

The Spent Nuclear Fuels Project (SNFP) is charged with moving to storage 2,100 metric tons of spent nuclear fuel elements left over from plutonium production at DOE'S Hanford site in Washington state. Two new facilities, the Cold Vacuum Drying Facility (CVDF) and the Canister Storage Building (CSB) are in final construction. In order to meet aggressive schedule commitments, the SNFP chose to prepare the safety analysis reports (SAR's) in phases that covered only specific portions of each facility's design as it was built. Each SAR also merged the preliminary and final safety analysis reports into a single SAR, thereby covering all aspects of design, construction, and operation for that portion (phase) of the facility. A policy of ''NRC equivalency'' was also implemented in parallel with this effort, with the goal of achieving a rigor of safety analysis equivalent to that of NRC-licensed fuel processing facilities. DOE Order 5480.23. ''Nuclear Safety Analysis Reports'' allows preparation of both a phased and a merged SAR to accelerate construction schedules. However, project managers must be aware that such acceleration is not guaranteed. Managers considering this approach for their project should be cognizant of numerous obstacles that will be encountered. Merging and phasing SAR's will create new, unique, and unanticipated difficulties which may actually slow construction unless expeditiously and correctly managed. Pitfalls to be avoided and good practices to be implemented in preparing phased and merged SAR's are presented. The value of applying NRC requirements to the DOE safety analysis process is also discussed. As of December, 1999, the SNFP has completed and approved a SAR for the CVDF. Approval of the SAR for the CSB is pending

Safety and immunogenicity of three different formulations of an adjuvanted varicella-zoster virus subunit candidate vaccine in older adults: a phase II, randomized, controlled study

NARCIS (Netherlands)

Chlibek, Roman; Smetana, Jan; Pauksens, Karlis; Rombo, Lars; van den Hoek, J. Anneke R.; Richardus, Jan H.; Plassmann, Georg; Schwarz, Tino F.; Ledent, Edouard; Heineman, Thomas C.

2014-01-01

This study investigated the safety and immunogenicity of different formulations and schedules of a candidate subunit herpes zoster vaccine containing varicella-zoster virus glycoprotein E (gE) with or without the adjuvant system AS01B. In this phase II, single-blind, randomized, controlled study,

Cardiovascular safety of liraglutide assessed in a patient-level pooled analysis of phase 2: 3 liraglutide clinical development studies.

Science.gov (United States)

Marso, Steven P; Lindsey, Jason B; Stolker, Joshua M; House, John A; Martinez Ravn, Gabriela; Kennedy, Kevin F; Jensen, Troels M; Buse, John B

2011-07-01

We assessed the cardiovascular safety of liraglutide, a glucagon-like peptide-1 receptor agonist, using existing clinical data. Patient-level results from all completed phase 2 and 3 studies from the liraglutide clinical development programme were pooled to determine rates of major adverse cardiovascular events (MACE): cardiovascular death, myocardial infarction, stroke. MACE were identified by querying the study database using Medical Dictionary for Regulatory Activities (MedDRA) terms combined with serious adverse events recorded by study investigators. Broad, narrow, and custom groups of MedDRA queries were used. Candidate events from each query were independently adjudicated post hoc. In 15 studies (6638 patients; 4257 liraglutide treated), there were 114 patients with MACE identified using the broad MedDRA query. Of these, 44 were classified as serious adverse events and 39 were adjudicated as MACE. The incidence ratio for adjudicated broad/serious MACE associated with liraglutide was 0.73 (95% CI 0.38-1.41) versus all comparator drugs (metformin, glimepiride, rosiglitazone, insulin glargine, placebo), within cardiovascular safety limits defined by the United States Food & Drug Administration for diabetes therapies under current investigation.

Simulation study of coal mine safety investment based on system dynamics

Institute of Scientific and Technical Information of China (English)

Tong Lei; Dou Yuanyuan

2014-01-01

To generate dynamic planning for coal mine safety investment, this study applies system dynamics to decision-making, classifying safety investments by accident type. It validates the relationship between safety investments and accident cost, by structurally analyzing the causality between safety investments and their influence factors. Our simulation model, based on Vensim software, conducts simulation anal-ysis on a series of actual data from a coalmine in Shanxi Province. Our results indicate a lag phase in safety investments, and that increasing pre-phase safety investment reduces accident costs. We found that a 24%increase in initial safety investment could help reach the target accident costs level 14 months earlier. Our simulation test included nine kinds of variation trends of accident costs brought by different investment ratios on accident prevention. We found an optimized ratio of accident prevention invest-ments allowing a mine to reach accident cost goals 4 months earlier, without changing its total investment.

On safety management and nuclear safety - A frame of reference for studies of safety management with examples from non-nuclear contects of relevance for nuclear safety

International Nuclear Information System (INIS)

Svenson, O.; Allwin, P.; Salo, I.

2004-03-01

The report includes three case studies of safety management. The studies are presented as chapters, but are written in a format that makes them easy to read separately. Two of the studies cover regulators (the Swedish Civil Aviation Safety Authority, Luftfartsinspektionen) and the Norwegian Petroleum Directorate) and one a regulated activity/industry (a car manufacturer, Volvo Car). The introduction outlines a living system framework and relates this to concepts used in organizational management. The report concludes with some findings with potential relevance for safety management in the nuclear power domain. In the next phase of the work, the regulated counterparts of the regulators here will be investigated in addition to a fourth case study of a regulated activity/industry. (au)

A Technique of Software Safety Analysis in the Design Phase for PLC Based Safety-Critical Systems

International Nuclear Information System (INIS)

Koo, Seo-Ryong; Kim, Chang-Hwoi

2017-01-01

The purpose of safety analysis, which is a method of identifying portions of a system that have the potential for unacceptable hazards, is firstly to encourage design changes that will reduce or eliminate hazards and, secondly, to conduct special analyses and tests that can provide increased confidence in especially vulnerable portions of the system. For the design and implementation phase of the PLC based systems, we proposed a technique for software design specification and analysis, and this technique enables us to generate software design specifications (SDSs) in nuclear fields. For the safety analysis in the design phase, we used architecture design blocks of NuFDS to represent the architecture of the software. On the basis of the architecture design specification, we can directly generate the fault tree and then use the fault tree for qualitative analysis. Therefore, we proposed a technique of fault tree synthesis, along with a universal fault tree template for the architecture modules of nuclear software. Through our proposed fault tree synthesis in this work, users can use the architecture specification of the NuFDS approach to intuitively compose fault trees that help analyze the safety design features of software.

Probabilistic Safety Goals. Phase 1 Status and Experiences in Sweden and Finland

International Nuclear Information System (INIS)

Holmberg, Jan-Erik; Knochenhauer, Michael

2007-02-01

unacceptable release. A number of important issues have been identified for continued studies in the next project phase. The results from the project can be used as a platform for discussions at the utilities on how to define and use quantitative safety goals. The results can also be used by safety authorities as a reference for risk-informed regulation. The outcome can have an impact on the requirements on PSA, e.g., regarding quality, scope, level of detail, and documentation. Finally, the results can be expected to support on-going activities concerning risk-informed applications

Probabilistic safety goals. Phase 1 - Status and experiences in Sweden and Finland

International Nuclear Information System (INIS)

Holmberg, J.E.; Knochenhauer, M.

2007-03-01

and for unacceptable release. A number of important issues have been identified for continued studies in the next project phase. The results from the project can be used as a platform for discussions at the utilities on how to define and use quantitative safety goals. The results can also be used by safety authorities as a reference for risk-informed regulation. The outcome can have an impact on the requirements on PSA, e.g., regarding quality, scope, level of detail, and documentation. Finally, the results can be expected to support ongoing activities concerning risk-informed applications. (au)

Probabilistic Safety Goals. Phase 1 Status and Experiences in Sweden and Finland

Energy Technology Data Exchange (ETDEWEB)

Holmberg, Jan-Erik (VTT, FI-02044 VTT (Finland)); Knochenhauer, Michael (Relcon Scandpower AB, SE-172 25 Sundbyberg (Sweden))

2007-02-15

unacceptable release. A number of important issues have been identified for continued studies in the next project phase. The results from the project can be used as a platform for discussions at the utilities on how to define and use quantitative safety goals. The results can also be used by safety authorities as a reference for risk-informed regulation. The outcome can have an impact on the requirements on PSA, e.g., regarding quality, scope, level of detail, and documentation. Finally, the results can be expected to support on-going activities concerning risk-informed applications

Probabilistic safety goals. Phase 1 - Status and experiences in Sweden and Finland

Energy Technology Data Exchange (ETDEWEB)

Holmberg, J.E. [VTT (Finland); Knochenhauer, M. [Relcon Scandpower AB (Sweden)

2007-03-15

and for unacceptable release. A number of important issues have been identified for continued studies in the next project phase. The results from the project can be used as a platform for discussions at the utilities on how to define and use quantitative safety goals. The results can also be used by safety authorities as a reference for risk-informed regulation. The outcome can have an impact on the requirements on PSA, e.g., regarding quality, scope, level of detail, and documentation. Finally, the results can be expected to support ongoing activities concerning risk-informed applications. (au)

Industrial safety and fire protection during the construction phase

International Nuclear Information System (INIS)

Zimmer, K.

1977-01-01

The questions and problems of industrial safety and fire prevention have to be treated like the activities planning, developing, assembly, etc. This statement is illustrated by statistics of the fire insurance companies, from which it can be seen that the number of fire accidents has decreased but that the damage caused has greatly increased. The sooner the fire prevention and industrial safety measures are integrated in the planning phase, the better for the total costs. Preventive measures that possibly have to be introduced at a later stage are not only generally much more expensive but are also seldom as effective. (orig./HK) [de

Accelerated safety analyses - structural analyses Phase I - structural sensitivity evaluation of single- and double-shell waste storage tanks

International Nuclear Information System (INIS)

Becker, D.L.

1994-11-01

Accelerated Safety Analyses - Phase I (ASA-Phase I) have been conducted to assess the appropriateness of existing tank farm operational controls and/or limits as now stipulated in the Operational Safety Requirements (OSRs) and Operating Specification Documents, and to establish a technical basis for the waste tank operating safety envelope. Structural sensitivity analyses were performed to assess the response of the different waste tank configurations to variations in loading conditions, uncertainties in loading parameters, and uncertainties in material characteristics. Extensive documentation of the sensitivity analyses conducted and results obtained are provided in the detailed ASA-Phase I report, Structural Sensitivity Evaluation of Single- and Double-Shell Waste Tanks for Accelerated Safety Analysis - Phase I. This document provides a summary of the accelerated safety analyses sensitivity evaluations and the resulting findings

Nuclear criticality safety basics for personnel working with nuclear fissionable materials. Phase I

International Nuclear Information System (INIS)

Vausher, A.L.

1984-10-01

DOE order 5480.1A, Chapter V, ''Safety of Nuclear Facilities,'' establishes safety procedures and requirements for DOE nuclear facilities. The ''Nuclear Criticality Safety Basic Program - Phase I'' is documented in this report. The revised program has been developed to clearly illustrate the concept of nuclear safety and to help the individual employee incorporate safe behavior in his daily work performance. Because of this, the subject of safety has been approached through its three fundamentals: scientific basis, engineering criteria, and administrative controls. Only basics of these three elements were presented. 5 refs

Probabilistic safety goals. Phase 2 - Status report

International Nuclear Information System (INIS)

Holmberg, J.-E.; Bjoerkman, K.; Rossi, J.; Knochenhauer, M.; Xuhong He; Persson, A.; Gustavsson, H.

2008-07-01

The second phase of the project, the outcome of which is described in this project report has mainly dealt with four issues: 1) Consistency in the usage of safety goals 2) Criteria for assessment of results from PSA level 2 3) Overview of international safety goals and experiences from their use 4) Safety goals related to other man-made risks in society. Consistency in judgement over time has been perceived to be one of the main problems in the usage of safety goals. Safety goals defined in the 80ies were met in the beginning with PSA:s performed to the standards of that time, i.e., by PSA:s that were quite limited in scope and level of detail compared to today's state of the art. This issue was investigated by performing a comparative review was performed of three generations of the same PSA, focusing on the impact from changes over time in component failure data, IE frequency, and modelling of the plant, including plant changes and changes in success criteria. It proved to be very time-consuming and in some cases next to impossible to correctly identify the basic causes for changes in PSA results. A multitude of different sub-causes turned out to combined and difficult to differentiate. Thus, rigorous book-keeping is needed in order to keep track of how and why PSA results change. This is especially important in order to differentiate 'real' differences due to plant changes and updated component and IE data from differences that are due to general PSA development (scope, level of detail, modelling issues). (au)

Probabilistic safety goals. Phase 2 - Status report

Energy Technology Data Exchange (ETDEWEB)

Holmberg, J.-E.; Bjoerkman, K. Rossi, J. (VTT (Finland)); Knochenhauer, M.; Xuhong He; Persson, A.; Gustavsson, H. (Relcon Scandpower AB, Sundbyberg (Sweden))

2008-07-15

The second phase of the project, the outcome of which is described in this project report has mainly dealt with four issues: 1) Consistency in the usage of safety goals 2) Criteria for assessment of results from PSA level 2 3) Overview of international safety goals and experiences from their use 4) Safety goals related to other man-made risks in society. Consistency in judgement over time has been perceived to be one of the main problems in the usage of safety goals. Safety goals defined in the 80ies were met in the beginning with PSA:s performed to the standards of that time, i.e., by PSA:s that were quite limited in scope and level of detail compared to today's state of the art. This issue was investigated by performing a comparative review was performed of three generations of the same PSA, focusing on the impact from changes over time in component failure data, IE frequency, and modelling of the plant, including plant changes and changes in success criteria. It proved to be very time-consuming and in some cases next to impossible to correctly identify the basic causes for changes in PSA results. A multitude of different sub-causes turned out to combined and difficult to differentiate. Thus, rigorous book-keeping is needed in order to keep track of how and why PSA results change. This is especially important in order to differentiate 'real' differences due to plant changes and updated component and IE data from differences that are due to general PSA development (scope, level of detail, modelling issues). (au)

COLD-SAT feasibility study safety analysis

Science.gov (United States)

Mchenry, Steven T.; Yost, James M.

1991-01-01

The Cryogenic On-orbit Liquid Depot-Storage, Acquisition, and Transfer (COLD-SAT) satellite presents some unique safety issues. The feasibility study conducted at NASA-Lewis desired a systems safety program that would be involved from the initial design in order to eliminate and/or control the inherent hazards. Because of this, a hazards analysis method was needed that: (1) identified issues that needed to be addressed for a feasibility assessment; and (2) identified all potential hazards that would need to be controlled and/or eliminated during the detailed design phases. The developed analysis method is presented as well as the results generated for the COLD-SAT system.

Main results of the german risk study, phase B

International Nuclear Information System (INIS)

Heuser, F.W.

1988-01-01

Work on the German Risk Study is under contract of the Federal Ministry of Research and Technology. The reference plant for the analysis is the Biblis nuclear power plant, Unit B, a KWU pressurized water reactor of the 1300 MWel class. The plant is in operation since 1976. First results on Phase A of the study have been published in 1979. Investigations on Phase B have been foreseen to endeepen the analysis. The principal purpose of these investigations is to improve and to optimize the plant's safety features on a more realistic basis. Main objectives of Phase B are: - Completeness of accident event tree analysis taking into account further accident initiating events. - Identification and analyses of accident management measures which are adequate to minimize accidental risk. - improvement of the analysis on an as far as possible realistic basis, thereby taking into account recent results of safety research. The paper deals with the most important results of the plant analyses (level 1 and level 2) which have been performed within the scope of Phases B of the study

Intelligent Information Processing for Enhanced Safety in the NAS, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — Our Phase I work focused on how improved information flow between actors in a flight deck environment can improve safety performance. An operational prototype was...

Safety studies on Korean fusion DEMO plant using integrated safety assessment methodology

International Nuclear Information System (INIS)

Oh, Kyemin; Kang, Myoung-suk; Heo, Gyunyoung; Kim, Hyoung-chan

2014-01-01

's viewpoint in interactive manner: qualitative safety features review (QSR), phenomena identification and ranking table (PIRT), objective provision tree (OPT), probabilistic safety assessment (PSA), and deterministic and phenomenological analysis (DPA). Considering the design phase of K-DEMO, the current study focused on the PIRT process with the fusion safety advisory group in South Korea

Safety studies on Korean fusion DEMO plant using integrated safety assessment methodology

Energy Technology Data Exchange (ETDEWEB)

Oh, Kyemin; Kang, Myoung-suk [Kyung Hee University, Youngin-si, Gyeonggi-do 446-701 (Korea, Republic of); Heo, Gyunyoung, E-mail: gheo@khu.ac.kr [Kyung Hee University, Youngin-si, Gyeonggi-do 446-701 (Korea, Republic of); Kim, Hyoung-chan [National Fusion Research Institute, Daejeon-si 305-333 (Korea, Republic of)

2014-10-15

's viewpoint in interactive manner: qualitative safety features review (QSR), phenomena identification and ranking table (PIRT), objective provision tree (OPT), probabilistic safety assessment (PSA), and deterministic and phenomenological analysis (DPA). Considering the design phase of K-DEMO, the current study focused on the PIRT process with the fusion safety advisory group in South Korea.

Safety verification for the ECCS driven by the electrically 4 trains during LBLOCA reflood phase using ATLAS

International Nuclear Information System (INIS)

Park, Yusun; Park, Hyun-sik; Kang, Kyoung-ho; Choi, Nam-hyun; Min, Kyoung-ho; Choi, Ki-yong

2014-01-01

Highlights: • Safety improvement by adopting 4 train emergency core cooling system was validated experimentally. • General thermal hydraulic behaviors of the system during LBLOCA reflood phase were successfully demonstrated. • Key parameters such as the liquid levels, the PCTs, the quenching time, and the ECC bypass ratios were investigated. • Asymmetric effects of the different combination of safety injection were negligible during the reflood period. - Abstract: The APR1400 is equipped with four safety injection pumps driven by two emergency diesel generators. However, the design has been changed so that the four safety injection pumps are driven by 4 emergency diesel generators during the design certification process from the U.S. NRC. Thus, 4 safety injection pumps (SIPs) are completely independent electrically and mechanically and three safety injection pumps are available in a single failure condition. This design change could have a certain effects on the thermal-hydraulic phenomenon occurring in the downcomer region during the late reflood phase of a large break loss of coolant accident (LBLOCA). Thus, in this study, a verification experiment for the reflood phase of a LBLOCA was performed to evaluate the core cooling performance of the 4 train emergency core cooling system (ECCS) with an assumption of a single failure. And the different combinations of three SIPs positions were tested to investigate the asymmetric effects on the reactor core cooling performance. The overall experimental results revealed the typical thermal–hydraulic trends expected to occur during the reflood phase of a large-break LOCA scenario for the APR1400. Experiment with the injection of three SIPs showed a faster core quenching time and lower bypass ratio than that of the case in which two SIPs were injected. The RPV wall temperature distributions showed the similar trend in spite of the different SIP combinations

Towards a Usability and Error "Safety Net": A Multi-Phased Multi-Method Approach to Ensuring System Usability and Safety.

Science.gov (United States)

Kushniruk, Andre; Senathirajah, Yalini; Borycki, Elizabeth

2017-01-01

The usability and safety of health information systems have become major issues in the design and implementation of useful healthcare IT. In this paper we describe a multi-phased multi-method approach to integrating usability engineering methods into system testing to ensure both usability and safety of healthcare IT upon widespread deployment. The approach involves usability testing followed by clinical simulation (conducted in-situ) and "near-live" recording of user interactions with systems. At key stages in this process, usability problems are identified and rectified forming a usability and technology-induced error "safety net" that catches different types of usability and safety problems prior to releasing systems widely in healthcare settings.

A single-arm, multicenter, safety-monitoring, phase IV study of icotinib in treating advanced non-small cell lung cancer (NSCLC).

Science.gov (United States)

Hu, Xingsheng; Han, Baohui; Gu, Aiqin; Zhang, Yiping; Jiao, Shun Chang; Wang, Chang-Li; He, Jintao; Jia, Xueke; Zhang, Li; Peng, Jiewen; Wu, Meina; Ying, Kejing; Wang, Junye; Ma, Kewei; Zhang, Shucai; You, Changxuan; Tan, Fenlai; Wang, Yinxiang; Ding, Lieming; Sun, Yan

2014-11-01

The phase 3 ICOGEN trial established the non-inferiority of icotinib to gefitinib in terms of progression-free survival (PFS) in non-small cell lung cancer (NSCLC) patients, and this led to the approval of icotinib for NSCLC by the China Food and Drug Administration. A phase 4 study was conducted to assess the safety and efficacy of icotinib in a broad range of patients with advanced NSCLC across China. This study retrospectively analyzed data from unresectable, recurrent, and/or advanced NSCLC patients who received oral icotinib 125 mg three times per day. The primary endpoint was safety. The secondary endpoints included objective response rate (ORR) and disease control rate (DCR), which were investigated overall and in subgroups such as patients with an EGFR mutation and elderly patients. Between August, 2011 and August, 2012, a total of 6087 advanced NSCLC patients were registered in this study, of which 5549 were evaluable for safety and tumor response. The median age was 63 years (range 21-95 years), and 1571 (28.3%) patients were over the age of 70. The majority of patients were non-smokers, and had adenocarcinoma and stage IV disease. The overall incidence of adverse drug reactions (ADRs) of any grade was 31.5%. The most common ADRs included rash (17.4%) and diarrhea (8.5%), and three patients experienced interstitial lung disease (ILD). The ORR and DCR were 30.0% and 80.6%, respectively, for the overall population, and 33.4% and 81.2%, 30.3% and 80.3%, and 30.4% and 89.3%, for first-line, second-line, and third-line or multiple line subsets, respectively. In 665 EGFR-mutated patients who were evaluable for tumor response, the ORR and DCR were 49.2% (327/665) and 92.3% (614/665), respectively. The data from over 6000 patients was consistent with the results of the ICOGEN study. Icotinib demonstrated a favorable toxicity profile and efficacy in the routine clinical setting. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Radiation safety study for conventional facility and siting pre project phase of International Linear Collider

International Nuclear Information System (INIS)

Sanami, Toshiya; Ban, Syuichi; Sasaki, Shin-ichi

2015-01-01

The International Linear Collider (ILC) is a proposed high-energy collider consisting of two linear accelerators, two dumping rings, electron and positron sources, and a single colliding hall with two detectors. The total length and CMS energy of the ILC will be 31 km and 500 GeV, respectively (and 50 km and 1 TeV after future upgrade). The design of the ILC has entered the pre-project phase, which includes site-dependent design. Radiation safety design for the ILC is on-going as a part of conventional facility and siting activities of the pre-project phase. The thickness of a central wall of normal concrete is designed to be 3.5 m under a pessimistic assumption of beam loss. The beam loss scenario is under discussion. Experience and knowledge relating to shielding design and radiation control operational work at other laboratories are required. (authors)

Monitoring human and organizational factors influencing common-cause failures of safety-instrumented system during the operational phase

International Nuclear Information System (INIS)

Rahimi, Maryam; Rausand, Marvin

2013-01-01

Safety-instrumented systems (SISs) are important safety barriers in many technical systems in the process industry. Reliability requirements for SISs are specified as a safety integrity level (SIL) with reference to the standard IEC 61508. The SIS reliability is often threatened by common-cause failures (CCFs), and the beta-factor model is the most commonly used model for incorporating the effects of CCFs. In the design phase, the beta-factor, β, is determined by answering a set of questions that is given in part 6 of IEC 61508. During the operational phase, there are several factors that influence β, such that the actual β differs from what was predicted in the design phase, and therefore the required reliability may not be maintained. Among the factors influencing β in the operational phase are human and organizational factors (HOFs). A number of studies within industries that require highly reliable products have shown that HOFs have significant influence on CCFs and therefore on β in the operational phase, but this has been neglected in the process industry. HOFs are difficult to predict, and susceptible to be changed during the operational phase. Without proper management, changing HOFs may cause the SIS reliability to drift out of its required value. The aim of this article is to highlight the importance of HOFs in estimation of β for SISs, and also to propose a framework to follow the HOFs effects and to manage them such that the reliability requirement can be maintained

A phase I clinical study to evaluate safety of orally administered, genetically engineered Salmonella enterica serovar Typhimurium for canine osteosarcoma

OpenAIRE

Fritz, Sara; Henson, Michael; Greengard, Emily; Winter, Amber; Stuebner, Kathleen; Yoon, Una; Wilk, Vicki; Borgatti, Antonella; Augustin, Lance; Modiano, Jaime; Saltzman, Daniel

2017-01-01

Abstract We conducted a prospective phase I study to evaluate safety of an orally administered Salmonella encoding IL‐2 (SalpIL2) in combination with amputation and adjuvant doxorubicin for canine appendicular osteosarcoma. Efficacy was assessed as a secondary measure. The first dose of SalpIL2 was administered to 19 dogs on Day 0; amputation was done after 10 days with chemotherapy following 2 weeks later. SalpIL2 was administered concurrent with chemotherapy, for a total of five doses of do...

200-ZP-1 phase II and III IRM groundwater pump and treat site safety plan

International Nuclear Information System (INIS)

St. John, C.H.

1996-07-01

This safety plan covers operations, maintenance, and support activities related to the 200-ZP-1 Phase II and III Ground Water Pump- and-Treat Facility. The purpose of the facility is to extract carbon tetrachloride contaminated groundwater underlying the ZP-1 Operable Unit; separate the contaminant from the groundwater; and reintroduce the treated water to the aquifer. An air stripping methodology is employed to convert volatile organics to a vapor phase for absorption onto granular activated carbon. The automated process incorporates a variety of process and safety features that shut down the process system in the event that process or safety parameters are exceeded or compromised

Intervention of French safety authorities during the design and construction phases of the Creys-Malville plant

International Nuclear Information System (INIS)

Orzoni, G.

1985-01-01

The intervention of French safety authorities during the design and construction phases of the Creys-Malville plant has been made by the different means of technical regulation, of several successive authorizations bound to different steps, and of numerous surveillance visits. Some safety-related problems have been met. Some of them are detailed, relating to the basis accident for containment design, decay heat removal, polar crane of reactor building, seismic resistance of main vessel internals, core cover plug, design and fabrication of steam generators. The main problems met during the design reviews and the construction phase of the plant have been solved in time; the safety level reached is provisionally judged acceptable by the French safety authorities

Assessing the impact of safety monitoring on the efficacy analysis in large Phase III group sequential trials with non-trivial safety event rate.

Science.gov (United States)

Weng, Yanqiu; Palesch, Yuko Y; DeSantis, Stacia M; Zhao, Wenle

2016-01-01

In Phase III clinical trials for life-threatening conditions, some serious but expected adverse events, such as early deaths or congestive heart failure, are often treated as the secondary or co-primary endpoint, and are closely monitored by the Data and Safety Monitoring Committee (DSMC). A naïve group sequential design (GSD) for such a study is to specify univariate statistical boundaries for the efficacy and safety endpoints separately, and then implement the two boundaries during the study, even though the two endpoints are typically correlated. One problem with this naïve design, which has been noted in the statistical literature, is the potential loss of power. In this article, we develop an analytical tool to evaluate this negative impact for trials with non-trivial safety event rates, particularly when the safety monitoring is informal. Using a bivariate binary power function for the GSD with a random-effect component to account for subjective decision-making in safety monitoring, we demonstrate how, under common conditions, the power loss in the naïve design can be substantial. This tool may be helpful to entities such as the DSMCs when they wish to deviate from the prespecified stopping boundaries based on safety measures.

A multidisciplinary three-phase approach to improve the clinical utility of patient safety indicators.

Science.gov (United States)

Najjar, Peter; Kachalia, Allen; Sutherland, Tori; Beloff, Jennifer; David-Kasdan, Jo Ann; Bates, David W; Urman, Richard D

2015-01-01

The AHRQ Patient Safety Indicators (PSIs) are used for calculation of risk-adjusted postoperative rates for adverse events. The payers and quality consortiums are increasingly requiring public reporting of hospital performance on these metrics. We discuss processes designed to improve the accuracy and clinical utility of PSI reporting in practice. The study was conducted at a 793-bed tertiary care academic medical center where PSI processes have been aggressively implemented to track patient safety events at discharge. A three-phased approach to improving administrative data quality was implemented. The initiative consisted of clinical review of all PSIs, documentation improvement, and provider outreach including active querying for patient safety events. This multidisciplinary effort to develop a streamlined process for PSI calculation reduced the reporting of miscoded PSIs and increased the clinical utility of PSI monitoring. Over 4 quarters, 4 of 41 (10%) PSI-11 and 9 of 138 (7%) PSI-15 errors were identified on review of clinical documentation and appropriate adjustments were made. A multidisciplinary, phased approach leveraging existing billing infrastructure for robust metric coding, ongoing clinical review, and frontline provider outreach is a novel and effective way to reduce the reporting of false-positive outcomes and improve the clinical utility of PSIs.

Post-licensure, phase IV, safety study of a live attenuated Japanese encephalitis recombinant vaccine in children in Thailand.

Science.gov (United States)

Chotpitayasunondh, Tawee; Pruekprasert, Pornpimol; Puthanakit, Thanyawee; Pancharoen, Chitsanu; Tangsathapornpong, Auchara; Oberdorfer, Peninnah; Kosalaraksa, Pope; Prommalikit, Olarn; Tangkittithaworn, Suwimon; Kerdpanich, Phirangkul; Techasaensiri, Chonnamet; Korejwo, Joanna; Chuenkitmongkol, Sunate; Houillon, Guy

2017-01-05

Japanese encephalitis is a mosquito-borne viral disease endemic in most countries in Asia. A recombinant live, attenuated Japanese encephalitis virus vaccine, JE-CV, is licensed in 14 countries, including Thailand, for the prevention of Japanese encephalitis in adults and children. This was a prospective, phase IV, open-label, multicentre, safety study of JE-CV conducted from November 2013 to April 2015, to evaluate rare serious adverse events (AEs). JE-CV was administered to 10,000 healthy children aged 9months to vaccination. Serious AEs (SAEs), including AEs of special interest, up to 60days after administration were evaluated. Immediate Grade 3 systemic AEs up to 30min after JE-CV administration were also described. The median age of participants was 1.1years in Group 1 and 3.8years in Group 2. SAEs were reported in 204 (3.0%) participants in Group 1 and 59 (1.9%) participants in Group 2. Among a total of 294 SAEs in 263 participants, only three events occurring in two participants were considered related to vaccination. All three cases were moderate urticaria, none of which met the definition of AEs of special interest for hypersensitivity. AEs of special interest were reported in 28 (0.4%) participants in Group 1 and 4 (0.1%) participants in Group 2; none were considered related to vaccination. Febrile convulsion was the most frequently reported AE of special interest: 25 (0.4%) participants in Group 1; and 2 (vaccination. Our study did not identify any new safety concerns with JE-CV and confirms its good safety profile. This study was registered on www.clinicaltrials.gov (NCT01981967; Universal Trial Number: U1111-1127-7052). Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Small modular biopower initiative Phase 1 feasibility studies executive summaries

Energy Technology Data Exchange (ETDEWEB)

Bain, R.

2000-03-06

The Phase 1 objective is a feasibility study that includes a market assessment, resource assessment, preliminary system design, and assessment of relevant environmental and safety considerations, and evaluation of financial and cost issues, and a preliminary business plan and commercialization strategy. Each participating company will share at least 20% of the cost of the first phase.

A Phase Ib dose-escalation study to evaluate safety and tolerability of the addition of the aminopeptidase inhibitor tosedostat (CHR-2797) to paclitaxel in patients with advanced solid tumours

NARCIS (Netherlands)

C.M.L. Herpen (Carla); F.A.L.M. Eskens (Ferry); M.J.A. de Jonge (Maja); I.M.E. Desar (Ingrid); L. Hooftman (Leon); E. Bone (Elisabeth); J.N.H. Timmerbonte (Johanna); J. Verweij (Jaap)

2010-01-01

textabstractBackground: This Phase Ib dose-escalating study investigated safety, maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK) and clinical antitumour activity of tosedostat (CHR-2797), an orally bioavailable aminopeptidase inhibitor, in combination with

A Phase Ib dose-escalation study to evaluate safety and tolerability of the addition of the aminopeptidase inhibitor tosedostat (CHR-2797) to paclitaxel in patients with advanced solid tumours.

NARCIS (Netherlands)

Herpen, C.M.L. van; Eskens, F.A.; Jonge, M. de; Desar, I.M.E.; Hooftman, L.; Bone, E.A.; Timmer-Bonte, J.N.H.; Verweij, J.

2010-01-01

BACKGROUND: This Phase Ib dose-escalating study investigated safety, maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK) and clinical antitumour activity of tosedostat (CHR-2797), an orally bioavailable aminopeptidase inhibitor, in combination with paclitaxel. METHODS:

Timing of Formal Phase Safety Reviews for Large-Scale Integrated Hazard Analysis

Science.gov (United States)

Massie, Michael J.; Morris, A. Terry

2010-01-01

Integrated hazard analysis (IHA) is a process used to identify and control unacceptable risk. As such, it does not occur in a vacuum. IHA approaches must be tailored to fit the system being analyzed. Physical, resource, organizational and temporal constraints on large-scale integrated systems impose additional direct or derived requirements on the IHA. The timing and interaction between engineering and safety organizations can provide either benefits or hindrances to the overall end product. The traditional approach for formal phase safety review timing and content, which generally works well for small- to moderate-scale systems, does not work well for very large-scale integrated systems. This paper proposes a modified approach to timing and content of formal phase safety reviews for IHA. Details of the tailoring process for IHA will describe how to avoid temporary disconnects in major milestone reviews and how to maintain a cohesive end-to-end integration story particularly for systems where the integrator inherently has little to no insight into lower level systems. The proposal has the advantage of allowing the hazard analysis development process to occur as technical data normally matures.

Integrated safety analysis of rolapitant with coadministered drugs from phase II/III trials

DEFF Research Database (Denmark)

Barbour, S; Smit, T.; Wang, X

2017-01-01

adverse events by use versus non-use of drug substrates of CYP2D6 or BCRP. Patients and methods: Patients were randomized to receive either 180 mg oral rolapitant or placebo approximately 1-2 hours before chemotherapy in combination with a 5-hydroxytryptamine type 3 RA and dexamethasone. Data...... cytochrome P450 (CYP) 3A4, but it does inhibit CYP2D6 and breast cancer resistance protein (BCRP). To analyze potential drug-drug interactions between rolapitant and concomitant medications, this integrated safety analysis of four double-blind, randomized phase II or III studies of rolapitant examined...... for treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) during cycle 1 were pooled across the four studies and summarized in the overall population and by concomitant use/non-use of CYP2D6 or BCRP substrate drugs. Results: In the integrated safety population, 828...

Study on operational safety issues in the Japanese disposal concept

International Nuclear Information System (INIS)

Suzuki, Satoru; Kitagawa, Yoshito; Hyodo, Hideaki; Kubota, Shigeru; Iijima, Masayoshi; Tamura, Akio; Ishiguro, Katsuhiko; Fujihara, Hiroshi

2014-01-01

In Japan, vitrified high-level radioactive waste (HLW) and certain types of low-level radioactive waste that results from the reprocessing of spent fuel and classified as TRU waste will be disposed of in deep geological formations. NUMO aims to ensure the safety of local residents and workers during the operational phase and after repository closure and will therefore establish a safety case for the geological disposal programme at the end of each stage of the stepwise siting process. Although the Japanese programme is still in the stage before initiation of the siting process, updating the generic (non-site-specific) safety case is required for building confidence among stakeholders. This study focuses on operational safety issues for the Japanese HLW disposal concept. (authors)

German risk study 'nuclear power plants, phase B'

International Nuclear Information System (INIS)

Heuser, F.W.

1989-01-01

The results of the German risk study 'Nuclear power plants, phase B' indicate that an accident in a nuclear power plant which cannot be managed by the safety systems according to design, is extremely improbable: Its probability is at about 3 to 100,000 per year and plant. Even if the safety systems fail, emergency measures can be effected in a nuclear power plant to prevent an accident. These in-plant emergency measures diminish the probability of a core meltdown to about 4 to 1,000,000 per year and plant. Hence, the accident risk is greatly reduced. The information given by the author are to smooth the emotional edge in the discussion about the safety of nuclear power plants. (orig.) [de

New developments in two-phase flow heat transfer with emphasis on nuclear safety research

International Nuclear Information System (INIS)

Mayinger, F.

1987-01-01

The literature on two-phase flow - with and without heat transfer - shows an explosive-like growth of published papers within the last ten years. Many of these papers were published as a result of nuclear safety research. It is impossible to deal with all new developments reported in this extensive literature. So one has to ask: Are there trends of special interest, where this report could be concentrated on? Looking over the situation, there seem to be three very promising fields of research having high actuality, especially for nuclear safety, namely: fluiddynamic and thermodynamic nonequilibrium in steady state, transient conditions, and scaling. The discussion on new developments in two-phase flow heat transfer, therefore, is limited on these subjects

Efficacy and safety of tolvaptan in heart failure patients with volume overload despite the standard treatment with conventional diuretics: a phase III, randomized, double-blind, placebo-controlled study (QUEST study).

Science.gov (United States)

Matsuzaki, Masunori; Hori, Masatsugu; Izumi, Tohru; Fukunami, Masatake

2011-12-01

Diuretics are recommended to treat volume overload with heart failure (HF), however, they may cause serum electrolyte imbalance, limiting their use. Moreover, patients with advanced HF could poorly respond to these diuretics. In this study, we evaluated the efficacy and safety of Tolvaptan, a competitive vasopressin V2-receptor antagonist developed as a new drug to treat volume overload in HF patients. A phase III, multicenter, randomized, double-blind, placebo-controlled parallel study was performed to assess the efficacy and safety of tolvaptan in treating HF patients with volume overload despite the use of conventional diuretics. One hundred and ten patients were randomly assigned to receive either placebo or 15 mg/day tolvaptan for 7 consecutive days. Compared with placebo, tolvaptan administered for 7 days significantly reduced body weight and improved symptoms associated with volume overload. The safety profile of tolvaptan was considered acceptable for clinical use with minimal adverse effects. Tolvaptan reduced volume overload and improved congestive symptoms associated with HF by a potent water diuresis (aquaresis).

Reliability and safety program plan outline for the operational phase of a waste isolation facility

International Nuclear Information System (INIS)

Ammer, H.G.; Wood, D.E.

1977-01-01

A Reliability and Safety Program plan outline has been prepared for the operational phase of a Waste Isolation Facility. The program includes major functions of risk assessment, technical support activities, quality assurance, operational safety, configuration monitoring, reliability analysis and support and coordination meetings. Detailed activity or task descriptions are included for each function. Activities are time-phased and presented in the PERT format for scheduling and interactions. Task descriptions include manloading, travel, and computer time estimates to provide data for future costing. The program outlined here will be used to provide guidance from a reliability and safety standpoint to design, procurement, construction, and operation of repositories for nuclear waste. These repositories are to be constructed under the National Waste Terminal Storage program under the direction of the Office of Waste Isolation, Union Carbide Corp. Nuclear Division

Tofacitinib, an oral Janus kinase inhibitor, for the treatment of Latin American patients with rheumatoid arthritis: Pooled efficacy and safety analyses of Phase 3 and long-term extension studies.

Science.gov (United States)

Radominski, Sebastião Cezar; Cardiel, Mario Humberto; Citera, Gustavo; Goecke, Annelise; Jaller, Juan Jose; Lomonte, Andrea Barranjard Vannucci; Miranda, Pedro; Velez, Patricia; Xibillé, Daniel; Kwok, Kenneth; Rojo, Ricardo; García, Erika Gabriela

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We assessed tofacitinib efficacy and safety in the Latin American (LA) subpopulation of global Phase 3 and long-term extension (LTE) studies. Data from LA patients with RA and inadequate response to disease-modifying antirheumatic drugs (DMARDs) were pooled across five Phase 3 studies. Phase 3 patients received tofacitinib 5 or 10mg twice daily (BID), adalimumab or placebo; patients in the single LTE study received tofacitinib 5 or 10mg BID; treatments were administered alone or with conventional synthetic DMARDs. Efficacy was reported up to 12 months (Phase 3) and 36 months (LTE) by American College of Rheumatology (ACR) 20/50/70 response rates, Disease Activity Score (DAS)28-4(erythrocyte sedimentation rate [ESR]) and Health Assessment Questionnaire-Disability Index (HAQ-DI). Incidence rates (IRs; patients with event/100 patient-years) of adverse events (AEs) of special interest were reported. The Phase 3 studies randomized 496 LA patients; the LTE study enrolled 756 LA patients from Phase 2 and Phase 3. In the Phase 3 studies, patients who received tofacitinib 5 and 10mg BID showed improvements vs placebo at Month 3 in ACR20 (68.9% and 75.7% vs 35.6%), ACR50 (45.8% and 49.7% vs 20.7%) and ACR70 (17.5% and 23.1% vs 6.9%) responses, mean change from baseline in HAQ-DI (-0.6 and -0.8 vs -0.3) and DAS28-4(ESR) score (-2.3 and -2.4 vs -1.4). The improvements were sustained up to Month 36 in the LTE study. In the Phase 3 studies, IRs with tofacitinib 5 and 10mg BID and placebo were 7.99, 6.57 and 9.84, respectively, for SAEs, and 3.87, 5.28 and 3.26 for discontinuation due to AEs. IRs of AEs of special interest in tofacitinib-treated LA patients were similar to the global population. In Phase 3 and LTE studies in LA patients with RA, tofacitinib demonstrated efficacy up to 36 months with a manageable safety profile up to 60 months, consistent with the overall tofacitinib

Sun Safety at Work Canada: a multiple case-study protocol to develop sun safety and heat protection programs and policies for outdoor workers.

Science.gov (United States)

Kramer, Desre M; Tenkate, Thomas; Strahlendorf, Peter; Kushner, Rivka; Gardner, Audrey; Holness, D Linn

2015-07-10

CAREX Canada has identified solar ultraviolet radiation (UV) as the second most prominent carcinogenic exposure in Canada, and over 75 % of Canadian outdoor workers fall within the highest exposure category. Heat stress also presents an important public health issue, particularly for outdoor workers. The most serious form of heat stress is heat stroke, which can cause irreversible damage to the heart, lungs, kidneys, and liver. Although the need for sun and heat protection has been identified, there is no Canada-wide heat and sun safety program for outdoor workers. Further, no prevention programs have addressed both skin cancer prevention and heat stress in an integrated approach. The aim of this partnered study is to evaluate whether a multi-implementation, multi-evaluation approach can help develop sustainable workplace-specific programs, policies, and procedures to increase the use of UV safety and heat protection. This 2-year study is a theory-driven, multi-site, non-randomized study design with a cross-case analysis of 13 workplaces across four provinces in Canada. The first phase of the study includes the development of workplace-specific programs with the support of the intensive engagement of knowledge brokers. There will be a three-points-in-time evaluation with process and impact components involving the occupational health and safety (OHS) director, management, and workers with the goal of measuring changes in workplace policies, procedures, and practices. It will use mixed methods involving semi-structured key informant interviews, focus groups, surveys, site observations, and UV dosimetry assessment. Using the findings from phase I, in phase 2, a web-based, interactive, intervention planning tool for workplaces will be developed, as will the intensive engagement of intermediaries such as industry decision-makers to link to policymakers about the importance of heat and sun safety for outdoor workers. Solar UV and heat are both health and safety hazards

Consequence model of the German reactor safety study

International Nuclear Information System (INIS)

Bayer, A.; Aldrich, D.; Burkart, K.; Horsch, F.; Hubschmann, W.; Schueckler, M.; Vogt, S.

1979-01-01

The consequency model developed for phase A of the German Reactor Safety Study (RSS) is similar in many respects to its counterpart in WASH-1400. As in that previous study, the model describes the atmosphere dispersion and transport of radioactive material released from the containment during a postulated reactor accident, and predicts its interaction with and influence on man. Differences do exist between the two models however, for the following reasons: (1) to more adequately reflect central European conditions, (2) to include improved submodels, and (3) to apply additional data and knowledge that have become available since publication of WASH-1400. The consequence model as used in phase A of the German RSS is described, highlighting differences between it and the U.S. model

Obtaining Valid Safety Data for Software Safety Measurement and Process Improvement

Science.gov (United States)

Basili, Victor r.; Zelkowitz, Marvin V.; Layman, Lucas; Dangle, Kathleen; Diep, Madeline

2010-01-01

We report on a preliminary case study to examine software safety risk in the early design phase of the NASA Constellation spaceflight program. Our goal is to provide NASA quality assurance managers with information regarding the ongoing state of software safety across the program. We examined 154 hazard reports created during the preliminary design phase of three major flight hardware systems within the Constellation program. Our purpose was two-fold: 1) to quantify the relative importance of software with respect to system safety; and 2) to identify potential risks due to incorrect application of the safety process, deficiencies in the safety process, or the lack of a defined process. One early outcome of this work was to show that there are structural deficiencies in collecting valid safety data that make software safety different from hardware safety. In our conclusions we present some of these deficiencies.

Operational readiness verification, phase 1: A study on safety during outage and restart of nuclear power plants

Energy Technology Data Exchange (ETDEWEB)

Hollnagel, E. [Linkoeping Univ. (Sweden). Dept. of Computer and Information Science; Gauthereau, V. [Linkoeping Univ. (Sweden). Dept. of Industrial Engineering

2001-06-01

This report contains the findings from the first phase of a study on safety during outage and restart of nuclear power plants. Operational Readiness Verification (ORV) - in Swedish called Driftklarhetsverifiering (DKV) - refers to the test and verification activities that are necessary to ensure that plant systems are able to provide their required functions when needed - more concretely that all plant systems are in their correct functional state when the plant is restarted after an outage period. The concrete background for this work is that nine ORV related incidents were reported in Sweden between July 1995 and October 1998. The work reported here comprised a literature survey of research relevant for ORV issues, and an assessment of the present situation at Swedish NPPs with respect to ORV. The literature survey was primarily aimed at research related to NPPs, but also looked at domains where similar problems have occurred, such as maintenance in commercial aviation. The survey looked specifically for organisational and MTO aspects relevant to the present situation in Swedish NPPs. One finding was that ORV should be seen as an integral part of maintenance, rather than as a separate activity. Another, that there is a characteristic distribution of error modes for maintenance and ORV, with many sequence errors and omissions, rather than a set of unique error modes. An international study further showed that there are important differences in how procedures are used, and in the balance between decentralisation and centralisation. Several studies also suggested that ORV could usefully be described as a barrier system in relation to the flow of work, for instance using the following five stages: (1) preventive actions during maintenance/outage, (2) post-test after completion of work, (3) pre-test before start-up, (4) the start-up sequence itself, and (5) preventive actions during power operation - possibly including automatic safety systems. In the field survey

Operational readiness verification, phase 1: A study on safety during outage and restart of nuclear power plants

International Nuclear Information System (INIS)

Hollnagel, E.; Gauthereau, V.

2001-06-01

This report contains the findings from the first phase of a study on safety during outage and restart of nuclear power plants. Operational Readiness Verification (ORV) - in Swedish called Driftklarhetsverifiering (DKV) - refers to the test and verification activities that are necessary to ensure that plant systems are able to provide their required functions when needed - more concretely that all plant systems are in their correct functional state when the plant is restarted after an outage period. The concrete background for this work is that nine ORV related incidents were reported in Sweden between July 1995 and October 1998. The work reported here comprised a literature survey of research relevant for ORV issues, and an assessment of the present situation at Swedish NPPs with respect to ORV. The literature survey was primarily aimed at research related to NPPs, but also looked at domains where similar problems have occurred, such as maintenance in commercial aviation. The survey looked specifically for organisational and MTO aspects relevant to the present situation in Swedish NPPs. One finding was that ORV should be seen as an integral part of maintenance, rather than as a separate activity. Another, that there is a characteristic distribution of error modes for maintenance and ORV, with many sequence errors and omissions, rather than a set of unique error modes. An international study further showed that there are important differences in how procedures are used, and in the balance between decentralisation and centralisation. Several studies also suggested that ORV could usefully be described as a barrier system in relation to the flow of work, for instance using the following five stages: (1) preventive actions during maintenance/outage, (2) post-test after completion of work, (3) pre-test before start-up, (4) the start-up sequence itself, and (5) preventive actions during power operation - possibly including automatic safety systems. In the field survey

Operational readiness verification, phase 1: A study on safety during outage and restart of nuclear power plants

Energy Technology Data Exchange (ETDEWEB)

Hollnagel, E [Linkoeping Univ. (Sweden). Dept. of Computer and Information Science; Gauthereau, V [Linkoeping Univ. (Sweden). Dept. of Industrial Engineering

2001-06-01

This report contains the findings from the first phase of a study on safety during outage and restart of nuclear power plants. Operational Readiness Verification (ORV) - in Swedish called Driftklarhetsverifiering (DKV) - refers to the test and verification activities that are necessary to ensure that plant systems are able to provide their required functions when needed - more concretely that all plant systems are in their correct functional state when the plant is restarted after an outage period. The concrete background for this work is that nine ORV related incidents were reported in Sweden between July 1995 and October 1998. The work reported here comprised a literature survey of research relevant for ORV issues, and an assessment of the present situation at Swedish NPPs with respect to ORV. The literature survey was primarily aimed at research related to NPPs, but also looked at domains where similar problems have occurred, such as maintenance in commercial aviation. The survey looked specifically for organisational and MTO aspects relevant to the present situation in Swedish NPPs. One finding was that ORV should be seen as an integral part of maintenance, rather than as a separate activity. Another, that there is a characteristic distribution of error modes for maintenance and ORV, with many sequence errors and omissions, rather than a set of unique error modes. An international study further showed that there are important differences in how procedures are used, and in the balance between decentralisation and centralisation. Several studies also suggested that ORV could usefully be described as a barrier system in relation to the flow of work, for instance using the following five stages: (1) preventive actions during maintenance/outage, (2) post-test after completion of work, (3) pre-test before start-up, (4) the start-up sequence itself, and (5) preventive actions during power operation - possibly including automatic safety systems. In the field survey

System and safety studies of accelerator driven systems for transmutation. Annual report 2007

International Nuclear Information System (INIS)

Arzhanov, Vasily; Fokau, Andrei; Persson, Calle; Runevall, Odd; Sandberg, Nils; Tesinsky, Milan; Wallenius, Janne; Youpeng Zhang

2008-05-01

Within the project 'System and safety studies of accelerator driven systems for transmutation', research on design and safety of sub-critical reactors for recycling of minor actinides is performed. During 2007, the reactor physics division at KTH has calculated safety parameters for EFIT-400 with cermet fuel, permitting to start the transient safety analysis. The accuracy of different reactivity meters applied to the YALINA facility was assessed and neutron detection studies were performed. A model to address deviations from point kinetic behaviour was developed. Studies of basic radiation damage physics included calculations of vacancy formation and activation enthalpies in bcc niobium. In order to predict the oxygen potential of inert matrix fuels, a thermo-chemical model for mixed actinide oxides was implemented in a phase equilibrium code

Safety of bazedoxifene in a randomized, double-blind, placebo- and active-controlled phase 3 study of postmenopausal women with osteoporosis

Directory of Open Access Journals (Sweden)

Palacios Santiago

2010-06-01

Full Text Available Abstract Background We report the safety findings from a 3-year phase 3 study (NCT00205777 of bazedoxifene, a novel selective estrogen receptor modulator under development for the prevention and treatment of postmenopausal osteoporosis. Methods Healthy postmenopausal osteoporotic women (N = 7,492; mean age, 66.4 years were randomized to daily doses of bazedoxifene 20 or 40 mg, raloxifene 60 mg, or placebo for 3 years. Safety and tolerability were assessed by adverse event (AE reporting and routine physical, gynecologic, and breast examination. Results Overall, the incidence of AEs, serious AEs, and discontinuations due to AEs in the bazedoxifene groups was not different from that seen in the placebo group. The incidence of hot flushes and leg cramps was higher with bazedoxifene or raloxifene compared with placebo. The rates of cardiac disorders and cerebrovascular events were low and evenly distributed among groups. Venous thromboembolic events, primarily deep vein thromboses, were more frequently reported in the active treatment groups compared with the placebo group; rates were similar with bazedoxifene and raloxifene. Bazedoxifene showed a neutral effect on the breast and an excellent endometrial safety profile. The incidence of fibrocystic breast disease was lower with bazedoxifene 20 and 40 mg versus raloxifene or placebo. Reductions in total and low-density lipoprotein levels and increases in high-density lipoprotein levels were seen with bazedoxifene versus placebo; similar results were seen with raloxifene. Triglyceride levels were similar among groups. Conclusion Bazedoxifene showed a favorable safety and tolerability profile in women with postmenopausal osteoporosis. Trial Registration Trial registration number: NCT00205777; Trial registration date: September 16, 2005

Preliminary study on functional performance of compound type multistage safety injection tank

International Nuclear Information System (INIS)

Bae, Youngmin; Kim, Young In; Kim, Keung Koo

2015-01-01

Highlights: • Functional performance of compound type multistage safety injection tanks is studied. • Effects of key design parameters are scrutinized. • Distinctive flow features in compound type safety injection tanks are explored. - Abstract: A parametric study is carried out to evaluate the functional performance of a compound type multistage safety injection tank that would be considered one of the components for the passive safety injection systems in nuclear power plants. The effects of key design parameters such as the initial volume fraction and charging pressure of gas, tank elevation, vertical location of a sparger, resistance coefficient, and operating condition on the injection flow rate are scrutinized along with a discussion of the relevant flow features. The obtained results indicate that the compound type multistage safety injection tank can effectively control the injection flow rate in a passive manner, by switching the driving force for the safety injection from gas pressure to gravity during the refill and reflood phases, respectively

Sunitinib in combination with trastuzumab for the treatment of advanced breast cancer: activity and safety results from a phase II study

International Nuclear Information System (INIS)

Bachelot, Thomas; Wang, Zhixiao; Cesari, Rossano; Tassell, Vanessa; Kern, Kenneth A; Blay, Jean-Yves; Lluch, Ana; Garcia-Saenz, Jose A; Verma, Sunil; Gutierrez, Maya; Pivot, Xavier; Kozloff, Mark F; Prady, Catherine; Huang, Xin; Khosravan, Reza

2014-01-01

This phase II study evaluated the efficacy and safety/tolerability of sunitinib plus trastuzumab in patients with HER2-positive advanced breast cancer (ABC). Eligible patients received sunitinib 37.5 mg/day and trastuzumab administered either weekly (loading, 4 mg/kg; then weekly 2 mg/kg) or 3-weekly (loading, 8 mg/kg; then 3-weekly 6 mg/kg). Prior trastuzumab and/or lapatinib treatment were permitted. The primary endpoint was objective response rate (ORR). Sixty patients were enrolled and evaluable for safety; 57 were evaluable for efficacy. The majority of patients (58%) had received no prior chemotherapy in the metastatic setting. The ORR was 37%; the clinical benefit rate (CBR; percent objective response plus stable disease ≥ 24 weeks) was 56%. Among patients who were treatment-naïve or had received only adjuvant therapy, the ORR was 44% and the CBR was 59%. Overall, median overall survival had not been reached and the 1-year survival rate was 91%. The majority of adverse events (AEs) were mild to moderate in severity. Forty percent of patients experienced AEs related to measured left ventricular ejection fraction (LVEF) declines, which occurred more frequently in patients who had received prior anthracycline treatment. Ten percent of patients exhibited symptoms related to LVEF declines. One patient died on study from cardiogenic shock. Antitumor response and several safety parameters appeared to correlate with sunitinib exposure. Sunitinib plus trastuzumab demonstrated antitumor activity in patients with HER2-positive ABC, particularly those who were treatment-naïve or had only received prior adjuvant treatment. Sunitinib plus trastuzumab had acceptable safety and tolerability in patients with HER2-positive ABC who had not received prior anthracycline therapy. clinicaltrials.gov/ct2/show/NCT00243503

Safety and efficacy of first-line bevacizumab with chemotherapy in Asian patients with advanced nonsquamous NSCLC: results from the phase IV MO19390 (SAiL) study.

