Long-term efficacy and tolerability of azilsartan medoxomil/chlorthalidone vs olmesartan medoxomil/hydrochlorothiazide in chronic kidney disease.

Science.gov (United States)

Bakris, George L; Zhao, Lin; Kupfer, Stuart; Juhasz, Attila; Hisada, Michie; Lloyd, Eric; Oparil, Suzanne

2018-04-01

An open-label, long-term study evaluated safety and tolerability of azilsartan medoxomil/chlorthalidone (AZL-M/CLD) vs olmesartan/hydrochlorothiazide (OLM/HCTZ) in hypertensive participants with stage 3 chronic kidney disease. Initial therapy was AZL-M/CLD 20/12.5 mg (n = 77) or OLM/HCTZ 20/12.5 mg (n = 76), but could be up-titrated (AZL-M/CLD to 40/25 mg; OLM/HCTZ to 40/25 mg [US] or 20/25 mg [Europe]) with other agents added during weeks 4-52. Primary endpoint was proportion of participants with ≥ 1 adverse event (AE) through week 52. Baseline demographics were similar. AEs did not differ between groups (88.3%, AZL-M/CLD vs 76.3%, OLM/HCTZ; P = .058). AZL-M/CLD showed greater systolic BP reductions after initial dosing (P = .037) but not during long-term follow-up (P = .588). A greater proportion of participants up-titrated to the highest dose with OLM/HCTZ (48.7%) vs AZL-M/CLD (29.9%) (P = .021) and were taking additional antihypertensive medications (26.3% vs 16.9%). Both AZL-M/CLD and OLM/HCTZ showed similar efficacy and tolerability. ©2018 Wiley Periodicals, Inc.

Long-term safety profile of belimumab plus standard therapy in patients with systemic lupus erythematosus.

Science.gov (United States)

Merrill, Joan T; Ginzler, Ellen M; Wallace, Daniel J; McKay, James D; Lisse, Jeffrey R; Aranow, Cynthia; Wellborne, Frank R; Burnette, Michael; Condemi, John; Zhong, Z John; Pineda, Lilia; Klein, Jerry; Freimuth, William W

2012-10-01

To evaluate the safety profile of long-term belimumab therapy combined with standard therapy for systemic lupus erythematosus (SLE) in patients with active disease. Patients who were randomized to receive intravenous placebo or belimumab 1, 4, or 10 mg/kg, plus standard therapy, and completed the initial 52-week double-blind treatment period were then allowed to enter a 24-week open-label extension phase. During the extension period, patients in the belimumab group either received the same dose or were switched to 10 mg/kg and patients in the placebo group were switched to belimumab 10 mg/kg. Patients who achieved a satisfactory response during the 24-week extension period were allowed to participate in the long-term continuation study of monthly belimumab 10 mg/kg. Adverse events (AEs) and abnormal laboratory results were analyzed per 100 patient-years in 1-year intervals. Of the 364 patients who completed the 52-week double-blind treatment period, 345 entered the 24-week extension, and 296 continued treatment with belimumab in the long-term continuation study. Safety data through 4 years of belimumab exposure (1,165 cumulative patient-years) are reported. Incidence rates of AEs, severe/serious AEs, infusion reactions, infections, malignancies, grades 3/4 laboratory abnormalities, and discontinuations due to AEs were stable or declined during 4-year belimumab exposure. The most common AEs included arthralgia, upper respiratory tract infection, headache, fatigue, and nausea. Serious infusion reactions were rare: only 1 occurred during the 4-year followup period. Rates of serious infection decreased from 5.9/100 patient-years to 3.4/100 patient-years, and no specific type of infection predominated. Belimumab added to standard therapy was generally well-tolerated over the 4-year treatment period in patients with SLE, which suggests that belimumab can be administered long term with an acceptable safety profile. Copyright © 2012 by the American College of Rheumatology.

Safety Aspects of Long Term Spent Fuel Dry Storage

International Nuclear Information System (INIS)

Botsch, Wolfgang; Smalian, S.; Hinterding, P.; Drotleff, H.; Voelzke, H.; Wolff, D.; Kasparek, E.