Science.gov (United States)

Tsai, Chun-Ming; Au, Joseph Siu-kie; Chang, Gee-Chen; Cheng, Ashley Chi-kin; Zhou, Caicun; Wu, Yi-long

2011-06-01

First-line treatment with bevacizumab combined with chemotherapy has been shown to improve outcomes in patients with advanced, nonsquamous non-small cell lung cancer (NSNSCLC) in phase III clinical trials. SAiL (MO19390), an open-label, multicenter, single-arm study, evaluated the safety and efficacy of first-line bevacizumab-based treatment in clinical practice. This report presents the results of a preplanned subanalysis of Asian patients enrolled in SAiL. Patients with untreated, locally advanced, metastatic or recurrent NSNSCLC received bevacizumab 7.5 or 15 mg/kg every 3 weeks plus chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. Eligibility criteria for SAiL permitted enrolment of a broad patient population. The primary end point was safety; secondary end points included time to disease progression and overall survival. The Asian intent-to-treat population comprised 314 of the 2212 patients enrolled in the SAiL trial. In the Asian subanalysis, patients received a median of nine cycles of bevacizumab, and the median follow-up was 16.4 months. The incidence of clinically significant adverse events (grade ≥3) of special interest was relatively low in this population (15.6% overall); proteinuria (7.6%), hypertension (4.8%), and bleeding (2.5%) were the most common. A total of five adverse events related to bevacizumab were reported as grade 5. Disease control rate was 94.1%, median time to disease progression was 8.3 months, and median overall survival was 18.9 months. The safety and efficacy of first-line bevacizumab-based treatment in Asian patients with advanced NSNSCLC is consistent with that demonstrated in phase III studies and in the overall SAiL population. There were no new safety signals.

A randomized, phase 1/2 trial of the safety, tolerability, and immunogenicity of bivalent rLP2086 meningococcal B vaccine in healthy infants.

Science.gov (United States)

Martinon-Torres, Federico; Gimenez-Sanchez, Francisco; Bernaola-Iturbe, Enrique; Diez-Domingo, Javier; Jiang, Qin; Perez, John L

2014-09-08

Neisseria meningitidis serogroup B (MnB) is a major cause of invasive meningococcal disease in infants. A conserved, surface-exposed lipoprotein, LP2086 (a factor H-binding protein [fHBP]), is a promising MnB vaccine target. A bivalent, recombinant vaccine targeting the fHBP (rLP2086) of MnB was developed. This phase 1/2 clinical study was designed to assess the immunogenicity, safety, and tolerability of a 4-dose series of the rLP2086 vaccine at 20-, 60-, 120-, or 200-μg dose levels in vaccine-naive infants when given with routine childhood vaccines. The study was to consist of two phases: a single-blind sentinel phase and an open-label full enrollment phase. During the sentinel phase, randomization of subjects to the next higher dose was delayed pending a 14-day safety review of dose 1 of the preceding dose cohort. The full enrollment phase was to occur after completion of the sentinel phase. Local reactions were generally mild and adverse events infrequent; however, after only 46 infants were randomized into the study, fever rates were 64% and 90% in subjects receiving one 20- or 60-μg rLP2086 dose, respectively. Most fevers were group and 1 subject in the 60-μg group experienced fevers >39.0°C; no fevers were >40.0°C. Due to these high fever rates, the study was terminated early. No immunogenicity data were collected. This report discusses the safety and acceptability of rLP2086 in infants after one 20- or 60-μg dose. Due to the high fever rate experienced in the 20- and 60-μg groups, rLP2086 in the current formulation may not be acceptable for infants. Copyright © 2014. Published by Elsevier Ltd.

Safety study application guide

International Nuclear Information System (INIS)

1993-07-01

Martin Marietta Energy Systems, Inc., (Energy Systems) is committed to performing and documenting safety analyses for facilities it manages for the Department of Energy (DOE). Included are analyses of existing facilities done under the aegis of the Safety Analysis Report Upgrade Program, and analyses of new and modified facilities. A graded approach is used wherein the level of analysis and documentation for each facility is commensurate with the magnitude of the hazard(s), the complexity of the facility and the stage of the facility life cycle. Safety analysis reports (SARs) for hazard Category 1 and 2 facilities are usually detailed and extensive because these categories are associated with public health and safety risk. SARs for Category 3 are normally much less extensive because the risk to public health and safety is slight. At Energy Systems, safety studies are the name given to SARs for Category 3 (formerly open-quotes lowclose quotes) facilities. Safety studies are the appropriate instrument when on-site risks are limited to irreversible consequences to a few people, and off-site consequences are limited to reversible consequences to a few people. This application guide provides detailed instructions for performing safety studies that meet the requirements of DOE Orders 5480.22, open-quotes Technical Safety Requirements,close quotes and 5480.23, open-quotes Nuclear Safety Analysis Reports.close quotes A seven-chapter format has been adopted for safety studies. This format allows for discussion of all the items required by DOE Order 5480.23 and for the discussions to be readily traceable to the listing in the order. The chapter titles are: (1) Introduction and Summary, (2) Site, (3) Facility Description, (4) Safety Basis, (5) Hazardous Material Management, (6) Management, Organization, and Institutional Safety Provisions, and (7) Accident Analysis

System and safety studies of accelerator driven systems for transmutation. Annual report 2007

Energy Technology Data Exchange (ETDEWEB)

Arzhanov, Vasily; Fokau, Andrei; Persson, Calle; Runevall, Odd; Sandberg, Nils; Tesinsky, Milan; Wallenius, Janne; Youpeng Zhang (Div. of Reactor Physics, Royal Institute of Technology, Stockholm (Sweden))

2008-05-15

Within the project 'System and safety studies of accelerator driven systems for transmutation', research on design and safety of sub-critical reactors for recycling of minor actinides is performed. During 2007, the reactor physics division at KTH has calculated safety parameters for EFIT-400 with cermet fuel, permitting to start the transient safety analysis. The accuracy of different reactivity meters applied to the YALINA facility was assessed and neutron detection studies were performed. A model to address deviations from point kinetic behaviour was developed. Studies of basic radiation damage physics included calculations of vacancy formation and activation enthalpies in bcc niobium. In order to predict the oxygen potential of inert matrix fuels, a thermo-chemical model for mixed actinide oxides was implemented in a phase equilibrium code

Los Angeles International Airport Runway Incursion Studies: Phase III--Center-Taxiway Simulation

Science.gov (United States)

Madson, Michael D.

2004-01-01

Phase III of the Los Angeles International Airport Runway Incursion Studies was conducted, under an agreement with HNTB Corporation, at the NASA Ames FutureFlight Central (FFC) facility in June 2003. The objective of the study was the evaluation of a new center-taxiway concept at LAX. This study is an extension of the Phase I and Phase II studies previously conducted at FFC. This report presents results from Phase III of the study, in which a center-taxiway concept between runways 25L and 25R was simulated and evaluated. Phase III data were compared objectively against the Baseline data. Subjective evaluations by participating LAX controllers were obtained with regard to workload, efficiency, and safety criteria. To facilitate a valid comparison between Baseline and Phase III data, the same scenarios were used for Phase III that were tested during Phases I and II. This required briefing participating controllers on differences in airport and airline operations between 2001 and today.

SAFETY AND ACTIVITY OF TEMSIROLIMUS AND BEVACIZUMAB IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA PREVIOUSLY TREATED WITH TYROSINE KINASE INHIBITORS: A PHASE 2 CONSORTIUM STUDY

Science.gov (United States)

Merchan, Jaime R.; Qin, Rui; Pitot, Henry; Picus, Joel; Liu, Glenn; Fitch, Tom; Maples, William J.; Flynn, Patrick J.; Fruth, Briant F.; Erlichman, Charles

2015-01-01

Purpose Bevacizumab or Temsirolimus regimens have clinical activity in the first line treatment of advanced renal cell carcinoma (RCC). This phase I/II trial was conducted to determine the safety of combining both agents and its efficacy in RCC patients who progressed on at least one prior anti-VEGF receptor tyrosine kinase inhibitor (RTKI) agent. Methods In the phase I portion, eligible patients were treated with Temsirolimus (25 mg IV weekly) and escalating doses of IV Bevacizumab (level 1=5mg/kg; level 2=10 mg/kg) every other week. The primary endpoint for the phase II portion (RTKI resistant patients) was the 6-month progression free rate. Secondary endpoints were response rate, toxicity evaluation, PFS and OS. Results MTD was not reached at the maximum dose administered in 12 phase I patients. Forty evaluable patients were treated with the phase II recommended dose (Temsirolimus 25 mg IV weekly and Bevacizumab 10 mg/kg IV every two weeks). The 6-month progression free rate was 40% (16/40 pts). Median PFS was 5.9 (4-7.8) months, and median OS was 20.6 (11.5-23.7) months. Partial response/stable/progressive disease were seen in 23%/63%/14% of patients. Most common grade 3-4 AEs included fatigue (17.8%), hypertriglyceridemia (11.1%), stomatitis (8.9%), proteinuria (8.9%), abdominal pain (6.7%), and anemia (6.7%). Baseline levels of serum sFLT-1 and VEGF-A were inversely correlated with PFS and OS, respectively. Conclusions Temsirolimus and Bevacizumab is a feasible combination in patients with advanced RCC previously exposed to oral anti-VEGF agents. The safety and efficacy results warrant further confirmatory studies in this patient population. PMID:25556030

A Multicenter, Open-Label, Controlled Phase II Study to Evaluate Safety and Immunogenicity of MVA Smallpox Vaccine (IMVAMUNE in 18-40 Year Old Subjects with Diagnosed Atopic Dermatitis.

Directory of Open Access Journals (Sweden)

Richard N Greenberg

Full Text Available Replicating smallpox vaccines can cause severe complications in individuals with atopic dermatitis (AD. Prior studies evaluating Modified Vaccinia Ankara virus (MVA, a non-replicating vaccine in humans, showed a favorable safety and immunogenicity profile in healthy volunteers.This Phase II study compared the safety and immunogenicity of MVA enrolling groups of 350 subjects with AD (SCORAD ≤ 30 and 282 healthy subjects.Subjects were vaccinated twice with MVA, each dose given subcutaneously 4 weeks apart. Adverse events, cardiac parameters, and the development of vaccinia virus humoral immune responses were monitored.The overall safety of the vaccine was similar in both groups. Adverse events affecting skin were experienced significantly more often in subjects with AD, but the majority of these events were mild to moderate in intensity. Seroconversion rates and geometric mean titers for total and neutralizing vaccinia-specific antibodies in the AD group were non-inferior compared to the healthy subjects.The size of the study population limited the detection of serious adverse events occurring at a frequency less than 1%.MVA has a favorable safety profile and the ability to elicit vaccinia-specific immune responses in subjects with AD.ClinicalTrials.gov NCT00316602.

Seismic safety margins research program. Phase I final report - Overview

International Nuclear Information System (INIS)

Smith, P.D.; Dong, R.G.; Bernreuter, D.L.; Bohn, M.P.; Chuang, T.Y.; Cummings, G.E.; Johnson, J.J.; Mensing, R.W.; Wells, J.E.

1981-04-01

The Seismic Safety Margins Research Program (SSMRP) is a multiyear, multiphase program whose overall objective is to develop improved methods for seismic safety assessments of nuclear power plants, using a probabilistic computational procedure. The program is being carried out at the Lawrence Livermore National Laboratory and is sponsored by the U.S. Nuclear Regulatory Commission, Office of Nuclear Regulatory Research. Phase I of the SSMRP was successfully completed in January 1981: A probabilistic computational procedure for the seismic risk assessment of nuclear power plants has been developed and demonstrated. The methodology is implemented by three computer programs: HAZARD, which assesses the seismic hazard at a given site, SMACS, which computes in-structure and subsystem seismic responses, and SEISIM, which calculates system failure probabilities and radioactive release probabilities, given (1) the response results of SMACS, (2) a set of event trees, (3) a family of fault trees, (4) a set of structural and component fragility descriptions, and (5) a curve describing the local seismic hazard. The practicality of this methodology was demonstrated by computing preliminary release probabilities for Unit 1 of the Zion Nuclear Power Plant north of Chicago, Illinois. Studies have begun aimed at quantifying the sources of uncertainty in these computations. Numerous side studies were undertaken to examine modeling alternatives, sources of error, and available analysis techniques. Extensive sets of data were amassed and evaluated as part of projects to establish seismic input parameters and to produce the fragility curves. (author)

Safety of intramedullary autologous peripheral nerve grafts for post-rehabilitated complete motor spinal cord injuries: a phase I study.

Directory of Open Access Journals (Sweden)

Nazi Derakhshanrad

2013-12-01

Full Text Available Many experimental studies have reported behavioral improvement after transplantation of peripheral nerve tissue into the contused spinal cord, even in large animals. The safety of this treatment in human remains unknown. In this translational phase 1 study, safety of peripheral nerve grafting for chronic spinal cord injuries and possible outcomes are being reported. Twelve complete motor spinal cord injury patients, who had finished their rehabilitation program, were enrolled. There were 4 thoracic and 8 cervical cases. Patients underwent sural nerve preconditioning in the calf, followed 1 week later, by intramedullary transplantation of the harvested nerve fascicles. The patients were followed up for potential complications periodically, and final assessment by American Spinal Injury association (ASIA and Spinal Cord Independence Measure (SCIM III were reported after 2 years of follow-up. The median duration of the spinal cord injury was 31 months. At two years of follow up, out of 7 cases with ASIA Impairment Scale (AIS A, 4(57.1% cases improved to AIS B and 1 (14.3% case became AIS C. There were 1 patient with transient increased spasm, one case of transient cystitis, 3 patients with transient increased neuropathic pain and 1 case with transient episode of autonomic dysreflexia, all being managed medically. There was no case of donor site infection. The above complications were transient as they responded to temporary medical treatment. It may be deduced that after two years follow-up of patients that the procedure may be safe, however further controlled studies are needed to prove its efficacy.

A multi-centre phase 3 study comparing efficacy and safety of Bemfola® versus Gonal-f® in women undergoing ovarian stimulation for IVF

DEFF Research Database (Denmark)

Rettenbacher, M; Andersen, A N; Garcia-Velasco, J A

2015-01-01

injection (n = 372) showed Bemfola yielding similar efficacy and safety profiles to Gonal-f. Women aged 20-38 years of age were randomized 2:1 to receive a single, daily, subcutaneous 150 IU dose of either Bemfola or Gonal-f. This study tested equivalence in the number of retrieved oocytes using a pre......Bemfola (follitropin alfa) (Finox AG, Switzerland), a new recombinant FSH, has a comparable pharmacological profile to that of Gonal-f (Merck Serono, Germany), the current standard for ovarian stimulation. A randomized, multi-centre, Phase 3 study in women undergoing IVF or intracytoplasmic sperm...

Use of a probabilistic safety study in the design of the Italian reference PWR

International Nuclear Information System (INIS)

Richardson, D.C.; Russino, G.; Valentini, V.

1985-01-01

The intent of this paper is to provide a description of the experience gained in having performed a Probabilistic Safety Study (PSS) on the proposed Italian reference pressurized water reactor. The experience revealed that through careful application of probabilistic techniques, Probabilistic Risk Assessment (PRA) can be used as a tool to develop an optimum plant design in terms of safety and cost. Furthermore, the PSS can also be maintained as a living document and a tool to assess additional regulatory requirements that may be imposed during the construction and operational life of the plant. Through the use of flexible probabilistic techniques, the probabilistic safety model can provide a living safety assessment starting from the conceptual design and continuing through the construction, testing and operational phases. Moreover, the probabilistic safety model can be used during the operational phase of the plant as a method to evaluate the operational experience and identify potential problems before they occur. The experience, overall, provided additional insights into the various aspects of the plants design and operation that would not have been identified through the use of traditional safety evaluation techniques

Evaluation of C-reactive protein as an inflammatory biomarker in rabbits for vaccine nonclinical safety studies

NARCIS (Netherlands)

Destexhe, E.; Prinsen, M.K.; Schöll, I. van; Kuper, C.F.; Garçon, N.; Veenstra, S.; Segal, L.

2013-01-01

Introduction: Inflammatory reactions are one of the potential safety concerns that are evaluated in the framework of vaccine safety testing. In nonclinical studies, the assessment of the inflammation relies notably on the measurement of biomarkers. C-reactive protein (CRP) is an acute-phase plasma

Probabilistic Safety Goals for Nuclear Power Plants; Phases 2-4 / Final Report

International Nuclear Information System (INIS)

Bengtsson, Lisa; Knochenhauer, Michael; Holmberg, Jan-Erik; Rossi, Jukka

2011-05-01

The outcome of a probabilistic safety assessment (PSA) for a nuclear power plant is a combination of qualitative and quantitative results. Quantitative results are typically presented as the Core Damage Frequency (CDF) and as the frequency of an unacceptable radioactive release. In order to judge the acceptability of PSA results, criteria for the interpretation of results and the assessment of their acceptability need to be defined. Safety goals are defined in different ways in different countries and also used differently. Many countries are presently developing them in connection to the transfer to risk-informed regulation of both operating nuclear power plants (NPP) and new designs. However, it is far from self-evident how probabilistic safety criteria should be defined and used. On one hand, experience indicates that safety goals are valuable tools for the interpretation of results from a probabilistic safety assessment (PSA), and they tend to enhance the realism of a risk assessment. On the other hand, strict use of probabilistic criteria is usually avoided. A major problem is the large number of different uncertainties in a PSA model, which makes it difficult to demonstrate the compliance with a probabilistic criterion. Further, it has been seen that PSA results can change a lot over time due to scope extensions, revised operating experience data, method development, changes in system requirements, or increases of level of detail, mostly leading to an increase of the frequency of the calculated risk. This can cause a problem of consistency in the judgments. The first phase of the project (2006) provided a general description of the issue of probabilistic safety goals for nuclear power plants, of important concepts related to the definition and application of safety goals, and of experiences in Finland and Sweden. The second, third and fourth phases (2007-2009) have been concerned with providing guidance related to the resolution of some of the problems

Pharmacokinetics and Safety of Amenamevir in Healthy Subjects: Analysis of Four Randomized Phase 1 Studies.

Science.gov (United States)

Kusawake, Tomohiro; Keirns, James J; Kowalski, Donna; den Adel, Martin; Groenendaal-van de Meent, Dorien; Takada, Akitsugu; Ohtsu, Yoshiaki; Katashima, Masataka

2017-12-01

Amenamevir (ASP2151) is a nonnucleoside antiherpesvirus compound available for the treatment of varicella-zoster virus infections. In this article we summarize the findings of four phase 1 studies in healthy participants. Four randomized phase 1 studies investigated the safety and pharmacokinetics of single and multiple doses of amenamevir, including the assessment of age group effect (nonelderly vs elderly), food effect, and the relative bioavailability of two formulations. Amenamevir was administered orally at various doses as a single dose (5-2400 mg) or daily (300 or 600 mg/day) for 7 days. Following single and multiple oral doses, amenamevir demonstrated a less than dose proportional increase in the pharmacokinetic parameters area under the plasma drug concentration versus time curve from time zero to infinity (AUC inf ) and C max . After single and multiple oral 300-mg doses of amenamevir, no apparent differences in pharmacokinetics were observed between nonelderly and elderly participants. In contrast, with the amenamevir 600-mg dose both the area under the plasma drug concentration versus time curve from time zero to 24 h and C max were slightly increased and renal clearance was decreased in elderly participants. The pharmacokinetics of amenamevir was affected by food, with AUC inf increased by about 90%. In the bioavailability study, AUC inf and C max were slightly lower following tablet versus capsule administration (decreased by 14 and 12%, respectively), with relative bioavailability of 86%. The different amenamevir doses and formulations were safe and well tolerated; no deaths or serious adverse events were reported. Amenamevir had less than dose proportional pharmacokinetic characteristics. Age may have an influence on amenamevir pharmacokinetics; however, the effect was considered minimal. The pharmacokinetics of amenamevir were affected by food, with AUC inf almost doubling when amenamevir was administered with food. The concentration versus

A Phase I proof-of-concept and safety trial of sildenafil to treat cerebral vasospasm following subarachnoid hemorrhage.

Science.gov (United States)

Washington, Chad W; Derdeyn, Colin P; Dhar, Rajat; Arias, Eric J; Chicoine, Michael R; Cross, DeWitte T; Dacey, Ralph G; Han, Byung Hee; Moran, Christopher J; Rich, Keith M; Vellimana, Ananth K; Zipfel, Gregory J

2016-02-01

Studies show that phosphodiesterase-V (PDE-V) inhibition reduces cerebral vasospasm (CVS) and improves outcomes after experimental subarachnoid hemorrhage (SAH). This study was performed to investigate the safety and effect of sildenafil (an FDA-approved PDE-V inhibitor) on angiographic CVS in SAH patients. A2-phase, prospective, nonrandomized, human trial was implemented. Subarachnoid hemorrhage patients underwent angiography on Day 7 to assess for CVS. Those with CVS were given 10 mg of intravenous sildenafil in the first phase of the study and 30 mg in the second phase. In both, angiography was repeated 30 minutes after infusion. Safety was assessed by monitoring neurological examination findings and vital signs and for the development of adverse reactions. For angiographic assessment, in a blinded fashion, pre- and post-sildenafil images were graded as "improvement" or "no improvement" in CVS. Unblinded measurements were made between pre- and post-sildenafil angiograms. Twelve patients received sildenafil; 5 patients received 10 mg and 7 received 30 mg. There were no adverse reactions. There was no adverse effect on heart rate or intracranial pressure. Sildenafil resulted in a transient decline in mean arterial pressure, an average of 17% with a return to baseline in an average of 18 minutes. Eight patients (67%) were found to have a positive angiographic response to sildenafil, 3 (60%) in the low-dose group and 5 (71%) in the high-dose group. The largest degree of vessel dilation was an average of 0.8 mm (range 0-2.1 mm). This corresponded to an average percentage increase in vessel diameter of 62% (range 0%-200%). The results from this Phase I safety and proof-of-concept trial assessing the use of intravenous sildenafil in patients with CVS show that sildenafil is safe and well tolerated in the setting of SAH. Furthermore, the angiographic data suggest that sildenafil has a positive impact on human CVS.

Safety study for HTR concepts under German site conditions. Main volume for phase I B

International Nuclear Information System (INIS)

1981-12-01

Within the spectrum of accidents, core heat-up, caused by failure of the power supplies to the reactor or by interruption of the cooling system, is of major significance. This accident causes no serious effects to the environment if the reactor containment building remains intact; however, in certain infrequent events the containment building could fail due to overpressure after about one week at the earliest and a significant environmental hazard would ensue. The other accidents - depressurisation, water and air ingress - are by comparison of distinctly lower importance to the overall risk. A common feature of all the significant accidents is that within the first five hours the maximum release of radioactivity to the reactor containment building is the inventory of the primary circuit, while the fission product inventory of the core is securely retained. The accidents investigated are characterised in the study by the probability of occurrence, by the types and quantities of the fission products released and by the period of release. It was stipulated that in this phase of the study the health risk to the neighbouring population should not be determined. However, the estimated quantities of released nuclides and their associated time of release lead to the conclusion that the worst possible damage to the environment is very limited. This arises from the inherent safety characteristics of the HTR and the comparatively long period available for counter measures. (orig./HP) [de

Seismic safety margins research program. Phase I final report - Plant/site selection and data collection (Project I)

International Nuclear Information System (INIS)

Chuang, T.Y.

1981-07-01

Project I of Phase I of the Seismic Safety Margins Research Program (SSMRP) comprised two parts: the selection of a representative nuclear power plant/site for study in Phase I and the collection of data needed by the other SSMRP projects. Unit 1 of the Zion Nuclear Power Plant in Zion, Illinois, was selected for the SSMRP Phase I studies. Unit 1 of the Zion plant has been validated as a good choice for the Phase I study plant. Although no single nuclear power plant can represent all such plants equally well, selection criteria were developed to maximize the generic implications of Phase I of the SSMRP. On the basis of the selection criteria, the Zion plant and its site were found to be reasonably representative of operating and future plants with regard to its nuclear steam supply system; the type of containment structure (prestressed concrete); its electrical capacity (1100 MWe); its location (the Midwest); the peak seismic acceleration used for design (0.17g); and the properties of the underlying soil (the low-strain shear-wave velocity is 1650 ft/s in a 50- to 100-ft-thick layer of soil overlying sedimentary bedrock). (author)

Situ leaching uranium mining conditions of the pilot phase of the safety management

International Nuclear Information System (INIS)

Liu Wenyuan

2014-01-01

With China's large, very large sandstone type uranium deposits have been discovered in the Ordos Basin, Inner Mongolia and its surrounding for uranium mining in the region has been carried out. Sandstone-type uranium mining, mainly used in China is 'to dip' and the technology is relatively mature. Situ leaching mining process, the deposit conditions Test conditions pilot phase, however, limited by cost control and field conditions, equipment shabby, out in the conditions of the pilot phase of security issues in the larger securityrisks. This will be Ordos ongoing test conditions situ leaching uranium mines, for example, raised situ leaching uranium mining conditions of the pilot phase a few safety measures recommended. (author)

Safety and long-term immunological effects of CryJ2-LAMP plasmid vaccine in Japanese red cedar atopic subjects: A phase I study.

Science.gov (United States)

Su, Yan; Romeu-Bonilla, Eliezer; Anagnostou, Athanasia; Fitz-Patrick, David; Hearl, William; Heiland, Teri

2017-12-02

Japanese Red Cedar (JRC) pollen induced allergy affects one third of Japanese and the development of effective therapies remains an unachieved challenge. We designed a DNA vaccine encoding CryJ2 allergen from the JRC pollen and Lysosomal Associated Membrane Protein 1 (LAMP-1) to treat JRC allergy. These Phase IA and IB trials assessed safety and immunological effects of the investigational CryJ2-LAMP DNA vaccine in both non-sensitive and sensitive Japanese expatriates living in Honolulu, Hawaii. In the Phase IA trial, 6 JRC non-sensitive subjects and 9 JRC and/or Mountain Cedar (MC) sensitive subjects were given 4 vaccine doses (each 4mg/1ml) intramuscularly (IM) at 14-day intervals. Nine JRC and/or MC sensitive subjects were given 4 doses (2 mg/0.5 ml) IM at 14-day intervals. The safety and functional biomarkers were followed for 132 d. Following this, 17 of 24 subjects were recruited into the IB trial and received one booster dose (2 mg/0.5 ml) IM approximately 300 d after the first vaccination dose to which they were randomized in the first phase of the trial. All safety endpoints were met and all subjects tolerated CryJ2-LAMP vaccinations well. At the end of the IA trial, 10 out of 12 JRC sensitive and 6 out of 11 MC sensitive subjects experienced skin test negative conversion, possibly related to the CryJ2-LAMP vaccinations. Collectively, these data suggested that the CryJ2-LAMP DNA vaccine is safe and may be immunologically effective in treating JRC induced allergy.

Software safety analysis on the model specified by NuSCR and SMV input language at requirements phase of software development life cycle using SMV

International Nuclear Information System (INIS)

Koh, Kwang Yong; Seong, Poong Hyun

2005-01-01

Safety-critical software process is composed of development process, verification and validation (V and V) process and safety analysis process. Safety analysis process has been often treated as an additional process and not found in a conventional software process. But software safety analysis (SSA) is required if software is applied to a safety system, and the SSA shall be performed independently for the safety software through software development life cycle (SDLC). Of all the phases in software development, requirements engineering is generally considered to play the most critical role in determining the overall software quality. NASA data demonstrate that nearly 75% of failures found in operational software were caused by errors in the requirements. The verification process in requirements phase checks the correctness of software requirements specification, and the safety analysis process analyzes the safety-related properties in detail. In this paper, the method for safety analysis at requirements phase of software development life cycle using symbolic model verifier (SMV) is proposed. Hazard is discovered by hazard analysis and in other to use SMV for the safety analysis, the safety-related properties are expressed by computation tree logic (CTL)

Safety culture and organisational issues specific to the transitional phase from operation to decommissioning of the Ignalina Nuclear Power Plant

International Nuclear Information System (INIS)

Medeliene, D.

2005-01-01

The PHARE project Support to State Nuclear Power Safety Inspectorate for safety culture and organisational issues specific to the pre-shutdown phase of Ignalina Nuclear Power Plant was aimed at providing assistance to VATESI in their task to oversee that the Ignalina Nuclear Power Plant's management and staff are able to provide an acceptable level of reactor safety taking into account possible safety culture related problems that may occur due to the decision of an early closure of both units. Safety culture is used as a concept to characterise the attitudes, behaviour and perceptions of people that are important in ensuring the safety of nuclear power facility. Since the Chernobyl accident, the International Atomic Energy Agency (IAEA) has been active in creating guidance for ensuring that an adequate safety culture can be created and maintained. The transition from operation to decommissioning introduces uncertainty for both the organisation and individuals. This creates new challenges that need to be dealt with. Although safety culture and organisational issues have to be addressed during the entire life cycle of a nuclear power plant, owing to these special challenges, it should be especially highlighted during the transitional period from operation to decommissioning. Nuclear safety experts from Sweden, Finland, Italy, the UK and Germany, as well as Lithuanian specialists, participated in the project, and it proved to be a most effective way to share experience. The aim of this brochure is to provide information about: the importance of safety culture issues during the transitional phase from operation to decommissioning of Ignalina Nuclear Power Plant; the purpose, activities and results of this PHARE project; recommendations that are provided by western experts concerning the management of safety culture issues specific to the pre-decommissioning phase of Ignalina Nuclear Power Plant. (author)

Phase I safety, tolerability and pharmacokinetic study of recombinant human mannan-binding lectin

DEFF Research Database (Denmark)

Petersen, K.A.; Matthiesen, F.; Agger, T.

2006-01-01

(rhMBL) is in development as a novel therapeutic approach. To assess the safety, tolerability, and pharmacokinetics of rhMBL, a placebo-controlled double-blinded study was performed in MBL-deficient healthy male subjects. rhMBL was administered as both single intravenous (i.v.) infusions (0.01, 0...... mild and no serious adverse events were recorded. There were no clinically significant changes in laboratory evaluations, ECG or vital signs, and no anti-MBL antibodies were detected following rhMBL administration. After single i.v. doses of rhMBL the maximal plasma levels increased in a dose...... of the complement system without non-specific activation of the complement cascade.In conclusion, no safety or tolerability concern was raised following rhMBL administration no signs of immunogenicity detected, and an rhMBL plasma level judged sufficient to achieve therapeutic benefit (>1000 ng/mL) can be achieved....

A study of leading indicators for occupational health and safety management systems in healthcare.

Science.gov (United States)

Almost, Joan M; VanDenKerkhof, Elizabeth G; Strahlendorf, Peter; Caicco Tett, Louise; Noonan, Joanna; Hayes, Thomas; Van Hulle, Henrietta; Adam, Ryan; Holden, Jeremy; Kent-Hillis, Tracy; McDonald, Mike; Paré, Geneviève C; Lachhar, Karanjit; Silva E Silva, Vanessa

2018-04-23

In Ontario, Canada, approximately $2.5 billion is spent yearly on occupational injuries in the healthcare sector. The healthcare sector has been ranked second highest for lost-time injury rates among 16 Ontario sectors since 2009 with female healthcare workers ranked the highest among all occupations for lost-time claims. There is a great deal of focus in Ontario's occupational health and safety system on compliance and fines, however despite this increased focus, the injury statistics are not significantly improving. One of the keys to changing this trend is the development of a culture of healthy and safe workplaces including the effective utilization of leading indicators within Occupational Health and Safety Management Systems (OHSMSs). In contrast to lagging indicators, which focus on outcomes retrospectively, a leading indicator is associated with proactive activities and consists of selected OHSMSs program elements. Using leading indicators to measure health and safety has been common practice in high-risk industries; however, this shift has not occurred in healthcare. The aim of this project is to conduct a longitudinal study implementing six elements of the Ontario Safety Association for Community and Healthcare (OSACH) system identified as leading indicators and evaluating the effectiveness of this intervention on improving selected health and safety workplace indicators. A quasi-experimental longitudinal research design will be used within two Ontario acute care hospitals. The first phase of the study will focus on assessing current OHSMSs using the leading indicators, determining potential facilitators and barriers to changing current OHSMSs, and identifying the leading indicators that could be added or changed to the existing OHSMS in place. Phase I will conclude with the development of an intervention designed to support optimizing current OHSMSs in participating hospitals based on identified gaps. Phase II will pilot test and evaluate the tailored

Safety probabilistic study of Almirante Alvaro Alberto nuclear power plant-Unit I

International Nuclear Information System (INIS)

Lederman, L.; Arrieta, L.A.I.; Fernandes Filho, T.L.; Gibelli, S.M.O.; Berthoud, J.S.; Ambros, P.C.; Soares, H.V.; Camargo, C.T.M.

1985-04-01

The phase A of probabilistic safety study of Angra I nuclear power plant is presented, to be used by CNEN and FURNAS Centrais Eletricas S.A. as standard model in operational and safety analysis. The methodology applied is a modernization of WASH 1400/2.11/ study. Angra I safety systems are described. The selection and qualification of initiating sequence accident events which can damage the reactor core are done. The accident scenes are developed using the method of event trees. The reactor in subcritical condition (pressure, fuel temperature within limits and controlled level of reactor vessel) is studied during 24 hours. The uncertainness in failure probabilities of systems and in the determination of sequence frequencies for core danification are evaluated. Total frequency of sequences which cause the fusion of reactor core are presented. (M.C.K.) [pt

A Fire Safety Certification System for Board and Care Operators and Staff. SBIR Phase II: Final Report.

Science.gov (United States)

Walker, Bonnie L.

This report describes Phase II of a project which developed a system for delivering fire safety training to board and care providers who serve adults with developmental disabilities. Phase II focused on developing and pilot testing a "train the trainers" workshop for instructors and field testing the provider's workshop. Evaluation of…

Preliminary Study of Single-Phase Natural Circulation for Lab-scaled Molten Salt Application

Energy Technology Data Exchange (ETDEWEB)

Shin, Yukyung; Kang, Sarah; Kim, In Guk; Seo, Seok Bin; Bang, In Cheol [UNIST, Ulsan (Korea, Republic of); Park, Seong Dae [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2015-10-15

Advanced reactors such as MSR (FHR), VHTR and AHTR utilized molten salt as a coolant for efficiency and safety which has advantages in higher heat capacity, lower pumping power and scale compared to liquid metal. It becomes more necessary to study on the characteristics of molten salt. However, due to several characteristics such as high operating temperature, large-scale facility and preventing solidification, satisfying that condition for study has difficulties. Thus simulant fluid was used with scaling method for lab-scale experiment. Scaled experiment enables simulant fluid to simulate fluid mechanics and heat transfer behavior of molten salt on lower operating temperature and reduced scale. In this paper, as a proof test of the scaled experiment, simplified single-phase natural circulation loop was designed in a lab-scale and applied to the passive safety system in advanced reactor in which molten salt is considered as a major coolant of the system. For the application of the improved safety system, prototype was based on the primary loop of the test-scale DRACS, the main passive safety system in FHR, developed at the OSU. For preliminary experiment, single-phase natural circulation under low power was performed. DOWTHERM A and DOWTHERM RP were selected as simulant candidates. Then, study of feasibility with simulant was conducted based on the scaling law for heat transfer characteristics and geometric parameters. Additionally, simulation with MARS code and ANSYS-CFX with the same condition of natural circulation was carried out as verification. For the accurate code simulation, thermo-physical properties of DOWTHERM A and RP were developed and implemented into MARS code. In this study, single-phase natural circulation experiment was performed with simulant oil, DOWTHERM RP, based on the passive safety system of FHR. Feasibility of similarity experiment for molten salt with oil simulant was confirmed by scaling method. In addition, simulation with two

Safety methodology implementation in the conceptual design phase of a fusion reactor

International Nuclear Information System (INIS)

Rodriguez-Rodrigo, L.; Elbez-Uzan, J.

2007-01-01

The licensing of ITER in France represents the first process for licensing a fusion facility in the framework of an experimental device with a total Tritium inventory of 3 kg. The main ITER parameters are far from those expected in the future demonstration reactors where the fusion power will be at least 5 times higher and the additional heating power could also reach up to 5 times the one foreseen in ITER. Main safety requirements for these reactors are based, among other conditions, on their inherent features as low amount of fuel, very low impurity content of structural materials, minimum waste repository, no active systems for safe shut-down, and no need for evacuation of population after the most severe accident. The design of such reactors is at the stage of conceptual studies and is mainly dealing with plasma performances, tritium breeding, blanket/divertor designs and solution of engineering issues, as well as bounding accidents or classification of waste. The methodological approach for integrating safety analysis as a tool for optimizing the design of the overall fusion installation for future reactors in the conceptual design phase is sketched, including the machine itself and the different auxiliary nuclear buildings. (author)

Plutonium disposition study phase 1b final report

International Nuclear Information System (INIS)

1993-01-01

This report provides the results of the Westinghouse activities performed as part of the Plutonium Disposition Study Phase 1b. These activities, which took place from May 16, 1993 to September 15, 1993, build upon the work completed in Phase 1a, which concluded on May 15, 1993. In Phase 1a, three Plutonium Disposal Reactor (PDR) options were developed for the disposal of excess weapons grade plutonium from returned and dismantled nuclear weapons. This report documents the results of several tasks that were performed to further knowledge in specific areas leading up to Phase 2 of the PDR Study. The Westinghouse activities for Phase 1b are summarized as follows: (1) resolved technical issues concerning reactor physics including equilibrium cycle calculations, use of gadolinium, moderator temperature coefficient, and others as documented in Section 2.0; (2) analyzed large Westinghouse commercial plants for plutonium disposal; (3) reactor safety issues including the steam line break were resolved, and are included in Section 2.0; (4) several tasks related to the PDR Fuel Cycle were examined; (5) cost and deployment options were examined to determine optimal configuration for both plutonium disposal and tritium production; (6) response to questions from DOE and National Academy of Scientists (NAS) reviewers concerning the PDR Phase 1a report are included in Appendix A

Safety in the Utilization and Modification of Research Reactors. Specific Safety Guide

Energy Technology Data Exchange (ETDEWEB)

NONE

2012-07-15

This Safety Guide is a revision of Safety Series No. 35-G2 on safety in the utilization and modification of research reactors. It provides recommendations on meeting the requirements for the categorization, safety assessment and approval of research reactor experiments and modification projects. Specific safety considerations in different phases of utilization and modification projects are covered, including the pre-implementation, implementation and post-implementation phases. Guidance is also provided on the operational safety of experiments, including in the handling, dismantling, post-irradiation examination and disposal of experimental devices. Examples of the application of the safety categorization process for experiments and modification projects and of the content of the safety analysis report for an experiment are also provided. Contents: 1. Introduction; 2. Management system for the utilization and modification of a research reactor; 3. Categorization, safety assessment and approval of an experiment or modification; 4. Safety considerations for the design of an experiment or modification; 5. Pre-implementation phase of a modification or utilization project; 6. Implementation phase of a modification or utilization project; 7. Post-implementation phase of a utilization or modification project; 8. Operational safety of experiments at a research reactor; 9. Safety considerations in the handling, dismantling, post-irradiation examination and disposal of experimental devices; 10. Safety aspects of out-of-reactor-core installations; Annex I: Example of a checklist for the categorization of an experiment or modification at a research reactor; Annex II: Example of the content of the safety analysis report for an experiment at a research reactor; Annex III: Examples of reasons for a modification at a research reactor.

Safety in the Utilization and Modification of Research Reactors. Specific Safety Guide

International Nuclear Information System (INIS)

2012-01-01

This Safety Guide is a revision of Safety Series No. 35-G2 on safety in the utilization and modification of research reactors. It provides recommendations on meeting the requirements for the categorization, safety assessment and approval of research reactor experiments and modification projects. Specific safety considerations in different phases of utilization and modification projects are covered, including the pre-implementation, implementation and post-implementation phases. Guidance is also provided on the operational safety of experiments, including in the handling, dismantling, post-irradiation examination and disposal of experimental devices. Examples of the application of the safety categorization process for experiments and modification projects and of the content of the safety analysis report for an experiment are also provided. Contents: 1. Introduction; 2. Management system for the utilization and modification of a research reactor; 3. Categorization, safety assessment and approval of an experiment or modification; 4. Safety considerations for the design of an experiment or modification; 5. Pre-implementation phase of a modification or utilization project; 6. Implementation phase of a modification or utilization project; 7. Post-implementation phase of a utilization or modification project; 8. Operational safety of experiments at a research reactor; 9. Safety considerations in the handling, dismantling, post-irradiation examination and disposal of experimental devices; 10. Safety aspects of out-of-reactor-core installations; Annex I: Example of a checklist for the categorization of an experiment or modification at a research reactor; Annex II: Example of the content of the safety analysis report for an experiment at a research reactor; Annex III: Examples of reasons for a modification at a research reactor.

Safety and efficacy of first-line bevacizumab-based therapy in advanced non-squamous non-small-cell lung cancer (SAiL, MO19390): a phase 4 study.

Science.gov (United States)

Crinò, Lucio; Dansin, Eric; Garrido, Pilar; Griesinger, Frank; Laskin, Janessa; Pavlakis, Nick; Stroiakovski, Daniel; Thatcher, Nick; Tsai, Chun-Ming; Wu, Yi-long; Zhou, Caicun

2010-08-01

Results of two phase 3 trials have shown first-line bevacizumab in combination with chemotherapy improves clinical outcomes in patients with advanced or recurrent non-squamous non-small-cell lung cancer (NSCLC). The SAiL (MO19390) study was undertaken to assess the safety and efficacy of first-line bevacizumab combined with standard chemotherapy regimens in clinical practice. Between August, 2006, and June, 2008, patients with untreated locally advanced, metastatic, or recurrent non-squamous NSCLC were recruited to this open-label, single group, phase 4 study from centres in 40 countries. Eligible patients had histologically or cytologically documented inoperable, locally advanced, metastatic, or recurrent disease (stage IIIB-IV); an Eastern Cooperative Oncology Group performance status of 0-2; and adequate haematological, hepatic, and renal function. Patients received bevacizumab (7.5 or 15 mg/kg every 3 weeks) plus standard chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. The primary endpoint was safety; analysis was by intention to treat (ITT). This study is registered with ClinicalTrials.gov, number NCT00451906. At the final data cutoff (July 24, 2009), an ITT population of 2212 patients was assessed. The incidence of clinically significant (grade > or = 3) adverse events of special interest was generally low; thromboembolism occurred in 172 (8%) patients, hypertension in 125 (6%), bleeding in 80 (4%), proteinuria in 67 (3%), and pulmonary haemorrhage in 15 (1%). 57 (3%) patients died because of these adverse events, with thromboembolism (26 patients, 1%) and bleeding (17, 1%) as the most common causes. The most common grade 3 or higher serious adverse events deemed by investigators to be associated with bevacizumab were pulmonary embolism (28 patients; 1%) and epistaxis, neutropenia, febrile neutropenia, and deep vein thrombosis (all of which occurred in 13 patients [1%]). Bevacizumab was temporarily

Phase I study of aerosolized SLIT cisplatin in the treatment of patients with carcinoma of the lung

NARCIS (Netherlands)

Wittgen, Bart P. H.; Kunst, Peter W. A.; van der Born, Kasper; van Wijk, Atie W.; Perkins, Walter; Pilkiewicz, Frank G.; Perez-Soler, Roman; Nicholson, Susan; Peters, Godefridus J.; Postmus, Pieter E.

2007-01-01

PURPOSE: To investigate the safety and pharmacokinetics of aerosolized Sustained Release Lipid Inhalation Targeting (SLIT) Cisplatin in patients with lung carcinoma. EXPERIMENTAL DESIGN: Phase I, dose-escalating study of SLIT Cisplatin given in two sessions daily. Safety data, including laboratory

Bosutinib efficacy and safety in chronic phase chronic myeloid leukemia after imatinib resistance or intolerance : Minimum 24-month follow-up

NARCIS (Netherlands)

Gambacorti-Passerini, Carlo; Brümmendorf, Tim H; Kim, Dong-Wook; Turkina, Anna G; Masszi, Tamas; Assouline, Sarit; Durrant, Simon; Kantarjian, Hagop M; Khoury, H Jean; Zaritskey, Andrey; Shen, Zhi-Xiang; Jin, Jie; Vellenga, Edo; Pasquini, Ricardo; Mathews, Vikram; Cervantes, Francisco; Besson, Nadine; Turnbull, Kathleen; Leip, Eric; Kelly, Virginia; Cortes, Jorge E

Bosutinib is an orally active, dual Src/Abl tyrosine kinase inhibitor for treatment of chronic myeloid leukemia (CML) following resistance/intolerance to prior therapy. Here, we report the data from the 2-year follow-up of a phase 1/2 open-label study evaluating the efficacy and safety of bosutinib

Safety analysis report for the cold vacuum drying facility, phase 1, supporting civil/structural construction

International Nuclear Information System (INIS)

Pili-Vincens, C.

1998-01-01

The Cold Vacuum Drying Facility is a subproject of the overall Spent Nuclear Fuel Project. This Phase 2 Safety Analysis Report incorporates the CVD systems design and will update the SAR per DOE Order 5480.23 for manual and other Hanford infrastructure changes

Conceptual design report for environmental, safety and health phase III FY-91 line item

Energy Technology Data Exchange (ETDEWEB)

NONE

1988-09-01

The Mound Facility (Mound), located in Miamisburg, Ohio, is a Department of Energy (DOE) development and production facility performing support work for DOE`s weapons and energy-related programs. EG&G Mound Applied Technologies (EG&G) is the Operating Contractor (OC) for this Government-Owned, Contractor-Operated (GOCO) facility. The work performed at Mound emphasizes nuclear energy and explosives technology. Mound is currently implementing an Environmental, Safety, and Health (ES&H) Program designed to protect its employees, the public, and the environment from adverse effects caused by the facility`s activities. Design has been completed, and construction is in progress for Phase I of this multiphase program. Phase II has been submitted for fiscal year (FY) 89 funding and Phase IV is being submitted as an FY 92 line item. This Conceptual Design Report (CDR) addresses Phase III of the ES&H program.

Efficacy and safety of cross-linked hyaluronic acid single injection on osteoarthritis of the knee: a post-marketing Phase IV study.

Science.gov (United States)

Bashaireh, Khaldoon; Naser, Ziad; Hawadya, Khaled Al; Sorour, Sorour; Al-Khateeb, Rami Nabeel

2015-01-01

The primary objective of this study was to evaluate the efficacy, safety, and duration of action of viscosupplementation with Crespine® Gel over a 9-month period. The study was a post-marketing Phase IV study. A total of 109 participants with osteoarthritis of the knee (grades 1-4) in the tibio-femoral compartment were recruited in Jordan. Data were collected from each participant during the baseline visit. Each participant received Crespine® Gel injection, and follow-up visits took place at 3 months, 6 months, and 9 months post-injection. An assessment of participants by phone was conducted at 1 month, 2 months, 4 months, 5 months, 7 months, and 8 months post-injection. Western Ontario and McMaster Universities Arthritis Index questionnaires were completed during each visit. A 72-hour visit questionnaire was used to assess the safety of the injection. Statistical analysis included a two-sided 95% confidence interval for the difference between pain scores across visits, and the percent change from baseline was calculated. The full analysis included 84 participants who gave their informed consent and finished the necessary baseline and follow-up visits needed to assess efficacy and safety. Peak improvement was noted at 5 months post-injection, when pain and physical performance scores had decreased to 2.60 and 9.90, respectively, and the stiffness score was 0.33. The peak improvement in stiffness was noted at 8 months post-injection, when the stiffness score had decreased to 0.32. Significant improvements were still apparent at 9 months post-injection, when the pain score was 3.36, the stiffness score was 0.42, and the physical performance score was 11.5. All side effects were local and transient, and included pain, swelling, and redness of the knee. Most side effects were treated. Hyaluronan should be encouraged as an alternative or adjunct treatment to oral analgesics to reduce their required doses, and delay potential future surgical intervention.