2014-01-01

As a consequence of the lack of a final repository for spent nuclear fuel (SF) and high level waste (HLW), long term interim storage of SF and HLW will be necessary. As with the storage of all radioactive materials, the long term storage of SF and HLW must conform to safety requirements. Safety aspects such as safe enclosure of radioactive materials, safe removal of decay heat, sub-criticality and avoidance of unnecessary radiation exposure must be achieved throughout the complete storage period. The implementation of these safety requirements can be achieved by dry storage of SF and HLW in casks as well as in other systems such as dry vault storage systems or spent fuel pools, where the latter is neither a dry nor a passive system. After the events of Fukushima, the advantages of passively and inherently safe dry storage systems have become more obvious. In Germany, dry storage of SF in casks fulfils both transport and storage requirements. Mostly, storage facilities are designed as concrete buildings above the ground; one storage facility has also been built as a rock tunnel. In all these facilities the safe enclosure of radioactive materials in dry storage casks is achieved by a double-lid sealing system with surveillance of the sealing system. The safe removal of decay heat is ensured by the design of the storage containers and the storage facility, which also secures to reduce the radiation exposure to acceptable levels. TUV and BAM, who work as independent experts for the competent authorities, inform about spent fuel management and issues concerning dry storage of spent nuclear fuel, based on their long experience in these fields. All relevant safety issues such as safe enclosure, shielding, removal of decay heat and sub-criticality are checked and validated with state-of-the-art methods and computer codes before the license approval. In our presentation we discuss which of these aspects need to be examined closer for a long term interim storage. It is shown

Long-term tolerability of telcagepant for acute treatment of migraine in a randomized trial

DEFF Research Database (Denmark)

Connor, Kathryn M; Aurora, Sheena K; Loeys, Tom

2011-01-01

To evaluate the long-term tolerability of telcagepant for acute treatment of intermittent migraine attacks. Background.- Telcagepant is a calcitonin gene-related peptide (CGRP) receptor antagonist being investigated for the acute treatment of migraine....

Long-term contextual memory in infant rats as evidenced by an ethanol conditioned tolerance procedure.

Science.gov (United States)

Castelló, Stefanía; Molina, Juan Carlos; Arias, Carlos

2017-08-14

Conditioned tolerance can be conceptualized as a particular case of Pavlovian conditioning in which contextual cues play the role of the conditioned stimulus. Although the evidence is contradictory, it is frequently assumed that long-term contextual conditioning in pre-weanling rats is weak or even absent. This hypothesis comes from and is sustained mainly by behavioral studies that explored different contextual effects in 16-18day-old rats using a fear-conditioning paradigm, but their conclusions are stated in terms of an immature (hippocampal-dependent) declarative memory system. The main goal of the present manuscript was based on a recent antecedent from our laboratory, to analyze whether context-dependent tolerance induced by ethanol during the pre-weanling period persists over time. Results showed that the context was able to modulate ethanol-induced tolerance in 2- and 3-week-old rats. Interestingly, contextual conditioned tolerance was stronger (in terms of persistence) during the third than during the second postnatal week. When subjects were tested 8days after training, when the context presumably lost its influence over tolerance, the opposite effect emerged (sensitization). These results are important for the ethanol literature, adding new evidence of long-term retention of ethanol effects acquired during infancy, whilst also showing striking ontogenetic differences in the sensitivity to ethanol between the 2nd and 3rd postnatal weeks. Importantly, contextual information modulates the expression of these ethanol effects even eight days after training, a result that is particularly relevant to the discussion of the ontogeny of contextual memory. Copyright © 2017 Elsevier B.V. All rights reserved.

Disposal of radioactive waste: can long-term safety be evaluated

International Nuclear Information System (INIS)

1991-01-01

The long-term safety of any hazardous waste disposal system must be convincingly shown prior to its implementation. For radioactive wastes, safety assessments over timescales far beyond the normal horizon of social and technical planning have already been conducted in many countries. These assessments provide the principal means to investigate, quantify, and explain long-term safety of each selected disposal concept and site for the appropriate authorities and the public. Such assessments are based on four main elements: definition of the disposal system and its environment, identification of possible processes and events that may affect the integrity of the disposal system, quantification of the radiological impact by predictive modelling, and description of associated uncertainties. The NEA Radioactive Waste Management Committee and the IAEA International Radioactive Waste Management Advisory Committee have carefully examined the current scientific methods for safety assessments of radioactive waste disposal systems, as briefly summarized in this report. The Committees have also reviewed the experience now available from using safety assessment methods in many countries, for different disposal concepts and formations, and in the framework of both nationally and internationally conducted studies, as referenced in this report [fr

Structured versus long-chain triglycerides: a safety, tolerance, and efficacy randomized study in colorectal surgical patients.