A phase 1–2, prospective, double blind, randomized study of the safety and efficacy of Sulfasalazine for the treatment of progressing malignant gliomas: study protocol of [ISRCTN45828668

International Nuclear Information System (INIS)

Robe, Pierre A; Martin, Didier; Albert, Adelin; Deprez, Manuel; Chariot, Alain; Bours, Vincent

2006-01-01

The prognosis of patients suffering from WHO grade 3 and 4 astrocytic glioma remains poor despite surgery, radiation therapy and the use of current chemotherapy regimen. Indeed, the median survival of glioblastoma multiforme (WHO grade 4) patients is at best 14.6 month with only 26.5 percents of the patients still alive after 2 years and the median survival of anaplastic astrocytomas (WHO grade 3) is 19.2 month. Recent evidence suggests that the transcription factor NF-kappaB is constitutively expressed in malignant gliomas and that its inhibition by drugs like Sulfasalazine may block the growth of astrocytic tumors in vitro and in experimental models of malignant gliomas. ULg-GBM-04/1 is a prospective, randomized, double blind single-center phase 1–2 study. A total of twenty patients with progressive malignant glioma despite surgery, radiation therapy and a first line of chemotherapy will be recruited and assigned to four dosage regimen of Sulfasalazine. This medication will be taken orally t.i.d. at a daily dose of 1.5–3–4 or 6 g, continuously until complete remission, evidence of progression or drug intolerance. Primary endpoints are drug safety in the setting of malignant gliomas and tumor response as measured according to MacDonald's criteria. An interim analysis of drug safety will be conducted after the inclusion of ten patients. The complete evaluation of primary endpoints will be conducted two years after the enrolment of the last patient or after the death of the last patient should this occur prematurely. The aim of this study is to evaluate the safety and efficacy of Sulfasalazine as a treatment for recurring malignant gliomas. The safety and efficacy of this drug are analyzed as primary endpoints. Overall survival and progression-free survival are secondary endpoint

Safety relevant failure mechanisms in the post-operational phase

International Nuclear Information System (INIS)

Mayer, Gerhard; Stiller, Jan Christopher; Roemer, Sarah

2017-03-01

When the 13"t"h amendment of the Atomic Energy Act came into force, eight Germ an nuclear power plant units had their power operating licences revoked and are now in the so-called post operation phase. Of the remaining nuclear power plants, one have by now also entered the post operation phase, with those left in operation bound for entering this phase sometime between now and the end of 2022. Therefore, failure mechanisms that are particularly relevant for post operation were to be identified and described in the frame of the present project. To do so, three major steps were taken: Firstly, recent national and international pertinent literature was evaluated to obtain indications of failure mechanisms in the post operation phase. It turned out that most of the national and international literature deals with the general procedure of the transition from power operation to decommissioning and dismantling. However, there were also some documents providing detailed indications of possible failure mechanisms in post operation. This includes e.g. the release of radioactive materials caused by the drop of containers, chemical impacts on systems important to safety in connection with decontamination work, and corrosion in connection with the storage of the core in the spent fuel pool, with the latter leading to the jamming of the fuel assemblies in the storage racks and a possible reduction of coolant circulation. In a second step, three safety analyses of pressurised water reactors prepared by the respective plant operators were evaluated to identify failure mechanisms based on systems engineering. The failure mechanisms that were found here include e.g. faults in the boric acid concentration of the reactor coolant, damage to the equipment airlock upon the unloading of Castor casks, leakages in connection with primary system decontamination, and the drop of packages holding radioactive residual materials or waste with subsequent mobilisation of radioactive aerosols

Development of ABWR-2 and its safety design

International Nuclear Information System (INIS)

Takafumi, Anegawa; Kenji, Tateiwa

2002-01-01

This paper reports the current status of development project on ABWR-II, a next generation reactor design based on ABWR, and its safety design. This project was initiated over a decade ago and has completed three phases to date. In Phase I (1991-92), basic design requirements were discussed and several plant concepts were studied. In Phase II (1993-95), key design features were selected in order to establish a reference reactor concept. In Phase III (1996-2000), based on the reference reactor concept, modifications and improvements were made to fulfill the design requirements. By adopting large electric output (1 700 MW), large fuel bundle, modified ECCS, and passive heat removal systems, among other design features, we achieved a design concept capable of increasing both economic competitiveness and safety performance. Main focus of this paper will be on the safety design, safety performance, and further research needs related to safety. (authors)

Analysis of gas-liquid metal two-phase flows using a reactor safety analysis code SIMMER-III

International Nuclear Information System (INIS)

Suzuki, Tohru; Tobita, Yoshiharu; Kondo, Satoru; Saito, Yasushi; Mishima, Kaichiro

2003-01-01

SIMMER-III, a safety analysis code for liquid-metal fast reactors (LMFRs), includes a momentum exchange model based on conventional correlations for ordinary gas-liquid flows, such as an air-water system. From the viewpoint of safety evaluation of core disruptive accidents (CDAs) in LMFRs, we need to confirm that the code can predict the two-phase flow behaviors with high liquid-to-gas density ratios formed during a CDA. In the present study, the momentum exchange model of SIMMER-III was assessed and improved using experimental data of two-phase flows containing liquid metal, on which fundamental information, such as bubble shapes, void fractions and velocity fields, has been lacking. It was found that the original SIMMER-III can suitably represent high liquid-to-gas density ratio flows including ellipsoidal bubbles as seen in lower gas fluxes. In addition, the employment of Kataoka-Ishii's correlation has improved the accuracy of SIMMER-III for gas-liquid metal flows with cap-shape bubbles as identified in higher gas fluxes. Moreover, a new procedure, in which an appropriate drag coefficient can be automatically selected according to bubble shape, was developed. Through this work, the reliability and the precision of SIMMER-III have been much raised with regard to bubbly flows for various liquid-to-gas density ratios

Improving safety culture through the health and safety organization: a case study.

Science.gov (United States)

Nielsen, Kent J

2014-02-01

International research indicates that internal health and safety organizations (HSO) and health and safety committees (HSC) do not have the intended impact on companies' safety performance. The aim of this case study at an industrial plant was to test whether the HSO can improve company safety culture by creating more and better safety-related interactions both within the HSO and between HSO members and the shop-floor. A quasi-experimental single case study design based on action research with both quantitative and qualitative measures was used. Based on baseline mapping of safety culture and the efficiency of the HSO three developmental processes were started aimed at the HSC, the whole HSO, and the safety representatives, respectively. Results at follow-up indicated a marked improvement in HSO performance, interaction patterns concerning safety, safety culture indicators, and a changed trend in injury rates. These improvements are interpreted as cultural change because an organizational double-loop learning process leading to modification of the basic assumptions could be identified. The study provides evidence that the HSO can improve company safety culture by focusing on safety-related interactions. © 2013. Published by Elsevier Ltd and National Safety Council.

Safety results from a phase III study (TURANDOT trial by CECOG) of first-line bevacizumab in combination with capecitabine or paclitaxel for HER-2-negative locally recurrent or metastatic breast cancer.

Science.gov (United States)

Lang, I; Inbar, M J; Kahán, Z; Greil, R; Beslija, S; Stemmer, S M; Kaufman, B; Zvirbule, Z; Steger, G G; Messinger, D; Brodowicz, T; Zielinski, C

2012-11-01

We report safety data from a randomised, phase III study (CECOG/BC.1.3.005) evaluating first-line bevacizumab plus paclitaxel or capecitabine for locally recurrent or metastatic breast cancer. Patients aged ≥18 years with human epidermal growth factor receptor-2-negative breast adenocarcinoma were randomised to Arm A: bevacizumab 10 mg/kg days 1 and 15; paclitaxel 90 mg/m(2) days 1, 8, and 15, every 4 weeks; or Arm B: bevacizumab 15 mg/kg day 1; capecitabine 1000 mg/m(2) b.i.d., days 1-14, every 3 weeks, until disease progression, unacceptable toxicity or consent withdrawal. A post hoc interim safety analysis included 561 patients (Arm A: 284, Arm B: 277). The regimens demonstrated similar frequencies of all-grade and serious adverse events (SAEs), but different safety profiles. Treatment-related events occurred in 85.2% (Arm A) and 78.0% (Arm B) of patients. Fatigue was most common in Arm A (30.6% versus 23.5% Arm B), and hand-foot syndrome (HFS) most common in Arm B (49.5% versus 2.5% Arm A). Diarrhoea (Arm A: 0.4%, Arm B: 1.4%) and pulmonary embolism (Arm A: 0.7%, Arm B: 1.1%) were the most frequently reported SAEs. These findings are in-line with safety data for bevacizumab plus paclitaxel or capecitabine, reported in previous phase III trials. Copyright © 2012 Elsevier Ltd. All rights reserved.

What do implementers need in terms of regulatory safety criteria for the post-closure phase?

International Nuclear Information System (INIS)

Cahen, B.

2010-01-01

Bruno Cahen, Director Safety Division (ANDRA) presented the point of view of the NEA Integration Group for the Safety Case (IGSC) on 'What do implementers need in terms of regulatory safety criteria for the post-closure phase?' B. Cahen acknowledged that the national experience in siting and developing conceptual designs of geological disposal is growing rapidly. It implies increasing opportunities for interactions between implementers and regulators. There has been large development of international guidance in the recent years. Many regulators have already developed a regulatory framework. The implementers need practical, transparent and deliverable regulations. These regulations should draw on experiences gained from development of geological disposal projects. The IGSC has identified five key questions that the RF may focus on: 1. Over what time frame are the waste deemed to present a hazard? 2. Over what time frames are regulatory criteria applied and do they change over time? 3. Over what time frame(s) are safety assessments required to be conducted? 4. How do implementers have to address uncertainties in the long time frames? 5. What happens after cut-offs: are additional analyses needed? What types of arguments are to be used? Stable, understandable and practical criteria mean, namely, that they need to be developed on a strong scientific and societal basis, that there is consistency of safety options and requirements for different types of waste, that, in the longer time frames, the emphasis is given to robust systems, passive safety and multiple safety functions and that the criteria should fit the various phases of the project (siting, designing, operating, closure and post-closure). Experience feedback from safety cases shows that safety priorities depend very much on time frames. The derived safety criteria for the individual components should lead to measurable, verifiable specifications. The assessment of geological repository post-closure safety

Study on the KALIMER safety approach

International Nuclear Information System (INIS)

Kim, Eui Kwang; Han, Do Hee; Kim, Young Cheol.

1997-01-01

This study describes KALIMER's safety approach, how to establish the safety criteria and temperature limit, how to define safety evaluation events, and some safety research and development needs items. It is recommended that the KALIMER's approach to safety use seven levels of safety design and a defense-in-depth design approach with particular emphasis on inherent passive features. In order to establish as set DBEs for KALIMER safety evaluation, the procedure is explained how to define safety evaluation events. Final selection is to be determined later with the final establishment of design concepts. On the basis of preliminary studies and evaluation of the plant safety related areas, the KALIMER and PRISM have following three main difference that may require special research and development for KALIMER. (author). 7 refs., 6 tabs., 6 figs

Quieter Cars and the Safety of Blind Pedestrians: Phase 1.

Science.gov (United States)

2010-04-01

The National Highway Traffic Safety Administration recognizes that quieter cars such as hybrid-electric vehicles in low-speed operation using their : electric motors, may introduce a safety issue for pedestrians who are blind. This study documents th...

10CFR50.59 safety evaluations

International Nuclear Information System (INIS)

Grime, L.; Page, E.

1987-01-01

As a plant changes from the design phase to the operational phase, new regulations and standards apply. One such regulation is 10CFR50.59 on safety evaluations. Once an operating license is issued, it is mandatory to submit all applicable changes, tests, and experiments to the safety evaluation process. As preparation for this transition, Detroit Edison had procedures in place and conducted personnel training. Reviews of the safety engineering were conducted by the on-site review board. The off-site board delegated detailed reviews of most safety evaluations to the independent safety evaluation group (ISEG). The on-site group review included presentation of complete design packages by engineers. The ISEG and off-site review group's activity focused on safety evaluation. This paper addresses industry trends that were studied, Detroit Edison's recent actions, and industry issues related to 10CFR50.59 safety evaluations

State partnership in environmental health and safety phase of Plowshare projects

Energy Technology Data Exchange (ETDEWEB)

Kinsman, S [California State Department of Public Health, Berkeley, CA (United States)

1969-07-01

When experiments on projects involving Plowshare devices are conceived, the state chosen for the project should be invited to participate in planning the health and safety aspects and be prepared to actively participate in the D-Day phase as well as the post-detonation activity. In California nuclear science technology and competence have preceded the social acceptance and use of nuclear devices for large scale Plowshare projects. However, the environmental surveillance program of the Bureau of Radiological Health in the State Department of Public Health has established an operative program which will be ready and able to function as an active participant or in a support role in environmental health phases of nuclear projects scheduled in the State. A description of our present program will be included in this paper. This will enable the attendees and readers to realize capabilities which will be activated for participation and/or support roles during Plowshare activities in the State or in a neighboring state if the need arises. (author)

State partnership in environmental health and safety phase of Plowshare projects

International Nuclear Information System (INIS)

Kinsman, S.

1969-01-01

When experiments on projects involving Plowshare devices are conceived, the state chosen for the project should be invited to participate in planning the health and safety aspects and be prepared to actively participate in the D-Day phase as well as the post-detonation activity. In California nuclear science technology and competence have preceded the social acceptance and use of nuclear devices for large scale Plowshare projects. However, the environmental surveillance program of the Bureau of Radiological Health in the State Department of Public Health has established an operative program which will be ready and able to function as an active participant or in a support role in environmental health phases of nuclear projects scheduled in the State. A description of our present program will be included in this paper. This will enable the attendees and readers to realize capabilities which will be activated for participation and/or support roles during Plowshare activities in the State or in a neighboring state if the need arises. (author)

Assessment of ALWR passive safety system reliability. Phase 1: Methodology development and component failure quantification

International Nuclear Information System (INIS)

Hake, T.M.; Heger, A.S.

1995-04-01

Many advanced light water reactor (ALWR) concepts proposed for the next generation of nuclear power plants rely on passive systems to perform safety functions, rather than active systems as in current reactor designs. These passive systems depend to a great extent on physical processes such as natural circulation for their driving force, and not on active components, such as pumps. An NRC-sponsored study was begun at Sandia National Laboratories to develop and implement a methodology for evaluating ALWR passive system reliability in the context of probabilistic risk assessment (PRA). This report documents the first of three phases of this study, including methodology development, system-level qualitative analysis, and sequence-level component failure quantification. The methodology developed addresses both the component (e.g. valve) failure aspect of passive system failure, and uncertainties in system success criteria arising from uncertainties in the system's underlying physical processes. Traditional PRA methods, such as fault and event tree modeling, are applied to the component failure aspect. Thermal-hydraulic calculations are incorporated into a formal expert judgment process to address uncertainties in selected natural processes and success criteria. The first phase of the program has emphasized the component failure element of passive system reliability, rather than the natural process uncertainties. Although cursory evaluation of the natural processes has been performed as part of Phase 1, detailed assessment of these processes will take place during Phases 2 and 3 of the program

Safety aspects of geological studies around nuclear installations sites

International Nuclear Information System (INIS)

Faure, J.

1988-01-01

The experience of geological studies of about forty french nuclear sites allows to set out the objectives, the phases and the geographic extensions of workings to be realized for confirming a site. The data to be collected for the safety analysis are specified; they concern the local and regional geology, the geotechnical characteristics and the essential elements for evaluating the hazards related to the soil liquefaction, the surface fracturing and in some cases the volcanic risks. It is necessary to follow up the geology during the installation construction and life. 8 refs. (F.M.)

The Barselina Project Phase 4 Summary report. Ignalina Unit 2 Probabilistic Safety Analysis

Energy Technology Data Exchange (ETDEWEB)

Johansson, Gunnar [ES-Konsult AB, Stockholm (Sweden); Hellstroem, P. [RELCON AB, Solna (Sweden); Zheltobriuch, G.; Bagdonas, A. [Ignalina Power Plant, Visaginas (Lithuania)

1996-12-01

The Barselina Project was initiated in the summer of 1991. The project is a multilateral co-operation between Lithuania, Russia and Sweden. The long range objective is to establish common perspectives and unified bases for assessment of severe accident risks and needs for remedial measures for the RBMK reactors. The Swedish BWR Barsebaeck is used as reference plant and the Lithuanian RBMK Ignalina as application plant. During phase 3, from March, 1993 to June, 1994, a full scope Probabilistic Safety Analysis (PSA) model of the Ignalina Nuclear Power Plant unit 2 (INPP-2) was developed to identify possible safety improvement of risk importance. The probabilistic methodology was applied on a plant specific basis for a channel type reactor of RBMK design. To increase the realism of the risk model a set of deterministic analyses were performed and plant/RBMK-specific data bases were developed and used. A general concept for analysing this type of reactor was developed. During phase 4, July 1994 to September 1996, the PSA was further developed, taking into account plant changes, improved modeling methods and extended plant information concerning dependencies (area events, dynamic effects, electrical and signal dependencies). The updated model is quantified and new results and conclusions are evaluated.

Safety Culture Enhancement Project. Final Report. A Field Study on Approaches to Enhancement of Safety Culture

Energy Technology Data Exchange (ETDEWEB)

Lowe, Andrew; Hayward, Brent (Dedale Asia Pacific, Albert Park VIC 3206 (Australia))

2006-08-15

This report documents a study with the objective of enhancing safety culture in the Swedish nuclear power industry. A primary objective of this study was to ensure that the latest thinking on human factors principles was being recognised and applied by nuclear power operators as a means of ensuring optimal safety performance. The initial phase of the project was conducted as a pilot study, involving the senior management group at one Swedish nuclear power-producing site. The pilot study enabled the project methodology to be validated after which it was repeated at other Swedish nuclear power industry sites, providing a broad-ranging analysis of opportunities across the industry to enhance safety culture. The introduction to this report contains an overview of safety culture, explains the background to the project and sets out the project rationale and objectives. The methodology used for understanding and analysing the important safety culture issues at each nuclear power site is then described. This section begins with a summary of the processes used in the information gathering and data analysis stage. The six components of the Management Workshops conducted at each site are then described. These workshops used a series of presentations, interactive events and group exercises to: (a) provide feedback to site managers on the safety culture and safety leadership issues identified at their site, and (b) stimulate further safety thinking and provide 'take-away' information and leadership strategies that could be applied to promote safety culture improvements. Section 3, project Findings, contains the main observations and output from the project. These include: - a brief overview of aspects of the local industry operating context that impinge on safety culture; - a summary of strengths or positive attributes observed within the safety culture of the Swedish nuclear industry; - a set of identified opportunities for further improvement; - the aggregated

Phase III, efficacy and safety study of ertugliflozin monotherapy in people with type 2 diabetes mellitus inadequately controlled with diet and exercise alone.

Science.gov (United States)

Terra, Steven G; Focht, Kristen; Davies, Melanie; Frias, Juan; Derosa, Giuseppe; Darekar, Amanda; Golm, Gregory; Johnson, Jeremy; Saur, Didier; Lauring, Brett; Dagogo-Jack, Sam

2017-05-01

To conduct a phase III study to evaluate the efficacy and safety of ertugliflozin monotherapy in people with type 2 diabetes. This was a 52-week, double-blind, multicentre, randomized, parallel-group study with a 26-week, placebo-controlled treatment period (phase A), followed by a 26-week active-controlled treatment period (phase B) in 461 men and women, aged ≥18 years with inadequate glycaemic control (glycated haemoglobin [HbA1c] concentration 7.0% to 10.5% [53-91 mmol/mol], inclusive) despite diet and exercise. Results from phase A are reported in the present paper. The primary endpoint was the change in HbA1c from baseline to week 26. At week 26, the placebo-adjusted least squares mean HbA1c changes from baseline were -0.99% and -1.16% for the ertugliflozin 5 and 15 mg doses, respectively ( P  < .001 for both doses). The odds of having HbA1c <7.0% (53 mmol/mol) were significantly greater in the ertugliflozin 5 and 15 mg groups compared with the placebo group. Both doses of ertugliflozin significantly lowered fasting plasma glucose and 2-hour postprandial glucose levels and body weight. The placebo-adjusted differences in changes from baseline in systolic blood pressure were not statistically significant. A higher incidence of genital mycotic infections occurred in men and women treated with ertugliflozin compared with placebo. There was no significant difference between treatments in the proportion of participants with symptomatic hypoglycaemia or adverse events associated with urinary tract infection or hypovolaemia. Ertugliflozin 5 and 15 mg treatment for 26 weeks provides effective glycaemic control, reduces body weight and is generally well tolerated, when used as monotherapy. © 2017 John Wiley & Sons Ltd.

Ventilatory function assessment in safety pharmacology: Optimization of rodent studies using normocapnic or hypercapnic conditions

International Nuclear Information System (INIS)

Goineau, Sonia; Rompion, Sonia; Guillaume, Philippe; Picard, Sandra

2010-01-01

Although the whole body plethysmography for unrestrained animals is the most widely used method to assess the respiratory risk of new drugs in safety pharmacology, non-appropriate experimental conditions may mask deleterious side effects of some substances. If stimulant or bronchodilatory effects can be easily evidenced in rodents under standard experimental conditions, i.e. normal air breathing and diurnal phase, drug-induced respiratory depression remains more difficult to detect. This study was aimed at comparing the responsiveness of Wistar rats, Duncan Hartley guinea-pigs or BALB/c mice to the respiratory properties of theophylline (50 or 100 mg/kg p.o.) or morphine (30 mg/kg i.p.) under varying conditions (100% air versus 5% CO 2 -enriched air, light versus dark day phase), in order to select the most appropriate experimental conditions to each species for safety airway investigations. Our results showed that under normocapnia the ventilatory depressant effects of morphine can be easily evidenced in mice, slightly observed in guinea-pigs and not detected in rats in any day phase. Slight hypercapnic conditions enhanced the responsiveness of rats to morphine but not that of guinea-pigs and importantly they did not blunt the airway responsiveness of rats to the stimulation and bronchodilation evoked by theophylline, the most widely used reference agent in safety pharmacology studies. In conclusion, hypercapnic conditions associated with the non-invasive whole body plethysmography should be considered for optimizing the assessment of both the ventilatory depressant potential of morphine-like substances or the respiratory stimulant effects of new drugs in the rat, the most extensively used species in rodent safety and toxicological investigations.

Long-term safety and efficacy of etanercept in patients with psoriasis: an open-label study.

NARCIS (Netherlands)

Leonardi, C.; Strober, B.; Gottlieb, A.B.; Elewski, B.E.; Ortonne, J.P.; Kerkhof, P.C.M. van de; Chiou, C.F.; Dunn, M.; Jahreis, A.

2010-01-01

BACKGROUND: In two previous phase 3 studies, up to 60 weeks of etanercept therapy significantly improved the symptoms of psoriasis and was well tolerated. OBJECTIVE: To evaluate the long-term safety of etanercept in an open-label extension study for up to 72 weeks in patients with moderate-to-severe

On Safety Management. A Frame of Reference for Studies of Safety Management with Examples From Non-Nuclear Contexts of Relevance for Nuclear Safety

International Nuclear Information System (INIS)

Svensson, Ola; Salo, Ilkka; Allwin, Pernilla

2004-11-01

operations, and safety management for each organization respectively. The analyses are described and summarized in detail in each chapter. To summarize some general themes from the analyzes the following are important to mention: -A distinct division of responsibilities for safety work between organizational units. -A clear communication about the organization's safety policy and how each member of the organization is a part of the policy. -Channels for information and information feedback are clearly represented in the system structure. -Availability to incident reporting systems and the responsibility of each member of the organization to report incidents. -The importance to differentiate between established structures for information management and established structures for information content. -To make clear the range and meaning of power and authority. -Identification of the organizations' competence and integrity in relation to safety management. -The importance of identifying threats to safety, not only for company activities and operations but also for authority activities and operations. In the next phase of the ongoing project, we wish to gain more insight in the companies' perspectives of safety management. The system theoretical framework outlined in this report will be used as a frame of reference for the analyses. We believe that the results from this and future studies in the project will give opportunities to take further steps towards improving safety in the nuclear power operations, both from a company and from a regulator perspective

International comparison of safety criteria applied to radwaste repositories. Safety aspects of the post-operational phase

International Nuclear Information System (INIS)

Baltes, B.

1994-01-01

There is a generally accepted system of framework safety conditions governing the construction, operation, and post-operational monitoring of radwaste repositories. Although the development of these framework conditions may vary from country to country, the resulting criteria are based on the commonly accepted system of priciples and purposes established for ultimate radioactive waste disposal. The experience accumulated by GRS in the course of the plan approval procedure for the Konrad mine site and the safety-relevant studies performed for the planned Morsleben repository clearly show demand for further development of the safety criteria. In Germany, it is especially the safety criteria and detailed requirements filling the framework safety conditions that need revision and in-depth definition, as well as comparison and harmonisation with internationally applied criteria. These activities will particularly consider the international convention on radioactive waste management currently in preparation under the auspieces of the IAEA. (orig.) [de

OECD/NEA expert group on uncertainty analysis for criticality safety assessment: Results of benchmark on sensitivity calculation (phase III)

Energy Technology Data Exchange (ETDEWEB)

Ivanova, T.; Laville, C. [Institut de Radioprotection et de Surete Nucleaire IRSN, BP 17, 92262 Fontenay aux Roses (France); Dyrda, J. [Atomic Weapons Establishment AWE, Aldermaston, Reading, RG7 4PR (United Kingdom); Mennerdahl, D. [E Mennerdahl Systems EMS, Starvaegen 12, 18357 Taeby (Sweden); Golovko, Y.; Raskach, K.; Tsiboulia, A. [Inst. for Physics and Power Engineering IPPE, 1, Bondarenko sq., 249033 Obninsk (Russian Federation); Lee, G. S.; Woo, S. W. [Korea Inst. of Nuclear Safety KINS, 62 Gwahak-ro, Yuseong-gu, Daejeon 305-338 (Korea, Republic of); Bidaud, A.; Sabouri, P. [Laboratoire de Physique Subatomique et de Cosmologie LPSC, CNRS-IN2P3/UJF/INPG, Grenoble (France); Patel, A. [U.S. Nuclear Regulatory Commission (NRC), Washington, DC 20555-0001 (United States); Bledsoe, K.; Rearden, B. [Oak Ridge National Laboratory ORNL, M.S. 6170, P.O. Box 2008, Oak Ridge, TN 37831 (United States); Gulliford, J.; Michel-Sendis, F. [OECD/NEA, 12, Bd des Iles, 92130 Issy-les-Moulineaux (France)

2012-07-01

The sensitivities of the k{sub eff} eigenvalue to neutron cross sections have become commonly used in similarity studies and as part of the validation algorithm for criticality safety assessments. To test calculations of the sensitivity coefficients, a benchmark study (Phase III) has been established by the OECD-NEA/WPNCS/EG UACSA (Expert Group on Uncertainty Analysis for Criticality Safety Assessment). This paper presents some sensitivity results generated by the benchmark participants using various computational tools based upon different computational methods: SCALE/TSUNAMI-3D and -1D, MONK, APOLLO2-MORET 5, DRAGON-SUSD3D and MMKKENO. The study demonstrates the performance of the tools. It also illustrates how model simplifications impact the sensitivity results and demonstrates the importance of 'implicit' (self-shielding) sensitivities. This work has been a useful step towards verification of the existing and developed sensitivity analysis methods. (authors)

Safety assessment in plant layout design using indexing approach: Implementing inherent safety perspective

International Nuclear Information System (INIS)

Tugnoli, Alessandro; Khan, Faisal; Amyotte, Paul; Cozzani, Valerio

2008-01-01

Layout planning plays a key role in the inherent safety performance of process plants since this design feature controls the possibility of accidental chain-events and the magnitude of possible consequences. A lack of suitable methods to promote the effective implementation of inherent safety in layout design calls for the development of new techniques and methods. In the present paper, a safety assessment approach suitable for layout design in the critical early phase is proposed. The concept of inherent safety is implemented within this safety assessment; the approach is based on an integrated assessment of inherent safety guideword applicability within the constraints typically present in layout design. Application of these guidewords is evaluated along with unit hazards and control devices to quantitatively map the safety performance of different layout options. Moreover, the economic aspects related to safety and inherent safety are evaluated by the method. Specific sub-indices are developed within the integrated safety assessment system to analyze and quantify the hazard related to domino effects. The proposed approach is quick in application, auditable and shares a common framework applicable in other phases of the design lifecycle (e.g. process design). The present work is divided in two parts: Part 1 (current paper) presents the application of inherent safety guidelines in layout design and the index method for safety assessment; Part 2 (accompanying paper) describes the domino hazard sub-index and demonstrates the proposed approach with a case study, thus evidencing the introduction of inherent safety features in layout design

Ciprofloxacin DPI: a randomised, placebo-controlled, phase IIb efficacy and safety study on cystic fibrosis.

Science.gov (United States)

Dorkin, Henry L; Staab, Doris; Operschall, Elisabeth; Alder, Jeff; Criollo, Margarita

2015-01-01

Treatment of infective bronchitis involving Pseudomonas aeruginosa is a cornerstone of care in patients with cystic fibrosis (CF). This phase IIb, randomised, double-blind, placebo-controlled study assessed the efficacy and safety of ciprofloxacin dry powder for inhalation (DPI) in this population. Patients with CF, ≥12 years of age (N=286), were randomised to ciprofloxacin DPI (32.5 mg (n=93) or 48.75 mg (n=93)), or corresponding placebo (32.5 mg, n=65; 48.75 mg, n=35) twice daily for 28 days. The primary objective was the change in forced expiratory volume in 1 s (FEV1) from baseline (day 0) to end of treatment (day 29) in the intent-to-treat population for ciprofloxacin DPI compared with the corresponding placebo group. The primary effectiveness objective was not met; there were no significant differences in change in FEV1 between ciprofloxacin DPI and the corresponding placebo group for either dose (p=0.154). However, in pooled analyses, FEV1 decline from baseline to treatment end was significantly lower with ciprofloxacin DPI than with placebo (pooled data; p=0.02). Ciprofloxacin DPI showed positive effects on sputum bacterial load and quality of life, but these effects were not maintained at the 4-week follow-up. Ciprofloxacin DPI was well tolerated and there were no significant differences in type/incidence of treatment-emergent adverse events by treatment group (p=0.115). Further investigations are needed to determine the full scope of the beneficial effects of ciprofloxacin DPI for patients with CF. Clinicaltrials.gov NCT00645788; EudraCT 2008-008314-40.

A study of water hammer phenomena in a one-component two-phase bubbly flow

International Nuclear Information System (INIS)

Fujii, Terushige; Akagawa, Koji

2000-01-01

Water hammer phenomena caused by a rapid valve closure, that is, shock phenomena in two-phase flows, are an important problem for the safety assessment of a hypothetical LOCA. This paper presents the results of experimental and analytical studies of the water hammer phenomena in a one-component tow-phase bubbly flow. In order to clarify the characteristics of water hammer phenomena, experiments for a one-component two-phase flow of Freon R-113 were conducted and a numerical simulation of pressure transients was developed. An overall picture of the water hammer phenomena in a one-component two-phase flow is presented an discussed. (author)

Integrated Safety Management System Phase 1 and 2 Verification for the Environmental Restoration Contractor Volumes 1 and 2

Energy Technology Data Exchange (ETDEWEB)

CARTER, R.P.

2000-04-04

DOE Policy 450.4 mandates that safety be integrated into all aspects of the management and operations of its facilities. The goal of an institutionalized Integrated Safety Management System (ISMS) is to have a single integrated system that includes Environment, Safety, and Health requirements in the work planning and execution processes to ensure the protection of the worker, public, environment, and the federal property over the life cycle of the Environmental Restoration (ER) Project. The purpose of this Environmental Restoration Contractor (ERC) ISMS Phase MI Verification was to determine whether ISMS programs and processes were institutionalized within the ER Project, whether these programs and processes were implemented, and whether the system had promoted the development of a safety conscious work culture.

Site Safety and Health Plan (Phase 3) for the treatability study for in situ vitrification at Seepage Pit 1 in Waste Area Grouping 7, Oak Ridge National Laboratory, Oak Ridge, TN

International Nuclear Information System (INIS)

Spalding, B.P.; Naney, M.T.

1995-06-01

This plan is to be implemented for Phase III ISV operations and post operations sampling. Two previous project phases involving site characterization have been completed and required their own site specific health and safety plans. Project activities will take place at Seepage Pit 1 in Waste Area Grouping 7 at ORNL, Oak Ridge, Tennessee. Purpose of this document is to establish standard health and safety procedures for ORNL project personnel and contractor employees in performance of this work. Site activities shall be performed in accordance with Energy Systems safety and health policies and procedures, DOE orders, Occupational Safety and Health Administration Standards 29 CFR Part 1910 and 1926; applicable United States Environmental Protection Agency requirements; and consensus standards. Where the word ''shall'' is used, the provisions of this plan are mandatory. Specific requirements of regulations and orders have been incorporated into this plan in accordance with applicability. Included from 29 CFR are 1910.120 Hazardous Waste Operations and Emergency Response; 1910.146, Permit Required - Confined Space; 1910.1200, Hazard Communication; DOE Orders requirements of 5480.4, Environmental Protection, Safety and Health Protection Standards; 5480.11, Radiation Protection; and N5480.6, Radiological Control Manual. In addition, guidance and policy will be followed as described in the Environmental Restoration Program Health and Safety Plan. The levels of personal protection and the procedures specified in this plan are based on the best information available from reference documents and site characterization data. Therefore, these recommendations represent the minimum health and safety requirements to be observed by all personnel engaged in this project

Site Safety and Health Plan (Phase 3) for the treatability study for in situ vitrification at Seepage Pit 1 in Waste Area Grouping 7, Oak Ridge National Laboratory, Oak Ridge, TN

Energy Technology Data Exchange (ETDEWEB)

Spalding, B.P.; Naney, M.T.

1995-06-01

This plan is to be implemented for Phase III ISV operations and post operations sampling. Two previous project phases involving site characterization have been completed and required their own site specific health and safety plans. Project activities will take place at Seepage Pit 1 in Waste Area Grouping 7 at ORNL, Oak Ridge, Tennessee. Purpose of this document is to establish standard health and safety procedures for ORNL project personnel and contractor employees in performance of this work. Site activities shall be performed in accordance with Energy Systems safety and health policies and procedures, DOE orders, Occupational Safety and Health Administration Standards 29 CFR Part 1910 and 1926; applicable United States Environmental Protection Agency requirements; and consensus standards. Where the word ``shall`` is used, the provisions of this plan are mandatory. Specific requirements of regulations and orders have been incorporated into this plan in accordance with applicability. Included from 29 CFR are 1910.120 Hazardous Waste Operations and Emergency Response; 1910.146, Permit Required - Confined Space; 1910.1200, Hazard Communication; DOE Orders requirements of 5480.4, Environmental Protection, Safety and Health Protection Standards; 5480.11, Radiation Protection; and N5480.6, Radiological Control Manual. In addition, guidance and policy will be followed as described in the Environmental Restoration Program Health and Safety Plan. The levels of personal protection and the procedures specified in this plan are based on the best information available from reference documents and site characterization data. Therefore, these recommendations represent the minimum health and safety requirements to be observed by all personnel engaged in this project.

Efficacy and safety of tolvaptan in heart failure patients with sustained volume overload despite the use of conventional diuretics: a phase III open-label study.

Science.gov (United States)

Fukunami, Masatake; Matsuzaki, Masunori; Hori, Masatsugu; Izumi, Tohru

2011-12-01

Volume overload is a common complication associated with heart failure (HF) and is recommended to be treated with loop or thiazide diuretics. However, use of diuretics can cause serum electrolyte imbalances and diuretic resistance. Tolvaptan, a selective, oral, non-peptide vasopressin V2-receptor antagonist, offers a new option for treating volume overload in HF patients. The aim of this study was to investigate the efficacy and safety of tolvaptan in Japanese HF patients with volume overload. Fifty-one HF patients with volume overload, despite using conventional diuretics, were treated with 15 mg/day tolvaptan for 7 days. If the response was insufficient at Day 7, tolvaptan was continued for a further 7 days at either 15 mg/day or 30 mg/day. Outcomes included changes in body weight, symptoms and safety parameters. Thirty-six patients discontinued treatment within 7 days, therefore 15 patients entered the second phase of treatment. In two patients, tolvaptan was increased to 30 mg/day after 7 days. Body weight was reduced on Day 7 (-1.95 ± 1.98 kg; n = 41) and Day 14 (-2.35 ± 1.44 kg; n = 11, 15 mg/day). Symptoms of volume overload, including lower limb edema, pulmonary congestion, jugular venous distention and hepatomegaly, were improved by tolvaptan treatment for 7 or 14 days. Neither tolvaptan increased the incidence of severe or serious adverse events when administered for 7-14 days. This study confirms the efficacy and safety of 15 mg/day tolvaptan for 7-14 days in Japanese HF patients with volume overload despite conventional diuretics.

Radioactive wastes. Safety of storage facilities

International Nuclear Information System (INIS)

Devillers, Ch.

2001-01-01

A radioactive waste storage facility is designed in a way that ensures the isolation of wastes with respect to the biosphere. This function comprises the damping of the gamma and neutron radiations from the wastes, and the confinement of the radionuclides content of the wastes. The safety approach is based on two time scales: the safety of the insulation system during the main phase of radioactive decay, and the assessment of the radiological risks following this phase. The safety of a surface storage facility is based on a three-barrier concept (container, storage structures, site). The confidence in the safety of the facility is based on the quality assurance of the barriers and on their surveillance and maintenance. The safety of a deep repository will be based on the site quality, on the design and construction of structures and on the quality of the safety demonstration. This article deals with the safety approach and principles of storage facilities: 1 - recall of the different types of storage facilities; 2 - different phases of the life of a storage facility and regulatory steps; 3 - safety and radiation protection goals (time scales, radiation protection goals); 4 - safety approach and principles of storage facilities: safety of the isolation system (confinement system, safety analysis, scenarios, radiological consequences, safety principles), assessment of the radiation risks after the main phase of decay; 5 - safety of surface storage facilities: safety analysis of the confinement system of the Aube plant (barriers, scenarios, modeling, efficiency), evaluation of radiological risks after the main phase of decay; experience feedback of the Manche plant; variants of surface storage facilities in France and abroad (very low activity wastes, mine wastes, short living wastes with low and average activity); 6 - safety of deep geological disposal facilities: legal framework of the French research; international context; safety analysis of the confinement system

Safety Culture Enhancement Project. Final Report. A Field Study on Approaches to Enhancement of Safety Culture

International Nuclear Information System (INIS)

Lowe, Andrew; Hayward, Brent

2006-08-01

This report documents a study with the objective of enhancing safety culture in the Swedish nuclear power industry. A primary objective of this study was to ensure that the latest thinking on human factors principles was being recognised and applied by nuclear power operators as a means of ensuring optimal safety performance. The initial phase of the project was conducted as a pilot study, involving the senior management group at one Swedish nuclear power-producing site. The pilot study enabled the project methodology to be validated after which it was repeated at other Swedish nuclear power industry sites, providing a broad-ranging analysis of opportunities across the industry to enhance safety culture. The introduction to this report contains an overview of safety culture, explains the background to the project and sets out the project rationale and objectives. The methodology used for understanding and analysing the important safety culture issues at each nuclear power site is then described. This section begins with a summary of the processes used in the information gathering and data analysis stage. The six components of the Management Workshops conducted at each site are then described. These workshops used a series of presentations, interactive events and group exercises to: (a) provide feedback to site managers on the safety culture and safety leadership issues identified at their site, and (b) stimulate further safety thinking and provide 'take-away' information and leadership strategies that could be applied to promote safety culture improvements. Section 3, project Findings, contains the main observations and output from the project. These include: - a brief overview of aspects of the local industry operating context that impinge on safety culture; - a summary of strengths or positive attributes observed within the safety culture of the Swedish nuclear industry; - a set of identified opportunities for further improvement; - the aggregated results of the

Nordic studies in reactor safety

International Nuclear Information System (INIS)

Pershagen, N.

1993-01-01

The Nordic Nuclear Safety Research Programme SIK programme in reactor safety is part of a major joint Nordic research effort in nuclear safety. The report summarizes the achievements of the SIK programme, which was carried out during 1990-1993 in collaboration between Nordic nuclear utilities, safety authorities, and research institutes. Three main projects were successfully completed dealing with: 1) development and application of a living PSA concept for monitoring the risk of core damage, and of safety indicators for early warning of possible safety problems; 2) review and intercomparison of severe accident codes, case studies of potential core melt accidents in nordic reactors, development of chemical models for the MAAP code, and outline of a system for computerized accident management support; 3) compilation of information about design and safety features of neighbouring reactors in Germany, Lithuania and Russia, and for naval reactors and nuclear submarines. The report reviews the state-of-the-art in each subject matter as an introduction to the individual project summaries. The main findings of each project are highlighted. The report also contains an overview of reactor safety research in the Nordic countries and a summary of fundamental reactor safety principles. (au) (69 refs.)

CENTERLINE RUMBLE STRIPS SAFETY IMPACT EVALUATION—PHASE 2

Science.gov (United States)

2018-02-02

Centerline rumble strips are used by various states as a low-cost countermeasure for mitigating cross-over crashes on two-way highways. This study performs a safety impact evaluation using an empirical Bayesian analysis. The researchers obtained a cr...

Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours.

Science.gov (United States)

Bahleda, Rastislav; Hollebecque, Antoine; Varga, Andrea; Gazzah, Anas; Massard, Christophe; Deutsch, Eric; Amellal, Nadia; Farace, Françoise; Ould-Kaci, Mahmoud; Roux, Flavien; Marzin, Kristell; Soria, Jean-Charles

2015-11-17

This Phase I study evaluated continuous- and intermittent-dosing (every other week) of afatinib plus nintedanib in patients with advanced solid tumours. In the dose-escalation phase (n=45), maximum tolerated doses (MTDs) were determined for continuous/intermittent afatinib 10, 20, 30 or 40 mg once daily plus continuous nintedanib 150 or 200 mg twice daily. Secondary objectives included safety and efficacy. Clinical activity of continuous afatinib plus nintedanib at the MTD was further evaluated in an expansion phase (n=25). The most frequent dose-limiting toxicities were diarrhoea (11%) and transaminase elevations (7%). Maximum tolerated doses were afatinib 30 mg continuously plus nintedanib 150 mg, and afatinib 40 mg intermittently plus nintedanib 150 mg. Treatment-related adverse events (mostly Grade⩽3) included diarrhoea (98%), asthenia (64%), nausea (62%) and vomiting (60%). In the dose-escalation phase, two patients had partial responses (PRs) and 27 (60%) had stable disease (SD). In the expansion phase, one complete response and three PRs were observed (all non-small cell lung cancer), with SD in 13 (52%) patients. No pharmacokinetic interactions were observed. MTDs of continuous or intermittent afatinib plus nintedanib demonstrated a manageable safety profile with proactive management of diarrhoea. Antitumour activity was observed in patients with solid tumours.

Status of the EU test blanket systems safety studies

International Nuclear Information System (INIS)

Panayotov, Dobromir; Poitevin, Yves; Ricapito, Italo; Zmitko, Milan

2015-01-01

Highlights: • TBS safety demonstration files. • Safety functions and related design features – detailed TBS components classifications. • Nuclear analyses, radiation shielding and protection. • TBS radiological waste management strategy and categorization. • Selection and definition of reference accidents scenarios and accidents analyses. - Abstract: The European joint undertaking for ITER and the development of fusion energy (‘Fusion for Energy’ – F4E) provides the European contributions to the ITER international fusion energy research project. Among others it includes also the development, design, technological demonstration and implementation of the European test blanket systems (TBS) in ITER. Currently two EU TBS designs are in the phase of conceptual design – helium-cooled lithium-lead (HCLL) and helium-cooled pebble-bed (HCPB). Safety demonstration is an important part of the work devoted to the achievement of the next key project milestone the conceptual design review. The paper reveals the details of the work on EU TBS safety performed in the last couple of years: update of the TBS safety demonstration files; safety functions and related design features; detailed TBS components classifications; nuclear analyses, radiation shielding and protection; TBS radiological waste management strategy and categorization; selection and definition of reference accidents scenarios, and accidents analyses. Finally the authors share the information on on-going and planned future EU TBS safety activities.

Status of the EU test blanket systems safety studies

Energy Technology Data Exchange (ETDEWEB)

Panayotov, Dobromir, E-mail: dobromir.panayotov@f4e.europa.eu; Poitevin, Yves; Ricapito, Italo; Zmitko, Milan

2015-10-15

Highlights: • TBS safety demonstration files. • Safety functions and related design features – detailed TBS components classifications. • Nuclear analyses, radiation shielding and protection. • TBS radiological waste management strategy and categorization. • Selection and definition of reference accidents scenarios and accidents analyses. - Abstract: The European joint undertaking for ITER and the development of fusion energy (‘Fusion for Energy’ – F4E) provides the European contributions to the ITER international fusion energy research project. Among others it includes also the development, design, technological demonstration and implementation of the European test blanket systems (TBS) in ITER. Currently two EU TBS designs are in the phase of conceptual design – helium-cooled lithium-lead (HCLL) and helium-cooled pebble-bed (HCPB). Safety demonstration is an important part of the work devoted to the achievement of the next key project milestone the conceptual design review. The paper reveals the details of the work on EU TBS safety performed in the last couple of years: update of the TBS safety demonstration files; safety functions and related design features; detailed TBS components classifications; nuclear analyses, radiation shielding and protection; TBS radiological waste management strategy and categorization; selection and definition of reference accidents scenarios, and accidents analyses. Finally the authors share the information on on-going and planned future EU TBS safety activities.

A Phase 1 biodistribution study of p-boronophenylalanine

International Nuclear Information System (INIS)

Coderre, J.A.

1991-01-01

The objectives of the Phase I BPA biodistribution study are as follows: Objective 1: To establish the safety of orally administered boronophenylalanine (BPA) as determined by monitoring of patient's vital signs and by clinical analysis of blood before and after BPA administration. Objective 2: To establish BPA pharmacokinetics by monitoring the rates of boron absorption into and clearance from the blood and the rate of urinary excretion of boron. Objective 3: To measure the amount of boron incorporated into human tumors (melanoma, glioma, and breast carcinoma) using samples obtained at surgery or biopsy. This report presents the results obtained from the first thirteen patients entered into the study. Three additional glioblastoma patients have been studied recently at Stony Brook, the tissues are still being analyzed

Heat transfer and friction correlations required to describe steam--water behavior in nuclear safety studies

International Nuclear Information System (INIS)

Solbrig, C.W.; McFadden, J.H.; Lyczkowski, R.W.; Hughes, E.D.

1975-01-01

The description of two-phase flow is important in nuclear safety studies. Recent two-phase flow descriptions are based upon unequal phase velocities and unequal phase temperatures (UVUT) theories with interphase interaction terms. These theories are more mechanistic than homogeneous theories and require more and different types of correlations than homogeneous theories. The UVUT theories require correlations (or models) which describe wall and interphase mass transfer, friction, momentum transfer, and heat transfer for all flow regimes and heat transfer regimes. A set of correlations is presented in this paper which can be used with UVUT theories. These correlations cover the complete range of parameters needed and in all cases are expected to yield reasonable numbers. (U.S.)

Measuring Safety Culture on Ships Using Safety Climate: A Study among Indian Officers

Directory of Open Access Journals (Sweden)

Yogendra Bhattacharya

2015-12-01

Full Text Available Workplace safety continues to be an area of concern in the maritime industry due to the international nature of the operations. The effectiveness of extensive legislation to manage shipboard safety remains in doubt. The focus must therefore shift towards the human element - seafarers and their perceptions of safety. The study aims to understand the alignment that exists between safety culture and safety climate on board ships as perceived by seafarers. The underlying factors of safety climate were identified using factor analysis which isolated seven factors - Support on Safety, Organizational Support, Resource Availability, Work Environment, Job Demands, ‘Just’ Culture, and Safety Compliance. The perception of safety level of seafarers was found to be low indicating the existence of misalignments between safety culture values and the actual safety climate. The study also reveals that the safety perceptions of officers employed directly by ship owners and those by managers do not differ significantly, nor do they differ between senior and junior officers. A shift in perspective towards how seafarers themselves feel towards safety might provide more effective solutions – instead of relying on regulations - and indeed aid in reducing incidents on board. This paper details practical suggestions on how to identify the factors that contribute towards a better safety climate on board ships.

Efficient runner safety assessment during early design phase and root cause analysis

International Nuclear Information System (INIS)

Liang, Q W; Lais, S; Gentner, C; Braun, O

2012-01-01

Fatigue related problems in Francis turbines, especially high head Francis turbines, have been published several times in the last years. During operation the runner is exposed to various steady and unsteady hydraulic loads. Therefore the analysis of forced response of the runner structure requires a combined approach of fluid dynamics and structural dynamics. Due to the high complexity of the phenomena and due to the limitation of computer power, the numerical prediction was in the past too expensive and not feasible for the use as standard design tool. However, due to continuous improvement of the knowledge and the simulation tools such complex analysis has become part of the design procedure in ANDRITZ HYDRO. This article describes the application of most advanced analysis techniques in runner safety check (RSC), including steady state CFD analysis, transient CFD analysis considering rotor stator interaction (RSI), static FE analysis and modal analysis in water considering the added mass effect, in the early design phase. This procedure allows a very efficient interaction between the hydraulic designer and the mechanical designer during the design phase, such that a risk of failure can be detected and avoided in an early design stage.The RSC procedure can also be applied to a root cause analysis (RCA) both to find out the cause of failure and to quickly define a technical solution to meet the safety criteria. An efficient application to a RCA of cracks in a Francis runner is quoted in this article as an example. The results of the RCA are presented together with an efficient and inexpensive solution whose effectiveness could be proven again by applying the described RSC technics. It is shown that, with the RSC procedure developed and applied as standard procedure in ANDRITZ HYDRO such a failure is excluded in an early design phase. Moreover, the RSC procedure is compatible with different commercial and open source codes and can be easily adapted to apply for

Efficient runner safety assessment during early design phase and root cause analysis

Science.gov (United States)

Liang, Q. W.; Lais, S.; Gentner, C.; Braun, O.

2012-11-01

Fatigue related problems in Francis turbines, especially high head Francis turbines, have been published several times in the last years. During operation the runner is exposed to various steady and unsteady hydraulic loads. Therefore the analysis of forced response of the runner structure requires a combined approach of fluid dynamics and structural dynamics. Due to the high complexity of the phenomena and due to the limitation of computer power, the numerical prediction was in the past too expensive and not feasible for the use as standard design tool. However, due to continuous improvement of the knowledge and the simulation tools such complex analysis has become part of the design procedure in ANDRITZ HYDRO. This article describes the application of most advanced analysis techniques in runner safety check (RSC), including steady state CFD analysis, transient CFD analysis considering rotor stator interaction (RSI), static FE analysis and modal analysis in water considering the added mass effect, in the early design phase. This procedure allows a very efficient interaction between the hydraulic designer and the mechanical designer during the design phase, such that a risk of failure can be detected and avoided in an early design stage.The RSC procedure can also be applied to a root cause analysis (RCA) both to find out the cause of failure and to quickly define a technical solution to meet the safety criteria. An efficient application to a RCA of cracks in a Francis runner is quoted in this article as an example. The results of the RCA are presented together with an efficient and inexpensive solution whose effectiveness could be proven again by applying the described RSC technics. It is shown that, with the RSC procedure developed and applied as standard procedure in ANDRITZ HYDRO such a failure is excluded in an early design phase. Moreover, the RSC procedure is compatible with different commercial and open source codes and can be easily adapted to apply for

Information about robustness, reliability and safety in early design phases

DEFF Research Database (Denmark)

Marini, Vinicius Kaster

methods, and an industrial case to assess how the use of information about robustness, reliability and safety as practised by current methods influences concept development. Current methods cannot be used in early design phases due to their dependence on detailed design information for the identification...... alternatives. This prompts designers to reuse working principles that are inherently flawed, as they are liable to disturbances, failures and hazards. To address this issue, an approach based upon individual records of early design issues consists of comparing failures and benefits from prior working...... principles, before making a decision, and improving the more suitable alternatives through this feedback. Workshops were conducted with design practitioners to evaluate the potential of the approach and to simulate decision-making and gain feedback on a proof-of-concept basis. The evaluation has demonstrated...

Two-Year Follow-up of the Collision Auto Repair Safety Study (CARSS)

Science.gov (United States)

Bejan, Anca; Parker, David L.; Brosseau, Lisa M.; Xi, Min; Skan, Maryellen

2015-01-01

This paper presents an evaluation of the sustainability of health and safety improvements in small auto collision shops 1 year after the implementation of a year-long targeted intervention. During the first year (active phase), owners received quarterly phone calls, written reminders, safety newsletters, and access to online services and in-person assistance with creating safety programs and respirator fit testing. During the second year (passive phase), owners received up to three postcard reminders regarding the availability of free health and safety resources. Forty-five shops received an evaluation at baseline and at the end of the first year (Y1). Of these, 33 were evaluated at the end of the second year (Y2), using the same 92-item assessment tool. At Y1, investigators found that between 70 and 81% of the evaluated items were adequate in each business (mean = 73% items, SD = 11%). At Y2, between 63 and 89% of items were deemed adequate (mean = 73% items, SD = 9.5%). Three safety areas demonstrated statistically significant (P < 0.05) changes: compressed gasses (8% improvement), personal protective equipment (7% improvement), and respiratory protection (6% decline). The number of postcard reminders sent to each business did not affect the degree to which shops maintained safety improvements made during the first year of the intervention. However, businesses that received more postcards were more likely to request assistance services than those receiving fewer. PMID:25539646

Safety balance: Analysis of safety systems

International Nuclear Information System (INIS)

Delage, M.; Giroux, C.

1990-12-01

Safety analysis, and particularly analysis of exploitation of NPPs is constantly affected by EDF and by the safety authorities and their methodologies. Periodic safety reports ensure that important issues are not missed on daily basis, that incidents are identified and that relevant actions are undertaken. French safety analysis method consists of three principal steps. First type of safety balance is analyzed at the normal start-up phase for each unit including the final safety report. This enables analysis of behaviour of units ten years after their licensing. Second type is periodic operational safety analysis performed during a few years. Finally, the third step consists of safety analysis of the oldest units with the aim to improve the safety standards. The three steps of safety analysis are described in this presentation in detail with the aim to present the objectives and principles. Examples of most recent exercises are included in order to illustrate the importance of such analyses

ROMANA 3: a phase 3 safety extension study of anamorelin in advanced non-small-cell lung cancer (NSCLC) patients with cachexia.

Science.gov (United States)

Currow, D; Temel, J S; Abernethy, A; Milanowski, J; Friend, J; Fearon, K C

2017-08-01

Cancer anorexia-cachexia is a debilitating condition frequently observed in NSCLC patients, characterized by decreased body weight, reduced food intake, and impaired quality of life. Anamorelin, a novel selective ghrelin receptor agonist, has anabolic and appetite-enhancing activities. ROMANA 3 was a safety extension study of two phase 3, double-blind studies that assessed safety and efficacy of anamorelin in advanced NSCLC patients with cachexia. Patients with preserved Eastern Cooperative Oncology Group ≤2 after completing 12 weeks (w) on the ROMANA 1 or ROMANA 2 trials (0-12 weeks) could enroll in ROMANA 3 and continue to receive anamorelin 100 mg or placebo once daily for an additional 12w (12-24 weeks). The primary endpoint of ROMANA 3 was anamorelin safety/tolerability (12-24 weeks). Secondary endpoints included changes in body weight, handgrip strength (HGS), and symptom burden (0-24 weeks). Of the 703 patients who completed ROMANA 1 and ROMANA 2, 513 patients entered ROMANA 3 (anamorelin, N = 345, mean age 62.0 years; placebo, N = 168; mean age 62.2 years). During ROMANA 3, anamorelin and placebo groups had similar incidences of treatment-emergent adverse events (TEAEs; 52.2% versus 55.7%), grade ≥3 TEAEs (22.4% versus 21.6%), and serious TEAEs (12.8% versus 12.6%). There were 36 (10.5%) and 23 (13.8%) deaths in the anamorelin and placebo groups, respectively; none were drug-related. Improvements in body weight and anorexia-cachexia symptoms observed in the original trials were consistently maintained over 12-24 weeks. Anamorelin, versus placebo, significantly increased body weight from baseline of original trials at all time points (P cachexia symptoms at weeks 3, 6, 9, 12, and 16 (P < 0.05). No significant improvement in HGS was seen in either group. During the 12-24 weeks ROMANA 3 trial, anamorelin continued to be well tolerated. Over the entire 0-24w treatment period, body weight and symptom burden were improved

Safety and immunogenicity of an intramuscular quadrivalent influenza vaccine in children 3 to 8 y of age: A phase III randomized controlled study.

Science.gov (United States)

Pepin, Stephanie; Szymanski, Henryk; Rochín Kobashi, Ilya Angélica; Villagomez Martinez, Sandra; González Zamora, José Francisco; Brzostek, Jerzy; Huang, Li-Min; Chiu, Cheng-Hsun; Chen, Po-Yen; Ahonen, Anitta; Forstén, Aino; Seppä, Ilkka; Quiroz, René Farfán; Korhonen, Tiina; Rivas, Enrique; Monfredo, Celine; Hutagalung, Yanee; Menezes, Josemund; Vesikari, Timo

2016-12-01

A quadrivalent, inactivated, split-virion influenza vaccine containing a strain from both B lineages (IIV4) has been developed, but its safety and immunogenicity in young children has not been described. This was a phase III, randomized, double-blind, active-controlled, multi-center study to examine the immunogenicity and safety of IIV4 in children 3-8 y of age (EudraCT no. 2011-005374-33). Participants were randomized 5:1:1 to receive the 2013/2014 Northern Hemisphere formulation of IIV4, an investigational trivalent comparator (IIV3) containing the B/Victoria lineage strain, or the licensed Northern Hemisphere IIV3 containing the B/Yamagata lineage strain. Participants who had not previously received a full influenza vaccination schedule received 2 doses of vaccine 28 d apart; all others received a single dose. 1242 children were included. For all 4 strains, IIV4 induced geometric mean haemagglutination inhibition titres non-inferior to those induced by the IIV3 comparators. For both B strains, geometric mean antibody titres induced by IIV4 were superior to those induced by the IIV3 with the alternative lineage strain. Similar proportions of participants vaccinated with IIV4 and IIV3 reported solicited injection-site reactions, solicited systemic reactions, and vaccine-related adverse events. A single vaccine-related serious adverse event, thrombocytopenia, was reported 9 d after vaccination with IIV4 and resolved without sequelae. In conclusion, in children aged 3-8 y who received one dose or 2 doses 28 d apart, IIV4 had an acceptable safety profile, was as immunogenic as IIV3 for the shared strains, and had superior immunogenicity for the additional B strain.

Safety and immunogenicity of a tetravalent dengue vaccine in healthy children aged 2-11 years in Malaysia: a randomized, placebo-controlled, Phase III study.

Science.gov (United States)

Hss, Amar-Singh; Koh, Mia-Tuang; Tan, Kah Kee; Chan, Lee Gaik; Zhou, Lynn; Bouckenooghe, Alain; Crevat, Denis; Hutagalung, Yanee

2013-12-02

Dengue disease is a major public health problem across the Asia-Pacific region for which there is no licensed vaccine or treatment. We evaluated the safety and immunogenicity of Phase III lots of a candidate vaccine (CYD-TDV) in children in Malaysia. In this observer-blind, placebo-controlled, Phase III study, children aged 2-11 years were randomized (4:1) to receive CYD-TDV or placebo at 0, 6 and 12 months. Primary endpoints included assessment of reactogenicity following each dose, adverse events (AEs) and serious AEs (SAEs) reported throughout the study, and immunogenicity expressed as geometric mean titres (GMTs) and distribution of dengue virus (DENV) neutralizing antibody titres. 250 participants enrolled in the study (CYD-TDV: n=199; placebo: n=51). There was a trend for reactogenicity to be higher with CYD-TDV than with placebo post-dose 1 (75.4% versus 68.6%) and post-dose 2 (71.6% versus 62.0%) and slightly lower post-dose 3 (57.9% versus 64.0%). Unsolicited AEs declined in frequency with each subsequent dose and were similar overall between groups (CYD-TDV: 53.8%; placebo: 49.0%). Most AEs were of Grade 1 intensity and were transient. SAEs were reported by 5.5% and 11.8% of participants in the CYD-TDV and placebo groups, respectively. No deaths were reported. Baseline seropositivity against each of the four DENV serotypes was similar between groups, ranging from 24.0% (DENV-4) to 36.7% (DENV-3). In the CYD-TDV group, GMTs increased post-dose 2 for all serotypes compared with baseline, ranging from 4.8 (DENV-1) to 8.1-fold (DENV-3). GMTs further increased post-dose 3 for DENV-1 and DENV-2. Compared with baseline, individual titre increases ranged from 6.1-fold (DENV-1) to 7.96-fold (DENV-3). This study demonstrated a satisfactory safety profile and a balanced humoral immune response against all four DENV serotypes for CYD-TDV administered via a three-dose regimen to children in Malaysia. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All

Establishing research priorities for patient safety in emergency medicine: a multidisciplinary consensus panel.

Science.gov (United States)

Plint, Amy C; Stang, Antonia S; Calder, Lisa A

2015-01-01

Patient safety in the context of emergency medicine is a relatively new field of study. To date, no broad research agenda for patient safety in emergency medicine has been established. The objective of this study was to establish patient safety-related research priorities for emergency medicine. These priorities would provide a foundation for high-quality research, important direction to both researchers and health-care funders, and an essential step in improving health-care safety and patient outcomes in the high-risk emergency department (ED) setting. A four-phase consensus procedure with a multidisciplinary expert panel was organized to identify, assess, and agree on research priorities for patient safety in emergency medicine. The 19-member panel consisted of clinicians, administrators, and researchers from adult and pediatric emergency medicine, patient safety, pharmacy, and mental health; as well as representatives from patient safety organizations. In phase 1, we developed an initial list of potential research priorities by electronically surveying a purposeful and convenience sample of patient safety experts, ED clinicians, administrators, and researchers from across North America using contact lists from multiple organizations. We used simple content analysis to remove duplication and categorize the research priorities identified by survey respondents. Our expert panel reached consensus on a final list of research priorities through an in-person meeting (phase 3) and two rounds of a modified Delphi process (phases 2 and 4). After phases 1 and 2, 66 unique research priorities were identified for expert panel review. At the end of phase 4, consensus was reached for 15 research priorities. These priorities represent four themes: (1) methods to identify patient safety issues (five priorities), (2) understanding human and environmental factors related to patient safety (four priorities), (3) the patient perspective (one priority), and (4) interventions for

Solid-phase microextraction for bioconcentration studies according to OECD TG 305

Energy Technology Data Exchange (ETDEWEB)

Duering, Rolf-Alexander; Boehm, Leonard [Land Use and Nutrition (IFZ) Justus Liebig University Giessen, Institute of Soil Science and Soil Conservation, Research Centre for BioSystems, Giessen (Germany); Schlechtriem, Christian [Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Schmallenberg (Germany)

2012-12-15

An important aim of the European Community Regulation on chemicals and their safe use is the identification of (very) persistent, (very) bioaccumulative, and toxic substances. In other regulatory chemical safety assessments (pharmaceuticals, biocides, pesticides), the identification of such (very) persistent, (very) bioaccumulative, and toxic substances is of increasing importance. Solid-phase microextraction is especially capable of extracting total water concentrations as well as the freely dissolved fraction of analytes in the water phase, which is available for bioconcentration in fish. However, although already well established in environmental analyses to determine and quantify analytes mainly in aqueous matrices, solid-phase microextraction is still a rather unusual method in regulatory ecotoxicological research. Here, the potential benefits and drawbacks of solid-phase microextraction are discussed as an analytical routine approach for aquatic bioconcentration studies according to OECD TG 305, with a special focus on the testing of hydrophobic organic compounds characterized by log K{sub OW}> 5. (orig.)

1982 annual status report: reactor safety

International Nuclear Information System (INIS)

1982-01-01

This report presents the projects of the Reactor Safety Program at the JRC: 1) Reliability and risk evolution; 2) LWR loss of coolant accident studies; 3) Primary system integrity; 4) LMFBR core accident initiation and transition phase; and, 5) LMFBR accident post disassembly phase

Efficacy and safety of cross-linked hyaluronic acid single injection on osteoarthritis of the knee: a post-marketing phase IV study

Directory of Open Access Journals (Sweden)

Bashaireh K

2015-04-01

Full Text Available Khaldoon Bashaireh,1 Ziad Naser,2 Khaled Al Hawadya,2 Sorour Sorour,2 Rami Nabeel Al-Khateeb3 1Department of Orthopedics Surgery, King Abdullah University Hospital, Jordan University of Science and Technology, Irbid, Jordan; 2Private Clinic, 3Elaf Medical Supplies Company, Amman, Jordan Purpose: The primary objective of this study was to evaluate the efficacy, safety, and duration of action of viscosupplementation with Crespine® Gel over a 9-month period.Materials and methods: The study was a post-marketing phase IV study. A total of 109 participants with osteoarthritis of the knee (grades 1–4 in the tibio–femoral compartment were recruited in Jordan. Data were collected from each participant during the baseline visit. Each participant received Crespine® Gel injection, and follow-up visits took place at 3 months, 6 months, and 9 months post-injection.Main outcome measure(s: An assessment of participants by phone was conducted at 1 month, 2 months, 4 months, 5 months, 7 months, and 8 months post-injection. Western Ontario and McMaster Universities Arthritis Index questionnaires were completed during each visit. A 72-hour visit questionnaire was used to assess the safety of the injection. Statistical analysis included a two-sided 95% confidence interval for the difference between pain scores across visits, and the percent change from baseline was calculated.Main results: The full analysis included 84 participants who gave their informed consent and finished the necessary baseline and follow-up visits needed to assess efficacy and safety. Peak improvement was noted at 5 months post-injection, when pain and physical performance scores had decreased to 2.60 and 9.90, respectively, and the stiffness score was 0.33. The peak improvement in stiffness was noted at 8 months post-injection, when the stiffness score had decreased to 0.32. Significant improvements were still apparent at 9 months post-injection, when the pain score was 3

Safety of Nuclear Power Plants: Design. Specific Safety Requirements

International Nuclear Information System (INIS)

2012-01-01

On the basis of the principles included in the Fundamental Safety Principles, IAEA Safety Standards Series No. SF-1, this Safety Requirements publication establishes requirements applicable to the design of nuclear power plants. It covers the design phase and provides input for the safe operation of the power plant. It elaborates on the safety objective, safety principles and concepts that provide the basis for deriving the safety requirements that must be met for the design of a nuclear power plant. Contents: 1. Introduction; 2. Applying the safety principles and concepts; 3. Management of safety in design; 4. Principal technical requirements; 5. General plant design; 6. Design of specific plant systems.

Phase 2 Comparison of A Novel Ammonia Scavenging Agent With Sodium Phenylbutyrate In Patients With Urea Cycle Disorders: Safety, Pharmacokinetics And Ammonia Control

OpenAIRE

Lee, Brendan; Rhead, William; Diaz, George A.; Scharschmidt, Bruce F.; Mian, Asad; Shchelochkov, Oleg; Marier, JF; Beliveau, Martin; Mauney, Joseph; Dickinson, Klara; Martinez, Antonia; Gargosky, Sharron; Mokhtarani, Masoud; Berry, Susan A.

2010-01-01

Glycerol phenylbutyrate (glyceryl tri (4-phenylbutyrate)) (GPB) is being studied as an alternative to sodium phenylbutyrate (NaPBA) for the treatment of urea cycle disorders (UCDs). This phase 2 study explored the hypothesis that GPB offers similar safety and ammonia control as NaPBA, which is currently approved as adjunctive therapy in the chronic management of UCDs, and examined correlates of 24-hour blood ammonia.

Contribution to the theoretical study of transient two-phase flows

International Nuclear Information System (INIS)

Achard, J.L.

1978-12-01

The work presented in this paper has been given rise from the existence of violent boiling phenomena of the coolant that have been revealed by reactor safety studies with water and sodium. The aim as to describe in a basic mammer, one of these phenomena called ''chugging'' or ''choucage''. The experimental part of this work concerns two original works concerning the temperature measurement at the wall; a device is proposed to evaluate the contact resistance and the thermal inertia of the thermocouple; from the measurements that have been obtained, the flux the wall transfers to the flow and the temperature of the internal wall surface are deduced. A statistical method is developed for dispersed two-phase flow study, to establish: 1) a mass transfer law, 2) a law of change of the flow configuration. The proposed model contains: 1) for the dispersed phase (vapor bubbles), the basic momentum transport equations; 2) for the continuous phase (liquid), the transport equations of the classical formulation. The statistical formulation introduces the interaction phenomenon between the phases before applying the operation of the average (homogenization method); it allows to introduce the coalescence phenomena of bubbles. Finally, structures of exchange laws for transient laminar flows are proposed: transient linear momentum exchange law; possible structures of heat exchange laws [fr

Assessing the general safety and tolerability of vildagliptin: value of pooled analyses from a large safety database versus evaluation of individual studies

Science.gov (United States)

Schweizer, Anja; Dejager, Sylvie; Foley, James E; Kothny, Wolfgang

2011-01-01

Aim: Analyzing safety aspects of a drug from individual studies can lead to difficult-to-interpret results. The aim of this paper is therefore to assess the general safety and tolerability, including incidences of the most common adverse events (AEs), of vildagliptin based on a large pooled database of Phase II and III clinical trials. Methods: Safety data were pooled from 38 studies of ≥12 to ≥104 weeks’ duration. AE profiles of vildagliptin (50 mg bid; N = 6116) were evaluated relative to a pool of comparators (placebo and active comparators; N = 6210). Absolute incidence rates were calculated for all AEs, serious AEs (SAEs), discontinuations due to AEs, and deaths. Results: Overall AEs, SAEs, discontinuations due to AEs, and deaths were all reported with a similar frequency in patients receiving vildagliptin (69.1%, 8.9%, 5.7%, and 0.4%, respectively) and patients receiving comparators (69.0%, 9.0%, 6.4%, and 0.4%, respectively), whereas drug-related AEs were seen with a lower frequency in vildagliptin-treated patients (15.7% vs 21.7% with comparators). The incidences of the most commonly reported specific AEs were also similar between vildagliptin and comparators, except for increased incidences of hypoglycemia, tremor, and hyperhidrosis in the comparator group related to the use of sulfonylureas. Conclusions: The present pooled analysis shows that vildagliptin was overall well tolerated in clinical trials of up to >2 years in duration. The data further emphasize the value of a pooled analysis from a large safety database versus assessing safety and tolerability from individual studies. PMID:21415917

Experiences from the LNPP-P and DSA review. Lessons learned from RBMK safety studies

International Nuclear Information System (INIS)

Mankamo, T.; Marttila, J.; Reponen, H.

2000-09-01

RBMK is the Russian acronym for 'Channelized Large Power Reactor'. The Soviet-designed RBMK plants deviate substantially from typical Western BWR or PWR plants. The safety of the RBMK plants has raised severe concerns since the major accident at Chernobyl Unit 4 in 1986. In addition, a fire destroyed the turbine hall of Chernobyl Unit 2 in 1991 resulting in a near-accident: the reactor cooling could only be maintained through improvised measures. Another well-known fire event is the control cable room fire at Ignalina Unit 2 in 1989, which led to a partial loss of the main control room functions. After the collapse of Soviet Union several multilateral safety programs were started to evaluate and improve the safety of the RBMK plants. A Probabilistic and Deterministic Safety Assessment (P and DSA) of the Leningrad Nuclear Power Plant (LNPP) Unit 2 was started in 1996. Phase 2 of the project was completed in January 1999. A Peer Review was performed by Russian and Western experts. This report describes the insights from the RBMK risk studies, especially from the LNPP P and DSA with emphasis on the deeper understanding of the risk-important design factors and identification of possible ways to increase safety. LNPP P and DSA has meant a significant progress in this respect. Despite of its certain limitations P and DSA Phase 2 could point out short-term measures, which substantially reduced the risk of identified weaknesses, mostly related to the reliability of the emergency feedwater function and its support systems. The findings of LNPP P and DSA and the review recommendations emphasise the extensions needed to the analysis scope. The spreading and other influences of fires and floods between connected spaces should be analysed because of incomplete separation and protection in these regards in the 16st generation RBMK plants. High priority should be given to the analysis of external hazards, which were found important at the Loviisa NPP on the Northern side of the

Experiences from the LNPP-P and DSA review. Lessons learned from RBMK safety studies

Energy Technology Data Exchange (ETDEWEB)

Mankamo, T. [Avaplan Oy (Finland); Marttila, J.; Reponen, H. [Radiation and Nuclear Safety Authority, Helsinki (Finland)

2000-09-01

RBMK is the Russian acronym for 'Channelized Large Power Reactor'. The Soviet-designed RBMK plants deviate substantially from typical Western BWR or PWR plants. The safety of the RBMK plants has raised severe concerns since the major accident at Chernobyl Unit 4 in 1986. In addition, a fire destroyed the turbine hall of Chernobyl Unit 2 in 1991 resulting in a near-accident: the reactor cooling could only be maintained through improvised measures. Another well-known fire event is the control cable room fire at Ignalina Unit 2 in 1989, which led to a partial loss of the main control room functions. After the collapse of Soviet Union several multilateral safety programs were started to evaluate and improve the safety of the RBMK plants. A Probabilistic and Deterministic Safety Assessment (P and DSA) of the Leningrad Nuclear Power Plant (LNPP) Unit 2 was started in 1996. Phase 2 of the project was completed in January 1999. A Peer Review was performed by Russian and Western experts. This report describes the insights from the RBMK risk studies, especially from the LNPP P and DSA with emphasis on the deeper understanding of the risk-important design factors and identification of possible ways to increase safety. LNPP P and DSA has meant a significant progress in this respect. Despite of its certain limitations P and DSA Phase 2 could point out short-term measures, which substantially reduced the risk of identified weaknesses, mostly related to the reliability of the emergency feedwater function and its support systems. The findings of LNPP P and DSA and the review recommendations emphasise the extensions needed to the analysis scope. The spreading and other influences of fires and floods between connected spaces should be analysed because of incomplete separation and protection in these regards in the 16st generation RBMK plants. High priority should be given to the analysis of external hazards, which were found important at the Loviisa NPP on the Northern

Study on thermal-hydraulics during a PWR reflood phase

Energy Technology Data Exchange (ETDEWEB)

Iguchi, Tadashi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

1998-10-01

In-core thermal-hydraulics during a PWR reflood phase following a large-break LOCA are quite unique in comparison with two-phase flow which has been studied widely in previous researches, because the geometry of the flow path is complicated (bundle geometry) and water is at extremely low superficial velocity and almost under stagnant condition. Hence, some phenomena realized during a PWR reflood phase are not understood enough and appropriate analytical models have not been developed, although they are important in a viewpoint of reactor safety evaluation. Therefore, author investigated some phenomena specified as important issues for quantitative prediction, i.e. (1) void fraction in a bundle during a PWR reflood phase, (2) effect of radial core power profile on reflood behavior, (3) effect of combined emergency core coolant injection on reflood behavior, and (4) the core separation into two thermal-hydraulically different regions and the in-core flow circulation behavior observed during a combined injection PWR reflood phase. Further, author made analytical models for these specified issues, and succeeded to predict reflood behaviors at representative types of PWRs, i.e.cold leg injection PWRs and Combined injection PWRs, in good accuracy. Above results were incorporated into REFLA code which is developed at JAERI, and they improved accuracy in prediction and enlarged applicability of the code. In the present study, models were intended to be utilized in a practical use, and hence these models are simplified ones. However, physical understanding on the specified issues in the present study is basic and principal for reflood behavior, and then it is considered to be used in a future advanced code development and improvement. (author). 110 refs.

Ready to Respond: Case Studies in Campus Safety and Security

Science.gov (United States)

Hyatt, James A.

2010-01-01

Is your campus primed for the next big emergency? The National Campus Safety and Security Project (NCSSP), led by NACUBO, sought to help colleges and universities develop comprehensive emergency management plans that address the four phases of emergency management: prevention/mitigation, preparedness, response, and recovery. A major component of…

Railway safety climate: a study on organizational development.

Science.gov (United States)

Cheng, Yung-Hsiang

2017-09-07

The safety climate of an organization is considered a leading indicator of potential risk for railway organizations. This study adopts the perceptual measurement-individual attribute approach to investigate the safety climate of a railway organization. The railway safety climate attributes are evaluated from the perspective of railway system staff. We identify four safety climate dimensions from exploratory factor analysis, namely safety communication, safety training, safety management and subjectively evaluated safety performance. Analytical results indicate that the safety climate differs at vertical and horizontal organizational levels. This study contributes to the literature by providing empirical evidence of the multilevel safety climate in a railway organization, presents possible causes of the differences under various cultural contexts and differentiates between safety climate scales for diverse workgroups within the railway organization. This information can be used to improve the safety sustainability of railway organizations and to conduct safety supervisions for the government.

A study of pedestrian compliance with traffic signals for exclusive and concurrent phasing.

Science.gov (United States)

Ivan, John N; McKernan, Kevin; Zhang, Yaohua; Ravishanker, Nalini; Mamun, Sha A

2017-01-01

This paper describes a comparison of pedestrian compliance at traffic signals with two types of pedestrian phasing: concurrent, where both pedestrians and vehicular traffic are directed to move in the same directions at the same time, and exclusive, where pedestrians are directed to move during their own dedicated phase while all vehicular traffic is stopped. Exclusive phasing is usually perceived to be safer, especially by senior and disabled advocacy groups, although these safety benefits depend upon pedestrians waiting for the walk signal. This paper investigates whether or not there are differences between pedestrian compliance at signals with exclusive pedestrian phasing and those with concurrent phasing and whether these differences continue to exist when compliance at exclusive phasing signals is evaluated as if they had concurrent phasing. Pedestrian behavior was observed at 42 signalized intersections in central Connecticut with both concurrent and exclusive pedestrian phasing. Binary regression models were estimated to predict pedestrian compliance as a function of the pedestrian phasing type and other intersection characteristics, such as vehicular and pedestrian volume, crossing distance and speed limit. We found that pedestrian compliance is significantly higher at intersections with concurrent pedestrian phasing than at those with exclusive pedestrian phasing, but this difference is not significant when compliance at exclusive phase intersections is evaluated as if it had concurrent phasing. This suggests that pedestrians treat exclusive phase intersections as though they have concurrent phasing, rendering the safety benefits of exclusive pedestrian phasing elusive. No differences were observed for senior or non-senior pedestrians. Published by Elsevier Ltd.

Efficacy and safety of paliperidone palmitate three-monthly formulation in East Asian patients with schizophrenia: subgroup analysis of a global, randomized, double-blind, Phase III, noninferiority study

Directory of Open Access Journals (Sweden)

Savitz AJ

2017-08-01

Full Text Available Adam J Savitz,1 Haiyan Xu,2 Srihari Gopal,1 Isaac Nuamah,2 Paulien Ravenstijn,3 David Hough,1 Maju Mathews,4 Yu Feng,5 Lu Yu,6 Masayoshi Takahashi,7 Dennis Liu,8 Gang Wang,9 Jin-Sang Yoon,10 Jiahn-Jyh Chen11 1Department of Central Nervous System, 2Department of Clinical Biostatistics, Janssen Research & Development, LLC, Titusville, NJ, USA; 3Department of Clinical Pharmacology, Janssen Research & Development, Beerse, Belgium; 4Global Medical Affairs, Neurosciences, Janssen Research & Development, NY, USA; 5Medical Affairs, Neurosciences, Janssen Pharmaceutical Companies of Johnson and Johnson, Singapore; 6Department of Clinical Development, Janssen Research & Development, Beijing, China; 7Department of Central Nervous System, Janssen Pharmaceutical KK, Tokyo, Japan; 8Playford Community Team, Northern Adelaide Local Health Network, Adelaide, SA, Australia; 9National Clinical Research Center for Mental Disorders, Beijing Anding Hospital, Affiliated Capital University of Medical Science, Beijing, China; 10Department of Psychiatry, Chonnam National University Hospital, Gwangju, South Korea; 11Department of Geriatric Psychiatry, Taoyuan Mental Hospital, Taoyuan, Taiwan Objective: To demonstrate the efficacy and safety of paliperidone palmitate three-monthly (PP3M formulation in an East Asian population with schizophrenia by subgroup analysis of a double-blind (DB, multicenter, noninferiority study. Patients and methods: Of 1,429 patients who entered the open-label (OL phase, 510 were East Asian (China: 296 [58%], Japan: 175 [34%], South Korea: 19 [4%] and Taiwan: 20 [4%]. In the 17-week OL phase, patients received paliperidone palmitate once-monthly (PP1M formulation on day 1 (150 mg eq., day 8 (100 mg eq. and once-monthly thereafter (50–150 mg eq., flexible. Following the OL phase, patients (n=344 East Asian entered DB phase and were randomized (1:1 to PP1M (n=174 or PP3M (n=170. Primary efficacy endpoint was the percentage of patients who

Laboratory safety and the WHO World Alliance for Patient Safety.

Science.gov (United States)

McCay, Layla; Lemer, Claire; Wu, Albert W

2009-06-01

Laboratory medicine has been a pioneer in the field of patient safety; indeed, the College of American Pathology first called attention to the issue in 1946. Delivering reliable laboratory results has long been considered a priority, as the data produced in laboratory medicine have the potential to critically influence individual patients' diagnosis and management. Until recently, most attention on laboratory safety has focused on the analytic stage of laboratory medicine. Addressing this stage has led to significant and impressive improvements in the areas over which laboratories have direct control. However, recent data demonstrate that pre- and post-analytical phases are at least as vulnerable to errors; to further improve patient safety in laboratory medicine, attention must now be focused on the pre- and post-analytic phases, and the concept of patient safety as a multi-disciplinary, multi-stage and multi-system concept better understood. The World Alliance for Patient Safety (WAPS) supports improvement of patient safety globally and provides a potential framework for considering the total testing process.

A Study of Cyber Security Activities for Development of Safety-related Controller

Energy Technology Data Exchange (ETDEWEB)

Lee, Myeongkyun; Song, Seunghwan; Yoo, Kwanwoo; Yun, Donghwa [Korea Univ., Seoul (Korea, Republic of)

2014-05-15

Nuclear Power Plant Regulatory guide describes the regulatory requirements to implement cyber security activities to ensure that design and operate to respond to cyber threats that exploited to vulnerability of digital-based technologies associated with safety-related digital instrumentation and control systems at nuclear power plants. Cyber security activities coverage is instrumentation and control systems to perform safety functions and digital-based equipment to use development, test, analysis and asset for instrumentation and control systems. Regulatory guidance is required to the cyber security activities that should be performed in each development phase of safety-related controller. Development organization should establish and implement to cyber security plans for responding to cyber threats throughout each lifecycle phase and the result of the cyber security activities should be generated to the documents. In addition, the independent verification and validation organization should perform simulated penetration test for enhancing response capabilities to cyber security threats and development organization should establish and implement response hardening solutions for the cyber security vulnerabilities identified in the simulated penetration test.

A Study of Cyber Security Activities for Development of Safety-related Controller

International Nuclear Information System (INIS)

Lee, Myeongkyun; Song, Seunghwan; Yoo, Kwanwoo; Yun, Donghwa

2014-01-01

Nuclear Power Plant Regulatory guide describes the regulatory requirements to implement cyber security activities to ensure that design and operate to respond to cyber threats that exploited to vulnerability of digital-based technologies associated with safety-related digital instrumentation and control systems at nuclear power plants. Cyber security activities coverage is instrumentation and control systems to perform safety functions and digital-based equipment to use development, test, analysis and asset for instrumentation and control systems. Regulatory guidance is required to the cyber security activities that should be performed in each development phase of safety-related controller. Development organization should establish and implement to cyber security plans for responding to cyber threats throughout each lifecycle phase and the result of the cyber security activities should be generated to the documents. In addition, the independent verification and validation organization should perform simulated penetration test for enhancing response capabilities to cyber security threats and development organization should establish and implement response hardening solutions for the cyber security vulnerabilities identified in the simulated penetration test

A Fire Safety Certification System for Board and Care Operators and Staff. SBIR Phase I: Final Report.

Science.gov (United States)

Walker, Bonnie L.

This report describes the development and pilot testing of a fire safety certification system for board and care operators and staff who serve clients with developmental disabilities. During Phase 1, training materials were developed, including a trainer's manual, a participant's coursebook a videotape, an audiotape, and a pre-/post test which was…

Krsko periodic safety review project prioritization process

International Nuclear Information System (INIS)

Basic, I.; Vrbanic, I.; Spiler, J.; Lambright, J.

2004-01-01

Definition of a Krsko Periodic Safety Review (PSR) project is a comprehensive safety review of a plant after last ten years of operation. The objective is a verification by means of a comprehensive review using current methods that Krsko NPP remains safety when judged against current safety objectives and practices and that adequate arrangements are in place to maintain plant safety. This objective encompasses the three main criteria or goals: confirmation that the plant is as safe as originally intended, determination if there are any structures, systems or components that could limit the life of the plant in the foreseeable future, and comparison the plant against modern safety standards and to identify where improvements would be beneficial at justifiable cost. Krsko PSR project is structured in the three phases: Phase 1: Preparation of Detailed 10-years PSR Program, Phase 2: Performing of 10-years PSR Program and preparing of associated documents (2001-2003), and Phase 3: Implementation of the prioritized compensatory measures and modifications (development of associated EEAR, DMP, etc.) after agreement with the SNSA on the design, procedures and time-scales (2004-2008). This paper presents the NEK PSR results of work performed under Phase 2 focused on the ranking of safety issues and prioritization of corrective measures needed for establishing an efficient action plan. Safety issues were identified in Phase 2 during the following review processes: Periodic Safety Review (PSR) task; Krsko NPP Regulatory Compliance Program (RCP) review; Westinghouse Owner Group (WOG) catalog items screening/review; SNSA recommendations (including IAEA RAMP mission suggestions/recommendations).(author)

Leadership and safety culture. Leadership for safety

International Nuclear Information System (INIS)

Fischer, Erwin; Nithack, Eckhard

2016-01-01

The meaning of leadership for safety in the nuclear industry is pointed out. This topic has became an increasing rank since the German ''Energiewende''. Despite the phase-out of the German NPP's nuclear safety and the belonging safety culture needs to be well maintained. A challenge for the whole organisation. Following the challenge to operate nuclear power plants towards Operational Excellence a highly skilled and motivated organisation is needed. Therefore Leadership is a valuable success factor.

Leadership and safety culture. Leadership for safety

Energy Technology Data Exchange (ETDEWEB)

Fischer, Erwin; Nithack, Eckhard [PreussenElektra GmbH, Hannover (Germany)

2016-08-15

The meaning of leadership for safety in the nuclear industry is pointed out. This topic has became an increasing rank since the German ''Energiewende''. Despite the phase-out of the German NPP's nuclear safety and the belonging safety culture needs to be well maintained. A challenge for the whole organisation. Following the challenge to operate nuclear power plants towards Operational Excellence a highly skilled and motivated organisation is needed. Therefore Leadership is a valuable success factor.

Safety evaluation of Elixir Paregorico in healthy volunteers: a phase I study.

Science.gov (United States)

de Moraes, Mea; Bezerra, Mm; Bezerra, Faf; de Moraes, Ra; Cavalcanti, Pp; Uchoa, Cra; Lima, Fav; Odorico de Moraes, M

2008-10-01

A liquid alcoholic extract of Papaver somniferum named Elixir Paregorico is extensively used for diarrheal diseases in Brazil. Its increased popularity has brought concerns and fears over the safety of this herbal product. Given the lack of investigative clinical studies, in this regard, this study investigated whether Elixir Paregorico administration causes any noticeable toxic effects in healthy volunteers. In all, 28 middle-aged healthy male (n = 14) and female (n = 14) were enrolled. After screening and a washout period, eligible subjects received four oral doses per day of Elixir Paregorico (3 mL diluted in 30 mL of water) over a 10-day period. Altogether, all 28 participants completed the study. The results of hematological and biochemical tests performed pre and post-treatment were within the normal range. In both male and female volunteers, there were no statistical differences (P > 0.05) in the results of clinical and laboratory tests performed at screening, on 5th and 10th day visits, and at final assessment. Although mild adverse events were related, which subsided spontaneously, no serious untoward reactions were reported following Elixir Paregorico administration. To our knowledge, this is the first demonstration that Elixir Paregorico administered four times a day for 10 days is safe and does not cause any noticeable toxic effect in healthy volunteers.

Assessing the general safety and tolerability of vildagliptin: value of pooled analyses from a large safety database versus evaluation of individual studies

Directory of Open Access Journals (Sweden)

Schweizer A

2011-02-01

Full Text Available Anja Schweizer1, Sylvie Dejager2, James E Foley3, Wolfgang Kothny31Novartis Pharma AG, Basel, Switzerland; 2Novartis Pharma SAS, Rueil-Malmaison, France; 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, USAAim: Analyzing safety aspects of a drug from individual studies can lead to difficult-to-interpret results. The aim of this paper is therefore to assess the general safety and tolerability, including incidences of the most common adverse events (AEs, of vildagliptin based on a large pooled database of Phase II and III clinical trials.Methods: Safety data were pooled from 38 studies of ≥12 to ≥104 weeks' duration. AE profiles of vildagliptin (50 mg bid; N = 6116 were evaluated relative to a pool of comparators (placebo and active comparators; N = 6210. Absolute incidence rates were calculated for all AEs, serious AEs (SAEs, discontinuations due to AEs, and deaths.Results: Overall AEs, SAEs, discontinuations due to AEs, and deaths were all reported with a similar frequency in patients receiving vildagliptin (69.1%, 8.9%, 5.7%, and 0.4%, respectively and patients receiving comparators (69.0%, 9.0%, 6.4%, and 0.4%, respectively, whereas drug-related AEs were seen with a lower frequency in vildagliptin-treated patients (15.7% vs 21.7% with comparators. The incidences of the most commonly reported specific AEs were also similar between vildagliptin and comparators, except for increased incidences of hypoglycemia, tremor, and hyperhidrosis in the comparator group related to the use of sulfonylureas.Conclusions: The present pooled analysis shows that vildagliptin was overall well tolerated in clinical trials of up to >2 years in duration. The data further emphasize the value of a pooled analysis from a large safety database versus assessing safety and tolerability from individual studies.Keywords: type 2 diabetes, dipeptidyl peptidase-4, edema, safety, vildagliptin

Safety test No. S-6, launch pad abort sequential test Phase II: solid propellant fire

International Nuclear Information System (INIS)

Snow, E.C.

1975-08-01

In preparation for the Lincoln Laboratory's LES 8/9 space mission, a series of tests was performed to evaluate the nuclear safety capability of the Multi-Hundred Watt (MHW) Radioisotope Thermoelectric Generator (RTG) to be used to supply power for the satellite. One such safety test is Test No. S-6, Launch Pad Abort Sequential Test. The objective of this test was to subject the RTG and its components to the sequential environments characteristic of a catastrophic launch pad accident to evaluate their capability to contain the 238 PuO 2 fuel. This sequence of environments was to have consisted of the blast overpressure and fragments, followed by the fireball, low velocity impact on the launch pad, and solid propellant fire. The blast overpressure and fragments were subsequently eliminated from this sequence. The procedures and results of Phase II of Test S-6, Solid Propellant Fire are presented. In this phase of the test, a simulant Fuel Sphere Assembly (FSA) and a mockup of a damaged Heat Source Assembly (HSA) were subjected to single proximity solid propellant fires of approximately 10-min duration. Steel was introduced into both tests to simulate the effects of launch pad debris and the solid rocket motor (SRM) casing that might be present in the fire zone. (TFD)

Deep Borehole Disposal Safety Analysis.

Energy Technology Data Exchange (ETDEWEB)

Freeze, Geoffrey A. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Stein, Emily [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Price, Laura L. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); MacKinnon, Robert J. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Tillman, Jack Bruce [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States)

2016-10-01

This report presents a preliminary safety analysis for the deep borehole disposal (DBD) concept, using a safety case framework. A safety case is an integrated collection of qualitative and quantitative arguments, evidence, and analyses that substantiate the safety, and the level of confidence in the safety, of a geologic repository. This safety case framework for DBD follows the outline of the elements of a safety case, and identifies the types of information that will be required to satisfy these elements. At this very preliminary phase of development, the DBD safety case focuses on the generic feasibility of the DBD concept. It is based on potential system designs, waste forms, engineering, and geologic conditions; however, no specific site or regulatory framework exists. It will progress to a site-specific safety case as the DBD concept advances into a site-specific phase, progressing through consent-based site selection and site investigation and characterization.

Mescalero Apache Tribe Monitored Retrievable Storage (MRS). Phase 1 feasibility study report

Energy Technology Data Exchange (ETDEWEB)

Peso, F.

1992-03-13

The Nuclear Waste Policy Act of 1982, as amended, authorizes the siting, construction and operation of a Monitored Retrievable Storage (MRS) facility. The MRS is intended to be used for the temporary storage of spent nuclear fuel from the nation`s nuclear power plants beginning as early as 1998. Pursuant to the Nuclear Waste Policy Act, the Office of the Nuclear Waste Negotiator was created. On October 7, 1991, the Nuclear Waste Negotiator invited the governors of states and the Presidents of Indian tribes to apply for government grants in order to conduct a study to assess under what conditions, if any, they might consider hosting an MRS facility. Pursuant to this invitation, on October 11, 1991 the Mescalero Apache Indian Tribe of Mescalero, NM applied for a grant to conduct a phased, preliminary study of the safety, technical, political, environmental, social and economic feasibility of hosting an MRS. The preliminary study included: (1) An investigative education process to facilitate the Tribe`s comprehensive understanding of the safety, environmental, technical, social, political, and economic aspects of hosting an MRS, and; (2) The development of an extensive program that is enabling the Tribe, in collaboration with the Negotiator, to reach an informed and carefully researched decision regarding the conditions, (if any), under which further pursuit of the MRS would be considered. The Phase 1 grant application enabled the Tribe to begin the initial activities necessary to determine whether further consideration is warranted for hosting the MRS facility. The Tribe intends to pursue continued study of the MRS in order to meet the following objectives: (1) Continuing the education process towards a comprehensive understanding of the safety, environmental, technical, social and economic aspects of the MRS; (2) Conducting an effective public participation and information program; (3) Participating in MRS meetings.

Studies of matrix diffusion in gas phase

International Nuclear Information System (INIS)

Hartikainen, K.; Timonen, J.; Vaeaetaeinen, K.; Pietarila, H.

1994-03-01

The diffusion of solutes from fractures into rock matrix is an important factor in the safety analysis of disposal of radioactive waste. Laboratory measurements are needed to complement field investigations for a reliable determination of the necessary transport parameters. Measurements of diffusion coefficients in tight rock samples are usually time consuming because the diffusion processes are slow. On the other hand it is well known that diffusion coefficients in the gas phase are roughly four orders of magnitude larger than those in the liquid phase. Therefore, for samples whose structures do not change much upon drying, it is possible to estimate the diffusion properties of the liquid phase when the properties of the gas phase are known. Advantages of the gas method are quick and easy measurements. In the measurements nitrogen was used as the carrier gas and helium as the tracer gas, and standard techniques have been used for helium detection. Techniques have been developed for both channel flow and through-diffusion measurements. The breakthrough curves have been measured in every experiment and all measurements have been modelled by using appropriate analytical models. As a result matrix porosities and effective diffusion coefficients in the gas phase have been determined. (12 refs., 21 figs., 6 tabs.)

Safety, efficacy and pharmacokinetics of neratinib (HKI-272) in Japanese patients with advanced solid tumors: a Phase 1 dose-escalation study.

Science.gov (United States)

Ito, Yoshinori; Suenaga, Mitsukuni; Hatake, Kiyohiko; Takahashi, Shunji; Yokoyama, Masahiro; Onozawa, Yusuke; Yamazaki, Kentaro; Hironaka, Shuichi; Hashigami, Kiyoshi; Hasegawa, Hirotaka; Takenaka, Nobuko; Boku, Narikazu

2012-04-01

Neratinib (HKI-272), a potent, irreversible, small-molecule, orally administered, pan-ErbB inhibitor that blocks signal transduction via inhibition of three epidermal growth factor receptors [ErbB1, ErbB2 (Her2) and ErbB4], is being developed for the treatment of solid tumors, including breast cancer. This Phase 1 dose-escalation study assessed the safety, tolerability, maximum-tolerated dose, antitumor activity and pharmacokinetics of neratinib in Japanese patients with advanced solid tumors. Patients received neratinib 80, 160, 240 or 320 mg orally; each patient enrolled in only one dose cohort. Patients received a single dose in week 1, followed by daily continuous doses. Blood samples collected were on days 1 and 21 for pharmacokinetic analyses. Twenty-one patients were enrolled (3 breast cancer; 17 colorectal cancer; 1 gastric cancer). Neratinib-related adverse events (all grades) included diarrhea (20 patients), fatigue (14 patients), nausea and abdominal pain (9 patients each) and anorexia (8 patients). Grade ≥3 neratinib-related adverse events in two or more patients were diarrhea and anorexia (two patients each). Dose-limiting toxicities were diarrhea and anorexia (two patients, 320 mg dose). The maximum-tolerated dose and recommended dose was neratinib 240 mg once daily. Of 21 evaluable patients, 2 with breast cancer had partial response, 3 had stable disease ≥24 weeks, 7 had stable disease ≥16 weeks and 9 had progressive disease. Pharmacokinetic analyses indicated that neratinib exposures increased with dose. The safety, efficacy and pharmacokinetic profiles of neratinib are consistent with those reported for non-Japanese patients and warrant further investigation of neratinib in Japanese patients with solid tumors.

RAMONA-4B development for SBWR safety studies

Energy Technology Data Exchange (ETDEWEB)

Rohatgi, U.S.; Aronson, A.L.; Cheng, H.S.; Khan, H.J.; Mallen, A.N.

1993-12-31

The Simplified Boiling Water Reactor (SBWR) is a revolutionary design of a boiling-water reactor. The reactor is based on passive safety systems such as natural circulation, gravity flow, pressurized gas, and condensation. SBWR has no active systems, and the flow in the vessel is by natural circulation. There is a large chimney section above the core to provide a buoyancy head for natural circulation. The reactor can be shut down by either of four systems; namely, scram, Fine Motion Control Rod Drive (FMCRD), Alternate Rod Insertion (ARI), and Standby Liquid Control System (SLCS). The safety injection is by gravity drain from the Gravity Driven Cooling System (GDCS) and Suppression Pool (SP). The heat sink is through two types of heat exchangers submerged in the tank of water. These heat exchangers are the Isolation Condenser (IC) and the Passive Containment Cooling System (PCCS). The RAMONA-4B code has been developed to simulate the normal operation, reactivity transients, and to address the instability issues for SBWR. The code has a three-dimensional neutron kinetics coupled to multiple parallel-channel thermal-hydraulics. The two-phase thermal hydraulics is based on a nonhomogeneous nonequilibrium drift-flux formulation. It employs an explicit integration to solve all state equations (except for neutron kinetics) in order to predict the instability without numerical damping. The objective of this project is to develop a Sun SPARC and IBM RISC 6000 based RAMONA-4B code for applications to SBWR safety analyses, in particular for stability and ATWS studies.

RAMONA-4B development for SBWR safety studies

International Nuclear Information System (INIS)

Rohatgi, U.S.; Aronson, A.L.; Cheng, H.S.; Khan, H.J.; Mallen, A.N.

1993-01-01

The Simplified Boiling Water Reactor (SBWR) is a revolutionary design of a boiling-water reactor. The reactor is based on passive safety systems such as natural circulation, gravity flow, pressurized gas, and condensation. SBWR has no active systems, and the flow in the vessel is by natural circulation. There is a large chimney section above the core to provide a buoyancy head for natural circulation. The reactor can be shut down by either of four systems; namely, scram, Fine Motion Control Rod Drive (FMCRD), Alternate Rod Insertion (ARI), and Standby Liquid Control System (SLCS). The safety injection is by gravity drain from the Gravity Driven Cooling System (GDCS) and Suppression Pool (SP). The heat sink is through two types of heat exchangers submerged in the tank of water. These heat exchangers are the Isolation Condenser (IC) and the Passive Containment Cooling System (PCCS). The RAMONA-4B code has been developed to simulate the normal operation, reactivity transients, and to address the instability issues for SBWR. The code has a three-dimensional neutron kinetics coupled to multiple parallel-channel thermal-hydraulics. The two-phase thermal hydraulics is based on a nonhomogeneous nonequilibrium drift-flux formulation. It employs an explicit integration to solve all state equations (except for neutron kinetics) in order to predict the instability without numerical damping. The objective of this project is to develop a Sun SPARC and IBM RISC 6000 based RAMONA-4B code for applications to SBWR safety analyses, in particular for stability and ATWS studies

Safety, tolerability, and immunogenicity of the novel antituberculous vaccine RUTI: randomized, placebo-controlled phase II clinical trial in patients with latent tuberculosis infection.

Science.gov (United States)

Nell, Andre S; D'lom, Eva; Bouic, Patrick; Sabaté, Montserrat; Bosser, Ramon; Picas, Jordi; Amat, Mercè; Churchyard, Gavin; Cardona, Pere-Joan

2014-01-01

To evaluate the safety, tolerability and immunogenicity of three different doses (5, 25 and 50 µg) of the novel antituberculous vaccine RUTI compared to placebo in subjects with latent tuberculosis infection. Double-blind, randomized, placebo-controlled Phase II Clinical Trial (95 patients randomized). Three different RUTI doses and placebo were tested, randomized both in HIV-positive (n = 47) and HIV-negative subjects (n = 48), after completion of one month isoniazid (INH) pre-vaccination. Each subject received two vaccine administrations, 28 Days apart. Five patients withdrew and 90 patients completed the study. Assessment of safety showed no deaths during study. Two subjects had serious adverse events one had a retinal detachment while taking INH and was not randomized and the other had a severe local injection site abscess on each arm and was hospitalized; causality was assessed as very likely and by the end of the study the outcome had resolved. All the patients except 5 (21%) patients of the placebo group (3 HIV+ and 2 HIV-) reported at least one adverse event (AE) during the study. The most frequently occurring AEs among RUTI recipients were (% in HIV+/-): injection site reactions [erythema (91/92), induration (94/92), local nodules (46/25), local pain (66/75), sterile abscess (6/6), swelling (74/83), ulcer (20/11), headache (17/22) and nasopharyngitis (20/5)]. These events were mostly mild and well tolerated. Overall, a polyantigenic response was observed, which differed by HIV- status. The best polyantigenic response was obtained when administrating 25 µg RUTI, especially in HIV-positive subjects which was not increased after the second inoculation. This Phase II clinical trial demonstrates reasonable tolerability of RUTI. The immunogenicity profile of RUTI vaccine in LTBI subjects, even being variable among groups, allows us considering one single injection of one of the highest doses in future trials, preceded by an extended safety clinical

Efficacy and safety of long-acting pasireotide in Japanese patients with acromegaly or pituitary gigantism: results from a multicenter, open-label, randomized, phase 2 study.

Science.gov (United States)

Tahara, Shigeyuki; Murakami, Mami; Kaneko, Tomomi; Shimatsu, Akira

2017-07-28

A multicenter, open-label, phase 2 study was conducted to investigate the efficacy and safety of long-acting pasireotide formulation in Japanese patients with acromegaly or pituitary gigantism. Medically naïve or inadequately controlled patients (on somatostatin analogues or dopamine agonists) were included. Primary end point was the proportion of all patients who achieved biochemical control (mean growth hormone [GH] levelsacromegaly, n=32; pituitary gigantism, n=1) were enrolled and randomized 1:1:1 to receive open-label pasireotide 20mg, 40mg, or 60mg. The median age was 52 years (range, 31-79) and 20 patients were males. At month 3, 18.2% of patients (6/33; 90% confidence interval: 8.2%, 32.8%) had biochemical control (21.2% [7/33] when including a patient with mean GHacromegaly or pituitary gigantism.

A Phase IIIb, Multicentre, Randomised, Parallel-Group, Placebo-Controlled, Double-Blind Study to Investigate the Efficacy and Safety of OROS Hydromorphone in Subjects with Moderate-to-Severe Chronic Pain Induced by Osteoarthritis of the Hip or the Knee

Directory of Open Access Journals (Sweden)

Jozef Vojtaššák

2011-01-01

Full Text Available Background. Opioid analgesics are included in treatment guidelines for the symptomatic management of osteoarthritis (OA. Starting with a low dose of opioid and slowly titrating to a higher dose may help avoid intolerable side effects. Methods. Subjects aged ≥40 years, with moderate to severe pain induced by OA of the hip or knee not adequately controlled by previous non-steroidal anti-inflammatory drugs (NSAIDs or paracetamol treatment, were enrolled. Subjects received OROS hydromorphone 4 mg or placebo once-daily. The dose was titrated every 3-4 days in case of unsatisfactory pain control during the 4-week titration phase. A 12 week maintenance phase followed. The primary efficacy endpoint was the change in “pain on average” measured on the Brief Pain Inventory (BPI scale from baseline to the end of the maintenance phase. Results. 139 subjects received OROS hydromorphone and 149 subjects received placebo. All efficacy endpoints showed similar improvements from baseline to end of study in the 2 groups. The safety results were consistent with the safety profile of OROS hydromorphone. Conclusion.The study did not meet the primary endpoint; although many subjects' pain was not adequately controlled at inclusion, their pain may have improved with continued paracetamol or NSAID treatment.

Feasibility Study on Two-phase Thermosiphon for External Vessel Cooling Application of SFR

Energy Technology Data Exchange (ETDEWEB)

Choi, Jae Young; Song, Sub Lee; Chang, Soon Heung [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

2014-05-15

This study shows that ex-vessel cooling by two-phase thermosiphon is feasible for large size of SFR. The result presents that further studies to increase heat transfer on condenser-air and gap is necessary and the experiment should be conducted for the validation. Also, the heat loss through evaporator during normal operation, corrosion, consideration of organic fluid to exclude the poison of mercury should be studied. As the necessity of sodium fast reactor in order to reduce spent fuel, the development of designing sodium fast reactor becomes an issue. Even though there is PDRC and RVACS for the decay heat removal (DHR) system, each system has disadvantage of sodium fire and low performance, respectively. Therefore, to increase the safety of SFR, the new passive safety system design is needed without sodium fire and high performance, which can applied for large SFR. The DHR system using two-phase thermosiphon for external vessel cooling application is suggested in this paper. The proposed design have advantage that there is no structure in reactor vessel, which means no system modification and no sodium fire with perfect isolation. Also, it provide the method to mitigate sodium fire in case of sodium leakage from reactor vessel.

Safety and immunogenicity of rVSVΔG-ZEBOV-GP Ebola vaccine in adults and children in Lambaréné, Gabon: A phase I randomised trial

NARCIS (Netherlands)

Agnandji, Selidji T.; Fernandes, José F.; Bache, Emmanuel B.; Obiang Mba, Régis M.; Brosnahan, Jessica S.; Kabwende, Lumeka; Pitzinger, Paul; Staarink, Pieter; Massinga-Loembe, Marguerite; Krähling, Verena; Biedenkopf, Nadine; Fehling, Sarah Katharina; Strecker, Thomas; Clark, David J.; Staines, Henry M.; Hooper, Jay W.; Silvera, Peter; Moorthy, Vasee; Kieny, Marie-Paule; Adegnika, Akim A.; Grobusch, Martin P.; Becker, Stephan; Ramharter, Michael; Mordmüller, Benjamin; Lell, Bertrand; Krishna, Sanjeev; Kremsner, Peter G.

2017-01-01

The rVSVΔG-ZEBOV-GP vaccine prevented Ebola virus disease when used at 2 × 107 plaque-forming units (PFU) in a trial in Guinea. This study provides further safety and immunogenicity data. A randomised, open-label phase I trial in Lambaréné, Gabon, studied 5 single intramuscular vaccine doses of 3 ×

Micro-Encapsulated Phase Change Materials: A Review of Encapsulation, Safety and Thermal Characteristics

Directory of Open Access Journals (Sweden)

Ahmed Hassan

2016-10-01

Full Text Available Phase change materials (PCMs have been identified as potential candidates for building energy optimization by increasing the thermal mass of buildings. The increased thermal mass results in a drop in the cooling/heating loads, thus decreasing the energy demand in buildings. However, direct incorporation of PCMs into building elements undermines their structural performance, thereby posing a challenge for building integrity. In order to retain/improve building structural performance, as well as improving energy performance, micro-encapsulated PCMs are integrated into building materials. The integration of microencapsulation PCMs into building materials solves the PCM leakage problem and assures a good bond with building materials to achieve better structural performance. The aim of this article is to identify the optimum micro-encapsulation methods and materials for improving the energy, structural and safety performance of buildings. The article reviews the characteristics of micro-encapsulated PCMs relevant to building integration, focusing on safety rating, structural implications, and energy performance. The article uncovers the optimum combinations of the shell (encapsulant and core (PCM materials along with encapsulation methods by evaluating their merits and demerits.

Safety and efficacy of everolimus in Chinese patients with metastatic renal cell carcinoma resistant to vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy: an open-label phase 1b study

International Nuclear Information System (INIS)

Guo, Jun; Straub, Patrick; Pirotta, Nicoletta; Gogov, Sven; Huang, Yiran; Zhang, Xu; Zhou, Fangjian; Sun, Yinghao; Qin, Shukui; Ye, Zhangqun; Wang, Hui; Jappe, Annette

2013-01-01

In China, there are currently no approved therapies for the treatment of metastatic renal cell carcinoma (mRCC) following progression with vascular endothelial growth factor (VEGF)-targeted agents. In the phase 3 RECORD-1 trial, the mammalian target of rapamycin (mTOR) inhibitor everolimus afforded clinical benefit with good tolerability in Western patients with mRCC whose disease had progressed despite VEGF receptor-tyrosine kinase inhibitor (VEGFr-TKI) therapy. This phase 1b study was designed to further evaluate the safety and efficacy of everolimus in VEGFr-TKI-refractory Chinese patients with mRCC. An open-label, multicenter phase 1b study enrolled Chinese patients with mRCC who were intolerant to, or progressed on, previous VEGFr-TKI therapy (N = 64). Patients received everolimus 10 mg daily until objective tumor progression (according to RECIST, version 1.0), unacceptable toxicity, death, or study discontinuation for any other reason. The final data analysis cut-off date was November 30, 2011. A total of 64 patients were included in the study. Median age was 52 years (range, 19–75 years) and 69% of patients were male. Median duration of everolimus therapy was 4.1 months (range, 0.0-16.1 months). Expected known class-effect toxicities related to mTOR inhibitor therapy were observed, including anemia (64%), hypertriglyceridemia (55%), mouth ulceration (53%), hyperglycemia (52%), hypercholesterolemia (50%), and pulmonary events (31%). Common grade 3/4 adverse events were anemia (20%), hyperglycemia (13%), increased gamma-glutamyltransferase (11%), hyponatremia (8%), dyspnea (8%), hypertriglyceridemia (6%), and lymphopenia (6%). Median PFS was 6.9 months (95% CI, 3.7-12.5 months) and the overall tumor response rate was 5% (95% CI, 1-13%). The majority of patients (61%) had stable disease as their best overall tumor response. Safety and efficacy results were comparable to those of the RECORD-1 trial. Everolimus is generally well tolerated and provides clinical

Defining safety culture and the nexus between safety goals and safety culture. 1. An Investigation Study on Practical Points of Safety Management

International Nuclear Information System (INIS)

Hasegawa, Naoko; Takano, Kenichi; Hirose, Ayako

2001-01-01

In a report after the Chernobyl accident, the International Atomic Energy Agency indicated the definition and the importance of safety culture and the ideal organizational state where safety culture pervades. However, the report did not mention practical approaches to enhance safety culture. In Japan, although there had been investigations that clarified the consciousness of employees and the organizational climate in the nuclear power and railway industries, organizational factors that clarified the level of organization safety and practical methods that spread safety culture in an organization had not been studied. The Central Research Institute of the Electric Power Industry conducted surveys of organizational culture for the construction, chemical, and manufacturing industries. The aim of our study was to clarify the organizational factors that influence safety in an organization expressed in employee safety consciousness, commitment to safety activities, rate of accidents, etc. If these areas were clarified, the level of organization safety might be evaluated, and practical ways could be suggested to enhance the safety culture. Consequently, a series of investigations was conducted to clarify relationships among organizational climate, employee consciousness, safety management and activities, and rate of accidents. The questionnaire surveys were conducted in 1998-1999. The subjects were (a) managers of the safety management sections in the head offices of the construction, chemical, and manufacturing industries; (b) responsible persons in factories of the chemical and manufacturing industries; and (c) general workers in factories of the chemical and manufacturing industries. The number of collected data was (a) managers in the head office: 48 from the construction industry and 58 from the chemical and manufacturing industries, (b) responsible persons in factories: 567, and (c) general workers: from 29 factories. Items in the questionnaires were selected from

To dimension safety valves. Probabilist study

International Nuclear Information System (INIS)

Noel, Robert; Couvreur, Denis

1982-01-01

The gauge of safety valves of a steam pressure apparatus is usually determined according to an operating situation envelope which it is admitted covers all that can happen in reality. For the safety of the dryer-superheaters of turbines in nuclear power stations, Electricite de France and Alsthom-Atlantique made a reliability study; its method is exposed and the results are discussed. Such a study is heavy going and complex, but in return it permits a better quantitative understanding of the various dimension and operating parameters of an installation which condition its safety. It is therefore a source of progress [fr

Model quality and safety studies

DEFF Research Database (Denmark)

Petersen, K.E.

1997-01-01

The paper describes the EC initiative on model quality assessment and emphasizes some of the problems encountered in the selection of data from field tests used in the evaluation process. Further, it discusses the impact of model uncertainties in safety studies of industrial plants. The model...... that most of these have never been through a procedure of evaluation, but nonetheless are used to assist in making decisions that may directly affect the safety of the public and the environment. As a major funder of European research on major industrial hazards, DGXII is conscious of the importance......-tain model is appropriate for use in solving a given problem. Further, the findings from the REDIPHEM project related to dense gas dispersion will be highlighted. Finally, the paper will discuss the need for model quality assessment in safety studies....

Immunogenicity and safety of tetravalent dengue vaccine in 2-11 year-olds previously vaccinated against yellow fever: randomized, controlled, phase II study in Piura, Peru.

Science.gov (United States)

Lanata, Claudio F; Andrade, Teresa; Gil, Ana I; Terrones, Cynthia; Valladolid, Omar; Zambrano, Betzana; Saville, Melanie; Crevat, Denis

2012-09-07

In a randomized, placebo-controlled, monocenter, observer blinded study conducted in an area where dengue is endemic, we assessed the safety and immunogenicity of a recombinant, live, attenuated, tetravalent dengue vaccine candidate (CYD-TDV) in 2-11 year-olds with varying levels of pre-existing yellow-fever immunity due to vaccination 1-7 years previously. 199 children received 3 injections of CYD-TDV (months 0, 6 and 12) and 99 received placebo (months 0 and 6) or pneumococcal polysaccharide vaccine (month 12). One month after the third dengue vaccination, serotype specific neutralizing antibody GMTs were in the range of 178-190 (1/dil) (versus 16.7-38.1 in the control group), a 10-20 fold-increase from baseline, and 94% of vaccines were seropositive to all four serotypes (versus 39% in the control group). There were no vaccine-related SAEs. The observed reactogenicity profile was consistent with phase I studies, with severity grade 1-2 injection site pain, headache, malaise and fever most frequently reported and no increase after subsequent vaccinations. Virologically confirmed dengue cases were seen after completion of the 3 doses: 1 in the CYD-TDV group (N=199), and 3 in the control group (N=99). A 3-dose regimen of CYD-TDV had a good safety profile in 2-11 year olds with a history of YF vaccination and elicited robust antibody responses that were balanced against the four serotypes. Copyright © 2012 Elsevier Ltd. All rights reserved.

A Randomized, Double-Blind, Placebo-Controlled, Phase 2b Study to Evaluate the Safety and Efficacy of Recombinant Human Soluble Thrombomodulin, ART-123, in Patients With Sepsis and Suspected Disseminated Intravascular Coagulation

NARCIS (Netherlands)

Vincent, Jean-Louis; Ramesh, Mayakonda K.; Ernest, David; Larosa, Steven P.; Pachl, Jan; Aikawa, Naoki; Hoste, Eric; Levy, Howard; Hirman, Joe; Levi, Marcel; Daga, Mradul; Kutsogiannis, Demetrios J.; Crowther, Mark; Bernard, Gordon R.; Devriendt, Jacques; Puigserver, Joan Vidal; Blanzaco, Daniel U.; Esmon, Charles T.; Parrillo, Joseph E.; Guzzi, Louis; Henderson, Seton J.; Pothirat, Chaicharn; Mehta, Parthiv; Fareed, Jawed; Talwar, Deepak; Tsuruta, Kazuhisa; Gorelick, Kenneth J.; Osawa, Yutaka; Kaul, Inder

2013-01-01

Objectives: To determine the safety and efficacy of recombinant thrombomodulin (ART-123) in patients with suspected sepsis-associated disseminated intravascular coagulation. Design: Phase 2b, international, multicenter, double-blind, randomized, placebo-controlled, parallel group, screening trial.

Safety of Nuclear Power Plants: Design. Specific Safety Requirements (Chinese Ed.)

International Nuclear Information System (INIS)

2012-01-01

On the basis of the principles included in the Fundamental Safety Principles, IAEA Safety Standards Series No. SF-1, this Safety Requirements publication establishes requirements applicable to the design of nuclear power plants. It covers the design phase and provides input for the safe operation of the power plant. It elaborates on the safety objective, safety principles and concepts that provide the basis for deriving the safety requirements that must be met for the design of a nuclear power plant. Contents: 1. Introduction; 2. Applying the safety principles and concepts; 3. Management of safety in design; 4. Principal technical requirements; 5. General plant design; 6. Design of specific plant systems.

Safety of Nuclear Power Plants: Design. Specific Safety Requirements (French Ed.)

International Nuclear Information System (INIS)

2012-01-01

On the basis of the principles included in the Fundamental Safety Principles, IAEA Safety Standards Series No. SF-1, this Safety Requirements publication establishes requirements applicable to the design of nuclear power plants. It covers the design phase and provides input for the safe operation of the power plant. It elaborates on the safety objective, safety principles and concepts that provide the basis for deriving the safety requirements that must be met for the design of a nuclear power plant. Contents: 1. Introduction; 2. Applying the safety principles and concepts; 3. Management of safety in design; 4. Principal technical requirements; 5. General plant design; 6. Design of specific plant systems.

Safety of Nuclear Power Plants: Design. Specific Safety Requirements (Arabic Ed.)

International Nuclear Information System (INIS)

2012-01-01

On the basis of the principles included in the Fundamental Safety Principles, IAEA Safety Standards Series No. SF-1, this Safety Requirements publication establishes requirements applicable to the design of nuclear power plants. It covers the design phase and provides input for the safe operation of the power plant. It elaborates on the safety objective, safety principles and concepts that provide the basis for deriving the safety requirements that must be met for the design of a nuclear power plant. Contents: 1. Introduction; 2. Applying the safety principles and concepts; 3. Management of safety in design; 4. Principal technical requirements; 5. General plant design; 6. Design of specific plant systems.

Safety and Efficacy of a Flexible Dosing Regimen of Ranibizumab in Neovascular Age-Related Macular Degeneration: The SUSTAIN Study

NARCIS (Netherlands)

Holz, Frank G.; Amoaku, Winfried; Donate, Juan; Guymer, Robyn H.; Kellner, Ulrich; Schlingemann, Reinier O.; Weichselberger, Andreas; Staurenghi, Giovanni

2011-01-01

Objective: To evaluate the safety and efficacy of individualized ranibizumab treatment in patients with neovascular age-related macular degeneration. Design: Twelve-month, phase III, multicenter, open-label, single-arm study. Participants: A total of 513 ranibizumab-naive SUSTAIN patients.

Evaluation of the Safety of Imatinib Mesylate in 200 Iraqi Patients with Chronic Myeloid Leukemia in the Chronic Phase: Single-Center Study

Directory of Open Access Journals (Sweden)

Bassam Francis Matti

2013-12-01

Full Text Available OBJECTIVE: Imatinib mesylate, a tyrosine kinase inhibitor, is presently the drug of choice for chronic myeloid leukemia (CML. During therapy, a few patients may develop hematological and non-hematological adverse effects. METHODS: The aim of this study was to evaluate the safety of imatinib therapy in patients with CML. Between December 2007 and October 2009 two hundred patients with CML in chronic phase were included in the study. Written informed consent was obtained from all patients prior to the start of the study. Imatinib was started at 400 mg orally daily. Patients were monitored carefully for any adverse effects. Complete blood count, liver, and renal function tests were done once in 2 weeks during the first month and on a monthly basis during follow-up. Toxicities that encountered were graded as per the National Cancer Institute common toxicity criteria version 2. Both hematologic and non-hematologic toxicities were managed with short interruptions of treatment and supportive measures, but the daily dose of imatinib was not reduced below 300 mg/day. RESULTS: Two hundred CML patients in chronic phase were included in this study; the male: female ratio was 0.7: 1 with mean age 39.06±13.21 years (ranged from 15-81 years. The study showed that the commonest hematological side effects were grade 2 anemia (12.5% followed by leukopenia (8% and thrombocytopenia (4%, while the most common non-hematological adverse effects were superficial edema and weight gain (51.5%, followed by musculoskeletal pain (35.5%, then gastro-intestinal symptoms (vomiting, diarrhea (19%. Fluid retention was the commonest side effect, which responded to low-dose diuretics. The drug was safe and well tolerated. There were no deaths due to toxicity. CONCLUSION: Imatinib mesylate a well-tolerated drug, and all undesirable effects could be ameliorated easily. The most common hematological and non-hematological side effects were anemia and fluid retention, respectively.

Preliminary Study of Applying Phase Change Materials (PCM) for Containment Passive Cooling

International Nuclear Information System (INIS)

Ko, A Reum; Lee, Jeong Ik; Yoon, Ho Joon

2016-01-01

Most of Pressurized Water Reactor (PWR) containments use fan cooler systems and containment spray systems. However, the importance of passive safety system has increased after the Fukushima accident. As the main passive safety system, Passive Containment Cooling System (PCCS), which utilizes natural phenomena to remove the heat released from the reactor, is suggested in the advanced pressurized water reactor (APWR). To increase the efficiency of passive cooling, additional passive containment cooling method using Phase Change Material (PCM) is suggested in this paper. For containment using PCMs, there are many advantages. Phase Change Material (PCM) is proposed as an additional passive containment cooling method to increase the efficiency of passive cooling in this paper. To apply proper PCMs to containment, commercially available PCMs were screened while reviewing thermophysical properties data and suggested selection criteria. A sensitivity study was also carried out to identify the effect of potential installation location of PCM using the CAP code. The pressure of containment in most cases showed slightly higher than that of the initial case. For the temperature of steam and water and humidity, similar results with the initial case were showed in most cases

Preliminary Study of Applying Phase Change Materials (PCM) for Containment Passive Cooling

Energy Technology Data Exchange (ETDEWEB)

Ko, A Reum; Lee, Jeong Ik [KAIST, Daejeon (Korea, Republic of); Yoon, Ho Joon [KUSTAR, Abu Dhabi (United Arab Emirates)

2016-05-15

Most of Pressurized Water Reactor (PWR) containments use fan cooler systems and containment spray systems. However, the importance of passive safety system has increased after the Fukushima accident. As the main passive safety system, Passive Containment Cooling System (PCCS), which utilizes natural phenomena to remove the heat released from the reactor, is suggested in the advanced pressurized water reactor (APWR). To increase the efficiency of passive cooling, additional passive containment cooling method using Phase Change Material (PCM) is suggested in this paper. For containment using PCMs, there are many advantages. Phase Change Material (PCM) is proposed as an additional passive containment cooling method to increase the efficiency of passive cooling in this paper. To apply proper PCMs to containment, commercially available PCMs were screened while reviewing thermophysical properties data and suggested selection criteria. A sensitivity study was also carried out to identify the effect of potential installation location of PCM using the CAP code. The pressure of containment in most cases showed slightly higher than that of the initial case. For the temperature of steam and water and humidity, similar results with the initial case were showed in most cases.

Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis (faSScinate) : a phase 2, randomised, controlled trial

NARCIS (Netherlands)

Khanna, Dinesh; Denton, Christopher P.; Jahreis, Angelika; van Laar, Jacob M.; Frech, Tracy M.; Anderson, Marina E.; Baron, Murray; Chung, Lorinda; Fierlbeck, Gerhard; Lakshminarayanan, Santhanam; Allanore, Yannick; Pope, Janet E.; Riemekasten, Gabriela; Steen, Virginia; Müller-Ladner, Ulf; Lafyatis, Robert; Stifano, Giuseppina; Spotswood, Helen; Chen-Harris, Haiyin; Dziadek, Sebastian; Morimoto, Alyssa; Sornasse, Thierry; Siegel, Jeffrey; Furst, Daniel E.

2016-01-01

Background Systemic sclerosis is a rare disabling autoimmune disease with few treatment options. The efficacy and safety of tocilizumab, an interleukin 6 receptor-α inhibitor, was assessed in the faSScinate phase 2 trial in patients with systemic sclerosis. Methods We did this double-blind,

Phase I expansion and pharmacodynamic study of the oral MEK inhibitor RO4987655 (CH4987655) in selected patients with advanced cancer with RAS-RAF mutations

NARCIS (Netherlands)

Zimmer, Lisa; Barlesi, Fabrice; Martinez-Garcia, Maria; Dieras, Veronique; Schellens, Jan H M; Spano, Jean-Philippe; Middleton, Mark R; Calvo, Emiliano; Paz-Ares, Luiz; Larkin, James; Pacey, Simon; Venturi, Miro; Kraeber-Bodéré, Françoise; Tessier, Jean J L; Eberhardt, Wilfried Ernst Erich; Paques, Michel; Guarin, Ernesto; Meresse, Valerie; Soria, Jean-Charles

2014-01-01

PURPOSE: This phase I expansion study assessed safety, pharmacodynamic effects, and antitumor activity of RO4987655, a pure MEK inhibitor, in selected patients with advanced solid tumor. EXPERIMENTAL DESIGN: We undertook a multicenter phase I two-part study (dose escalation and cohort expansion).

77 FR 27776 - Safety and Occupational Health Study Section (SOHSS), National Institute for Occupational Safety...

Science.gov (United States)

2012-05-11

... Occupational Health Study Section (SOHSS), National Institute for Occupational Safety and Health (NIOSH) In... Services Office, CDC, pursuant to Public Law 92-463. Purpose: The Safety and Occupational Health Study... standard grants review and funding cycles pertaining to research issues in occupational safety and health...

76 FR 18220 - Safety and Occupational Health Study Section (SOHSS), National Institute for Occupational Safety...

Science.gov (United States)

2011-04-01

... Occupational Health Study Section (SOHSS), National Institute for Occupational Safety and Health (NIOSH) In... Services Office, CDC, pursuant to Public Law 92-463. Purpose: The Safety and Occupational Health Study... standard grants review and funding cycles pertaining to research issues in occupational safety and health...

Efficacy and safety of tofacitinib as monotherapy in Japanese patients with active rheumatoid arthritis: a 12-week, randomized, phase 2 study.

Science.gov (United States)

Tanaka, Yoshiya; Takeuchi, Tsutomu; Yamanaka, Hisashi; Nakamura, Hiroyuki; Toyoizumi, Shigeyuki; Zwillich, Samuel

2015-07-01

To evaluate oral tofacitinib versus placebo for treatment of active rheumatoid arthritis in Japanese patients with inadequate response to disease-modifying antirheumatic drugs. In this double-blind, placebo-controlled, randomized, parallel-group, 12-week, phase 2 study (clinicaltrials.gov NCT00687193), 317 patients received tofacitinib: 1, 3, 5, 10, or 15 mg as monotherapy or placebo twice daily (BID). response rate by American College of Rheumatology (ACR) ≥ 20% improvement criteria (ACR20) at week 12. ACR20 response rates: 37.7% (20/53), 67.9% (36/53), 73.1% (38/52), 84.9% (45/53), and 90.7% (49/54) with tofacitinib: 1, 3, 5, 10, and 15 mg BID, respectively, versus 15.4% (8/52) with placebo (p tofacitinib versus placebo occurred from week 2 onward (p tofacitinib versus placebo from week 4 (p tofacitinib patients experienced treatment-related serious adverse events (AEs). Most common treatment-emergent AEs: nasopharyngitis (10% vs 12%) and hyperlipidemia (5% vs 0%). Serum creatinine, hemoglobin, and total-, low-, and high-density lipoprotein-cholesterol levels increased with tofacitinib. Tofacitinib produced dose-dependent ACR20 responses and reduced disease activity. The safety profile was consistent with that reported from global monotherapy trials.

Fusion reactor safety studies, FY 1977

International Nuclear Information System (INIS)

Darby, J.B. Jr.

1978-04-01

This report reviews the technical progress in the fusion reactor safety studies performed during FY 1977 in the Fusion Power Program at the Argonne National Laboratory. The subjects reported on include safety considerations of the vacuum vessel and first-wall design for the ANL/EPR, the thermal responses of a tokamak reactor first wall, the vacuum wall electrical resistive requirements in relationship to magnet safety, and a major effort is reported on considerations and experiments on air detritiation

Metholology for the selection of LWR safety R and D projects. Phase I, status report

International Nuclear Information System (INIS)

El-Sheikh, K.A.

1980-03-01

The objective of the LWR R and D Selection Methodology Program is to develop and demonstrate an R and D selection methodology appropriate for LWR safety technology. This report documents the development work from the program beginning in April, 1979 to the end of Fiscal Year 1979. The scope of work for this period included three tasks; methodology review (Task 1), measures development (Task 2), and methodology development for the first phase of application (Task 3). The accomplishments of these tasks are presented

Technical Guidance from the International Safety Framework for Nuclear Power Source Applications in Outer Space for Design and Development Phases

Science.gov (United States)

Summerer, Leopold

2014-08-01

In 2009, the International Safety Framework for Nuclear Power Source Applications in Outer Space [1] has been adopted, following a multi-year process that involved all major space faring nations in the frame of the International Atomic Energy Agency and the UN Committee on the Peaceful Uses of Outer Space. The safety framework reflects an international consensus on best practices. After the older 1992 Principles Relevant to the Use of Nuclear Power Sources in Outer Space, it is the second document at UN level dedicated entirely to space nuclear power sources.This paper analyses aspects of the safety framework relevant for the design and development phases of space nuclear power sources. While early publications have started analysing the legal aspects of the safety framework, its technical guidance has not yet been subject to scholarly articles. The present paper therefore focuses on the technical guidance provided in the safety framework, in an attempt to assist engineers and practitioners to benefit from these.

75 FR 26266 - Safety and Occupational Health Study Section (SOHSS), National Institute for Occupational Safety...

Science.gov (United States)

2010-05-11

... Occupational Health Study Section (SOHSS), National Institute for Occupational Safety and Health (NIOSH) In...) Public Law 92-463. Purpose: The Safety and Occupational Health Study Section will review, discuss, and... cycles pertaining to research issues in occupational safety and health, and allied areas. It is the...

Immunogenicity and safety of the new reduced-dose tetanus-diphtheria vaccine in healthy Korean adolescents: A comparative active control, double-blind, randomized, multicenter phase III study.

Science.gov (United States)

Han, Seung Beom; Rhim, Jung-Woo; Shin, Hye Jo; Kim, Sang Yong; Kim, Jong-Hyun; Kim, Hyun-Hee; Lee, Kyung-Yil; Kim, Hwang Min; Choi, Young Youn; Ma, Sang Hyuk; Kim, Chun Soo; Kim, Dong Ho; Ahn, Dong Ho; Kang, Jin Han

2017-04-01

A new reduced-dose tetanus-diphtheria (Td) vaccine was developed in Korea, and phase I and II clinical trials were successfully undertaken. We conducted this double-blind, randomized, multicenter phase III clinical trial to assess the immunogenicity and safety of the new Td vaccine. Healthy adolescents 11-12 years of age were enrolled and randomized to receive the new Td vaccine (study group) or a commercially available Td vaccine (control group). Blood samples were collected prior to and 4 weeks after the vaccination. Between the study and control groups, seroprotection rate, booster response, and geometric mean titer of antibodies against diphtheria and tetanus toxoids were compared after the vaccination. All solicited and unsolicited adverse events and serious adverse events during the 6-week study period were monitored. A total of 164 adolescents received vaccination, and 156 of them were evaluated to assess immunogenicity. The seroprotection rate and geometric mean titer for antibodies against diphtheria were significantly higher in the study group, whereas those against tetanus were significantly higher in the control group. However, all seroprotection rates against diphtheria and tetanus in the study and control groups were high: 100% against diphtheria and tetanus in the study group, and 98.7% against diphtheria and 100% against tetanus in the control group. No significant differences in the frequency of solicited and unsolicited adverse events were observed between the two vaccine groups. The new Td vaccine is highly immunogenic and safe, and this new Td vaccine can be effectively used for preventing diphtheria and tetanus. Copyright © 2015. Published by Elsevier B.V.

Safety Profile of Eslicarbazepine Acetate as Add-On Therapy in Adults with Refractory Focal-Onset Seizures: From Clinical Studies to 6 Years of Post-Marketing Experience.

Science.gov (United States)

Gama, Helena; Vieira, Mariana; Costa, Raquel; Graça, Joana; Magalhães, Luís M; Soares-da-Silva, Patrício

2017-12-01

Eslicarbazepine acetate was first approved in the European Union in 2009 as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization. The objective of this study was to review the safety profile of eslicarbazepine acetate analyzing the data from several clinical studies to 6 years of post-marketing surveillance. We used a post-hoc pooled safety analysis of four phase III, double-blind, randomized, placebo-controlled studies (BIA-2093-301, -302, -303, -304) of eslicarbazepine acetate as add-on therapy in adults. Safety data of eslicarbazepine acetate in special populations of patients aged ≥65 years with partial-onset seizures (BIA-2093-401) and subjects with moderate hepatic impairment (BIA-2093-111) and renal impairment (BIA-2093-112) are also considered. The incidences of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and serious adverse events were analyzed. The global safety database of eslicarbazepine acetate was analyzed for all cases from post-marketing surveillance from 1 October, 2009 to 21 October, 2015. From a pooled analysis of four phase III studies, it was concluded that the incidence of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and adverse drug reactions were dose dependent. Dizziness, somnolence, headache, and nausea were the most common treatment-emergent adverse events (≥10% of patients) and the majority were of mild-to-moderate intensity. No dose-dependent trend was observed for serious adverse events and individual serious adverse events were reported in less than 1% of patients. Hyponatremia was classified as a possibly related treatment-emergent adverse event in phase III studies (1.2%); however, after 6 years of post-marketing surveillance it represents the most frequently (10.2%) reported adverse drug reaction, with more than half of these cases occurring with eslicarbazepine acetate at

Rationale and design of the VISION study: a randomized, open-label study to evaluate the long-term safety of vonoprazan as maintenance treatment in patients with erosive esophagitis

Directory of Open Access Journals (Sweden)

Uemura N

2018-01-01

Full Text Available Naomi Uemura,1 Yoshikazu Kinoshita,2 Ken Haruma,3 Takashi Yao,4 Ryoji Kushima,5 Tatsuhiro Kanoo6 1Department of Gastroenterology and Hepatology, National Center for Global Health and Medicine, Kohnodai Hospital, Chiba, Japan; 2Department of Gastroenterology and Hepatology, Faculty of Medicine, Shimane University, Shimane, Japan; 3Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan; 4Department of Human Pathology, Juntendo University Graduate School of Medicine, Tokyo, Japan; 5Department of Clinical Laboratory Medicine, Shiga University of Medical Science Hospital, Shiga, Japan; 6Takeda Pharmaceutical Co., Ltd, Osaka, Japan Abstract: Erosive esophagitis (EE occurs when the epithelial mucosa is damaged due to gastric acid reflux, and the incidence of this disease is increasing in Japan due to changes in diet and lifestyle. The condition can be treated using proton pump inhibitors (PPIs that act by irreversibly blocking the H+,K+-ATPase responsible for acid secretion. Vonoprazan is a K+ competitive channel inhibitor, which reversibly and potently inhibits gastric acid secretion. However, long-term data on vonoprazan use are limited. The aim of the VISION trial is to investigate the long-term efficacy and safety of vonoprazan in comparison with the PPI lansoprazole. This randomized, multicenter, 5-year, open-label study has a planned recruitment of 195 participants (2:1 allocation vonoprazan:lansoprazole from 33 sites in Japan. The study comprises an 8-week “healing” phase (vonoprazan 20 mg or lansoprazole 30 mg p.o. and a 260-week “maintenance” phase (vonoprazan 10 mg or lansoprazole 15 mg. Safety populations in both phases are defined as participants who receive at least one dose of the study or control drug in the healing and maintenance phases, respectively. The full analysis set in both phases is defined as participants who are randomized and receive at least one dose of the study or

Study of Iodine Behavior in the Gas Phase during a Severe Accident

International Nuclear Information System (INIS)

Kim, Hanchul; Cho, Yeonghun; Ryu, Myunghyun

2014-01-01

Among the iodine species, the organic iodides produced from the reaction between iodine and organics such as paint, are not easily trapped by the filters during the containment venting following a severe accident. Korea Institute of Nuclear Safety (KINS) has been studying this issue, joining international research programs such as ISTP-EPICUR, OECDBIP and OECD-STEM. In the course of this study, a simple iodine model, RAIM (Radio-Active Iodine chemistry Model) has been developed (Oh et al., 2011), based on the IMOD methodology, and other previous studies. This paper deals with our recent activities on this study, including the development of the model for the iodine reactions in gas phase. Iodine reactions in gas phase were modeled and added to the RAIM code, taking into account several relevant reactions such as formation of ARP, iodine oxide, and organic iodides in gas phase. RAIM was then applied to analyze the S2-6-5-2 test for which iodine-loaded coupons were tested in gas phase. The analysis results show a reasonable estimation of volatile iodine concentration with the desorption rate constant of about 10 -6 s -1 , while those of the other iodine species overestimated for the whole period of the test. It reveals the need to determine appropriate values for the rate constants for formation of iodine oxides and organic iodides

Phase I randomized safety study of twice daily dosing of acidform vaginal gel: candidate antimicrobial contraceptive.

Directory of Open Access Journals (Sweden)

Marla J Keller

Full Text Available BACKGROUND: Acidform gel, an acid-buffering product that inactivates spermatozoa, may be an effective topical non-hormonal contraceptive. This study was designed to evaluate the safety of vaginal dosing and effects of Acidform on mucosal immune mediators, antimicrobial properties of genital secretions, and vaginal microbiota. METHODS: Thirty-six sexually abstinent U.S. women were randomized to apply Acidform or hydroxyethylcellulose (HEC placebo gel twice daily for 14 consecutive days. Safety was assessed by symptoms and pelvic examination. The impact of gel on mucosal immunity was assessed by quantifying cytokines, chemokines, antimicrobial proteins and antimicrobial activity of genital secretions collected by cervicovaginal lavage (CVL at screening, 2 hours after gel application, and on days 7, 14 and 21. Vaginal microbiota was characterized at enrollment and day 14 using species-specific quantitative PCR assays. RESULTS: The median vaginal and cervical pH was significantly lower 2 hours after application of Acidform and was associated with an increase in the bactericidal activity of CVL against E. coli. However, 65% of women who received Acidform had at least one local adverse event compared with 11% who received placebo (p = 0.002. While there was no increase in inflammatory cytokines or chemokines, CVL concentrations of lactoferrin and interleukin-1 receptor antagonist (IL-1ra, an anti-inflammatory protein, were significantly lower following Acidform compared to HEC placebo gel application. There were no significant changes in Lactobacillus crispatus or Lactobacillus jensenii in either group but there was a decrease in Gardnerella vaginalis in the Acidform group (p = 0.08. CONCLUSIONS: Acidform gel may augment mucosal defense as evidenced by an increase in bactericidal activity of genital secretions against E. coli and a decrease in Gardnerella vaginalis colonization. However, Acidform was associated with more irritation than

Phase I Randomized Safety Study of Twice Daily Dosing of Acidform Vaginal Gel: Candidate Antimicrobial Contraceptive

Science.gov (United States)

Keller, Marla J.; Carpenter, Colleen A.; Lo, Yungtai; Einstein, Mark H.; Liu, Congzhou; Fredricks, David N.; Herold, Betsy C.

2012-01-01

Background Acidform gel, an acid-buffering product that inactivates spermatozoa, may be an effective topical non-hormonal contraceptive. This study was designed to evaluate the safety of vaginal dosing and effects of Acidform on mucosal immune mediators, antimicrobial properties of genital secretions, and vaginal microbiota. Methods Thirty-six sexually abstinent U.S. women were randomized to apply Acidform or hydroxyethylcellulose (HEC) placebo gel twice daily for 14 consecutive days. Safety was assessed by symptoms and pelvic examination. The impact of gel on mucosal immunity was assessed by quantifying cytokines, chemokines, antimicrobial proteins and antimicrobial activity of genital secretions collected by cervicovaginal lavage (CVL) at screening, 2 hours after gel application, and on days 7, 14 and 21. Vaginal microbiota was characterized at enrollment and day 14 using species-specific quantitative PCR assays. Results The median vaginal and cervical pH was significantly lower 2 hours after application of Acidform and was associated with an increase in the bactericidal activity of CVL against E. coli. However, 65% of women who received Acidform had at least one local adverse event compared with 11% who received placebo (p = 0.002). While there was no increase in inflammatory cytokines or chemokines, CVL concentrations of lactoferrin and interleukin-1 receptor antagonist (IL-1ra), an anti-inflammatory protein, were significantly lower following Acidform compared to HEC placebo gel application. There were no significant changes in Lactobacillus crispatus or Lactobacillus jensenii in either group but there was a decrease in Gardnerella vaginalis in the Acidform group (p = 0.08). Conclusions Acidform gel may augment mucosal defense as evidenced by an increase in bactericidal activity of genital secretions against E. coli and a decrease in Gardnerella vaginalis colonization. However, Acidform was associated with more irritation than placebo and lower levels

Study of reactor parameters on the critical systems. Phase I; Ispitivanje reaktorskih parametara na kriticnim sistemima, I faza

Energy Technology Data Exchange (ETDEWEB)

Raisic, N et al [Boris Kidric Institute of Nuclear Sciences Vinca, Belgrade (Yugoslavia)

1962-08-15

Phase 1 of the report on reactor parameters study describes the preparation of the RB reactor for operation including the following tasks: Completing and verification of reactor safety system; arranging dosimetry instruments; formation of fuel elements with 2% enriched fuel and aluminium holders; improvement of the heavy water level-meter; mounting the horizontal experimental channel; formation of reactor lattice with 16 cm pitch; testing the reactor system; filling the tank with heavy water and preparing the safety report.

Pharmacokinetic and safety profile of tofacitinib in children with polyarticular course juvenile idiopathic arthritis: results of a phase 1, open-label, multicenter study.

Science.gov (United States)

Ruperto, Nicolino; Brunner, Hermine I; Zuber, Zbigniew; Tzaribachev, Nikolay; Kingsbury, Daniel J; Foeldvari, Ivan; Horneff, Gerd; Smolewska, Elzbieta; Vehe, Richard K; Hazra, Anasuya; Wang, Rong; Mebus, Charles A; Alvey, Christine; Lamba, Manisha; Krishnaswami, Sriram; Stock, Thomas C; Wang, Min; Suehiro, Ricardo; Martini, Alberto; Lovell, Daniel J

2017-12-28

Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease and a leading cause of childhood disability. The objective of this study was to characterize the PK, safety, and taste acceptability of tofacitinib in patients with JIA. This Phase 1, open-label, multiple-dose (twice daily [BID] for 5 days) study of tofacitinib in patients with active (≥ 5 joints) polyarticular course JIA was conducted from March 2013-December 2015. Patients were allocated to one of three age-based cohorts: Cohort 1, 12 to Tofacitinib was administered according to age and body weight as tablets or oral solution (grape flavor). PK were assessed on Day 5; safety was assessed at screening, Day 1, and Day 5. Taste acceptability of the oral solution was evaluated. Twenty-six patients (age range 2-17 years) were enrolled: Cohort 1, N = 8; Cohort 2, N = 9; Cohort 3, N = 9; median tofacitinib doses were 5.0, 2.5, and 3.0 mg BID, respectively. The higher median tofacitinib dose in Cohort 3 versus Cohort 2 reflected implementation of an amended dosing scheme following an interim PK analysis after Cohort 2 recruitment. Geometric mean AUC at steady state (AUC tau ) was 156.6 ng•h/mL in Cohort 1, 118.8 ng•h/mL in Cohort 2, and 142.5 ng•h/mL in Cohort 3; C max (ng/mL) was 47.0, 41.7, and 66.2, respectively. C trough , C min , and t 1/2 were similar in Cohorts 2 and 3, but higher in Cohort 1. Median time to C max (T max ) was similar between cohorts. Apparent clearance and volume of distribution decreased with decreasing age. Tofacitinib was well tolerated, with no serious adverse events or discontinuations due to adverse events reported. Taste acceptability was confirmed. PK findings from this study in children with polyarticular course JIA established dosing regimens and acceptable taste for use in subsequent studies within the tofacitinib pediatric development program. ClinicalTrials.gov: NCT01513902 .

The French underground research laboratory program, contribution to the feasibility and safety studies of geological disposal

International Nuclear Information System (INIS)

Hoorelbeke, J.M.; Niezborala, J.M.; Ben Slimane, K.

2001-01-01

The paper presents the content of the research program to be performed during the construction and the operation of the National Agency for Radioactive Waste Management's (ANDRA) underground laboratory, located in the east of France. The general architecture of the program is presented. Emphasis is put on an iterative process, the purpose of which is mainly to: Prepare site behavior models before starting each phase of the field work (bore hole drilling, shaft sinking, construction of underground galleries, specific experiments); Test and check each model through actual observations and measurements; Adjust the models to take into account the results of the former phase and predict the results expected during the following one. All these models, after validation, will be exploited during the assessment of the safety related performance of the components of the potential repository as well as the whole facility; Obtain necessary data related to the feasibility study of the disposal facility (mechanical design, thermal design, etc.,) and its safety assessment. The relationship between the experimental program, the conceptual design program and the safety evaluation program is explained in order to reach the project objectives which is the final document set to be provided to French authorities in 2006 according to the French law of December 1991. (author)

Application of the statistical process control method for prospective patient safety monitoring during the learning phase: robotic kidney transplantation with regional hypothermia (IDEAL phase 2a-b).

Science.gov (United States)

Sood, Akshay; Ghani, Khurshid R; Ahlawat, Rajesh; Modi, Pranjal; Abaza, Ronney; Jeong, Wooju; Sammon, Jesse D; Diaz, Mireya; Kher, Vijay; Menon, Mani; Bhandari, Mahendra

2014-08-01

Traditional evaluation of the learning curve (LC) of an operation has been retrospective. Furthermore, LC analysis does not permit patient safety monitoring. To prospectively monitor patient safety during the learning phase of robotic kidney transplantation (RKT) and determine when it could be considered learned using the techniques of statistical process control (SPC). From January through May 2013, 41 patients with end-stage renal disease underwent RKT with regional hypothermia at one of two tertiary referral centers adopting RKT. Transplant recipients were classified into three groups based on the robotic training and kidney transplant experience of the surgeons: group 1, robot trained with limited kidney transplant experience (n=7); group 2, robot trained and kidney transplant experienced (n=20); and group 3, kidney transplant experienced with limited robot training (n=14). We employed prospective monitoring using SPC techniques, including cumulative summation (CUSUM) and Shewhart control charts, to perform LC analysis and patient safety monitoring, respectively. Outcomes assessed included post-transplant graft function and measures of surgical process (anastomotic and ischemic times). CUSUM and Shewhart control charts are time trend analytic techniques that allow comparative assessment of outcomes following a new intervention (RKT) relative to those achieved with established techniques (open kidney transplant; target value) in a prospective fashion. CUSUM analysis revealed an initial learning phase for group 3, whereas groups 1 and 2 had no to minimal learning time. The learning phase for group 3 varied depending on the parameter assessed. Shewhart control charts demonstrated no compromise in functional outcomes for groups 1 and 2. Graft function was compromised in one patient in group 3 (pcontrol chart analytic techniques. These methods allow determination of the duration of mentorship and identification of adverse events in a timely manner. A new operation

Center for Maritime Safety and Health Studies

Data.gov (United States)

Federal Laboratory Consortium — Established in November 2015, the Center for Maritime Safety and Health Studies (CMSHS) promotes safety and health for all maritime workers, including those employed...

Reliability analysis of the recirculation phase of the safety injection system of Angra-1

International Nuclear Information System (INIS)

Rivera, R.R.J.M.

1981-09-01

The calculation of several reliability parameters-failure probability, unavailability and unreliability - of the recirculation phase of the safety injection system of Angra-1, was done. This system has two distinct modes of operation (short term and long term) which were fault tree analysed both separately and as a whole. To obtain quantitative results the computer codes SAMPLE and PRET-KITT were utilized. The former was used to consider the uncertainties in the failure data (drawn integrally from WASH-1400) and the latter to obtain time dependent unreliability values. Hardware failures and common-mode failures were considered. Altough the analysis methods employed here differ somewhat from those used in WASH-1400, the results which could be compared were found to have the order of magnitude. A viability study of some suggestions of system's modifications was performed, and it has shown that some significant reliability improvements can be achieved with reasonably simple changes. (Author) [pt

Study of reactor parameters of on critical systems, Phase I: Safety report for RB zero power reactor

International Nuclear Information System (INIS)

Raisic, N.

1962-09-01

In addition to the safety analysis for the zero power RB reactor, this report contains a general description of the reactor, reactor components, auxiliary equipment and the reactor building. Reactor Rb has been reconstructed during 1961-1962 and supplied with new safety-control system as well as with a complete dosimetry instrumentation. Since RB reactor was constructed without shielding special attention is devoted to safety and protection of the staff performing experiments. Due to changed circumstances in the Institute ( start-up of the RA 7 MW power reactor) the role of the RB reactor was redefined

Phase I/Phase II Study of Blinatumomab in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia.

Science.gov (United States)

von Stackelberg, Arend; Locatelli, Franco; Zugmaier, Gerhard; Handgretinger, Rupert; Trippett, Tanya M; Rizzari, Carmelo; Bader, Peter; O'Brien, Maureen M; Brethon, Benoît; Bhojwani, Deepa; Schlegel, Paul Gerhardt; Borkhardt, Arndt; Rheingold, Susan R; Cooper, Todd Michael; Zwaan, Christian M; Barnette, Phillip; Messina, Chiara; Michel, Gérard; DuBois, Steven G; Hu, Kuolung; Zhu, Min; Whitlock, James A; Gore, Lia

2016-12-20

Purpose Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19 on B-cell lymphoblasts. We evaluated the safety, pharmacokinetics, recommended dosage, and potential for efficacy of blinatumomab in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Methods This open-label study enrolled children treatment cycles. Primary end points were maximum-tolerated dosage (phase I) and complete remission rate within the first two cycles (phase II). Results We treated 49 patients in phase I and 44 patients in phase II. Four patients had dose-limiting toxicities in cycle 1 (phase I). Three experienced grade 4 cytokine-release syndrome (one attributed to grade 5 cardiac failure); one had fatal respiratory failure. The maximum-tolerated dosage was 15 µg/m 2 /d. Blinatumomab pharmacokinetics was linear across dosage levels and consistent among age groups. On the basis of the phase I data, the recommended blinatumomab dosage for children with relapsed/refractory ALL was 5 µg/m 2 /d for the first 7 days, followed by 15 µg/m 2 /d thereafter. Among the 70 patients who received the recommended dosage, 27 (39%; 95% CI, 27% to 51%) achieved complete remission within the first two cycles, 14 (52%) of whom achieved complete minimal residual disease response. The most frequent grade ≥ 3 adverse events were anemia (36%), thrombocytopenia (21%), and hypokalemia (17%). Three patients (4%) and one patient (1%) had cytokine-release syndrome of grade 3 and 4, respectively. Two patients (3%) interrupted treatment after grade 2 seizures. Conclusion This trial, which to the best of our knowledge was the first such trial in pediatrics, demonstrated antileukemic activity of single-agent blinatumomab with complete minimal residual disease response in children with relapsed/refractory BCP-ALL. Blinatumomab may represent an important new treatment option in this setting, requiring further investigation in curative indications.

The first symposium of Research Center for Radiation Safety, NIRS. Perspective of future studies of radiation safety

International Nuclear Information System (INIS)

Shimo, Michikuni

2002-03-01

This paper summarizes presentations given in the title symposium, held at the Conference Room of National Institute of Radiological Sciences (NIRS) on November 29 and 30, 2001. Contained are Introductory remarks: Basic presentations concerning exposure dose in man; Environmental levels of radiation and radioactivity, environmental radon level and exposure dose, and radiation levels in the specific environment (like in the aircraft): Special lecture (biological effects given by space environment) concerning various needs for studies of radiation safety; Requirement for open investigations, from the view of utilization, research and development of atomic energy, from the clinical aspect, and from the epidemiological aspect: Special lecture (safety in utilization of atomic energy and radiation-Activities of Nuclear Safety Commission of Japan) concerning present state and perspective of studies of radiation safety; Safety of radiation and studies of biological effects of radiation-perspective, and radiation protection and radiation safety studies: Studies in the Research Center for Radiation Safety; Summary of studies in the center, studies of the biological effects of neutron beam, carcinogenesis by radiation and living environmental factors-complicated effects, and studies of hereditary effects: Panel discussion (future direction of studies of radiation safety for the purpose of the center's direction): and concluding remarks. (N.I.)

Efficacy and safety of the biosimilar ABP 501 compared with adalimumab in patients with moderate to severe rheumatoid arthritis: a randomised, double-blind, phase III equivalence study.

Science.gov (United States)

Cohen, Stanley; Genovese, Mark C; Choy, Ernest; Perez-Ruiz, Fernando; Matsumoto, Alan; Pavelka, Karel; Pablos, Jose L; Rizzo, Warren; Hrycaj, Pawel; Zhang, Nan; Shergy, William; Kaur, Primal

2017-10-01

ABP 501 is a Food and Drug Administration-approved biosimilar to adalimumab; structural, functional and pharmacokinetic evaluations have shown that the two are highly similar. We report results from a phase III study comparing efficacy, safety and immunogenicity between ABP 501 and adalimumab. In this randomised, double-blind, active comparator-controlled, 26-week equivalence study, patients with moderate to severe active rheumatoid arthritis (RA) despite methotrexate were randomised (1:1) to ABP 501 or adalimumab (40 mg) every 2 weeks. Primary endpoint was risk ratio (RR) of ACR20 between groups at week 24. Primary hypothesis that the treatments were equivalent would be confirmed if the 90% CI for RR of ACR20 at week 24 fell between 0.738 and 1.355, demonstrating that ABP 501 is similar to adalimumab. Secondary endpoints included Disease Activity Score 28-joint count-C reactive protein (DAS28-CRP). Safety was assessed via adverse events (AEs) and laboratory evaluations. Antidrug antibodies were assessed to determine immunogenicity. A total of 526 patients were randomised (n=264, ABP 501; n=262 adalimumab) and 494 completed the study. ACR20 response at week 24 was 74.6% (ABP 501) and 72.4% (adalimumab). At week 24, the RR of ACR20 (90% CI) between groups was 1.039 (0.954, 1.133), confirming the primary hypothesis. Changes from baseline in DAS28-CRP, ACR50 and ACR70 were similar. There were no clinically meaningful differences in AEs and laboratory abnormalities. A total of 38.3% (ABP 501) and 38.2% (adalimumab) of patients tested positive for binding antidrug antibodies. Results from this study demonstrate that ABP 501 is similar to adalimumab in clinical efficacy, safety and immunogenicity in patients with moderate to severe RA. NCT01970475; Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Safety and tolerability of a cell culture derived trivalent subunit inactivated influenza vaccine administered to healthy children and adolescents: A Phase III, randomized, multicenter, observer-blind study.

Science.gov (United States)

Nolan, Terry; Chotpitayasunondh, Tawee; Capeding, Maria Rosario; Carson, Simon; Senders, Shelly David; Jaehnig, Peter; de Rooij, Richard; Chandra, Richa

2016-01-04

Cell culture-derived inactivated influenza vaccines (TIVc) are necessary for scale and predictability of production to meet global demand. This study compared the safety and tolerability of TIVc with an egg-derived trivalent influenza vaccine (TIVf) in 4-17 yearolds. A Phase 3 observer blind, multicenter study enrolled 2055 healthy participants randomized 2:1 to receive either TIVc or TIVf, respectively (1372 TIVc and 683 TIVf evaluable subjects). Participants received one dose each on Days 1 and 28 (4-8 year-olds not previously vaccinated [NPV]) or one dose on Day 1 (4-8 and 9-17 yearolds previously vaccinated [PV]). Solicited adverse events (AEs) occurring within 7 days after each vaccination were assessed; participants were followed up for 6 months after their last dose for safety. Most solicited and unsolicited AEs were mild to moderate with vaccine-related SAEs were reported. TIVc and TIVf were similar in percentages of participants reporting solicited reactions in 4-8 years NPV group after the 1st dose: local reactions, TIVc: 48%, TIVf: 43%; systemic reactions, TIVc: 34%, TIVf: 32%; percentages were lower following the 2nd dose in TIVc; local reactions: TIVc: 40%; TIVf: 43%; systemic reactions: TIVc: 21%; TIVf: 22%. In 4-17 years PV group, solicited reactions were lower following TIVf, local reactions: TIVc: 53%; TIVf: 43%; systemic reactions: TIVc: 37%, TIVf: 30%. Injection-site pain was the most common solicited reaction, and was similar following TIVc and TIVf in 4-8 yearolds (TIVc: 56%; TIVf: 55%), and lower following TIVf in 9-17 years group (TIVc: 52%; TIVf: 42%). Reporting of unsolicited AEs was similar for TIVc and TIVf across the two age groups. TIVc was well tolerated and had a safety and reactogenicity profile similar to that of TIVf in healthy 4-17 yearolds (NCT01857206). Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Probabilistic safety goals for nuclear power plants; Phases 2-4. Final report

Energy Technology Data Exchange (ETDEWEB)

Bengtsson, L.; Knochenhauer, M. (Scandpower AB (Sweden)); Holmberg, J.-E.; Rossi, J. (VTT Technical Research Centre of Finland (Finland))

2011-05-15

Safety goals are defined in different ways in different countries and also used differently. Many countries are presently developing them in connection to the transfer to risk-informed regulation of both operating nuclear power plants (NPP) and new designs. However, it is far from self-evident how probabilistic safety criteria should be defined and used. On one hand, experience indicates that safety goals are valuable tools for the interpretation of results from a probabilistic safety assessment (PSA), and they tend to enhance the realism of a risk assessment. On the other hand, strict use of probabilistic criteria is usually avoided. A major problem is the large number of different uncertainties in a PSA model, which makes it difficult to demonstrate the compliance with a probabilistic criterion. Further, it has been seen that PSA results can change a lot over time due to scope extensions, revised operating experience data, method development, changes in system requirements, or increases of level of detail, mostly leading to an increase of the frequency of the calculated risk. This can cause a problem of consistency in the judgments. This report presents the results from the second, third and fourth phases of the project (2007-2009), which have dealt with providing guidance related to the resolution of some specific problems, such as the problem of consistency in judgement, comparability of safety goals used in different industries, the relationship between criteria on different levels, and relations between criteria for level 2 and 3 PSA. In parallel, additional context information has been provided. This was achieved by extending the international overview by contributing to and benefiting from a survey on PSA safety criteria which was initiated in 2006 within the OECD/NEA Working Group Risk. The results from the project can be used as a platform for discussions at the utilities on how to define and use quantitative safety goals. The results can also be used by

Probabilistic safety goals for nuclear power plants; Phases 2-4. Final report

International Nuclear Information System (INIS)

Bengtsson, L.; Knochenhauer, M.; Holmberg, J.-E.; Rossi, J.

2011-05-01

Safety goals are defined in different ways in different countries and also used differently. Many countries are presently developing them in connection to the transfer to risk-informed regulation of both operating nuclear power plants (NPP) and new designs. However, it is far from self-evident how probabilistic safety criteria should be defined and used. On one hand, experience indicates that safety goals are valuable tools for the interpretation of results from a probabilistic safety assessment (PSA), and they tend to enhance the realism of a risk assessment. On the other hand, strict use of probabilistic criteria is usually avoided. A major problem is the large number of different uncertainties in a PSA model, which makes it difficult to demonstrate the compliance with a probabilistic criterion. Further, it has been seen that PSA results can change a lot over time due to scope extensions, revised operating experience data, method development, changes in system requirements, or increases of level of detail, mostly leading to an increase of the frequency of the calculated risk. This can cause a problem of consistency in the judgments. This report presents the results from the second, third and fourth phases of the project (2007-2009), which have dealt with providing guidance related to the resolution of some specific problems, such as the problem of consistency in judgement, comparability of safety goals used in different industries, the relationship between criteria on different levels, and relations between criteria for level 2 and 3 PSA. In parallel, additional context information has been provided. This was achieved by extending the international overview by contributing to and benefiting from a survey on PSA safety criteria which was initiated in 2006 within the OECD/NEA Working Group Risk. The results from the project can be used as a platform for discussions at the utilities on how to define and use quantitative safety goals. The results can also be used by

Safety and tolerability of tegaserod in patients with chronic constipation: pooled data from two phase III studies.

LENUS (Irish Health Repository)

Quigley, Eamonn M M

2012-02-03

BACKGROUND & AIMS: Studies show that tegaserod effectively relieves the symptoms of chronic constipation\\/idiopathic constipation (CC). This pooled analysis assessed the safety and tolerability of tegaserod in a large dataset of CC patients. METHODS: Adverse event (AE) data were pooled from 2 double-blind, placebo-controlled phase III trials of 12 weeks\\' duration. Post hoc analysis was conducted for the most frequent AEs (incidence, >or=3%). RESULTS: Eight hundred eighty-one, 861, and 861 patients received tegaserod 6 mg twice a day, 2 mg twice a day, or placebo, respectively. Most AEs were mild\\/moderately severe. AE incidence was similar for the tegaserod 6 mg and 2 mg twice a day (57.1% and 56.3%, respectively) and placebo groups (59.6%) and most frequent in the gastrointestinal system (tegaserod 6 mg twice a day, 25.8%; 2 mg twice a day, 22.5%; placebo, 24.6%). Headache, the most common AE, was slightly more frequent in the placebo group (tegaserod 6 mg twice a day, 11.0%; 2 mg twice a day, 10.1%; placebo, 13.2%). Diarrhea (generally transient and resolved with continued treatment) was the only AE with a statistically significant difference between groups (tegaserod 6 mg twice a day 6.6% vs placebo 3.0%, P=.0005). Serious AE incidence (1.4% overall) was comparable across treatment groups, although abdominal surgery was less common in the combined tegaserod (0.5%) than the placebo group (1.0%). Discontinuation as a result of AEs was slightly higher in tegaserod 6 mg twice a day patients (5.7%; 2 mg twice a day, 3.3%; placebo, 3.7%), mainly because of diarrhea. Laboratory and electrocardiogram parameters were comparable across groups. CONCLUSIONS: Tegaserod is well tolerated by patients with CC during 12 weeks of treatment.

Lessons learned from measuring safety culture: an Australian case study.

Science.gov (United States)

Allen, Suellen; Chiarella, Mary; Homer, Caroline S E

2010-10-01

adverse events in maternity care are relatively common but often avoidable. International patient safety strategies advocate measuring safety culture as a strategy to improve patient safety. Evidence suggests it is necessary to fully understand the safety culture of an organisation to make improvements to patient safety. this paper reports a case study examining the safety culture in one maternity service in Australia and considers the benefits of using surveys and interviews to understand safety culture as an approach to identify possible strategies to improve patient safety in this setting. the study took place in one maternity service in two public hospitals in NSW, Australia. Concurrently, both hospitals were undergoing an organisational restructure which was part of a major health reform agenda. The priorities of the reform included improving the quality of care and patient safety; and, creating a more efficient health system by reducing administration inefficiencies and duplication. a descriptive case study using three approaches: the safety culture was identified to warrant improvement across all six safety culture domains. There was reduced infrastructure and capacity to support incident management activities required to improve safety, which was influenced by instability from the organisational restructure. There was a perceived lack of leadership at all levels to drive safety and quality and improving the safety culture was neither a key priority nor was it valued by the organisation. the safety culture was complex as was undertaking this study. We were unable to achieve a desired 60% response rate highlighting the limitations of using safety culture surveys in isolation as a strategy to improve safety culture. Qualitative interviews provided greater insight into the factors influencing the safety culture. The findings of this study provide evidence of the benefits of including qualitative methods with quantitative surveys when examining safety culture

Safety assessment in plant layout design using indexing approach: implementing inherent safety perspective. Part 1 - guideword applicability and method description.

Science.gov (United States)

Tugnoli, Alessandro; Khan, Faisal; Amyotte, Paul; Cozzani, Valerio

2008-12-15

Layout planning plays a key role in the inherent safety performance of process plants since this design feature controls the possibility of accidental chain-events and the magnitude of possible consequences. A lack of suitable methods to promote the effective implementation of inherent safety in layout design calls for the development of new techniques and methods. In the present paper, a safety assessment approach suitable for layout design in the critical early phase is proposed. The concept of inherent safety is implemented within this safety assessment; the approach is based on an integrated assessment of inherent safety guideword applicability within the constraints typically present in layout design. Application of these guidewords is evaluated along with unit hazards and control devices to quantitatively map the safety performance of different layout options. Moreover, the economic aspects related to safety and inherent safety are evaluated by the method. Specific sub-indices are developed within the integrated safety assessment system to analyze and quantify the hazard related to domino effects. The proposed approach is quick in application, auditable and shares a common framework applicable in other phases of the design lifecycle (e.g. process design). The present work is divided in two parts: Part 1 (current paper) presents the application of inherent safety guidelines in layout design and the index method for safety assessment; Part 2 (accompanying paper) describes the domino hazard sub-index and demonstrates the proposed approach with a case study, thus evidencing the introduction of inherent safety features in layout design.

Professional conceptualisation and accomplishment of patient safety in mental healthcare: an ethnographic approach

Directory of Open Access Journals (Sweden)

Braithwaite Jeffrey

2011-05-01

Full Text Available Abstract Background This study seeks to broaden current understandings of what patient safety means in mental healthcare and how it is accomplished. We propose a qualitative observational study of how safety is produced or not produced in the complex context of everyday professional mental health practice. Such an approach intentionally contrasts with much patient safety research which assumes that safety is achieved and improved through top-down policy directives. We seek instead to understand and articulate the connections and dynamic interactions between people, materials, and organisational, legal, moral, professional and historical safety imperatives as they come together at particular times and places to perform safe or unsafe practice. As such we advocate an understanding of patient safety 'from the ground up'. Methods/Design The proposed project employs a six-phase data collection framework in two mental health settings: an inpatient unit and a community team. The first four phases comprise multiple modes of focussed, unobtrusive observation of professionals at work, to enable us to trace the conceptualisation and enactment of safety as revealed in dialogue and narrative, use of artefacts and space, bodily activity and patterns of movement, and in the accomplishment of specific work tasks. An interview phase and a social network analysis phase will subsequently be conducted to offer comparative perspectives on the observational data. This multi-modal and holistic approach to studying patient safety will complement existing research, which is dominated by instrumentalist approaches to discovering factors contributing to error, or developing interventions to prevent or manage adverse events. Discussion This ethnographic research framework, informed by the principles of practice theories and in particular actor-network ideas, provides a tool to aid the understanding of patient safety in mental healthcare. The approach is novel in that it

Professional conceptualisation and accomplishment of patient safety in mental healthcare: an ethnographic approach

Science.gov (United States)

2011-01-01

Background This study seeks to broaden current understandings of what patient safety means in mental healthcare and how it is accomplished. We propose a qualitative observational study of how safety is produced or not produced in the complex context of everyday professional mental health practice. Such an approach intentionally contrasts with much patient safety research which assumes that safety is achieved and improved through top-down policy directives. We seek instead to understand and articulate the connections and dynamic interactions between people, materials, and organisational, legal, moral, professional and historical safety imperatives as they come together at particular times and places to perform safe or unsafe practice. As such we advocate an understanding of patient safety 'from the ground up'. Methods/Design The proposed project employs a six-phase data collection framework in two mental health settings: an inpatient unit and a community team. The first four phases comprise multiple modes of focussed, unobtrusive observation of professionals at work, to enable us to trace the conceptualisation and enactment of safety as revealed in dialogue and narrative, use of artefacts and space, bodily activity and patterns of movement, and in the accomplishment of specific work tasks. An interview phase and a social network analysis phase will subsequently be conducted to offer comparative perspectives on the observational data. This multi-modal and holistic approach to studying patient safety will complement existing research, which is dominated by instrumentalist approaches to discovering factors contributing to error, or developing interventions to prevent or manage adverse events. Discussion This ethnographic research framework, informed by the principles of practice theories and in particular actor-network ideas, provides a tool to aid the understanding of patient safety in mental healthcare. The approach is novel in that it seeks to articulate an 'anatomy

Fire safety assessment of tunnel structures

DEFF Research Database (Denmark)

Gkoumas, Konstantinos; Giuliani, Luisa; Petrini, Francesco

2011-01-01

.g. structural and non structural, organizational, human behavior). This is even more truth for the fire safety design of such structures. Fire safety in tunnels is challenging because of the particular environment, bearing in mind also that a fire can occur in different phases of the tunnel’s lifecycle. Plans...... for upgrading fire safety provisions and tunnel management are also important for existing tunnels. In this study, following a brief introduction of issues regarding the above mentioned aspects, the structural performance of a steel rib for a tunnel infrastructure subject to fire is assessed by means...

Phase II study of the safety and antitumor activity of the hypoxia-activated prodrug TH-302 in combination with doxorubicin in patients with advanced soft tissue sarcoma.

Science.gov (United States)

Chawla, Sant P; Cranmer, Lee D; Van Tine, Brian A; Reed, Damon R; Okuno, Scott H; Butrynski, James E; Adkins, Douglas R; Hendifar, Andrew E; Kroll, Stew; Ganjoo, Kristen N

2014-10-10

TH-302, a prodrug of the cytotoxic alkylating agent bromo-isophosphoramide mustard, is preferentially activated in hypoxic conditions. This phase II study investigated TH-302 in combination with doxorubicin, followed by single-agent TH-302 maintenance therapy in patients with first-line advanced soft tissue sarcoma (STS) to assess progression-free survival (PFS), response rate, overall survival, safety, and tolerability. In this open-label phase II study, TH-302 300 mg/m(2) was administered intravenously on days 1 and 8 with doxorubicin 75 mg/m(2) on day 1 of each 21-day cycle. After six cycles, patients with stable and/or responding disease could receive maintenance monotherapy with TH-302. Ninety-one patients initiated TH-302 plus doxorubicin induction treatment. The PFS rate at 6 months (primary efficacy measure) was 58% (95% CI, 46% to 68%). Median PFS was 6.5 months (95% CI, 5.8 to 7.7 months); median overall survival was 21.5 months (95% CI, 16.0 to 26.2 months). Best tumor responses were complete response (n = 2 [2%]) and partial response (n = 30 [34%]). During TH-302 maintenance (n = 48), five patients improved from stable disease to partial response, and one patient improved from partial to complete response. The most common adverse events during induction were fatigue, nausea, and skin and/or mucosal toxicities as well as anemia, thrombocytopenia, and neutropenia. These were less severe and less frequent during maintenance. There was no evidence of TH-302-related hepatic, renal, or cardiac toxicity. PFS, overall survival, and tumor response compared favorably with historical outcomes achieved with other first-line chemotherapies for advanced STS. A phase III study of TH-302 is ongoing (NCT01440088). © 2014 by American Society of Clinical Oncology.

Comparative study of runaway electron diffusion in the rise phase of ...

Indian Academy of Sciences (India)

The behaviour of runaway electrons in the SINP tokamak, which can be operated in a normal edge safety factor () (NQ) discharge configuration as well as in a low (LQ) configuration, was experimentally investigated, during the initial plasma generation phase. An energy analysis of the runaway electron dynamics in ...

Behavioral integrity for safety, priority of safety, psychological safety, and patient safety : a team-level study

NARCIS (Netherlands)

Leroy, H.; Dierynck, B.; Anseel, F.; Simons, T.; Halbesleben, J.R.; McCaughey, D.; Savage, G.T.; Sels, L.

2012-01-01

This article clarifies how leader behavioral integrity for safety helps solve follower's double bind between adhering to safety protocols and speaking up about mistakes against protocols. Path modeling of survey data in 54 nursing teams showed that head nurse behavioral integrity for safety

Closure of the condensed-phase organic-nitrate reaction unreviewed safety question at Hanford site

International Nuclear Information System (INIS)

COWLEY, W.L.

1999-01-01

A discovery Unreviewed Safety Question (USQ) was declared on the underground waste storage tanks at the Hanford Site in May 1996. The USQ was for condensed-phase organic-nitrate reactions (sometimes called organic complexant reactions) in the tanks. This paper outlines the steps taken to close the USQ, and resolve the related safety issue. Several processes were used at the Hanford Site to extract and/or process plutonium. These processes resulted in organic complexants (for chelating multivalent cations) and organic extraction solvents being sent to the underground waste storage tanks. This paper addresses the organic complexant hazard. The organic complexants are in waste matrices that include inert material, diluents, and potential oxidizers. In the presence of oxidizing material, the complexant salts can be made to react exothermically by heating to high temperatures or by applying an external ignition source of sufficient energy. The first organic complexant hazard assessments focused on determining whether a hulk runaway reaction could occur, similar to the 1957 accident at Kyshtm (a reprocessing plant in the former U.S.S.R.). Early analyses (1977 through 1994) examined organic-nitrate reaction onset temperatures and concluded that a bulk runaway reaction could not occur at the Hanford Site because tank temperatures were well below that necessary for bulk runaway. Therefore, it was believed that organic-nitrate reactions were adequately described in the then current Authorization Basis (AB). Subsequent studies examined a different accident scenario, propagation resulting from an external ignition source (e.g., lightning or welding slag) that initiates a combustion front that propagates through the organic waste. A USQ evaluation determined that localized high energy ignition sources were credible, and that point source ignition of organic complexant waste was not adequately addressed i n the then existing AB. Consequently, the USQ was declared on the

A study on safety climate at nuclear power plants

International Nuclear Information System (INIS)

Fukui, Hirokazu; Yoshida, Michio; Yoshiyama, Naohiro

2001-01-01

In the current study, we define safety climate as an organizational environment that induces members of the organization to give consideration to safety or take safety actions. It is of utmost importance that people holding managerial positions in an organization have a good understanding of the characteristics of the safety climate of the organization and implement safety promotion activities effectively. In the current research, we studied the rating scales and the characteristics of a safety climate. A survey was conducted, targeting technical engineers who belong to the three power stations of Kansai Electric Power Co., Inc. The questionnaire mainly consisted of questions concerning safety measures taken by individuals and questions concerning safety measures taken by the organization, to which the individuals belong. As a result of a factor analysis of the responses, we extracted five factors, namely, 'confidence in knowledge and skill', attitude of supervisors,' 'safety education in workplace', 'clarity of tasks' and 'safety confirmation/report'. In studying the rating scales of the safety climate, we selected five items from each of the above five factors, and used the total scores of the ratings of the five items as scores of each factor. Then, we examined the correlation between scores of personal factors and scores of organizational environment factors. We treated the scores of safety confirmation/report' and 'confidence in knowledge and skill', which are personal factors, as criterion variables, and the scores of 'attitude of supervisors', 'safety education in workplace' and 'clarity of tasks', which are organizational environment factors, as predictor variables. As a result, we found that levels of 'safety confirmation/report' and 'confidence in knowledge and skill' can be deduced from the scores of 'attitude of supervisors', 'safety education in workplace' and 'clarity of tasks.' Hence, we have decided to use these three organizational environment

Safety and immunogenicity of a live attenuated mumps vaccine: a phase I clinical trial.

Science.gov (United States)

Liang, Yan; Ma, Jingchen; Li, Changgui; Chen, Yuguo; Liu, Longding; Liao, Yun; Zhang, Ying; Jiang, Li; Wang, Xuan-Yi; Che, Yanchun; Deng, Wei; Li, Hong; Cui, Xiaoyu; Ma, Na; Ding, Dong; Xie, Zhongping; Cui, Pingfang; Ji, Qiuyan; Wang, JingJing; Zhao, Yuliang; Wang, Junzhi; Li, Qihan

2014-01-01

Mumps, a communicable, acute and previously well-controlled disease, has had recent and occasional resurgences in some areas. A randomized, double-blind, controlled and multistep phase I study of an F-genotype attenuated mumps vaccine produced in human diploid cells was conducted. A total of 300 subjects were enrolled and divided into 4 age groups: 16-60 years, 5-16 years, 2-5 years and 8-24 months. The groups were immunized with one injection per subject. Three different doses of the F-genotype attenuated mumps vaccine, A (3.5 ± 0.25 logCCID50), B (4.25 ± 0.25 logCCID50) and C (5.0 ± 0.25 logCCID50), as well as a placebo control and a positive control of a licensed A-genotype vaccine (S79 strain) were used. The safety and immunogenicity of this vaccine were compared with those of the controls. The safety evaluation suggested that mild adverse reactions were observed in all groups. No serious adverse event (SAE) was reported throughout the trial. The immunogenicity test showed a similar seroconversion rate of the neutralizing and ELISA antibody in the 2- to 5-year-old and 8- to 24-month-old groups compared with the seroconversion rate in the positive control. The GMT of the neutralizing anti-F-genotype virus antibodies in the vaccine groups was slightly higher than that in the positive control group. The F-genotype attenuated mumps vaccine evaluated in this clinical trial was demonstrated to be safe and have effective immunogenicity vs. control.

Comparative study of runaway electron diffusion in the rise phase of ...

Indian Academy of Sciences (India)

Abstract. The behaviour of runaway electrons in the SINP tokamak, which can be operated in a normal edge safety factor (qa) (NQ) discharge configuration as well as in a low qa (LQ) configuration, was experimentally investigated, during the initial plasma generation phase. An energy analysis of the runaway electron ...

Criticality safety basics, a study guide

Energy Technology Data Exchange (ETDEWEB)

V. L. Putman

1999-09-01

This document is a self-study and classroom guide, for criticality safety of activities with fissile materials outside nuclear reactors. This guide provides a basic overview of criticality safety and criticality accident prevention methods divided into three parts: theory, application, and history. Except for topic emphasis, theory and history information is general, while application information is specific to the Idaho National Engineering and Environmental Laboratory (INEEL). Information presented here should be useful to personnel who must know criticality safety basics to perform their assignments safely or to design critically safe equipment or operations. However, the guide's primary target audience is fissile material handler candidates.

Criticality safety basics, a study guide

International Nuclear Information System (INIS)

Putman, V.L.

1999-01-01

This document is a self-study and classroom guide, for criticality safety of activities with fissile materials outside nuclear reactors. This guide provides a basic overview of criticality safety and criticality accident prevention methods divided into three parts: theory, application, and history. Except for topic emphasis, theory and history information is general, while application information is specific to the Idaho National Engineering and Environmental Laboratory (INEEL). Information presented here should be useful to personnel who must know criticality safety basics to perform their assignments safely or to design critically safe equipment or operations. However, the guide's primary target audience is fissile material handler candidates

Phase I clinical studies of the advanced glycation end-product (AGE)-breaker TRC4186: safety, tolerability and pharmacokinetics in healthy subjects.

Science.gov (United States)

Chandra, Kumar P; Shiwalkar, Ajay; Kotecha, Jignesh; Thakkar, Purav; Srivastava, Ambrish; Chauthaiwale, Vijay; Sharma, Sanjay K; Cross, Maurice R; Dutt, Chaitanya

2009-01-01

Advanced glycation end-products (AGEs) have been implicated in the pathogenesis of diabetic complications through a variety of mechanisms including endothelial dysfunction and structural abnormalities in the vasculature and myocardium. Reducing the AGEs burden and their ensuing pro-inflammatory, pro-oxidative and pro-coagulant effect with associated dysfunctional proteins in various target tissues may retard the progression of and even reverse diabetic macro- and microvascular complications. Pyridinium, 3-[[2-(methylsulfonyl) hydrazino] carbonyl]-1-[2-oxo-2-2-thienyl) ethyl]-chloride (TRC4186) has demonstrated AGE-breaking activities in in vitro experiments and improvement in the endothelial and myocardial function in animal models of diabetes mellitus with reduction of AGEs accumulation in tissues over time. The safety of TRC4186 has been established in in vitro and in vivo preclinical studies. Thus, this drug is being developed for the treatment of complications associated with diabetes. This investigation set out to evaluate the safety, tolerability and pharmacokinetics of TRC4186 in healthy human subjects after single and multiple ascending doses, fixed doses in elderly male and female subjects, and with food and different formulations of the compound. Four studies were conducted during phase I clinical development of TRC4186. These were: (i) a randomized, double-blind, placebo-controlled, single-dose, dose-ascending study in healthy male subjects with doses of TRC4186 ranging from 250 to 2500 mg administered as an oral solution (total six doses); (ii) a randomized, double-blind, placebo-controlled, multiple-dose, dose-ascending study in healthy male subjects with three doses of TRC4186 ranging from 500 to 2000 mg twice daily for 6 days with a final single dose on day 7; (iii) a randomized, open-label, three-way crossover study to assess the effect of food (fasted vs fed) and formulation (solution vs tablet) with TRC4186 500 mg; (iv) a randomized, double

Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: Long-term efficacy and safety results from 2 randomized phase-III studies and 1 open-label long-term extension study.

Science.gov (United States)

Papp, Kim A; Krueger, James G; Feldman, Steven R; Langley, Richard G; Thaci, Diamant; Torii, Hideshi; Tyring, Stephen; Wolk, Robert; Gardner, Annie; Mebus, Charles; Tan, Huaming; Luo, Yingchun; Gupta, Pankaj; Mallbris, Lotus; Tatulych, Svitlana

2016-05-01

Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. We sought to report longer-term tofacitinib efficacy and safety in patients with moderate to severe psoriasis. Data from 2 identical phase-III studies, Oral-treatment Psoriasis Trial Pivotal 1 and 2, were pooled with data from these patients in an ongoing open-label long-term extension study. Patients (n = 1861) were randomized 2:2:1 to tofacitinib 5 mg, 10 mg, or placebo twice daily (BID). At week 16, placebo patients were rerandomized to tofacitinib. Pivotal study participants could enroll into the long-term extension where they received tofacitinib at 10 mg BID for 3 months, after which dosing could be 5 or 10 mg BID. At week 28, the proportions of patients randomized to tofacitinib 5 and 10 mg BID achieving 75% or greater reduction in Psoriasis Area and Severity Index score from baseline were 55.6% and 68.8%, and achieving Physician Global Assessment of clear or almost clear were 54.7% and 65.9%. Efficacy was maintained in most patients through 24 months. Serious adverse events and discontinuations because of adverse events were reported in less than 11% of patients over 33 months of tofacitinib exposure. There was no dose comparison beyond week 52. Oral tofacitinib demonstrated sustained efficacy in patients with psoriasis through 2 years, with 10 mg BID providing greater efficacy than 5 mg BID. No unexpected safety findings were observed. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Model Transformation for a System of Systems Dependability Safety Case

Science.gov (United States)

Murphy, Judy; Driskell, Steve

2011-01-01

The presentation reviews the dependability and safety effort of NASA's Independent Verification and Validation Facility. Topics include: safety engineering process, applications to non-space environment, Phase I overview, process creation, sample SRM artifact, Phase I end result, Phase II model transformation, fault management, and applying Phase II to individual projects.

An open-label extension study of the safety and efficacy of risperidone in children and adolescents with autistic disorder.

Science.gov (United States)

Kent, Justine M; Hough, David; Singh, Jaskaran; Karcher, Keith; Pandina, Gahan

2013-12-01

The purpose of this study was to evaluate the long-term safety and efficacy of risperidone in treating irritability and related behaviors in children and adolescents with autistic disorders. In this 6 month (26 week) open-label extension (OLE) study, patients (5-17 years of age, who completed the previous fixed-dose, 6 week, double-blind [DB] phase) were flexibly dosed with risperidone based on body weight. The maximum allowed dose was 1.25 mg/day for those weighing 20 to autistic, psychiatric, and behavioral disorders. Patients experienced some additional improvement in irritability and related behaviors. This phase-4 study is registered at ClinicalTrials.gov (NCT00576732).

Safety and immunogenicity of a meningococcal B recombinant vaccine when administered with routine vaccines to healthy infants in Taiwan: A phase 3, open-label, randomized study.

Science.gov (United States)

Chiu, Nan-Chang; Huang, Li-Min; Willemsen, Arnold; Bhusal, Chiranjiwi; Arora, Ashwani Kumar; Mojares, Zenaida Reynoso; Toneatto, Daniela

2018-01-16

Neisseria meningitidis is associated with high mortality and morbidity in infants and children worldwide. This phase 3 study (NCT02173704) evaluated safety and immunogenicity of a 4-component serogroup B recombinant meningococcal vaccine (4CMenB) co-administered with routine vaccines in Taiwanese infants. In total, 225 healthy infants were randomized (2 : 1 ) to receive 4CMenB and routine vaccines (4CMenB+Routine) or routine vaccines only (Routine group) at 2, 4, 6 and 12 months of age. Routine vaccines were diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b, 13-valent pneumococcal, hepatitis B, measles-mumps-rubella and varicella vaccines. Immune responses to 4CMenB components (factor H binding protein [fHbp], Neisserial adhesin A [NadA], porin A [PorA] and Neisseria heparin-binding antigen [NHBA]) were evaluated at 1 month post-primary and post-booster vaccination, using human serum bactericidal assay (hSBA). Reactogenicity and safety were also assessed. A sufficient immune response was demonstrated for fHbp, NadA and PorA, at 1 month post-primary and booster vaccination. In the 4CMenB+Routine group, hSBA titers ≥5 were observed in all infants for fHbp and NadA, in 79% and 59% of infants for PorA and NHBA, respectively, at 1 month post-primary vaccination and in 92-99% of infants for all antigens, at 1 month post-booster vaccination. In the 4CMenB+Routine group, hSBA geometric mean titers for all antigens increased post-primary (8.41-963) and post-booster vaccination (17-2315) compared to baseline (1.01-1.36). Immunogenicity of 4CMenB was not impacted by co-administration with routine pediatric vaccines in infants. Reactogenicity was slightly higher in the 4CMenB+Routine group compared with Routine group, but no safety concerns were identified.

Safety analysis procedures for PHWR

International Nuclear Information System (INIS)

Min, Byung Joo; Kim, Hyoung Tae; Yoo, Kun Joong

2004-03-01

The methodology of safety analyses for CANDU reactors in Canada, a vendor country, uses a combination of best-estimate physical models and conservative input parameters so as to minimize the uncertainty of the plant behavior predictions. As using the conservative input parameters, the results of the safety analyses are assured the regulatory requirements such as the public dose, the integrity of fuel and fuel channel, the integrity of containment and reactor structures, etc. However, there is not the comprehensive and systematic procedures for safety analyses for CANDU reactors in Korea. In this regard, the development of the safety analyses procedures for CANDU reactors is being conducted not only to establish the safety analyses system, but also to enhance the quality assurance of the safety assessment. In the first phase of this study, the general procedures of the deterministic safety analyses are developed. The general safety procedures are covered the specification of the initial event, selection of the methodology and accident sequences, computer codes, safety analysis procedures, verification of errors and uncertainties, etc. Finally, These general procedures of the safety analyses are applied to the Large Break Loss Of Coolant Accident (LBLOCA) in Final Safety Analysis Report (FSAR) for Wolsong units 2, 3, 4

Results of FY 2002 of feasibility study on commercialized fast reactor cycle systems. Phase 2

International Nuclear Information System (INIS)

2003-06-01

Japan Nuclear Cycle Development Institute (JNC) and Japan Atomic Power Company (JAPC, that is the representative of the electric utilities in Japan) established a new organization to develop a commercialized fast reactor (FR) cycle system on July 1, 1999 and feasibility study (F/S) was undertaken in order to determine the promising concepts and to define the necessary R and D tasks. During Phase 1 (JFY 1999 and 2000), a number of candidate concepts were screened from various options, featuring innovative technologies. In the F/S, the options were evaluated and conceptual designs were examined considering the attainable perspectives for following: 1) ensuring safety, 2) economic competitiveness to future LWRs, 3) efficient utilization of resources, 4) reduction of environmental burden and 5) enhancement of nuclear non-proliferation. The F/S should also guide the necessary R and D to commercialize FR cycle system. To begin with the study of feasible candidate concepts screened in Phase I, Phase 2 started in the plan for five years in 2001. This aims at clarifying several feasible candidate concepts and deciding the research plan after Phase 3 as taking into consideration the innovative technology. As for this plan, an interim report will be carried out in 2003 as one pause and the prospect to clarify the feasible candidates will be expected. Furthermore, after the completion of this research and investigation program, research and development activities will be carried out under a rolling plan in which reviews will be carried out approximately every five years. The objective of these R and D activities is to make a proposal regarding highly attractive and competitive FR cycle system technology that assures safety by 2015. This report summarizes the results of F/S of Phase 2 in 2002. In 2002, the second year of Phase 2, the study was advanced along with the plan which was evaluated by the committee for the Evaluation. Then, in the study of FR system and fuel cycle

Safety certification of airborne software: An empirical study

International Nuclear Information System (INIS)

Dodd, Ian; Habli, Ibrahim

2012-01-01

Many safety-critical aircraft functions are software-enabled. Airborne software must be audited and approved by the aerospace certification authorities prior to deployment. The auditing process is time-consuming, and its outcome is unpredictable, due to the criticality and complex nature of airborne software. To ensure that the engineering of airborne software is systematically regulated and is auditable, certification authorities mandate compliance with safety standards that detail industrial best practice. This paper reviews existing practices in software safety certification. It also explores how software safety audits are performed in the civil aerospace domain. The paper then proposes a statistical method for supporting software safety audits by collecting and analysing data about the software throughout its lifecycle. This method is then empirically evaluated through an industrial case study based on data collected from 9 aerospace projects covering 58 software releases. The results of this case study show that our proposed method can help the certification authorities and the software and safety engineers to gain confidence in the certification readiness of airborne software and predict the likely outcome of the audits. The results also highlight some confidentiality issues concerning the management and retention of sensitive data generated from safety-critical projects.

Longterm Safety and Efficacy of Subcutaneous Abatacept in Patients with Rheumatoid Arthritis: 5-year Results from a Phase IIIb Trial.

Science.gov (United States)

Genovese, Mark C; Pacheco-Tena, César; Covarrubias, Arturo; Leon, Gustavo; Mysler, Eduardo; Keiserman, Mauro; Valente, Robert M; Nash, Peter; Simon-Campos, J Abraham; Box, Jane; Legerton, Clarence W; Nasonov, Evgeny; Durez, Patrick; Elegbe, Ayanbola; Wong, Robert; Li, Xiaohui; Banerjee, Subhashis; Alten, Rieke

2018-04-15

To assess 5-year safety, tolerability, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate (MTX)-refractory patients with rheumatoid arthritis (RA). The Abatacept Comparison of sub[QU]cutaneous versus intravenous in Inadequate Responders to methotrexatE (ACQUIRE) phase IIIb, randomized, double-dummy, multinational trial compared efficacy and safety of SC and intravenous (IV) ABA in patients with RA. In the initial 6-month double-blind (DB) period, patients received IV or SC ABA, plus MTX, and in the subsequent open-label longterm extension (LTE) period, all patients received SC ABA (125 mg/wk). The final 5-year safety, tolerability, and efficacy analyses are reported. Of 1385 patients who completed the DB period, 1372 entered LTE and 945 (68.8%) completed ≥ 5 years of treatment. During LTE, 97 (7.1%) patients discontinued treatment because of an adverse event (AE). Incidence rate (IR; event/100 patient-yrs of exposure; based on LTE data, 95% CI) for AE of interest were the following: serious AE 7.73 (6.96-8.58), infection 38.60 (36.24-41.12), serious infection 1.68 (1.35-2.07), malignancies 1.09 (0.84-1.42), and autoimmune disorders 1.33 (1.05-1.69), and were stable over time. No association between immunogenicity and either worsening of ABA safety or loss of efficacy was noted. Efficacy in the LTE was consistent with the DB period and was maintained to the end of the study. These 5-year data establish that SC ABA (125 mg/wk) has a consistent safety profile and durable efficacy for longterm treatment of patients with RA who had an inadequate response to MTX.

Charged-particle beam: a safety mandate

International Nuclear Information System (INIS)

Young, K.C.

1983-01-01

The Advanced Test Accelerator (ATA) is a recent development in the field of charged particle beam research at Lawrence Livermore National Laboratory. With this experimental apparatus, researchers will characterize intense pulses of electron beams propagated through air. Inherent with the ATA concept was the potential for exposure to hazards, such as high radiation levels and hostile breathing atmospheres. The need for a comprehensive safety program was mandated; a formal system safety program was implemented during the project's conceptual phase. A project staff position was created for a safety analyst who would act as a liaison between the project staff and the safety department. Additionally, the safety analyst would be responsible for compiling various hazards analyses reports, which formed the basis of th project's Safety Analysis Report. Recommendations for safety features from the hazards analysis reports were incorporated as necessary at appropriate phases in project development rather than adding features afterwards. The safety program established for the ATA project faciliated in controlling losses and in achieving a low-level of acceptable risk

Quality management of pharmacology and safety pharmacology studies

DEFF Research Database (Denmark)

Spindler, Per; Seiler, Jürg P

2002-01-01

to safety pharmacology studies, and, when indicated, to secondary pharmacodynamic studies, does not influence the scientific standards of studies. However, applying formal GLP standards will ensure the quality, reliability and integrity of studies, which reflect sound study management. It is important...... to encourage a positive attitude among researchers and academics towards these lines, whenever possible. GLP principles applied to the management of non-clinical safety studies are appropriate quality standards when studies are used in the context of protecting public health, and these quality standards...... of pharmacology studies (ICH S7A): primary pharmacodynamic, secondary pharmacodynamic and safety pharmacology studies, and guidance on the quality standards (expectations for GLP conformity) for these study types have been provided. Primary pharmacodynamic studies are the only study types that are fully exempt...

U18 : Traffic signal safety (phase B).

Science.gov (United States)

2009-08-01

Efficiently scheduling traffic, particularly heavy vehicles, remains a key challenge in transportation engineering. This project has focused on the development of a novel trafficsignal-control methodology to improve the safety of heavy vehicles on...

A study on safety climate at nuclear power plants

Energy Technology Data Exchange (ETDEWEB)

Fukui, Hirokazu [Institute of Nuclear Safety System Inc., Mihama, Fukui (Japan); Yoshida, Michio; Yoshiyama, Naohiro [Japan Institute for Group Dynamics, Fukuoka (Japan)

2001-09-01

In the current study, we define safety climate as an organizational environment that induces members of the organization to give consideration to safety or take safety actions. It is of utmost importance that people holding managerial positions in an organization have a good understanding of the characteristics of the safety climate of the organization and implement safety promotion activities effectively. In the current research, we studied the rating scales and the characteristics of a safety climate. A survey was conducted, targeting technical engineers who belong to the three power stations of Kansai Electric Power Co., Inc. The questionnaire mainly consisted of questions concerning safety measures taken by individuals and questions concerning safety measures taken by the organization, to which the individuals belong. As a result of a factor analysis of the responses, we extracted five factors, namely, 'confidence in knowledge and skill', attitude of supervisors,' 'safety education in workplace', 'clarity of tasks' and 'safety confirmation/report'. In studying the rating scales of the safety climate, we selected five items from each of the above five factors, and used the total scores of the ratings of the five items as scores of each factor. Then, we examined the correlation between scores of personal factors and scores of organizational environment factors. We treated the scores of safety confirmation/report' and 'confidence in knowledge and skill', which are personal factors, as criterion variables, and the scores of 'attitude of supervisors', 'safety education in workplace' and 'clarity of tasks', which are organizational environment factors, as predictor variables. As a result, we found that levels of 'safety confirmation/report' and 'confidence in knowledge and skill' can be deduced from the scores of 'attitude of supervisors', 'safety

Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies.

Science.gov (United States)

Andrade, E L; Bento, A F; Cavalli, J; Oliveira, S K; Schwanke, R C; Siqueira, J M; Freitas, C S; Marcon, R; Calixto, J B

2016-12-12

The process of drug development involves non-clinical and clinical studies. Non-clinical studies are conducted using different protocols including animal studies, which mostly follow the Good Laboratory Practice (GLP) regulations. During the early pre-clinical development process, also known as Go/No-Go decision, a drug candidate needs to pass through several steps, such as determination of drug availability (studies on pharmacokinetics), absorption, distribution, metabolism and elimination (ADME) and preliminary studies that aim to investigate the candidate safety including genotoxicity, mutagenicity, safety pharmacology and general toxicology. These preliminary studies generally do not need to comply with GLP regulations. These studies aim at investigating the drug safety to obtain the first information about its tolerability in different systems that are relevant for further decisions. There are, however, other studies that should be performed according to GLP standards and are mandatory for the safe exposure to humans, such as repeated dose toxicity, genotoxicity and safety pharmacology. These studies must be conducted before the Investigational New Drug (IND) application. The package of non-clinical studies should cover all information needed for the safe transposition of drugs from animals to humans, generally based on the non-observed adverse effect level (NOAEL) obtained from general toxicity studies. After IND approval, other GLP experiments for the evaluation of chronic toxicity, reproductive and developmental toxicity, carcinogenicity and genotoxicity, are carried out during the clinical phase of development. However, the necessity of performing such studies depends on the new drug clinical application purpose.

A-Part Gel, an adhesion prophylaxis for abdominal surgery: a randomized controlled phase I-II safety study [NCT00646412].

Science.gov (United States)

Lang, Reinhold; Baumann, Petra; Schmoor, Claudia; Odermatt, Erich K; Wente, Moritz N; Jauch, Karl-Walter

2015-01-01

Intra-abdominal surgical intervention can cause the development of intra-peritoneal adhesions. To reduce this problem, different agents have been tested to minimize abdominal adhesions; however, the optimal adhesion prophylaxis has not been found so far. Therefore, the A-Part(®) Gel was developed as a barrier to diminish postsurgical adhesions; the aim of this randomized controlled study was a first evaluation of its safety and efficacy. In this prospective, controlled, randomized, patient-blinded, monocenter phase I-II study, 62 patients received either the hydrogel A-Part-Gel(®) as an anti-adhesive barrier or were untreated after primary elective median laparotomy. Primary endpoint was the occurrence of peritonitis and/or wound healing impairment 28 ± 10 days postoperatively. As secondary endpoints anastomotic leakage until 28 days after surgery, adverse events and adhesions were assessed until 3 months postoperatively. A lower rate of wound healing impairment and/or peritonitis was observed in the A-Part Gel(®) group compared to the control group: (6.5 vs. 13.8 %). The difference between the two groups was -7.3%, 90 % confidence interval [-20.1, 5.4 %]. Both treatment groups showed similar frequency of anastomotic leakage but incidence of adverse events and serious adverse events were slightly lower in the A-Part Gel(®) group compared to the control. Adhesion rates were comparable in both groups. A-Part Gel(®) is safe as an adhesion prophylaxis after abdominal wall surgery but no reduction of postoperative peritoneal adhesion could be found in comparison to the control group. This may at least in part be due to the small sample size as well as to the incomplete coverage of the incision due to the used application. NCT00646412.

2005 dossier: granite. Tome: safety analysis of the geologic disposal

International Nuclear Information System (INIS)

2005-01-01

This document makes a status of the researches carried out by the French national agency of radioactive wastes (ANDRA) about the safety aspects of the geologic disposal of high-level and long-lived (HLLL) radioactive wastes in granite formations. Content: 1 - safety approach: context and general goal, references, design approach by safety functions, safety approach during the construction-exploitation-observation-closure phase, safety analysis during the post-closure phase; 2 - general description: HLLL wastes, granitic environment, general structure of the architecture of a disposal facility; 3 - safety functions and disposal design: general context, safety functions of the long-term disposal, design dispositions retained to answer the functions; 4 - operational safety: people's protection, radiological risks during exploitation, risk analysis in accident situation; 5 - qualitative safety analysis: methodology, main results of the analysis of the features, events and processes (FEP) database; 6 - disposal efficiency evaluation during post-closure phase: calculation models, calculation tools used for the modeling of radionuclides transport, calculation results and main lessons. (J.S.)

Optimal dose selection accounting for patient subpopulations in a randomized Phase II trial to maximize the success probability of a subsequent Phase III trial.

Science.gov (United States)

Takahashi, Fumihiro; Morita, Satoshi

2018-02-08

Phase II clinical trials are conducted to determine the optimal dose of the study drug for use in Phase III clinical trials while also balancing efficacy and safety. In conducting these trials, it may be important to consider subpopulations of patients grouped by background factors such as drug metabolism and kidney and liver function. Determining the optimal dose, as well as maximizing the effectiveness of the study drug by analyzing patient subpopulations, requires a complex decision-making process. In extreme cases, drug development has to be terminated due to inadequate efficacy or severe toxicity. Such a decision may be based on a particular subpopulation. We propose a Bayesian utility approach (BUART) to randomized Phase II clinical trials which uses a first-order bivariate normal dynamic linear model for efficacy and safety in order to determine the optimal dose and study population in a subsequent Phase III clinical trial. We carried out a simulation study under a wide range of clinical scenarios to evaluate the performance of the proposed method in comparison with a conventional method separately analyzing efficacy and safety in each patient population. The proposed method showed more favorable operating characteristics in determining the optimal population and dose.

Efficacy and safety outcomes in vitamin D supplement users in the fingolimod phase 3 trials.

Science.gov (United States)

Hongell, Kira; Silva, Diego G; Ritter, Shannon; Meier, Daniela Piani; Soilu-Hänninen, Merja

2018-02-01

Low serum levels of 25-hydroxyvitamin D have been associated with worse outcomes in multiple sclerosis (MS) patients treated with interferon-beta. Association of vitamin D nutrition on the outcomes of other MS therapies has been studied less. Whether patients in the phase 3 fingolimod trials using vitamin D supplements have better clinical, MRI and safety outcomes than non-users. Pooled data from phase 3 FREEDOMS trials was analyzed post hoc. Vitamin D use was defined as 'non-users' (n = 562), 'casual users' (n = 157) and 'daily users' (usage 100% time in the study, n = 110). Expanded Disability Status Scale change from baseline to month 24, and annual relapse rate and proportion of patients with relapses were similar across the vitamin D user groups. Proportion of patients free of new/enlarging T2 lesions significantly favored vitamin D 'daily users' versus 'non-users'. Mean number of lesions were lower and proportion of patients free of gadolinium-enhanced T1-lesions were higher in the 'daily users'. At month 12, percent brain volume change was significantly lower in the 'daily users' versus 'non-users' and remained low at month 24 (non-significant). Incidence of depression was lower for vitamin D 'daily users' (non-significant). We observed improved MRI outcomes on percent brain volume change and proportion of patients free of new/enlarging T2 lesions, and a trend of less depression in the 'daily users' of vitamin D supplement in patients in the FREEDOMS trials.

Efficient cascaded parameter scan approach for studying top-off safety in storage rings

Directory of Open Access Journals (Sweden)

Yongjun Li

2011-03-01

Full Text Available We introduce a new algorithm, which we call the cascaded parameter scan method, to efficiently carry out the scan over magnet parameters in the safety analysis for top-off injection in synchrotron radiation storage rings. In top-off safety analysis, one must track particles populating phase space through a beam line containing magnets and apertures and clearly demonstrate that, for all possible magnet settings and errors, all particles are lost on scrapers within the properly shielded region. In the usual approach, if one considers m magnets and scans each magnet through n setpoints, then one must carry out n^{m} tracking runs. In the cascaded parameter scan method, the number of tracking runs is reduced to n×m. This reduction of exponential to linear dependence on the number of setpoints n greatly reduces the required computation time and allows one to more densely populate phase space and to increase the number n of setpoints scanned for each magnet.

Study on 'Safety qualification of process computers used in safety systems of nuclear power plants'

International Nuclear Information System (INIS)

Bertsche, K.; Hoermann, E.

1991-01-01

The study aims at developing safety standards for hardware and software of computer systems which are increasingly used also for important safety systems in nuclear power plants. The survey of the present state-of-the-art of safety requirements and specifications for safety-relevant systems and, additionally, for process computer systems has been compiled from national and foreign rules. In the Federal Republic of Germany the KTA safety guides and the BMI/BMU safety criteria have to be observed. For the design of future computer-aided systems in nuclear power plants it will be necessary to apply the guidelines in [DIN-880] and [DKE-714] together with [DIN-192]. With the aid of a risk graph the various functions of a system, or of a subsystem, can be evaluated with regard to their significance for safety engineering. (orig./HP) [de

Safety of nuclear power plants: Operation. Safety requirements

International Nuclear Information System (INIS)

2004-01-01

The safety of a nuclear power plant is ensured by means of its proper siting, design, construction and commissioning, followed by the proper management and operation of the plant. In a later phase, proper decommissioning is required. This Safety Requirements publication supersedes the Code on the Safety of Nuclear Power Plants: Operation, which was issued in 1988 as Safety Series No. 50-C-O (Rev. 1). The purpose of this revision was: to restructure Safety Series No. 50-C-O (Rev. 1) in the light of the basic objectives, concepts and principles in the Safety Fundamentals publication The Safety of Nuclear Installations. To be consistent with the requirements of the International Basic Safety Standards for Protection against Ionizing Radiation and for the Safety of Radiation Sources. And to reflect current practice and new concepts and technical developments. Guidance on fulfillment of these Safety Requirements may be found in the appropriate Safety Guides relating to plant operation. The objective of this publication is to establish the requirements which, in the light of experience and the present state of technology, must be satisfied to ensure the safe operation of nuclear power plants. These requirements are governed by the basic objectives, concepts and principles that are presented in the Safety Fundamentals publication The Safety of Nuclear Installations. This publication deals with matters specific to the safe operation of land based stationary thermal neutron nuclear power plants, and also covers their commissioning and subsequent decommissioning

Safety of nuclear power plants: Operation. Safety requirements

International Nuclear Information System (INIS)

2003-01-01

The safety of a nuclear power plant is ensured by means of its proper siting, design, construction and commissioning, followed by the proper management and operation of the plant. In a later phase, proper decommissioning is required. This Safety Requirements publication supersedes the Code on the Safety of Nuclear Power Plants: Operation, which was issued in 1988 as Safety Series No. 50-C-O (Rev. 1). The purpose of this revision was: to restructure Safety Series No. 50-C-O (Rev. 1) in the light of the basic objectives, concepts and principles in the Safety Fundamentals publication The Safety of Nuclear Installations. To be consistent with the requirements of the International Basic Safety Standards for Protection against Ionizing Radiation and for the Safety of Radiation Sources. And to reflect current practice and new concepts and technical developments. Guidance on fulfillment of these Safety Requirements may be found in the appropriate Safety Guides relating to plant operation. The objective of this publication is to establish the requirements which, in the light of experience and the present state of technology, must be satisfied to ensure the safe operation of nuclear power plants. These requirements are governed by the basic objectives, concepts and principles that are presented in the Safety Fundamentals publication The Safety of Nuclear Installations. This publication deals with matters specific to the safe operation of land based stationary thermal neutron nuclear power plants, and also covers their commissioning and subsequent decommissioning

Safety of nuclear power plants: Operation. Safety requirements

International Nuclear Information System (INIS)

2000-01-01

The safety of a nuclear power plant is ensured by means of its proper siting, design, construction and commissioning, followed by the proper management and operation of the plant. In a later phase, proper decommissioning is required. This Safety Requirements publication supersedes the Code on the Safety of Nuclear Power Plants: Operation, which was issued in 1988 as Safety Series No. 50-C-O (Rev. 1). The purpose of this revision was: to restructure Safety Series No. 50-C-O (Rev. 1) in the light of the basic objectives, concepts and principles in the Safety Fundamentals publication The Safety of Nuclear Installations; to be consistent with the requirements of the International Basic Safety Standards for Protection against Ionizing Radiation and for the Safety of Radiation Sources; and to reflect current practice and new concepts and technical developments. Guidance on fulfillment of these Safety Requirements may be found in the appropriate Safety Guides relating to plant operation. The objective of this publication is to establish the requirements which, in the light of experience and the present state of technology, must be satisfied to ensure the safe operation of nuclear power plants. These requirements are governed by the basic objectives, concepts and principles that are presented in the Safety Fundamentals publication The Safety of Nuclear Installations. This publication deals with matters specific to the safe operation of land based stationary thermal neutron nuclear power plants, and also covers their commissioning and subsequent decommissioning

Implementation of the INEEL safety analyst training standard

International Nuclear Information System (INIS)

Hochhalter, E. E.

2000-01-01

The Idaho Nuclear Technology and Engineering Center (INTEC) safety analysis units at the Idaho National Engineering and Environmental Laboratory (INEEL) are in the process of implementing the recently issued INEEL Safety Analyst Training Standard (STD-1107). Safety analyst training and qualifications are integral to the development and maintenance of core safety analysis capabilities. The INEEL Safety Analyst Training Standard (STD-1107) was developed directly from EFCOG Training Subgroup draft safety analyst training plan template, but has been adapted to the needs and requirements of the INEEL safety analysis community. The implementation of this Safety Analyst Training Standard is part of the Integrated Safety Management System (ISMS) Phase II Implementation currently underway at the INEEL. The objective of this paper is to discuss (1) the INEEL Safety Analyst Training Standard, (2) the development of the safety analyst individual training plans, (3) the implementation issues encountered during this initial phase of implementation, (4) the solutions developed, and (5) the implementation activities remaining to be completed

Pirfenidone gel in patients with localized scleroderma: a phase II study.

Science.gov (United States)

Rodríguez-Castellanos, Marco; Tlacuilo-Parra, Alberto; Sánchez-Enríquez, Sergio; Vélez-Gómez, Ezequiel; Guevara-Gutiérrez, Elizabeth

2015-01-28

Localized scleroderma is an inflammatory disease in its first stages and a fibrotic process in later stages, principally mediated by the transforming growth factor β. To date, there is no standard treatment. The objective of this study was to determine the effectiveness and safety of 8% pirfenidone gel in patients with localized scleroderma. This was an open phase II clinical trial that included 12 patients. Treatment with pirfenidone was indicated, three times daily for 6 months. Patients were evaluated clinically with the modified Localized Scleroderma Skin Severity Index (mLoSSI), as well with a durometer and histologically using hematoxylin and eosin stain and Masson's trichrome stain. The baseline mLoSSI average scores were 5.83 ± 4.80 vs. 0.83 ± 1.75 (P = 0.002) at 6 months. The initial durometer induration of the scleroderma plaques was 35.79 ± 9.10 vs. 32.47 ± 8.97 at 6 months (P = 0.05). We observed histopathological improvement with respect to epidermal atrophy, inflammation, dermal or adipose tissue fibrosis and annex atrophy from 12.25 ± 3.25 to 9.75 ± 4.35 (P = 0.032). The 8% pirfenidone gel application was well tolerated, and no side effects were detected. This is the first study on the therapeutic use of pirfenidone gel in localized scleroderma. It acts on both the inflammatory and the fibrotic phases. Considering its effectiveness, good safety profile and the advantage of topical application, pirfenidone is a treatment option in this condition.

First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children

DEFF Research Database (Denmark)

Agnandji, Selidji Todagbe; Lell, Bertrand; Soulanoudjingar, Solange Solmeheim

2011-01-01

An ongoing phase 3 study of the efficacy, safety, and immunogenicity of candidate malaria vaccine RTS,S/AS01 is being conducted in seven African countries.......An ongoing phase 3 study of the efficacy, safety, and immunogenicity of candidate malaria vaccine RTS,S/AS01 is being conducted in seven African countries....

Environmental Regulation and Food Safety: Studies of Protection ...

International Development Research Centre (IDRC) Digital Library (Canada)

Environmental Regulation and Food Safety: Studies of Protection and Protectionism. Book cover Environmental Regulation and Food Safety: Studies of Protection and Protectionism. Directeur(s) : Veena Jha. Maison(s) d'édition : Edward Elgar, IDRC. 1 janvier 2006. ISBN : 184542512X. 250 pages. e-ISBN : 155250185X.

Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: A phase I/II, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty.

Science.gov (United States)

Golpanian, Samuel; DiFede, Darcy L; Pujol, Marietsy V; Lowery, Maureen H; Levis-Dusseau, Silvina; Goldstein, Bradley J; Schulman, Ivonne H; Longsomboon, Bangon; Wolf, Ariel; Khan, Aisha; Heldman, Alan W; Goldschmidt-Clermont, Pascal J; Hare, Joshua M

2016-03-15

Frailty is a syndrome associated with reduced physiological reserves that increases an individual's vulnerability for developing increased morbidity and/or mortality. While most clinical trials have focused on exercise, nutrition, pharmacologic agents, or a multifactorial approach for the prevention and attenuation of frailty, none have studied the use of cell-based therapies. We hypothesize that the application of allogeneic human mesenchymal stem cells (allo-hMSCs) as a therapeutic agent for individuals with frailty is safe and efficacious. The CRATUS trial comprises an initial non-blinded phase I study, followed by a blinded, randomized phase I/II study (with an optional follow-up phase) that will address the safety and pre-specified beneficial effects in patients with the aging frailty syndrome. In the initial phase I protocol, allo-hMSCs will be administered in escalating doses via peripheral intravenous infusion (n=15) to patients allocated to three treatment groups: Group 1 (n=5, 20 million allo-hMSCs), Group 2 (n=5, 100 million allo-hMSCs), and Group 3 (n=5, 200 million allo-hMSCs). Subsequently, in the randomized phase, allo-hMSCs or matched placebo will be administered to patients (n=30) randomly allocated in a 1:1:1 ratio to one of two doses of MSCs versus placebo: Group A (n=10, 100 million allo-hMSCs), Group B (n=10, 200 million allo-hMSCs), and Group C (n=10, placebo). Primary and secondary objectives are, respectively, to demonstrate the safety and efficacy of allo-hMSCs administered in frail older individuals. This study will determine the safety of intravenous infusion of stem cells and compare phenotypic outcomes in patients with aging frailty.

Nitrogen-system safety study: Portsmouth Gaseous Diffusion Plant

International Nuclear Information System (INIS)

1982-07-01

The Department of Energy has primary responsibility for the safety of operations at DOE-owned nuclear facilities. The guidelines for the analysis of credible accidents are outlined in DOE Order 5481.1. DOE has requested that existing plant facilities and operations be reviewed for potential safety problems not covered by standard industrial safety procedures. This review is being conducted by investigating individual facilities and documenting the results in Safety Study Reports which will be compiled to form the Existing Plant Final Safety Analysis Report which is scheduled for completion in September, 1984. This Safety Study documents the review of the Plant Nitrogen System facilities and operations and consists of Section 4.0, Facility and Process Description, and Section 5.0, Accident Analysis, of the Final Safety Analysis Report format. The existing nitrogen system consists of a Superior Air Products Company Type D Nitrogen Plant, nitrogen storage facilities, vaporization facilities and a distribution system. The system is designed to generate and distribute nitrogen gas used in the cascade for seal feed, buffer systems, and for servicing equipment when exceptionally low dew points are required. Gaseous nitrogen is also distributed to various process auxiliary buildings. The average usage is approximately 130,000 standard cubic feet per day

Usability Methods for Ensuring Health Information Technology Safety: Evidence-Based Approaches. Contribution of the IMIA Working Group Health Informatics for Patient Safety.

Science.gov (United States)

Borycki, E; Kushniruk, A; Nohr, C; Takeda, H; Kuwata, S; Carvalho, C; Bainbridge, M; Kannry, J

2013-01-01

Issues related to lack of system usability and potential safety hazards continue to be reported in the health information technology (HIT) literature. Usability engineering methods are increasingly used to ensure improved system usability and they are also beginning to be applied more widely for ensuring the safety of HIT applications. These methods are being used in the design and implementation of many HIT systems. In this paper we describe evidence-based approaches to applying usability engineering methods. A multi-phased approach to ensuring system usability and safety in healthcare is described. Usability inspection methods are first described including the development of evidence-based safety heuristics for HIT. Laboratory-based usability testing is then conducted under artificial conditions to test if a system has any base level usability problems that need to be corrected. Usability problems that are detected are corrected and then a new phase is initiated where the system is tested under more realistic conditions using clinical simulations. This phase may involve testing the system with simulated patients. Finally, an additional phase may be conducted, involving a naturalistic study of system use under real-world clinical conditions. The methods described have been employed in the analysis of the usability and safety of a wide range of HIT applications, including electronic health record systems, decision support systems and consumer health applications. It has been found that at least usability inspection and usability testing should be applied prior to the widespread release of HIT. However, wherever possible, additional layers of testing involving clinical simulations and a naturalistic evaluation will likely detect usability and safety issues that may not otherwise be detected prior to widespread system release. The framework presented in the paper can be applied in order to develop more usable and safer HIT, based on multiple layers of evidence.

Safety and efficacy of venom immunotherapy: a real life study.

Science.gov (United States)

Kołaczek, Agnieszka; Skorupa, Dawid; Antczak-Marczak, Monika; Kuna, Piotr; Kupczyk, Maciej

2017-04-01

Venom immunotherapy (VIT) is recommended as the first-line treatment for patients allergic to Hymenoptera venom. To analyze the safety and efficacy of VIT in a real life setting. One hundred and eighty patients undergoing VIT were studied to evaluate the safety, efficacy, incidence and nature of symptoms after field stings and adverse reactions to VIT. Significantly more patients were allergic to wasp than bee venom (146 vs. 34, p bees, and were not associated with angiotensin convertase inhibitors (ACEi) or β-adrenergic antagonists use. Systemic reactions were observed in 4 individuals on wasp VIT (2.7%) and in 6 patients allergic to bees (17.65%). The VIT was efficacious as most patients reported no reactions (50%) or reported only mild local reactions (43.75%) to field stings. The decrease in sIgE at completion of VIT correlated with the dose of vaccine received ( r = 0.53, p = 0.004). Beekeeping (RR = 29.54, p venom allergy. Venom immunotherapy is highly efficacious and safe as most of the adverse events during the induction and maintenance phase are mild and local. Side effects of VIT are more common in subjects on bee VIT. Beekeeping and female sex are associated with a higher risk of allergy to Hymenoptera venom.

Results of a phase I/II open-label, safety and efficacy trial of coagulation factor IX (recombinant), albumin fusion protein in haemophilia B patients.

Science.gov (United States)

Martinowitz, U; Lissitchkov, T; Lubetsky, A; Jotov, G; Barazani-Brutman, T; Voigt, C; Jacobs, I; Wuerfel, T; Santagostino, E

2015-11-01

rIX-FP is a coagulation factor IX (recombinant), albumin fusion protein with more than fivefold half-life prolongation over other standard factor IX (FIX) products available on the market. This prospective phase II, open-label study evaluated the safety and efficacy of rIX-FP for the prevention of bleeding episodes during weekly prophylaxis and assessed the haemostatic efficacy for on-demand treatment of bleeding episodes in previously treated patients with haemophilia B. The study consisted of a 10-14 day evaluation of rIX-FP pharmacokinetics (PK), and an 11 month safety and efficacy evaluation period with subjects receiving weekly prophylaxis treatment. Safety was evaluated by the occurrence of related adverse events, and immunogenic events, including development of inhibitors. Efficacy was evaluated by annualized spontaneous bleeding rate (AsBR), and the number of injections to achieve haemostasis. Seventeen subjects participated in the study, 13 received weekly prophylaxis and 4 received episodic treatment only. No inhibitors were detected in any subject. The mean and median AsBR were 1.25, and 1.13 respectively in the weekly prophylaxis arm. All bleeding episodes were treated with 1 or 2 injections of rIX-FP. Three prophylaxis subjects who were treated on demand prior to study entry had >85% reduction in AsBR compared to the bleeding rate prior to study entry. This study demonstrated the efficacy for weekly routine prophylaxis of rIX-FP to prevent spontaneous bleeding episodes and for the treatment of bleeding episodes. In addition no safety issues were detected during the study and an improved PK profile was demonstrated. © 2015 CSL Behring. Haemophilia published by John Wiley & Sons Ltd.

Present status of promotion of advanced safety vehicle in phase 2 (ASV2); Dai 2 ki senshin anzen jidosha (ASV) suishin keikaku ni okeru kenkyu jokyo

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-11-01

For active safety enhancement, drivers will be provided with information and warning that will help them drive with safety. Studies are under way about functions to facilitate drivers' perception and to lighten the burdens imposed on them. As for accident avoidance techniques, onboard systems will perform controls involving vehicle maneuver for safety enhancement. This includes the improvement of vehicle maneuvering performance, in addition to brake control and steering control, for lightening drivers' burdens and for complementing their operating skill. Danger avoidance is based on the concept that the related system is to work in case warnings alone are not enough to avoid a collision. Full automation will be implemented by two ways, the autonomous way aided by the existing infrastructures such as GPS (Global Positioning System) or the way in which infrastructures to be newly built will be utilized. Passive safety technologies aim at minimizing damage upon collision, and involve structural improvement, air bags, etc. Disaster aggravation prevention means to prevent disaster from spreading after collision. Communication is one of safety-related elements on which studies will continue. Under the Phase 2 ASV program, research and development will be conducted for putting passenger cars to practical use, and the same will be conducted, in the case of large vehicles and motorcycles, for the construction of their prototypes. (NEDO)

Studying the Safety Impact of Autonomous Vehicles Using Simulation-Based Surrogate Safety Measures

Directory of Open Access Journals (Sweden)

Mark Mario Morando

2018-01-01

Full Text Available Autonomous vehicle (AV technology has advanced rapidly in recent years with some automated features already available in vehicles on the market. AVs are expected to reduce traffic crashes as the majority of crashes are related to driver errors, fatigue, alcohol, or drugs. However, very little research has been conducted to estimate the safety impact of AVs. This paper aims to investigate the safety impacts of AVs using a simulation-based surrogate safety measure approach. To this end, safety impacts are explored through the number of conflicts extracted from the VISSIM traffic microsimulator using the Surrogate Safety Assessment Model (SSAM. Behaviours of human-driven vehicles (HVs and AVs (level 4 automation are modelled within the VISSIM’s car-following model. The safety investigation is conducted for two case studies, that is, a signalised intersection and a roundabout, under various AV penetration rates. Results suggest that AVs improve safety significantly with high penetration rates, even when they travel with shorter headways to improve road capacity and reduce delay. For the signalised intersection, AVs reduce the number of conflicts by 20% to 65% with the AV penetration rates of between 50% and 100% (statistically significant at p<0.05. For the roundabout, the number of conflicts is reduced by 29% to 64% with the 100% AV penetration rate (statistically significant at p<0.05.

Contribution of operating feedback to probabilistic safety studies

International Nuclear Information System (INIS)

Guio, J.M. de; Lannoy, A.

1992-03-01

This paper presents the method used for PWR unit operation feedback analysis and its contribution to probabilistic safety studies. The targets were as follows: - use of failure data banks to assess reliability parameters, - use of event data banks to identify and quantify main system initiating events, - determination of a standard operating profile. These studies, performed in the context of nuclear power plant safety programs, prove useful not only to safety engineers but also to equipment experts, designers, operators and maintenance specialists. They constitute basic data for studies in all these areas or the departure point for new investigations. (authors). 3 figs., 3 tabs., 3 refs

Criticality safety studies at VTT Energy

International Nuclear Information System (INIS)

Roine, T.; Anttila, M.

1995-01-01

At VTT Energy a compact reactor physics calculation system is applied in many kind of problems. Generation of group constants for static and dynamic core calculations, flux and dose rate calculations as well as criticality safety studies are performed basically with the same codes. In the presentation a short overview of the wide variety of criticality safety problems analyzed at VTT Energy is given. The calculation system with some illustrative examples is also described. (12 refs., 1 tab.)

Safety culture in nuclear power enterprise

International Nuclear Information System (INIS)

Zou Zhengyu; Su Luming

2008-01-01

The International Atomic Energy Agency (IAEA) introduced the concept of safety culture when analyzing the Chernobyl accident. Safety culture has now been widely accepted and practiced by nuclear enterprise in the world. As an important safeguard for nuclear safety, safety culture has become the core of nuclear power enterprise and entitled as the soul of nuclear enterprise. This paper analyzes the three levels of safety culture and describes its three developing phases. (authors)

The German nuclear power plant safety study

International Nuclear Information System (INIS)

1979-01-01

With this study a new approach has been chosen, taking nuclear power plants as an example to assess and to describe the risks arising from the use of modern technology, including those hazards emanating from the rather hypothetical possibility of occurrence of very serious accidents. Following the definition of basic concepts and methods to be applied in risk assessment studied, as well as a brief account of the design and operating mode of nuclear power plants with PWRs', accidents and failures to be considered in a safety study are described. Using the course-of-event and fault tree analysis, the probability of fission product release as a consequence of failures in safety systems or of core meltdown is evaluated. Subsequently, the theoretical model for assessment of reactor accident consequences is presented, discussing such aspects as the dispersion of radioactivity in the atmosphere, the radiation dose model, safety and countermeasures, the model for the evaluation of health hazards as well as methods and calculations for estimating the reliability of risk assessments together with the remaining uncertainties. In an appendix to this study, the analyses presented in the study are discussed in the light of the TMI-2 event. This safety study showing the possibilities of detecting, keeping in check and minimizing harmful effects, can be regarded as a contribution to a better understanding of our modern, highly industrialised society, and eventually to an improvement of the quality of life. (GL) 891 GL/GL 892 MB [de

On Safety Management. A Frame of Reference for Studies of Safety Management with Examples From Non-Nuclear Contexts of Relevance for Nuclear Safety

Energy Technology Data Exchange (ETDEWEB)

Svensson, Ola; Salo, Ilkka; Allwin, Pernilla (Risk Analysis, Social and Decision Research Unit, Dept. of Psychology, Stockholm Univ., Stockholm (Sweden))

2004-11-15

A good knowledge about safety management from risk technologies outside the area of nuclear power may contribute to both broaden the perspectives on safety management in general, and point at new opportunities for improving safety measures within the nuclear industry. First, a theoretical framework for the study of safety management in general is presented, followed by three case studies on safety management from different non-nuclear areas with potential relevance for nuclear safety. The chapters are written as separate reports and can be read independently of each other. The nuclear industry has a long experience about the management of risky activities, involving all the stages from planing to implementation, both on a more generalized level and in the specific branches of activities (management, administration, operation, maintenance, etc.). Here, safety management is a key concept related to these areas of activities. Outside the field of nuclear power there exist a number of different non-nuclear risk technologies, each one with their own specific needs and experiences about safety management. The differences between the areas consist partly of the different experiences caused by the different technologies. Besides using own experiences in safety practices within the own areas of activities, it may be profitable to take advantage in knowledge and experiences from one area and put it in practice in another area. In order to facilitate knowledge transfer from one technological area to another it may be possible to adapt a common theoretical model, for descriptions and explanations, to the different technologies. Such a model should admit that common denominators for safety management across the areas might be identified and described with common concepts. Systems theory gives the opportunity to not only create models that are descriptive for events within the limits of a given technology, but also to generate knowledge that can be transferred to other

Phase 2 study of sodium phenylbutyrate in ALS.

Science.gov (United States)

Cudkowicz, Merit E; Andres, Patricia L; Macdonald, Sally A; Bedlack, Richard S; Choudry, Rabia; Brown, Robert H; Zhang, Hui; Schoenfeld, David A; Shefner, Jeremy; Matson, Samantha; Matson, Wayne R; Ferrante, Robert J

2009-04-01

The objective of the study was to establish the safety and pharmacodynamics of escalating dosages of sodium phenylbutyrate (NaPB) in participants with ALS. Transcription dysregulation may play a role in the pathogenesis of ALS. Sodium phenylbutyrate, a histone deacetylase inhibitor, improves transcription and post-transcriptional pathways, promoting cell survival in a mouse model of motor neuron disease. Forty research participants at eight sites enrolled in an open-label study. Study medication was increased from 9 to 21 g/day. The primary outcome measure was tolerability. Secondary outcome measures included adverse events, blood histone acetylation levels, and NaPB blood levels at each dosage. Twenty-six participants completed the 20-week treatment phase. NaPB was safe and tolerable. No study deaths or clinically relevant laboratory changes occurred with NaPB treatment. Histone acetylation was decreased by approximately 50% in blood buffy-coat specimens at screening and was significantly increased after NaPB administration. Blood levels of NaPB and the primary metabolite, phenylacetate, increased with dosage. While the majority of subjects tolerated higher dosages of NaPB, the lowest dose (9 g/day), was therapeutically efficient in improving histone acetylation levels.

Safety of gadobutrol in more than 1,000 pediatric patients: subanalysis of the GARDIAN study, a global multicenter prospective non-interventional study

International Nuclear Information System (INIS)

Glutig, Katja; Bhargava, Ravi; Hahn, Gabriele; Hirsch, Wolfgang; Kunze, Christian; Mentzel, Hans-Joachim; Schaefer, Juergen F.; Willinek, Winfried; Palkowitsch, Petra

2016-01-01

Gadobutrol is a gadolinium-based contrast agent, uniquely formulated at 1.0 mmol/ml. Although there is extensive safety evidence on the use of gadobutrol in adults, few studies have addressed the safety and tolerability of gadobutrol in pediatric patients. This subanalysis of data from the GARDIAN study evaluated the safety and use of gadobutrol in pediatric patients (age <18 years). The GARDIAN study was a large phase IV non-interventional prospective multicenter post-authorization safety study performed in Europe, Asia, North America and Africa. A total of 23,708 patients were included who were scheduled to undergo cranial or spinal MRI, liver or kidney MRI, or MR angiography with gadobutrol enhancement. The primary study endpoint was the overall incidence of adverse drug reactions (ADRs) and serious adverse events (SAEs) following gadobutrol administration. The GARDIAN study included 1,142 children (age <18 years) who received gadobutrol at a mean dose of 0.13 (range 0.04-0.50) mmol/kg body weight. Gadobutrol was well tolerated in these children, with low rates of ADRs (0.5%) and no SAEs, consistent with results in adults enrolled in the GARDIAN study. Rates of adverse events and ADRs were unrelated to pediatric age or gadobutrol weight-adjusted dose. There were no symptoms suggestive of nephrogenic systemic fibrosis. Investigators rated the contrast quality of gadobutrol-enhanced images as good or excellent in 97.8% of pediatric patients, similar to the main study population. Gadobutrol is very well tolerated and provides excellent contrast quality at the recommended weight-adjusted dose in children (age <18 years), similar to the profile in adults. (orig.)

Intranet-based safety documentation in management of major hazards and occupational health and safety.

Science.gov (United States)

Leino, Antti

2002-01-01

In the European Union, Council Directive 96/82/EC requires operators producing, using, or handling significant amounts of dangerous substances to improve their safety management systems in order to better manage the major accident potentials deriving from human error. A new safety management system for the Viikinmäki wastewater treatment plant in Helsinki, Finland, was implemented in this study. The system was designed to comply with both the new safety liabilities and the requirements of OHSAS 18001 (British Standards Institute, 1999). During the implementation phase experiences were gathered from the development processes in this small organisation. The complete documentation was placed in the intranet of the plant. Hyperlinks between documents were created to ensure convenience of use. Documentation was made accessible for all workers from every workstation.

Radioembolisation for liver metastases: results from a prospective 151 patient multi-institutional phase II study.

Science.gov (United States)

Benson, Al B; Geschwind, Jean-Francois; Mulcahy, Mary F; Rilling, William; Siskin, Gary; Wiseman, Greg; Cunningham, James; Houghton, Bonny; Ross, Mason; Memon, Khairuddin; Andrews, James; Fleming, Chad J; Herman, Joseph; Nimeiri, Halla; Lewandowski, Robert J; Salem, Riad

2013-10-01

To investigate the safety, response rate, progression-free and overall survival of patients with liver metastases treated with (90)Y (glass) radioembolisation in a prospective, multicenter phase II study. 151 patients with liver metastases (colorectal n=61, neuroendocrine n=43 and other tumour types n=47) refractory to standard of care therapies were enrolled in this prospective, multicenter, phase II study under an investigational device exemption. Clinical/laboratory/imaging follow-up were obtained at 30 days followed by 3-month intervals for 1 year and every 6 months thereafter. The primary end-point was progression-free survival (PFS); secondary end-points included safety, hepatic progression-free survival (HPFS), response rate and overall survival. Median age was 66 (range 25-88). Grade 3/4 adverse events included pain (12.8%), elevated alkaline phospatase (8.1%), hyperbilirubinemia (5.3%), lymphopaenia (4.1%), ascites (3.4%) and vomiting (3.4%). Treatment parameters including dose delivery were reproducible among centers. Disease control rates were 59%, 93% and 63% for colorectal, neuroendocrine and other primaries, respectively. Median PFS was 2.9 and 2.8 months for colorectal and other primaries, respectively. PFS was not achieved in the neuroendocrine group. Median survival from (90)Y treatment was 8.8 months for colorectal and 10.4 months for other primaries. Median survival for neuroendocrine patients has not been reached. Patients with liver metastases can be safely treated with (90)Y microspheres. This study is the first to demonstrate technical and dose reproducibility of (90)Y glass microspheres between centers in a prospective setting. Based on these promising data, three international, multicenter, randomised phase III studies in colorectal and hepatocellular carcinoma have been initiated. Copyright © 2013 Elsevier Ltd. All rights reserved.

Safety Training: Basic Safety and Access Courses

CERN Multimedia

Antonella Vignes

2005-01-01

Objective The purpose of the basic safety courses is to increase awareness for everyone working on the CERN site (CERN staff, associates, outside companies, students and apprentices) of the various existing on-site hazards, and how to recognize and avoid them. Safety course changes The current organization for basic safety courses is changing. There will be two main modifications: the organization of the courses and the implementation of a specific new training course for the LHC machine during the LHC tests and hardware commissioning phase. Organizational changes This concerns the existing basic safety training, currently called level1, level2 and level3. Under the new procedure, a video will be projected in registration building 55 and will run every day at 14.00 and 15.00 in English. The duration of the video will be 50 minutes. The course contents will be the same as the slides currently used, plus a video showing real situations. With this new organization, attendees will systematically follow the...

Safety Training: basic safety and access courses

CERN Multimedia

2005-01-01

Objective The purpose of the basic safety courses is to increase awareness for everyone working on the CERN site (CERN staff, associates, outside companies, students and apprentices) of the various hazards existing on site, and how to recognise and avoid them. Safety course changes The current organisation of basic safety courses is changing. There will be two main modifications: the organisation of the courses and the implementation of a specific new training course for the LHC machine during the LHC tests and hardware commissioning phase. Organisational changes This concerns the existing basic safety training, currently called level 1, level 2 and level 3. Under the new procedure, a video will be projected in registration building 55 and will run every day at 14.00 and 15.00 in English. The duration of the video will be 50 minutes. The course contents will be the same as the slides currently used, plus a video showing real situations. With this new organization, participants will systematically follow...

A Safety and Dosing Study of Glucagon-Like Peptide 2 in Children With Intestinal Failure

DEFF Research Database (Denmark)

Sigalet, David L; Brindle, Mary; Boctor, Dana

2015-01-01

BACKGROUND AND AIMS: A glucagon-like peptide 2 (GLP-2) analogue is approved for adults with intestinal failure, but no studies of GLP-2 have included children. This study examined the pharmacokinetics, safety, and nutritional effects of GLP-2 in children with intestinal failure. METHODS: Native...... human GLP-2(1-33) was synthesized following good manufacturing practices. In an open-label trial, with parental consent, 7 parenteral nutrition-dependent pediatric patients were treated with subcutaneous GLP-2 (20 µg/kg/d) for 3 days (phase 1) and, if tolerated, continued for 42 days (phase 2...... nutrition. GLP-2 treatment had no effect on vital signs (blood pressure, heart rate, and temperature) and caused no significant adverse events. Peak GLP-2 levels were 380 pM (day 3) and 295 pM (day 42), with no change in half-life or endogenous GLP-2 levels. Nutritional indices showed a numeric improvement...

Preliminary study on improving safety culture in Malaysian nuclear industries

International Nuclear Information System (INIS)

Ibrahim, Sabariah Kader; Lee, Y. E.

2012-01-01

This paper presents preliminary study on safety culture and its implementation in Malaysian nuclear industries by realizing the importance of safety culture; identification of important safety culture attributes; safety culture assessment and the practices to incorporate the identified safety culture attributes in organization. The first section of this paper explains the terms and definitions related to safety culture. Second, for the realization of importance of safety culture in organization, the international operational experiences emphasizing the importance of safety culture are described. Third, important safety culture attributes which are frequently cited in literature are provided. Fourth, methods to assess safety culture in operating organization are described. Finally, the practices to enhance the safety culture in an organization are discussed

Preliminary study on improving safety culture in Malaysian nuclear industries

Energy Technology Data Exchange (ETDEWEB)

Ibrahim, Sabariah Kader [KAIST, Daejeon (Korea, Republic of); Lee, Y. E. [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

2012-10-15

This paper presents preliminary study on safety culture and its implementation in Malaysian nuclear industries by realizing the importance of safety culture; identification of important safety culture attributes; safety culture assessment and the practices to incorporate the identified safety culture attributes in organization. The first section of this paper explains the terms and definitions related to safety culture. Second, for the realization of importance of safety culture in organization, the international operational experiences emphasizing the importance of safety culture are described. Third, important safety culture attributes which are frequently cited in literature are provided. Fourth, methods to assess safety culture in operating organization are described. Finally, the practices to enhance the safety culture in an organization are discussed.

Bridging probabilistic safety assessment studies with information Management System

International Nuclear Information System (INIS)

Luanco, E. M.

2010-01-01

Probabilistic Safety Assessment (PSA) is a critical business often known in conjunction with either new build or life extension of nuclear power plant. However, it is not so often referred to the operation phase of the plant, although it could bring a lot of long term benefits to the operator. The purpose of this paper is to discuss the potential contribution of PSA with day to day operation in bridging the deficiencies and specific failures characteristics of critical Structure System and Component (SSC) with the results of PSA studies. From and Information System prospective, the use of Information Management system (IMS) -also known as EAM solution -widely used by the majority of nuclear operators- is the potential vehicle to bridge the 2 worlds of PSA and daily operation. Most EAM solution get reliability management functionalities which are not really integrated with PSA tools and data and thus cannot provide the anticipated benefits of addressing typical aging phenomena beyond the only predictive models used by the PSA studies. The paper will also discuss potential integration scenario between PSA tools and EAM solutions. (authors)

Review of studies on criticality safety evaluation and criticality experiment methods

International Nuclear Information System (INIS)

Naito, Yoshitaka; Yamamoto, Toshihiro; Misawa, Tsuyoshi; Yamane, Yuichi

2013-01-01

Since the early 1960s, many studies on criticality safety evaluation have been conducted in Japan. Computer code systems were developed initially by employing finite difference methods, and more recently by using Monte Carlo methods. Criticality experiments have also been carried out in many laboratories in Japan as well as overseas. By effectively using these study results, the Japanese Criticality Safety Handbook was published in 1988, almost the intermediate point of the last 50 years. An increased interest has been shown in criticality safety studies, and a Working Party on Nuclear Criticality Safety (WPNCS) was set up by the Nuclear Science Committee of Organisation Economic Co-operation and Development in 1997. WPNCS has several task forces in charge of each of the International Criticality Safety Benchmark Evaluation Program (ICSBEP), Subcritical Measurement, Experimental Needs, Burn-up Credit Studies and Minimum Critical Values. Criticality safety studies in Japan have been carried out in cooperation with WPNCS. This paper describes criticality safety study activities in Japan along with the contents of the Japanese Criticality Safety Handbook and the tasks of WPNCS. (author)

Phase II study of biweekly cetuximab in combination with irinotecan as second-line treatment in patients with platinum-resistant gastro-oesophageal cancer

DEFF Research Database (Denmark)

Schønnemann, K R; Yilmaz, Mette Karen; Bjerregaard, J K

2012-01-01

The purpose of this phase II trial was to evaluate the efficacy and safety of cetuximab and irinotecan as second-line treatment in patients with gastro-oesophageal adenocarcinoma.......The purpose of this phase II trial was to evaluate the efficacy and safety of cetuximab and irinotecan as second-line treatment in patients with gastro-oesophageal adenocarcinoma....

A study of passive safety conditions for fast reactor core

International Nuclear Information System (INIS)

Shimizu, Akinao

1991-01-01

A study has been made for passive safety conditions of fast reactor cores. Objective of the study is to develop a concept of a core with passive safety as well as a simple safety philosophy. A simple safety philosophy, which is wore easy to explain to the public, is needed to enhance the public acceptance for nuclear reactors. The present paper describes a conceptual plan of the study including the definition of the problem a method of approach and identification of tasks to be solved

Study of industry safety management

International Nuclear Information System (INIS)

Park, Pil Su

1987-06-01

This book deals with general remarks, industrial accidents, statistics of industrial accidents, unsafe actions, making machinery and facilities safe, safe activities, having working environment safe, survey of industrial accidents and analysis of causes, system of safety management and operations, safety management planning, safety education, human engineering such as human-machines system, system safety, and costs of disaster losses. It lastly adds individual protective equipment and working clothes including protect equipment for eyes, face, hands, arms and feet.

Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomised, double-blind, placebo-controlled, phase 2 trial.

Science.gov (United States)

Sun, Hong; Dodick, David W; Silberstein, Stephen; Goadsby, Peter J; Reuter, Uwe; Ashina, Messoud; Saper, Joel; Cady, Roger; Chon, Yun; Dietrich, Julie; Lenz, Robert

2016-04-01

The calcitonin gene-related peptide (CGRP) pathway is a promising target for preventive therapies in patients with migraine. We assessed the safety and efficacy of AMG 334, a fully human monoclonal antibody against the CGRP receptor, for migraine prevention. In this multicentre, randomised, double-blind, placebo-controlled, phase 2 trial, patients aged 18-60 years with 4 to 14 migraine days per month were enrolled at 59 headache and clinical research centres in North America and Europe, and randomly assigned in a 3:2:2:2 ratio to monthly subcutaneous placebo, AMG 334 7 mg, AMG 334 21 mg, or AMG 334 70 mg using a sponsor-generated randomisation sequence centrally executed by an interactive voice response or interactive web response system. Study site personnel, patients, and the sponsor study personnel were masked to the treatment assignment. The primary endpoint was the change in monthly migraine days from baseline to the last 4 weeks of the 12-week double-blind treatment phase. The primary endpoint was calculated using the least squares mean at each timepoint from a generalised linear mixed-effect model for repeated measures. Safety endpoints were adverse events, clinical laboratory values, vital signs, and anti-AMG 334 antibodies. The study is registered with ClinicalTrials.gov, number NCT01952574. An open-label extension phase of up to 256 weeks is ongoing and will assess the long-term safety of AMG 334. From Aug 6, 2013, to June 30, 2014, 483 patients were randomly assigned to placebo (n=160), AMG 334 7 mg (n=108), AMG 334 21 mg (n=108), or AMG 334 70 mg (n=107). The mean change in monthly migraine days at week 12 was -3·4 (SE 0·4) days with AMG 334 70 mg versus -2·3 (0·3) days with placebo (difference -1·1 days [95% CI -2·1 to -0·2], p=0·021). The mean reductions in monthly migraine days with the 7 mg (-2·2 [SE 0·4]) and the 21 mg (-2·4 [0·4]) doses were not significantly different from that with placebo. Adverse events were recorded in 82 (54

Safety Culture in New Build Projects

International Nuclear Information System (INIS)

Reiman, T.

2016-01-01

The concept of culture emphasises the social factors that have an effect on the way hazards are perceived, risks are evaluated, risk management is conducted, the current safety level is interpreted, and what is considered normal and what abnormal. It also contributes to defining the correct ways to behave in situations and correct ways to talk about safety, risks or uncertainty. Culture is something the company has created for itself that then has an effect on the company. This effect is not necessarily perceived by the company itself, since the members of the organization consider all things that happen according to their cultural taken-for-granted assumptions (“business as usual”). Thus, safety culture can either hinder or advance nuclear safety. This depends on what the shared values and assumptions are, and how they are in line with, and influence, the organizational structures, practices, personnel and technology. Safety culture requires constant and systematic development, monitoring and review during the entire life-cycle of a nuclear facility. The pre-operational phase sets many unique requirements for nuclear safety culture. For example, some of the organizations and individuals involved in the project may have no insight on how safety culture relates to nuclear power plants. Companies that work in the conventional industry typically associate safety with occupational safety issues, not with nuclear safety. Further, it may be unclear how the construction phase affects nuclear safety of an operating plant. When workers are asked to perform their work differently than previously (e.g., in conventional construction sites), explanation has to be given. For example, structures, systems and components may have different functions during emergency that exceed or differ from their quality requirements during normal operation. The strict quality requirements and use of certain methods and procedures, documentation requirements, etc., may seem unimportant if

Methodology and applicability of a safety and demonstration concept for a HAW final repository on clays. Safety concept and verification strategy

International Nuclear Information System (INIS)

Ruebel, Andre; Meleshyn, Artur

2014-08-01

The report describes the site independent frame for a safety concept and verification strategy for a final repository for heat generating wastes in clay rock. In the safety concept planning specifications and technical measures are summarized that are supposed to allow a safe inclusion of radionuclides in the host rock. The verification strategy defines the systematic procedures for the development of fundamentals and scenarios as basis for the demonstration of the safety case and to allow the prognosis of appropriateness. The report includes the boundary conditions, the safety concept for the post-closure phase and the verification strategy for the post-closure phase.

Health and Safety Management Plan for the Plutonium Stabilization and Packaging System

International Nuclear Information System (INIS)

1996-01-01

This Health and Safety Management Plan (HSMP) presents safety and health policies and a project health and safety organizational structure designed to minimize potential risks of harm to personnel performing activities associated with Plutonium Stabilization and Packaging System (Pu SPS). The objectives of the Pu SPS are to design, fabricate, install, and startup of a glovebox system for the safe repackaging of plutonium oxides and metals, with a requirement of a 50-year storage period. This HSMP is intended as an initial project health and safety submittal as part of a three phase effort to address health and safety issues related to personnel working the Pu SPS project. Phase 1 includes this HSMP and sets up the basic approach to health and safety on the project and addresses health and safety issues related to the engineering and design effort. Phase 2 will include the Site Specific Construction health and Safety Plan (SSCHSP). Phase 3 will include an additional addendum to this HSMP and address health and safety issues associated with the start up and on-site test phase of the project. This initial submittal of the HSMP is intended to address those activities anticipated to be performed during phase 1 of the project. This HSMP is intended to be a living document which shall be modified as information regarding the individual tasks associated with the project becomes available. These modifications will be in the form of addenda to be submitted prior to the initiation of each phase of the project. For additional work authorized under this project this HSMP will be modified as described in section 1.4

Probabilistic studies for a safety assurance program

International Nuclear Information System (INIS)

Iyer, S.S.; Davis, J.F.

1985-01-01

The adequate supply of energy is always a matter of concern for any country. Nuclear power has played, and will continue to play an important role in supplying this energy. However, safety in nuclear power production is a fundamental prerequisite in fulfilling this role. This paper outlines a program to ensure safe operation of a nuclear power plant utilizing the Probabilistic Safety Studies

Activities on safety culture study. Study status in public and private sectors

International Nuclear Information System (INIS)

Makino, Maomi; Takano, Kenichi

2004-01-01

Around after entering in the 21st century, organizational accidents had occurred in Japan at various industries including nuclear industry, which were caused directly by unsafe action, human error and illegal conduct of personnel but there were problems in safety culture of organization such as slow retreat of safety system stimulated by management, schedule control and procedure management becoming a dead letter, lack of safety education, and workplace climate of schedule priority. This article referred to organizational factors common to many severe accidents and introduced safety culture study in public and private sectors to overcome those factors. Safety Culture Evaluation Support Tool (SCEST) was developed for self-evaluation of safety culture of organization as well as Organizational Reliability model (OR model) for analysis of initiation and propagation process of risk event. Safety diagnosis system and feedback type risk assessment system for promoting safe organizational climate and culture were also developed. (T. Tanaka)

A combination of ascorbic acid and α-tocopherol to test the effectiveness and safety in the fragile X syndrome: study protocol for a phase II, randomized, placebo-controlled trial.

Science.gov (United States)

de Diego-Otero, Yolanda; Calvo-Medina, Rocio; Quintero-Navarro, Carolina; Sánchez-Salido, Lourdes; García-Guirado, Francisco; del Arco-Herrera, Ignacio; Fernández-Carvajal, Isabel; Ferrando-Lucas, Teresa; Caballero-Andaluz, Rafaela; Pérez-Costillas, Lucia

2014-09-03

Fragile X syndrome (FXS) is an inherited neurodevelopmental condition characterised by behavioural, learning disabilities, physical and neurological symptoms. In addition, an important degree of comorbidity with autism is also present. Considered a rare disorder affecting both genders, it first becomes apparent during childhood with displays of language delay and behavioural symptoms.Main aim: To show whether the combination of 10 mg/kg/day of ascorbic acid (vitamin C) and 10 mg/kg/day of α-tocopherol (vitamin E) reduces FXS symptoms among male patients ages 6 to 18 years compared to placebo treatment, as measured on the standardized rating scales at baseline, and after 12 and 24 weeks of treatment.Secondary aims: To assess the safety of the treatment. To describe behavioural and cognitive changes revealed by the Developmental Behaviour Checklist Short Form (DBC-P24) and the Wechsler Intelligence Scale for Children-Revised. To describe metabolic changes revealed by blood analysis. To measure treatment impact at home and in an academic environment. A phase II randomized, double-blind pilot clinical trial. male children and adolescents diagnosed with FXS, in accordance with a standardized molecular biology test, who met all the inclusion criteria and none of the exclusion criteria. clinical data, blood analysis, Wechsler Intelligence Scale for Children-Revised, Conners parent and teacher rating scale scores and the DBC-P24 results will be obtained at the baseline (t0). Follow up examinations will take place at 12 weeks (t1) and 24 weeks (t2) of treatment. A limited number of clinical trials have been carried out on children with FXS, but more are necessary as current treatment possibilities are insufficient and often provoke side effects. In the present study, we sought to overcome possible methodological problems by conducting a phase II pilot study in order to calculate the relevant statistical parameters and determine the safety of the proposed treatment. The

Phase 1 dose-escalation study of the antiplacental growth factor monoclonal antibody RO5323441 combined with bevacizumab in patients with recurrent glioblastoma

DEFF Research Database (Denmark)

Lassen, Ulrik; Chinot, Olivier L; McBain, Catherine

2015-01-01

BACKGROUND: We conducted a phase 1 dose-escalation study of RO5323441, a novel antiplacental growth factor (PlGF) monoclonal antibody, to establish the recommended dose for use with bevacizumab and to investigate the pharmacokinetics, pharmacodynamics, safety/tolerability, and preliminary clinica...

Learning health 'safety' within non-technical skills interprofessional simulation education: a qualitative study.

Science.gov (United States)

Gordon, Morris; Fell, Christopher W R; Box, Helen; Farrell, Michael; Stewart, Alison

2017-01-01

Healthcare increasingly recognises and focusses on the phenomena of 'safe practice' and 'patient safety.' Success with non-technical skills (NTS) training in other industries has led to widespread transposition to healthcare education, with communication and teamwork skills central to NTS frameworks. This study set out to identify how the context of interprofessional simulation learning influences NTS acquisition and development of 'safety' amongst learners. Participants receiving a non-technical skills (NTS) safety focussed training package were invited to take part in a focus group interview which set out to explore communication, teamwork, and the phenomenon of safety in the context of the learning experiences they had within the training programme. The analysis was aligned with a constructivist paradigm and took an interactive methodological approach. The analysis proceeded through three stages, consisting of open, axial, and selective coding, with constant comparisons taking place throughout each phase. Each stage provided categories that could be used to explore the themes of the data. Additionally, to ensure thematic saturation, transcripts of observed simulated learning encounters were then analysed. Six themes were established at the axial coding level, i.e., analytical skills, personal behaviours, communication, teamwork, context, and pedagogy. Underlying these themes, two principal concepts emerged, namely: intergroup contact anxiety - as both a result of and determinant of communication - and teamwork, both of which must be considered in relation to context. These concepts have subsequently been used to propose a framework for NTS learning. This study highlights the role of intergroup contact anxiety and teamwork as factors in NTS behaviour and its dissipation through interprofessional simulation learning. Therefore, this should be a key consideration in NTS education. Future research is needed to consider the role of the affective non

Prescribing safety, negotiating expertise

International Nuclear Information System (INIS)

Rolina, Gregory

2010-01-01

Owing to their presumed impact on the safety of high-risk installations, the interactions between regulators and the regulated are a major but seldom explored subject of research in risk management. A study by experts on human and organizational factors in nuclear safety sheds light on the various phases (and their effects) of the process whereby experts produce assessments. Light is shed on a 'negotiated expertise' typical of the French style of safety regulations in nuclear installations. It is based on an ongoing technical dialog between experts and operators ('French cooking' for Anglo-Saxons). This analysis of 'expertise' and thus of the 'logics of action' implemented by experts proposes a typology of actions that can be transposed to other sorts of risk or other fields of activity. It hands us the keys for understanding a very contemporary activity. (author)

Safety and Immunogenicity of a Tetravalent Dengue Vaccine Candidate in Healthy Children and Adults in Dengue-Endemic Regions: A Randomized, Placebo-Controlled Phase 2 Study.

Science.gov (United States)

Sirivichayakul, Chukiat; Barranco-Santana, Elizabeth A; Esquilin-Rivera, Inés; Oh, Helen M L; Raanan, Marsha; Sariol, Carlos A; Shek, Lynette P; Simasathien, Sriluck; Smith, Mary Kathryn; Velez, Ivan Dario; Wallace, Derek; Gordon, Gilad S; Stinchcomb, Dan T

2016-05-15

A safe, effective tetravalent dengue vaccine is a global health priority. The safety and immunogenicity of a live attenuated, recombinant tetravalent dengue vaccine candidate (TDV) were evaluated in healthy volunteers from dengue-endemic countries. This multicenter, double-blind, phase 2 study was conducted in Puerto Rico, Colombia, Singapore, and Thailand. During stage I, 148 volunteers aged 1.5-45 years were sequentially enrolled into 4 age-descending groups and randomized at a ratio of 2:1 to receive TDV or placebo. In stage II (group 5), 212 children aged 1.5-11 years were randomized at a ratio of 3:1 to receive TDV or placebo. Participants received a subcutaneous injection of TDV or placebo on days 0 and 90 and were followed for analysis of safety, seropositivity, and neutralizing antibodies to DENV-1-4. Injection site pain, itching, and erythema (mostly mild) were the only solicited adverse events more frequently reported with TDV than with placebo in all age groups. After 2 TDV doses, seropositivity was >95% in all 5 groups for DENV-1-3 and 72.7%-100% for DENV-4; geometric mean titers ranged from 582 to 1187 for DENV-1, from 582 to 1187 for DENV-2, from 196 to 630 for DENV-3, and from 41 to 210 for DENV-4 among the 5 groups. TDV was well tolerated and immunogenic in volunteers aged 1.5-45 years, irrespective of prevaccination dengue exposure. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mailjournals.permissions@oup.com.

Safety assessment for the above ground storage of Cadmium Safety and Control Rods at the Solid Waste Management Facility

International Nuclear Information System (INIS)

Shaw, K.W.

1993-11-01

The mission of the Savannah River Site is changing from radioisotope production to waste management and environmental restoration. As such, Reactor Engineering has recently developed a plan to transfer the safety and control rods from the C, K, L, and P reactor disassembly basin areas to the Transuranic (TRU) Waste Storage Pads for long-term, retrievable storage. The TRU pads are located within the Solid Waste Management Facilities at the Savannah River Site. An Unreviewed Safety Question (USQ) Safety Evaluation has been performed for the proposed disassembly basin operations phase of the Cadmium Safety and Control Rod Project. The USQ screening identified a required change to the authorization basis; however, the Proposed Activity does not involve a positive USQ Safety Evaluation. A Hazard Assessment for the Cadmium Safety and Control Rod Project determined that the above-ground storage of the cadmium rods results in no change in hazard level at the TRU pads. A Safety Assessment that specifically addresses the storage (at the TRU pads) phase of the Cadmium Safety and Control Rod Project has been performed. Results of the Safety Assessment support the conclusion that a positive USQ is not involved as a result of the Proposed Activity

Safety Culture Perspective. Managing the pre Managing the pre-operational phases of new NPPs and creating the safety culture

International Nuclear Information System (INIS)

Cowan, Pamela B.; Oh, Chaewoon; Dahlgren Persson, Kerstin; Carnino, Annick

2008-01-01

Nuclear safety is a key for the revival of nuclear energy future programmes. Lots of competent people will be needed worldwide for ensuring the safety of the installations both existing ones and future ones. Their expertise should range from design to operation, from regulatory role to operators, from fuel fabrication to waste disposal. The challenge in front of us will be to prepare for the right recruitment, the development of the needed expertise in order to face the demand in developed countries, in countries with economies in transition and in developing countries. Time allocated for the panel does not allow for covering all aspects but the panelists will cover some of the important aspects of the challenge in terms of needs, of new competencies, of learning from operation and licensing requirements including for new designs. The key objectives of the panel are: 1- Maintaining safe operation, learning from experience, licensing including aging management and re-licensing with safety improvements for existing installations: - Presentation by Junko Ogawa of the experience and lessons learned from the earthquake on Kashiwasaki Kariwa NPP: effects in terms of manpower involved in the investigation, effects on regulations and licensing, expertise used. - Presentation by Pamela Cowan of her experience in preparing licensing actions, regulatory compliance and interface with the Regulator for both operating plants and modern requirements for constructing new ones. 2 - Special training needed for the human aspect of safety: what are the challenges in areas of safety culture and management of safety: - Presentation by Chae Woon Oh of the Korean safety culture features developed nationally, at the regulator and at the operating organizations and their integration within the safety training programmes. - Presentation by Kerstin Dahlgren Person of the needs in terms of safety culture and safety management, in terms of expertise, practitioners and assessors. 3 - How to

Safety Culture Perspective. Managing the pre Managing the pre-operational phases of new NPPs and creating the safety culture

Energy Technology Data Exchange (ETDEWEB)

Cowan, Pamela B. [Exelon Generation, 200 Exelon Way, 19348 Kennett Square, PA 19348 (United States); Oh, Chaewoon [Korea Institute of Nuclear Safety, 19 Gusung-Dong, Yuseong-Ku, 305-338 Daejeon (Korea, Republic of); Dahlgren Persson, Kerstin [International Atomic Energy Agency, Wagramer Strasse 5, PO BOX 100 A-1400 Vienna (Austria); Carnino, Annick [IAEA, Division of Nuclear Installation Safety, Wagramer Strasse 5, PO BOX 100 A-1400 Vienna (Austria)

2008-07-01

Nuclear safety is a key for the revival of nuclear energy future programmes. Lots of competent people will be needed worldwide for ensuring the safety of the installations both existing ones and future ones. Their expertise should range from design to operation, from regulatory role to operators, from fuel fabrication to waste disposal. The challenge in front of us will be to prepare for the right recruitment, the development of the needed expertise in order to face the demand in developed countries, in countries with economies in transition and in developing countries. Time allocated for the panel does not allow for covering all aspects but the panelists will cover some of the important aspects of the challenge in terms of needs, of new competencies, of learning from operation and licensing requirements including for new designs. The key objectives of the panel are: 1- Maintaining safe operation, learning from experience, licensing including aging management and re-licensing with safety improvements for existing installations: - Presentation by Junko Ogawa of the experience and lessons learned from the earthquake on Kashiwasaki Kariwa NPP: effects in terms of manpower involved in the investigation, effects on regulations and licensing, expertise used. - Presentation by Pamela Cowan of her experience in preparing licensing actions, regulatory compliance and interface with the Regulator for both operating plants and modern requirements for constructing new ones. 2 - Special training needed for the human aspect of safety: what are the challenges in areas of safety culture and management of safety: - Presentation by Chae Woon Oh of the Korean safety culture features developed nationally, at the regulator and at the operating organizations and their integration within the safety training programmes. - Presentation by Kerstin Dahlgren Person of the needs in terms of safety culture and safety management, in terms of expertise, practitioners and assessors. 3 - How to

Everolimus for Previously Treated Advanced Gastric Cancer: Results of the Randomized, Double-Blind, Phase III GRANITE-1 Study

Science.gov (United States)

Ohtsu, Atsushi; Ajani, Jaffer A.; Bai, Yu-Xian; Bang, Yung-Jue; Chung, Hyun-Cheol; Pan, Hong-Ming; Sahmoud, Tarek; Shen, Lin; Yeh, Kun-Huei; Chin, Keisho; Muro, Kei; Kim, Yeul Hong; Ferry, David; Tebbutt, Niall C.; Al-Batran, Salah-Eddin; Smith, Heind; Costantini, Chiara; Rizvi, Syed; Lebwohl, David; Van Cutsem, Eric

2013-01-01

Purpose The oral mammalian target of rapamycin inhibitor everolimus demonstrated promising efficacy in a phase II study of pretreated advanced gastric cancer. This international, double-blind, phase III study compared everolimus efficacy and safety with that of best supportive care (BSC) in previously treated advanced gastric cancer. Patients and Methods Patients with advanced gastric cancer that progressed after one or two lines of systemic chemotherapy were randomly assigned to everolimus 10 mg/d (assignment schedule: 2:1) or matching placebo, both given with BSC. Randomization was stratified by previous chemotherapy lines (one v two) and region (Asia v rest of the world [ROW]). Treatment continued until disease progression or intolerable toxicity. Primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), overall response rate, and safety. Results Six hundred fifty-six patients (median age, 62.0 years; 73.6% male) were enrolled. Median OS was 5.4 months with everolimus and 4.3 months with placebo (hazard ratio, 0.90; 95% CI, 0.75 to 1.08; P = .124). Median PFS was 1.7 months and 1.4 months in the everolimus and placebo arms, respectively (hazard ratio, 0.66; 95% CI, 0.56 to 0.78). Common grade 3/4 adverse events included anemia, decreased appetite, and fatigue. The safety profile was similar in patients enrolled in Asia versus ROW. Conclusion Compared with BSC, everolimus did not significantly improve overall survival for advanced gastric cancer that progressed after one or two lines of previous systemic chemotherapy. The safety profile observed for everolimus was consistent with that observed for everolimus in other cancers. PMID:24043745

A study for soundness of turbine blade root using ultrasonic and phased array

International Nuclear Information System (INIS)

Gil, Doo Song; Park, Sang Ki; Cho, Yong Sang; Lee, Sang Gug; Huh, Kuang Bum

2003-01-01

Power plant is consisted of many component parts for the generation of the electricity and occasionally, turbine equipment may be caused in break-down because of the damage of the blade root. Phased array ultrasonic testing system has become available for power industry. This research describes the characteristics of phased array ultrasonic testing signal for various type of blade roots in thermal power plant turbines. This application of Phased array ultrasonic testing system has been promoted mainly to save inspection time and labor cost of turbine inspection. The characteristic of phased array ultrasonic testing signal for power plant component in very simple to understand but to difficult for perform the inspection. This paper is focused on the safety of the turbine equipment by the ultrasonic measurement and phased array analysis. As a result of the test through ultrasonic and phased array method, we have concluded that the main damage in these turbine blade roots parts could be generated by the concentrated stress and centrifugal force.

Seismic Safety Margins Research Program: Phase II program plan (FY 83-FY 84)

International Nuclear Information System (INIS)

Bohn, M.P.; Bernreuter, D.L.; Cover, L.E.; Johnson, J.J.; Shieh, L.C.; Shukla, S.N.; Wells, J.E.

1982-01-01

The Seismic Safety Margins Research Program (SSMRP) is an NRC-funded, multiyear program conducted by Lawrence Livermore National Laboratory (LLNL). Its goal is to develop a complete, fully coupled analysis procedure (including methods and computer codes) for estimating the risk of an earthquake-caused radioactive release from a commercial nuclear power plant. The analysis procedure is based upon a state-of-the-art evaluation of the current seismic analysis and design process and explicitly includes the uncertainties inherent in such a process. The results will be used to improve seismic licensing requirements for nuclear power plants. As currently planned, the SSMRP will be completed in September, 1984. This document presents the program plan for work to be done during the remainder of the program. In Phase I of the SSMRP, the necessary tools (both computer codes and data bases) for performing a detailed seismic risk analysis were identified and developed. Demonstration calculations were performed on the Zion Nuclear Power Plant. In the remainder of the program (Phase II) work will be concentrated on developing a simplified SSMRP methodology for routine probabilistic risk assessments, quantitative validation of the tools developed and application of the simplified methodology to a Boiling Water Reactor. (The Zion plant is a pressurized water reactor.) In addition, considerable effort will be devoted to making the codes and data bases easily accessible to the public

Nanotechnology Safety Self-Study

Energy Technology Data Exchange (ETDEWEB)

Grogin, Phillip W. [Los Alamos National Laboratory

2016-03-29

Nanoparticles are near-atomic scale structures between 1 and 100 nanometers (one billionth of a meter). Engineered nanoparticles are intentionally created and are used in research and development at Sandia National Laboratories (SNL) and Los Alamos National Laboratory (LANL). This course, Nanotechnology Safety Self-Study, presents an overview of the hazards, controls, and uncertainties associated with the use of unbound engineered nanoscale particles (UNP) in a laboratory environment.

Probiotic helminth administration in relapsing-remitting multiple sclerosis: a phase 1 study.

Science.gov (United States)

Fleming, J O; Isaak, A; Lee, J E; Luzzio, C C; Carrithers, M D; Cook, T D; Field, A S; Boland, J; Fabry, Z

2011-06-01

Probiotic treatment strategy based on the hygiene hypothesis, such as administration of ova from the non-pathogenic helminth, Trichuris suis, (TSO) has proven safe and effective in autoimmune inflammatory bowel disease. To study the safety and effects of TSO in a second autoimmune disease, multiple sclerosis (MS), we conducted the phase 1 Helminth-induced Immunomodulatory Therapy (HINT 1) study. Five subjects with newly diagnosed, treatment-naive relapsing-remitting multiple sclerosis (RRMS) were given 2500 TSO orally every 2 weeks for 3 months in a baseline versus treatment control exploratory trial. The mean number of new gadolinium-enhancing magnetic resonance imaging (MRI) lesions (n-Gd+) fell from 6.6 at baseline to 2.0 at the end of TSO administration, and 2 months after TSO was discontinued, the mean number of n-Gd+ rose to 5.8. No significant adverse effects were observed. In preliminary immunological investigations, increases in the serum level of the cytokines IL-4 and IL-10 were noted in four of the five subjects. TSO was well tolerated in the first human study of this novel probiotic in RRMS, and favorable trends were observed in exploratory MRI and immunological assessments. Further investigations will be required to fully explore the safety, effects, and mechanism of action of this immunomodulatory treatment.

Gefitinib plus cisplatin and radiotherapy in previously untreated head and neck squamous cell carcinoma: A phase II, randomized, double-blind, placebo-controlled study

International Nuclear Information System (INIS)

Gregoire, Vincent; Hamoir, Marc; Chen Changhu; Kane, Madeleine; Kawecki, Andrzej; Julka, Pramod K.; Wang, Hung-Ming; Prasad, Srihari; D'Cruz, Anil K.; Radosevic-Jelic, Ljiljana; Kumar, Rejnish R.; Korzeniowski, Stanislaw; Fijuth, Jacek; Machiels, Jean-Pascal; Sellers, Mark V.; Tchakov, Ilian; Raben, David

2011-01-01

Background and purpose: To assess the efficacy and safety of gefitinib given concomitantly and/or as maintenance therapy to standard cisplatin/radiotherapy for previously untreated, unresected, stage III/IV non-metastatic SCCHN. Materials and methods: In this phase II, double-blind, study, 226 patients were randomized to gefitinib 250 mg/day, 500 mg/day or placebo in two phases: a concomitant phase (gefitinib or placebo with chemoradiotherapy), followed by a maintenance phase (gefitinib or placebo alone). Primary endpoint was local disease control rate (LDCR) at 2 years; secondary endpoints were LDCR at 1 year, objective response rate, progression-free survival, overall survival, and safety and tolerability. Results: Gefitinib (250 and 500 mg/day) did not improve 2-year LDCR compared with placebo either when given concomitantly with chemoradiotherapy (32.7% vs. 33.6%, respectively; OR 0.921, 95% CI 0.508, 1.670 [1-sided p = 0.607]) or as maintenance therapy (28.8% vs. 37.4%, respectively; OR 0.684, 95% CI 0.377, 1.241 [1-sided p = 0.894]). Secondary efficacy outcomes were broadly consistent with the 2-year LDCR results. In both doses, gefitinib was well-tolerated and did not adversely affect the safety and tolerability of concomitant chemoradiotherapy. Conclusion: Gefitinib was well-tolerated, but did not improve efficacy compared with placebo when given concomitantly with chemoradiotherapy, or as maintenance therapy alone.

78 FR 64504 - Safety and Occupational Health Study Section (SOHSS), National Institute for Occupational Safety...

Science.gov (United States)

2013-10-29

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Safety and Occupational Health Study Section (SOHSS), National Institute for Occupational Safety and Health (NIOSH or..., Number 177, Pages 56235-56236. Contact Person for More Information: Price Connor, Ph.D., NIOSH Health...

Canadian Consumer Food Safety Practices and Knowledge: Foodbook Study.

Science.gov (United States)

Murray, Regan; Glass-Kaastra, Shiona; Gardhouse, Christine; Marshall, Barbara; Ciampa, Nadia; Franklin, Kristyn; Hurst, Matt; Thomas, M Kate; Nesbitt, Andrea

2017-10-01

Understanding consumers' food safety practices and knowledge supports food safety education for the prevention of foodborne illness. The objective of this study was to describe Canadian consumer food safety practices and knowledge. This study identifies demographic groups for targeted food safety education messaging and establishes a baseline measurement to assess the effectiveness of food safety interventions over time. Questions regarding consumer food safety practices and knowledge were included in a population-based telephone survey, Foodbook, conducted from November 2014 to March 2015. The results were analyzed nationally by age group and by gender. The results showed that approximately 90% of Canadians reported taking the recommended cleaning and separating precautions when handling raw meat to prevent foodborne illness. Only 29% of respondents reported using a food thermometer when cooking any meat, and even fewer (12%) reported using a food thermometer for small cuts of meat such as chicken pieces. The majority (>80%) of Canadians were aware of the foodborne illness risks related to chicken and hamburger, but fewer (poultry.

Safety study of high-frequency transcranial magnetic stimulation in patients with chronic stroke.

Science.gov (United States)

Lomarev, M P; Kim, D Y; Richardson, S Pirio; Voller, B; Hallett, M

2007-09-01

Repetitive transcranial magnetic stimulation (rTMS) is a potential therapeutic tool to rehabilitate chronic stroke patients. In this study, the safety of high-frequency rTMS in stroke was investigated (Phase I). The safety of 20 and 25 Hz rTMS over the motor cortex (MC) of the affected hemisphere, with intensities of 110-130% of the motor threshold (MT), was evaluated using surface electromyography (EMG) of hand and arm muscles. Brief EMG bursts, possibly representing peripheral manifestations of after discharges, and spread of excitation to proximal muscles are considered to be associated with a high risk of seizure occurrence. These events were recorded after the rTMS trains. Neither increased MC excitability nor improved pinch force dynamometry was found after rTMS. Stimulation parameters for rTMS, which are safe for healthy volunteers, may lead to a higher risk for seizure occurrence in chronic stroke patients. rTMS at rates of 20 and 25 Hz using above threshold stimulation potentially increases the risk of seizures in patients with chronic stroke.

A phase I, dose-escalation study of TB-403, a monoclonal antibody directed against PlGF, in patients with advanced solid tumours

DEFF Research Database (Denmark)

Lassen, U; Nielsen, D L; Sørensen, M

2012-01-01

BACKGROUND: TB-403 (RO 5323441), a humanised monoclonal antibody, is a novel antiangiogenesis agent directed against placental growth factor. The safety, pharmacokinetics (PK), and antitumour activity of TB-403 were assessed in a phase I, dose-escalation study in patients with advanced solid...

The Chemistry of iodine in reactor safety: summary and conclusions: OECD Workshop

International Nuclear Information System (INIS)

1996-01-01

About seventy experts from fourteen OECD member countries attended this Fourth OECD Workshop on the chemistry of iodine in reactor safety, as well as experts from Latvia and the Commission of the European Communities. Thirty four papers were presented, in five sessions: national and international programmes (integral and intermediate-scale experiments), experimental homogeneous phase chemistry, surface processes, thermodynamic and kinetic studies, safety applications. A final session is devoted to a general discussion on remaining research studies relevant to reactor safety

Flammable Gas Safety Self-Study 52827

Energy Technology Data Exchange (ETDEWEB)

Glass, George [Los Alamos National Laboratory

2016-03-17

This course, Flammable Gas Safety Self-Study (COURSE 52827), presents an overview of the hazards and controls associated with commonly used, compressed flammable gases at Los Alamos National Laboratory (LANL).

Phase I study of safety and immunogenicity of an Escherichia coli-derived recombinant protective antigen (rPA) vaccine to prevent anthrax in adults.

Science.gov (United States)

Brown, Bruce K; Cox, Josephine; Gillis, Anita; VanCott, Thomas C; Marovich, Mary; Milazzo, Mark; Antonille, Tanya Santelli; Wieczorek, Lindsay; McKee, Kelly T; Metcalfe, Karen; Mallory, Raburn M; Birx, Deborah; Polonis, Victoria R; Robb, Merlin L

2010-11-05

The fatal disease caused by Bacillus anthracis is preventable with a prophylactic vaccine. The currently available anthrax vaccine requires a lengthy immunization schedule, and simpler and more immunogenic options for protection against anthrax are a priority for development. In this report we describe a phase I clinical trial testing the safety and immunogenicity of an anthrax vaccine using recombinant Escherichia coli-derived, B. anthracis protective antigen (rPA). A total of 73 healthy adults ages 18-40 were enrolled and 67 received 2 injections separated by 4 weeks of either buffered saline placebo, or rPA formulated with or without 704 µg/ml Alhydrogel® adjuvant in increasing doses (5, 25, 50, 100 µg) of rPA. Participants were followed for one year and safety and immunologic data were assessed. Tenderness and warmth were the most common post-injection site reactions. No serious adverse events related to the vaccine were observed. The most robust humoral immune responses were observed in subjects receiving 50 µg of rPA formulated with Alhydrogel® with a geometric mean concentration of anti-rPA IgG antibodies of 283 µg/ml and a toxin neutralizing geometric 50% reciprocal geometric mean titer of 1061. The highest lymphoproliferative peak cellular response (median Lymphocyte Stimulation Index of 29) was observed in the group receiving 25 µg Alhydrogel®-formulated rPA. The vaccine was safe, well tolerated and stimulated a robust humoral and cellular response after two doses. ClinicalTrials.gov NCT00057525.

Safety and efficacy of ranibizumab in diabetic macular edema (RESOLVE Study): a 12-month, randomized, controlled, double-masked, multicenter phase II study

DEFF Research Database (Denmark)

Massin, Pascale; Bandello, Francesco; Garweg, Justus G

2010-01-01

The expression of vascular endothelial growth factor (VEGF) is elevated in diabetic macular edema (DME). Ranibizumab binds to and inhibits multiple VEGF variants. We investigated the safety and efficacy of ranibizumab in DME involving the foveal center.......The expression of vascular endothelial growth factor (VEGF) is elevated in diabetic macular edema (DME). Ranibizumab binds to and inhibits multiple VEGF variants. We investigated the safety and efficacy of ranibizumab in DME involving the foveal center....

On application of CFD codes to problems of nuclear reactor safety

International Nuclear Information System (INIS)

Muehlbauer, Petr

2005-01-01

The 'Exploratory Meeting of Experts to Define an Action Plan on the Application of Computational Fluid Dynamics (CFD) Codes to Nuclear Reactor Safety Problems' held in May 2002 at Aix-en-Province, France, recommended formation of writing groups to report the need of guidelines for use and assessment of CFD in single-phase nuclear reactor safety problems, and on recommended extensions to CFD codes to meet the needs of two-phase problems in nuclear reactor safety. This recommendations was supported also by Working Group on the Analysis and Management of Accidents and led to formation oaf three Writing Groups. The first writing Group prepared a summary of existing best practice guidelines for single phase CFD analysis and made a recommendation on the need for nuclear reactor safety specific guidelines. The second Writing Group selected those nuclear reactor safety applications for which understanding requires or is significantly enhanced by single-phase CFD analysis, and proposed a methodology for establishing assesment matrices relevant to nuclear reactor safety applications. The third writing group performed a classification of nuclear reactor safety problems where extension of CFD to two-phase flow may bring real benefit, a classification of different modeling approaches, and specification and analysis of needs in terms of physical and numerical assessments. This presentation provides a review of these activities with the most important conclusions and recommendations (Authors)

Immunogenicity, reactogenicity and safety of 2 doses of an adjuvanted herpes zoster subunit vaccine administered 2, 6 or 12 months apart in older adults: Results of a phase III, randomized, open-label, multicenter study.

Science.gov (United States)

Lal, Himal; Poder, Airi; Campora, Laura; Geeraerts, Brecht; Oostvogels, Lidia; Vanden Abeele, Carline; Heineman, Thomas C

2018-01-02

In phase III trials, 2 doses of a herpes zoster (HZ) subunit vaccine (HZ/su; 50 µg varicella-zoster virus glycoprotein E [gE] and AS01 B Adjuvant System) administered 2-months apart in older adults (≥50 and ≥70 years) demonstrated >90% efficacy in preventing HZ and had a clinically acceptable safety profile. Here we report immunogenicity, reactogenicity and safety following administration of 2 HZ/su doses at intervals longer than 2 months. In this Phase III, open-label trial conducted in the US and Estonia, 354 adults ≥50 years were randomized 1:1:1 to receive 2 HZ/su doses 2, 6, or 12 months apart. gE-specific humoral immune responses were evaluated at pre-vaccination, 1 and 12 months post-dose 2. Co-primary objectives were to compare immune responses to HZ/su 1 month post-dose 2 when given 6-months or 12-months apart to those administered 2-months apart. For each participant, safety information was collected from dose 1 to 12 months post-dose 2. 346 participants completed the study and 343 were included in the according-to-protocol cohort for immunogenicity. One month post-dose 2, vaccine response rates were 96.5% (97.5% confidence interval [CI]: 90.4; 99.2) and 94.5% (97.5% CI: 87.6; 98.3) for the 0, 6- and 0, 12-month schedules, respectively, both schedules meeting the pre-defined criterion. Non-inferiority of anti-gE geometric mean concentrations was demonstrated for HZ/su administered on 0, 6-month compared to a 0, 2-month schedule; however, HZ/su administered on a 0, 12-month schedule did not meet the non-inferiority criterion. Injection site pain was the most commonly reported solicited adverse event (AE). 26 participants each reported at least 1 serious AE; none were assessed as related to vaccination. Immune responses to HZ/su administered at 0, 6-month were non-inferior to those elicited by a 0, 2-month schedule. HZ/su exhibited a clinically acceptable safety profile for all dosing intervals. Clinicaltrials.gov (NCT01751165

Modeling the Relationship between Safety Climate and Safety Performance in a Developing Construction Industry: A Cross-Cultural Validation Study.

Science.gov (United States)

Zahoor, Hafiz; Chan, Albert P C; Utama, Wahyudi P; Gao, Ran; Zafar, Irfan

2017-03-28

This study attempts to validate a safety performance (SP) measurement model in the cross-cultural setting of a developing country. In addition, it highlights the variations in investigating the relationship between safety climate (SC) factors and SP indicators. The data were collected from forty under-construction multi-storey building projects in Pakistan. Based on the results of exploratory factor analysis, a SP measurement model was hypothesized. It was tested and validated by conducting confirmatory factor analysis on calibration and validation sub-samples respectively. The study confirmed the significant positive impact of SC on safety compliance and safety participation , and negative impact on number of self-reported accidents/injuries . However, number of near-misses could not be retained in the final SP model because it attained a lower standardized path coefficient value. Moreover, instead of safety participation , safety compliance established a stronger impact on SP. The study uncovered safety enforcement and promotion as a novel SC factor, whereas safety rules and work practices was identified as the most neglected factor. The study contributed to the body of knowledge by unveiling the deviations in existing dimensions of SC and SP. The refined model is expected to concisely measure the SP in the Pakistani construction industry, however, caution must be exercised while generalizing the study results to other developing countries.

Demonstration of inherent safety features of HTGRs using the HTTR

International Nuclear Information System (INIS)

Tachibana, Yukio; Nakagawa, Shigeaki; Nakazawa, Toshio; Iyoku, Tatsuo

2004-01-01

Safety demonstration tests using the High Temperature Engineering Test Reactor (HTTR) are conducted for the purpose of demonstrating inherent safety features of High Temperature Gas-cooled Reactors (HTGRs) quantitatively as well as providing the core and plant transient data for validation of HTGR analysis codes for safety evaluation. The safety demonstration test are divided to the first phase and second phase tests. In the first phase tests, simulation tests of anticipated operational occurrences and anticipated transients without scram (ATWS) are conducted. The second phase tests will simulate accidents such as a depressurization accident (loss of coolant accident). The first phase test simulating reactivity insertion events and coolant flow reduction events stared in FY 2002. Post-test analyses have been conducted to reproduced the test results by using the core and plant dynamics analysis code, ACCORD and Monte Carlo code, MVP. The analysis results agreed fairly well with the test results of a control rod withdrawal test simulating reactivity insertion, and gas circulators trip test simulating coolant flow reduction, at power levels of 50% and 30% of the rated power, respectively. It is shown that improvement of the ACCORD code by taking into consideration vertical and horizontal temperature distribution gives better analysis results in the control rod withdrawal test. The fist phase safety demonstration tests will continue until FY 2005, and the second phase tests are planned to be started in FY 2006. (author)

ADTT safety aspects

International Nuclear Information System (INIS)

Thedeen, T.

1997-01-01

Beside the technical problems of ADTT which remain to be solved it is crucial for the ADTT progress that safety and economical aspects are considered already during the research and planning phases. Safety here stands for the converse of risk, negative consequences for human life and health and the environment together with the corresponding probabilities. The system to be considered includes all phases of an ADTT plant, a life cycle analysis (LCA). The risk analysis is useful for two purposes: comparison with other ways of handling nuclear waste, e.g. geological repository and for valuation of different construction designs. Due to lack of precise plans and adequate data the analysis will be more of a qualitative than quantitative type. The main risks appear in connection with repair and replacement work. 2 refs., 1 fig

Procedures and results of the probabilistic safety study of the HTR-1160 plant

International Nuclear Information System (INIS)

Kroeger, W.; Bongartz, R.

1981-01-01

A research team of the Institute for Nuclear Safety Research of the Juelich Nuclear Research Center (KFA) and staff members of the Gesellschaft fuer Reaktorsicherheit, sponsored by the Federal Ministry of the Interior, carried out a safety and risk analysis of high temperature reactors. The studies, which included the transfer to German conditions and the modification in some points of methodology of the American AIPA Study, were performed on the German concept of an 1160 MWe HTR with block-type fuel elements. They referred to accidents and possible impacts on the environment, residual risks and measures to reduce them. The study covered a total of approx. 15 groups of initiating events, including potential external impacts. The dominating initiating events are transients in a pressurized reactor. Differences relative to the light water reactor concept arise with respect to releases as a result of accidents and, above all, release times; they are due to different physical characteristics. HTR'S are characterized by thermal inertia and resistance to temperatures. If the results of the study are extended to the HTR line with a pebble bed core currently in the planning phase, the power densities alone, which are considerably lower in some designs, are indicative of an even more effective fission product retention than is already found in the HTR-1160 plant analyzed here. (orig.) [de

Spent nuclear fuel project cold vacuum drying facility safety equipment list

International Nuclear Information System (INIS)

IRWIN, J.J.

1999-01-01

This document provides the safety equipment list (SEL) for the Cold Vacuum Drying Facility (CVDF). The SEL was prepared in accordance with the procedure for safety structures, systems, and components (SSCs) in HNF-PRO-516, ''Safety Structures, Systems, and Components,'' Revision 0 and HNF-PRO-097, Engineering Design and Evaluation, Revision 0. The SEL was developed in conjunction with HNF-SO-SNF-SAR-O02, Safety Analysis Report for the Cold Vacuum Drying Facility, Phase 2, Supporting Installation of Processing Systems (Garvin 1998). The SEL identifies the SSCs and their safety functions, the design basis accidents for which they are required to perform, the design criteria, codes and standards, and quality assurance requirements that are required for establishing the safety design basis of the SSCs. This SEL has been developed for the CVDF Phase 2 Safety Analysis Report (SAR) and shall be updated, expanded, and revised in accordance with future phases of the CVDF SAR until the CVDF final SAR is approved

Impact of workflow on the use of the Surgical Safety Checklist: a qualitative study.

Science.gov (United States)

Gillespie, Brigid M; Marshall, Andrea P; Gardiner, Therese; Lavin, Joanne; Withers, Teresa K

2016-11-01

Regardless of the benefits associated of the Surgical Safety Checklist, adherence across its three phases remains inconsistent. The aim of this study was to systematically identify issues around workflow that impact on surgical teams' ability to use the Surgical Safety Checklist in a large tertiary facility in Queensland, Australia. Observational audit of 10 surgical teams and 33 semi-structured interviews with 70 participants from nursing, medicine and the community were conducted. Data were collected during 2014-2015. Inductive and deductive approaches were used to analyse field observations and interview transcripts. The domain, impact of workflow on checklist utilization, was identified. Within this domain, seven categories illustrated the causal conditions which determined the ways in which workflow influenced checklist use. These categories included: 'busy doing the task'; 'clashing task priorities'; 'being pressured, running out of time'; 'adapting processes to work patterns'; 'doubling up on work'; 'a domino effect, leading to delays' and 'reality of the workflow'. One of the greatest systemic challenges to checklist use in surgery is workflow. Process changes in the way that surgical safety checklists are used need to incorporate the temporal demands of the workflow. Any changes made must ensure the process is reliable, is easily embedded into existing work routines and is not disruptive. © 2016 Royal Australasian College of Surgeons.

Safety and efficacy of neratinib in combination with weekly paclitaxel and trastuzumab in women with metastatic HER2‑positive breast cancer: an NSABP Foundation Research Program phase I study.

Science.gov (United States)

Jankowitz, Rachel C; Abraham, Jame; Tan, Antoinette R; Limentani, Steven A; Tierno, Marni B; Adamson, Laura M; Buyse, Marc; Wolmark, Norman; Jacobs, Samuel A

2013-12-01

Neratinib is an oral, small-molecule inhibitor that irreversibly binds to pan-HER (ErbB) receptor tyrosine kinases. Studies suggest that dual anti-HER therapies utilized in breast cancer patients are more efficacious than single agents in both the metastatic and neoadjuvant settings. In this phase I study, neratinib was combined with trastuzumab and paclitaxel in metastatic HER2-positive patients. Twenty-one patients entered this dose-escalation study to determine the maximum-tolerated dose, safety, and efficacy of neratinib (120 up to 240 mg/day) with trastuzumab (4 mg/kg IV loading dose, then 2 mg/kg IV weekly), and paclitaxel (80 mg/m(2) IV days 1, 8, and 15 of a 28-day cycle) in women with HER2-positive metastatic breast cancer previously treated with anti-HER agent(s) and a taxane. The recommended phase II dose of neratinib with trastuzumab and paclitaxel was 200 mg/day. Common grade 3/4 adverse events were diarrhea (38 %), dehydration (14 %), electrolyte imbalance (19 %), and fatigue (19 %). With mandated primary diarrheal prophylaxis, ≥grade 3 diarrhea was not observed. Objective responses, complete (CR) and partial (PR), occurred in eight patients (38 %), with a clinical benefit of CR + PR+ stable disease (SD) ≥24 weeks in 11 patients (52 %). Median time-to-disease progression was 3.7 months. Dual anti-HER blockade with neratinib and trastuzumab resulted in significant clinical benefit despite prior exposure to trastuzumab, lapatinib, T-DM1, a taxane, and multiple lines of chemotherapy. In selected populations, inhibiting multiple ErbB-family receptors may be more advantageous than single-agent inhibition. Based on favorable tolerance and efficacy, this three-drug combination will be further assessed in a randomized phase II neoadjuvant trial (NSABP FB-7:NCT01008150).

Case study: the Argentina Road Safety Project: lessons learned for the decade of action for road safety, 2011-2020.

Science.gov (United States)

Raffo, Veronica; Bliss, Tony; Shotten, Marc; Sleet, David; Blanchard, Claire

2013-12-01

This case study of the Argentina Road Safety Project demonstrates how the application of World Bank road safety project guidelines focused on institution building can accelerate knowledge transfer, scale up investment and improve the focus on results. The case study highlights road safety as a development priority and outlines World Bank initiatives addressing the implementation of the World Report on Road Traffic Injury's recommendations and the subsequent launch of the Decade of Action for Road Safety, from 2011-2020. The case study emphasizes the vital role played by the lead agency in ensuring sustainable road safety improvements and promoting the shift to a 'Safe System' approach, which necessitated the strengthening of all elements of the road safety management system. It summarizes road safety performance and institutional initiatives in Argentina leading up to the preparation and implementation of the project. We describe the project's development objectives, financing arrangements, specific components and investment staging. Finally, we discuss its innovative features and lessons learned, and present a set of supplementary guidelines, both to assist multilateral development banks and their clients with future road safety initiatives, and to encourage better linkages between the health and transportation sectors supporting them.

Seismic Safety Margins Research Program (Phase I). Project IV. Structural building response; Structural Building Response Review

International Nuclear Information System (INIS)

Healey, J.J.; Wu, S.T.; Murga, M.

1980-02-01

As part of the Phase I effort of the Seismic Safety Margins Research Program (SSMRP) being performed by the University of California Lawrence Livermore Laboratory for the US Nuclear Regulatory Commission, the basic objective of Subtask IV.1 (Structural Building Response Review) is to review and summarize current methods and data pertaining to seismic response calculations particularly as they relate to the objectives of the SSMRP. This material forms one component in the development of the overall computational methodology involving state of the art computations including explicit consideration of uncertainty and aimed at ultimately deriving estimates of the probability of radioactive releases due to seismic effects on nuclear power plant facilities

Safety analysis and related studies

International Nuclear Information System (INIS)

Lelievre, J.

1979-12-01

Several examples of reactor safety studies are given. For light water reactors, the consequences of loss of coolant, the disposition of the fuel elements and the behaviour under irradiation of the steels used for containment are described. For fast reactors, the disposition of fuel elements in the case of cooling accidents and sodium fies are described. Examples given of studies not specific to a particular reactor type include studies of non-destructive testing and those of reliability

Comprehensive Lifecycle for Assuring System Safety

Science.gov (United States)

Knight, John C.; Rowanhill, Jonathan C.

2017-01-01

CLASS is a novel approach to the enhancement of system safety in which the system safety case becomes the focus of safety engineering throughout the system lifecycle. CLASS also expands the role of the safety case across all phases of the system's lifetime, from concept formation to decommissioning. As CLASS has been developed, the concept has been generalized to a more comprehensive notion of assurance becoming the driving goal, where safety is an important special case. This report summarizes major aspects of CLASS and contains a bibliography of papers that provide additional details.

The advanced neutron source facility: Safety philosophy and studies

International Nuclear Information System (INIS)

Greene, S.R.; Harrington, R.M.

1988-01-01

The Advanced Neutron Source (ANS) is currently the only new civilian nuclear reactor facility proposed for construction in the United States. Even though the thermal power of this research-oriented reactor is a relatively low 300 MW, the design will undoubtedly receive intense scrutiny before construction is allowed to proceed. Safety studies are already under way to ensure that the maximum degree of safety in incorporated into the design and that the design is acceptable to the Department of Energy (DOE) and can meet the Nuclear Regulatory Commission regulations. This document discusses these safety studies

Patient safety: Safety culture and patient safety ethics

DEFF Research Database (Denmark)

Madsen, Marlene Dyrløv

2006-01-01

,demonstrating significant, consistent and sometimes large differences in terms of safety culture factors across the units participating in the survey. Paper 5 is the results of a study of the relation between safety culture, occupational health andpatient safety using a safety culture questionnaire survey......Patient safety - the prevention of medical error and adverse events - and the initiative of developing safety cultures to assure patients from harm have become one of the central concerns in quality improvement in healthcare both nationally andinternationally. This subject raises numerous...... challenging issues of systemic, organisational, cultural and ethical relevance, which this dissertation seeks to address through the application of different disciplinary approaches. The main focus of researchis safety culture; through empirical and theoretical studies to comprehend the phenomenon, address...

Development of safety analysis technology for integral reactor

International Nuclear Information System (INIS)

Kim, Hee Cheol; Kim, K. K.; Kim, S. H.

2002-04-01

The state-of-the-arts for the integral reactor was performed to investigate the safety features. The safety and performance of SMART were assessed using the technologies developed during the study. For this purpose, the computer code system and the analysis methodology were developed and the safety and performance analyses on SMART basic design were carried out for the design basis event and accident. The experimental facilities were designed for the core flow distribution test and the self-pressurizing pressurizer performance test. The tests on the 2-phase critical flow with non-condensable gas were completed and the results were used to assess the critical flow model. Probabilistic Safety Assessment(PSA) was carried out to evaluate the safety level and to optimize the design by identifying and remedying any weakness in the design. A joint study with KINS was carried out to promote licensing environment. The generic safety issues of integral reactors were identified and the solutions were formulated. The economic evaluation of the SMART desalination plant and the activities related to the process control were carried out in the scope of the study

Efficacy and Safety of Sarecycline, a Novel, Once-Daily, Narrow Spectrum Antibiotic for the Treatment of Moderate to Severe Facial Acne Vulgaris: Results of a Phase 2, Dose-Ranging Study.

Science.gov (United States)

Leyden, James J; Sniukiene, Vilma; Berk, David R; Kaoukhov, Alexandre

2018-03-01

There is a need for new oral antibiotics for acne with improved safety profiles and targeted antibacterial spectra. Sarecycline is a novel, tetracycline-class antibiotic specifically designed for acne, offering a narrow spectrum of activity compared with currently available tetracyclines, including less activity against enteric Gram-negative bacteria. This phase 2 study evaluated the efficacy and safety of three doses of sarecycline for moderate to severe facial acne vulgaris. In this multicenter, double-blind, placebo-controlled study, patients aged 12 to 45 years were randomized to once-daily sarecycline 0.75 mg/kg, 1.5 mg/kg, 3.0 mg/kg, or placebo. Efficacy analyses included change from baseline in inflammatory and noninflammatory lesion counts at week 12, with between-group comparisons using analysis of covariance. Safety assessments included adverse events (AEs), clinical laboratories, vital signs, electrocardiograms, and physical examinations. Overall, 285 randomized patients received at least one dose of study drug. At week 12, sarecycline 1.5 mg/kg and 3.0 mg/kg groups demonstrated significantly reduced inflammatory lesions from baseline (52.7% and 51.8%, respectively) versus placebo (38.3%; P=0.02 and P=0.03, respectively). Sarecycline was safe and well tolerated, with similar gastrointestinal AE rates in sarecycline and placebo groups. Vertigo and photosensitivity AEs occurred in less than 1% of patients when pooling sarecycline groups; no vulvovaginal candidiasis AEs occurred. Discontinuation rates due to AEs were low. No serious AEs occurred. Once-daily sarecycline 1.5 mg/kg significantly reduced inflammatory lesions versus placebo and was safe and well tolerated with low rates of AEs, including gastrointestinal AEs. Sarecycline 3.0 mg/kg did not result in additional efficacy versus 1.5 mg/kg. Sarecycline may represent a novel, once-daily treatment for patients with moderate to severe acne. It offers a narrow antibacterial spectrum relative to other

Study on European Nuclear Safety Practices during Planned Outages at Nuclear Power Plants

International Nuclear Information System (INIS)

2001-12-01

The present project was aimed at providing: a description of the current status of nuclear safety practices during planned outages at nuclear power plants followed in Europe; the criteria for the safety analysis of future reactors at the design stage; proposing a set of recommendations on good practices and criteria leading to the improvement of nuclear safety during those conditions. The work was organised in 3 phases: Collecting data on current practices; Analysis of questionnaire answers and drawing up of safety good practices references and recommendations; Collecting relevant ideas related to the future reactors at design stage (European Pressurised Water Reactor, European Passive Plant project, European Utilities Requirements and Utilities Requirement Document project). The key element of the performed work was the detailed questionnaire, based on bibliographical review, expert experience and outage practices available in the working team. Different safety areas and activities were covered: outage context; nuclear safety; outage strategy, organisation and control; operating feedback; use of Probabilistic Safety Assessment. The questionnaire was answered by 12 European nuclear power plants, representing 9 different European countries and three different types of reactors (Pressurised Water Reactor, Boiling Water Reactor and Water Water Energy Reactor). Conclusions were drawn under the following headers: Organisational survey and generalities Organisational effectiveness Quality of maintenance Quality of operation Engineering support, management of modification Specific aspects Each analysed subject includes the following topics: Questions background with a summary and the aim of the questions. Current status, that describes common practices, as derived from the answers to the questionnaire, and some examples of good specific practices. Identified good practices. (author)

A phase Ia/Ib clinical trial of metronomic chemotherapy based on a mathematical model of oral vinorelbine in metastatic non-small cell lung cancer and malignant pleural mesothelioma: rationale and study protocol

International Nuclear Information System (INIS)

Elharrar, Xavier; Barbolosi, Dominique; Ciccolini, Joseph; Meille, Christophe; Faivre, Christian; Lacarelle, Bruno; André, Nicolas; Barlesi, Fabrice

2016-01-01

Metronomic oral vinorelbine is effective in metastatic NSCLC and malignant pleural mesothelioma, but all the studies published thus far were based upon a variety of empirical and possibly suboptimal schedules, with inconsistent results. Mathematical modelling showed by simulation that a new metronomic protocol could lead to a better safety and efficacy profile. This phase Ia/Ib trial was designed to confirm safety (phase Ia) and evaluate efficacy (phase Ib) of a new metronomic oral vinorelbine schedule. Patients with metastatic NSCLC or malignant pleural mesothelioma in whom standard treatments failed and who exhibited ECOG performance status 0–2 and adequate organ function will be eligible. Our mathematical PK-PD model suggested an alternative weekly D1, D2 and D4 schedule (named Vinorelbine Theoretical Protocol) with a respective dose of 60, 30 and 60 mg. Trial recruitment will be two-staged, as 12 patients are planned to participate in phase Ia to confirm safety and consolidate the calibration of the model parameters. Depending on the phase Ia results and after a favourable decision from a consultative committee, the extension phase (phase Ib) will be an efficacy study including 20 patients who will receive the Optimal Vinorelbine Theoretical Protocol. The primary endpoint is the tolerance (assessed by CTC v4.0) for the phase Ia and the objective response according to RECIST 1.1 for phase Ib. An ancillary study on circulating angiogenesis biomarkers will be a subproject of the trial. This ongoing trial is the first to prospectively test a mathematically optimized schedule in metronomic chemotherapy. As such, this trial can be considered as a proof-of-concept study demonstrating the feasibility to run a computational-driven protocol to ensure an optimal efficacy/toxicity balance in patients with cancer

Preliminary Study on the Revision of Nuclear Safety Policy Statement

International Nuclear Information System (INIS)

Lee, Y. E.; Lee, S. H.; Chang, H. S.; Choi, K. S.; Jung, S. J.

2011-01-01

Nuclear safety policy in Korea is currently declared in the Nuclear Safety Charter as the highest tier document and safety principles and directions are announced in the Nuclear Safety Policy Statement. As the circumstances affecting on the nuclear safety policy change, it needs to revise the Statement. This study aims to develop the revised Nuclear Safety Policy Statement to declare that securing safety is a prerequisite to the utilization of nuclear energy, and that all workers in nuclear industry and regulatory body must adhere to the principle of priority to safety. As a result, two different types of revision are being prepared as of August. One is based on the spirit of Nuclear Safety Charter as well as the direction of future-oriented safety policies including the changes in the environment after declaration of the Statement. The other is to declare the fundamental safety objective and safety principles as the top philosophy of national nuclear safety policy by adopting the '10 Safety Principles in IAEA Safety Fundamental' instead of the current Charter. Both versions of revision are subject to further in-depth discussion. However once the revision is finalized and declared, it would be useful to accomplish effectively the organizational responsibilities and to enhance the public confidence in nuclear safety by performing the regulatory activities in a planned and systematic manner and promulgating the government's dedication to priority to safety

Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study.

Science.gov (United States)

Burger, Jan A; Keating, Michael J; Wierda, William G; Hartmann, Elena; Hoellenriegel, Julia; Rosin, Nathalie Y; de Weerdt, Iris; Jeyakumar, Ghayathri; Ferrajoli, Alessandra; Cardenas-Turanzas, Marylou; Lerner, Susan; Jorgensen, Jeffrey L; Nogueras-González, Graciela M; Zacharian, Gracy; Huang, Xuelin; Kantarjian, Hagop; Garg, Naveen; Rosenwald, Andreas; O'Brien, Susan

2014-09-01

Ibrutinib, an orally administered covalent inhibitor of Bruton's tyrosine kinase (BTK), is an effective treatment for relapsed chronic lymphocytic leukaemia (CLL). We investigated the activity and safety of the combination of ibrutinib with the monoclonal antibody rituximab in patients with high-risk CLL. In this single-arm phase 2 study, we enrolled adult patients with high-risk CLL at the MD Anderson Cancer Center (Houston, TX, USA). All enrolled participants had high-risk cytogenetic abnormalities (deletion 17p, TP53 mutation, or deletion 11q) or a short progression-free survival (PFS ibrutinib 420 mg together with rituximab (375 mg/m(2), intravenously, every week during cycle 1, then once per cycle until cycle 6), followed by continuous daily single-agent ibrutinib 420 mg until disease progression or until toxicities or complications precluded further treatment. The primary endpoint was progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov number NCT01520519, and is no longer accruing patients. Between Feb 28, 2012, and Sept 11, 2012, we enrolled 40 patients with CLL with high-risk disease features, 20 of whom had deletion 17p (del[17p]) or TP53 mutations (16 previously treated, four untreated), 13 had relapsed CLL with deletion 11q (del[11q]), and seven a PFS less than 36 months after first-line chemoimmunotherapy. 18-month PFS in all patients was 78·0% (95% CI 60·6-88·5), whereas in those with a del(17p) or TP53 mutation it was 72·4% (45·6-87·6) Toxicity was mainly mild to moderate in severity (grade 1-2). Diarrhoea occurred in ten (25%) patients (grade 1 in nine patients and grade 2 in one), bleeding events in 14 (33%) patients (eight grade 1 and five grade 2), nausea or vomiting in 15 patients (38%) (ten grade 1 and five grade 2), and fatigue in seven (18%) patients (four grade 1 and three grade 2). Five patients (13%) had grade 3 infections (two lung infections, one upper respiratory tract

Topical administration of regorafenib eye drops: phase I dose-escalation study in healthy volunteers.

Science.gov (United States)

Zimmermann, Torsten; Höchel, Joachim; Becka, Michael; Boettger, Michael K; Rohde, Beate; Schug, Barbara; Kunert, Kathleen S; Donath, Frank

2018-05-01

Regorafenib is a multikinase inhibitor under investigation for use in neovascular age-related macular degeneration. In this phase I study, regorafenib eye drops were administered to healthy volunteers to provide information on safety, tolerability and systemic exposure. This was a single-centre, randomized, double-masked, parallel-group, dose-escalation, placebo-controlled study. Subjects received regorafenib eye drops (30 mg ml -1 , 25 μl) as a 0.75 mg single dose (Cohort 1), 0.75 mg twice daily (bid) or thrice daily (tid) over 14 days (Cohorts 2 and 3, respectively), 1.5 mg tid unilaterally for 3 days, then bilaterally for up to 14 days (Cohort 4), or placebo. Plasma samples were taken to estimate systemic exposure. Safety and functional assessments were performed throughout the study. Thirty-six subjects received regorafenib and 12 received placebo. Regorafenib was safe and well tolerated over the dose range. No pathological changes occurred in the anterior, vitreous or posterior eye compartments. Mild eyelid redness, oedema and conjunctival hyperaemia were observed across all regorafenib cohorts; these were comparable with the effects seen with placebo. Predominant symptoms were blurred vision in the active and placebo groups. Systemic safety evaluations showed no clinically relevant findings. Absolute systemic exposure after multiple administrations of regorafenib eye drops at a dose of 0.75 mg was 600-700-fold lower than after multiple oral administration of 160 mg day -1 , the dose approved in cancer indications. These results indicate a favourable safety and tolerability profile of regorafenib eye drops up to 30 mg ml -1 tid for use in clinical studies. © 2018 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Progress in the development of methodology for fusion safety systems studies

International Nuclear Information System (INIS)

Ho, S.K.; Cambi, G.; Ciattaglia, S.; Fujii-e, Y.; Seki, Y.

1994-01-01

The development of fusion safety systems-study methodology, including the aspects of schematic classification of overall fusion safety system, qualitative assessment of fusion system for identification of critical accident scenarios, quantitative analysis of accident consequences and risk for safety design evaluation, and system-level analysis of accident consequences and risk for design optimization, by a consortium of international efforts is presented. The potential application of this methodology into reactor design studies will facilitate the systematic assessment of safety performance of reactor designs and enhance the impacts of safety considerations on the selection of design configurations

Safety analysis report for the Cold Vacuum Drying Facility, phase 1, supporting civil/structural construction

International Nuclear Information System (INIS)

Pili-Vincens, C.

1997-01-01

The US Department of Energy established the K Basins Spent Nuclear Fuel Project to address safety and environmental concerns associated with deteriorating spent nuclear fuel presently stored under water in the Hanford Site's K Basins, which are located near the Columbia River. Recommendations for a series of aggressive projects to construct and operate systems and facilities to manage the safe removal of K Basins fuel were made in WHC-EP-0830, Hanford Spent Nuclear Fuel Recommended Path Forward,' and its subsequent update, WHC-SD-SNF-SP-005, Hanford Spent Nuclear Fuel Project Integrated Process Strategy for K Basins Fuel. The integrated process strategy recommendations include the following process steps: fuel preparation activities at the K Basins, including removing the fuel elements from their K Basin canisters, separating fuel particulate from fuel elements and fuel fragments greater than 0.6 cm (0.25 in.) in any dimension, removing excess sludge from the fuel and fuel fragments by means of flushing, as necessary, and packaging the fuel into multicanister overpacks; removal of free water by draining and vacuum drying at the Cold Vacuum Drying Facility (CVDF), a new facility in the 100 K Area of the Hanford Site. This report is contains the safety analysis for the Cold Vacuum Drying Facility, Phase 1

Dose Escalation Methods in Phase I Cancer Clinical Trials

OpenAIRE

Le Tourneau, Christophe; Lee, J. Jack; Siu, Lillian L.

2009-01-01

Phase I clinical trials are an essential step in the development of anticancer drugs. The main goal of these studies is to establish the recommended dose and/or schedule of new drugs or drug combinations for phase II trials. The guiding principle for dose escalation in phase I trials is to avoid exposing too many patients to subtherapeutic doses while preserving safety and maintaining rapid accrual. Here we review dose escalation methods for phase I trials, including the rule-based and model-...

Project safety studies - nuclear waste management (PSE)

International Nuclear Information System (INIS)

1981-10-01

The project 'Safety Studies-Nuclear Waste Management' (PSE) is a research project performed by order of the Federal Minister for Research and Technology, the general purpose of which is to deepen and ensure the understanding of the safety aspects of the nuclear waste management and to prepare a risk analysis which will have to be established in the future. Owing to this the project is part of a series of projects which serve the further development of the concept of nuclear waste management and its safety, and which are set up in such a way as to accompany the realization of that concept. This report contains the results of the first stage of the project from 1978 to mid-1981. (orig./RW) [de

Pooled efficacy and safety of eslicarbazepine acetate as add-on treatment in patients with focal-onset seizures: Data from four double-blind placebo-controlled pivotal phase III clinical studies.

Science.gov (United States)

Elger, Christian; Koepp, Mathias; Trinka, Eugen; Villanueva, Vicente; Chaves, João; Ben-Menachen, Elinor; Kowacs, Pedro A; Gil-Nagel, António; Moreira, Joana; Gama, Helena; Rocha, José-Francisco; Soares-da-Silva, Patrício

2017-12-01

Pooled evaluation of the key efficacy and safety profile of eslicarbazepine acetate (ESL) added-on to stable antiepileptic therapy in adults with focal-onset seizures. Data from 1703 patients enrolled in four phase III double-blind, randomized, placebo-controlled studies were pooled and analyzed. Following a 2 week titration period, ESL was administered at 400 mg, 800 mg, and 1200 mg once-daily doses for 12 weeks (maintenance period). Pooled efficacy variable was standardized (/4 weeks) seizure frequency (SSF) analyzed over the maintenance period as reduction in absolute and relative SSF and proportion of responders (≥50% reduction in SSF). Pooled safety was analyzed by means of adverse events and clinical laboratory assessments. SSF was significantly reduced with ESL 800 mg (P ESL 800 mg and 37.8% for 1200 mg (placebo: 17.6%), and responder rate was 33.8% and 43.1% (placebo: 22.2%). ESL was more efficacious than placebo regardless of gender, geographical region, epilepsy duration, age at time of diagnosis, seizure type, and type of concomitant antiepileptic drugs (AED). Incidence of adverse events (AEs) and AEs leading to discontinuation was dose dependent. Most common AEs (>10% patients) were dizziness, somnolence, and nausea. The incidence of treatment-emergent AEs (dizziness, somnolence, ataxia, vomiting, and nausea) was lower in patients who began taking ESL 400 mg (followed by 400 mg increments to 800 or 1200 mg) than in those who began taking ESL 600 mg or 800 mg. Once-daily ESL 800 mg and 1200 mg showed consistent results across all efficacy and safety endpoints, independent of study population characteristics and type of concomitant AEDs. Treatment initiated with ESL 400 mg followed by 400 mg increments to 800 or 1200 mg provides optimal balance of efficacy and tolerability. © 2017 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

Design aspects of safety critical instrumentation of nuclear installations

Energy Technology Data Exchange (ETDEWEB)

Swaminathan, P. [Electronics Group, Indira Gandhi Centre for Atomic Research, Kalpakkam 603 102, Tamil Nadu (India)]. E-mail: swamy@igcar.ernet.in

2005-07-01

Safety critical instrumentation systems ensure safe shutdown/configuration of the nuclear installation when process status exceeds the safety threshold limits. Design requirements for safety critical instrumentation such as functional and electrical independence, fail-safe design, and architecture to ensure the specified unsafe failure rate and safe failure rate, human machine interface (HMI), etc., are explained with examples. Different fault tolerant architectures like 1/2, 2/2, 2/3 hot stand-by are compared for safety critical instrumentation. For embedded systems, software quality assurance is detailed both during design phase and O and M phase. Different software development models such as waterfall model and spiral model are explained with examples. The error distribution in embedded system is detailed. The usage of formal method is outlined to reduce the specification error. The guidelines for coding of application software are outlined. The interface problems of safety critical instrumentation with sensors, actuators, other computer systems, etc., are detailed with examples. Testability and maintainability shall be taken into account during design phase. Online diagnostics for safety critical instrumentation is detailed with examples. Salient details of design guides from Atomic Energy Regulatory Board, International Atomic Energy Agency and standards from IEEE, BIS are given towards the design of safety critical instrumentation systems. (author)

Design aspects of safety critical instrumentation of nuclear installations

International Nuclear Information System (INIS)

Swaminathan, P.

2005-01-01

Safety critical instrumentation systems ensure safe shutdown/configuration of the nuclear installation when process status exceeds the safety threshold limits. Design requirements for safety critical instrumentation such as functional and electrical independence, fail-safe design, and architecture to ensure the specified unsafe failure rate and safe failure rate, human machine interface (HMI), etc., are explained with examples. Different fault tolerant architectures like 1/2, 2/2, 2/3 hot stand-by are compared for safety critical instrumentation. For embedded systems, software quality assurance is detailed both during design phase and O and M phase. Different software development models such as waterfall model and spiral model are explained with examples. The error distribution in embedded system is detailed. The usage of formal method is outlined to reduce the specification error. The guidelines for coding of application software are outlined. The interface problems of safety critical instrumentation with sensors, actuators, other computer systems, etc., are detailed with examples. Testability and maintainability shall be taken into account during design phase. Online diagnostics for safety critical instrumentation is detailed with examples. Salient details of design guides from Atomic Energy Regulatory Board, International Atomic Energy Agency and standards from IEEE, BIS are given towards the design of safety critical instrumentation systems. (author)

A phase I study evaluating the pharmacokinetics, safety and tolerability of an antibody-based tissue factor antagonist in subjects with acute lung injury or acute respiratory distress syndrome

Directory of Open Access Journals (Sweden)

Morris Peter E

2012-02-01

Full Text Available Abstract Background The tissue factor (TF-dependent extrinsic pathway has been suggested to be a central mechanism by which the coagulation cascade is locally activated in the lungs of patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS and thus represents an attractive target for therapeutic intervention. This study was designed to determine the pharmacokinetic and safety profiles of ALT-836, an anti-TF antibody, in patients with ALI/ARDS. Methods This was a prospective, randomized, placebo-controlled, dose-escalation Phase I clinical trial in adult patients who had suspected or proven infection, were receiving mechanical ventilation and had ALI/ARDS (PaO2/FiO2 ≤ 300 mm. Eighteen patients (6 per cohort were randomized in a 5:1 ratio to receive ALT-836 or placebo, and were treated within 48 hours after meeting screening criteria. Cohorts of patients were administered a single intravenously dose of 0.06, 0.08 or 0.1 mg/kg ALT-836 or placebo. Blood samples were taken for pharmacokinetic and immunogenicity measurements. Safety was assessed by adverse events, vital signs, ECGs, laboratory, coagulation and pulmonary function parameters. Results Pharmacokinetic analysis showed a dose dependent exposure to ALT-836 across the infusion range of 0.06 to 0.1 mg/kg. No anti-ALT-836 antibody response was observed in the study population during the trial. No major bleeding episodes were reported in the ALT-836 treated patients. The most frequent adverse events were anemia, observed in both placebo and ALT-836 treated patients, and ALT-836 dose dependent, self-resolved hematuria, which suggested 0.08 mg/kg as an acceptable dose level of ALT-836 in this patient population. Conclusions Overall, this study showed that ALT-836 could be safely administered to patients with sepsis-induced ALI/ARDS. Trial registration ClinicalTrials.gov: NCT01438853

A study on optimization of the nuclear safety system

International Nuclear Information System (INIS)

Lee, Sang Hoon; Koh, Byung Joon; Kim, Jin Soo; Kim, Byoung Do; Cho, Seong Won; Kwon, Seog Kwon; Choi, Kwang Sik

1986-12-01

The number of nuclear facilities (nuclear power plants, research reactors, nuclear fuel facilities) under construction or in operation in Korea continues to increase and this has brought about increased importance and concerns toward nuclear safety in Korea. Also, domestic nuclear related organizations are increasingly carrying out the design/construction of nuclear power plants and the development /supply of nuclear fuels. In order to flexibly respond to these changes and to suggest direction to take, it is necessary to re-examine the current nuclear safety regulation system. This study is carried out in two stages and this report describes the results of the analysis and the assessment of the nuclear licencing system of such foreign countries as sweden and German, as the first of the two. In this regard, this study includes the analysis on the backgrounds on the choice of nuclear licensing system, the analysis on the licensing procedures, the analysis on the safety inspection system and the enforcement laws, the analysis on the structure and function of the regulatory, business and research organizations as well as the analysis on the relationship between the safety research and the regulatory duties. In this study, the German safety inspection system and the enforcement procedures and the Swedish nuclear licensing system are analyzed in detail. By comparing and assessing the finding with the current Korea Nuclear Licensing System, this study points out some reform measures of the Korean system that needs to improved. With the changing situations in mind, this study aims to develop the nuclear safety regulation system optimized for Korean situation by re-examining the current regulation system. (Author)

LIMBO computer code for analyzing coolant-voiding dynamics in LMFBR safety tests

International Nuclear Information System (INIS)

Bordner, G.L.

1979-10-01

The LIMBO (liquid metal boiling) code for the analysis of two-phase flow phenomena in an LMFBR reactor coolant channel is presented. The code uses a nonequilibrium, annular, two-phase flow model, which allows for slip between the phases. Furthermore, the model is intended to be valid for both quasi-steady boiling and rapid coolant voiding of the channel. The code was developed primarily for the prediction of, and the posttest analysis of, coolant-voiding behavior in the SLSF P-series in-pile safety test experiments. The program was conceived to be simple, efficient, and easy to use. It is particularly suited for parametric studies requiring many computer runs and for the evaluation of the effects of model or correlation changes that require modification of the computer program. The LIMBO code, of course, lacks the sophistication and model detail of the reactor safety codes, such as SAS, and is therefore intended to compliment these safety codes

An experimental study of gravity-driven countercurrent two-phase flow in horizontal and inclined channels

International Nuclear Information System (INIS)

Lillibridge, K.H.; Ghiaasiaan, S.M.; Abdel-Khalik, S.I.

1994-01-01

Countercurrent two-phase flow in horizontal and inclined channels, connecting a sealed liquid-filled reservoir to the atmosphere, is experimentally studied. This type of gravity-driven countercurrent two-phase flow can occur during the operation of passive safety coolant injection systems of advanced reactors. It can also occur in the pressurizer surge line of pressurized water reactors during severe accidents when the hot leg becomes voided. Four distinct flow regimes are identified: (a) stratified countercurrent, which mainly occurs when the channel is horizontal; (b) intermittent stratified-slug; (c) oscillating, which occurs when the angle of inclination is ≥30 deg; and (d) annular countercurrent. The characteristics of each regime and their sensitivity to important geometric parameters are examined. The superficial velocities in the stratified countercurrent and oscillating regimes are empirically correlated

Study on some safety-related aspects of tyre use

NARCIS (Netherlands)

Jansen, S.T.H.; Schmeitz, A.J.C.; Maas, S.; Rodarius, C.; Akkermans, L.

2014-01-01

The tyre is a key component that affects road safety. The European commission has posted a tender aimed to study what measures on a European level can be taken in relation to the use of tyres to improve road safety. The results of this study, supported by a cost benefit analyses and carried out by

Multicenter phase II study of sequential radioembolization-sorafenib therapy for inoperable hepatocellular carcinoma.