Science.gov (United States)

Bellantone, R; Bossola, M; Carriero, C; Malerba, M; Nucera, P; Ratto, C; Crucitti, P; Pacelli, F; Doglietto, G B; Crucitti, F

1999-01-01

After trauma or surgery, researchers have suggested that medium-chain triglycerides have metabolic advantages, although they are toxic in large doses. To try to reduce this potential toxicity, structured lipids, which provide a higher oxidation rate, faster clearance from blood, improved nitrogen balance, and less accumulation in the reticuloendothelial system, could be used. Therefore, we evaluated, through a blind randomized study, the safety, tolerance, and efficacy of structured triglycerides, compared with long-chain triglycerides (LCT), in patients undergoing colorectal surgery. Nineteen patients were randomized to receive long-chain or structured triglycerides as a lipid source. They received the same amount of calories (27.2/kg/d), glucose (4 g/kg/d), protein (0.2 g/kg/d), and lipids (11.2 kcal/kg/d). Patients were evaluated during and after the treatment for clinical and laboratory variables, daily and cumulative nitrogen balance, urinary excretion of 3-methyl-histidine, and urinary 3-methylhistidine/creatinine ratio. No adverse effect that required the interruption of the treatment was observed. Triglyceride levels and clinical and laboratory variables were similar in the two groups. A predominantly positive nitrogen balance was observed from day 2 until day 5 in the LCT group and from day 1 until day 4 in the structured triglycerides group. The cumulative nitrogen balance (in grams) for days 1 to 3 was 9.7+/-5.2 in the experimental group and 4.4+/-11.8 in the control group (p = .2). For days 1 to 5 it was 10.7+/-10.5 and 6.5+/-17.9 (p = .05), respectively. The excretion of 3-methylhistidine was higher in the control group but decreased in the following days and was similar to the experimental group on day 5. This study represents the first report in which structured triglycerides are administered in postoperative patients to evaluate safety, tolerance, and efficacy. It suggests that Fe73403 is safe, well tolerated, and efficacious in terms of nitrogen

Long-term efficacy of rasagiline in early Parkinson's disease.

Science.gov (United States)

Lew, Mark F; Hauser, Robert A; Hurtig, Howard I; Ondo, William G; Wojcieszek, Joanne; Goren, Tamar; Fitzer-Attas, Cheryl J

2010-06-01

This study was designed to follow the long-term efficacy, safety, and tolerability of rasagiline for Parkinson's disease (PD) with data collected from all patients who had ever taken rasagiline during the 12-month TEMPO monotherapy trial (N = 398) and subsequent open-label extension. Patients were followed for up to 6.5 years with a mean of 3.5 +/- 2.1 years. After 12 months, additional PD medications were added as required. Of patients remaining in the trial at 2 years, 46% were maintained on rasagiline monotherapy. The majority of patients received a dopamine agonist prior to levodopa as the first additional dopaminergic agent. Analysis using a Kaplan-Meier method indicated that by 5.4 years only 25% of patients progressed to Hoehn & Yahr stage III. Rasagiline was well tolerated, with 11.3% of patients (45/398) withdrawing because of an adverse event. Rasagiline therapy for PD was effective, well tolerated, and safe in this long-term trial.

Long-term (5 year) safety of bronchial thermoplasty: Asthma Intervention Research (AIR) trial

DEFF Research Database (Denmark)

Thomson, Neil C; Rubin, Adalberto S; Niven, Robert M

2011-01-01

Bronchial thermoplasty (BT) is a bronchoscopic procedure that improves asthma control by reducing excess airway smooth muscle. Treated patients have been followed out to 5 years to evaluate long-term safety of this procedure.......Bronchial thermoplasty (BT) is a bronchoscopic procedure that improves asthma control by reducing excess airway smooth muscle. Treated patients have been followed out to 5 years to evaluate long-term safety of this procedure....

Long-term tolerance of airway silicone stent in patients with post-tuberculosis tracheobronchial stenosis.

Science.gov (United States)

Verma, Akash; Um, Sang-Won; Koh, Won-Jung; Suh, Gee Young; Chung, Man Pyo; Kwon, O Jung; Kim, Hojoong

2012-01-01

Surgery is a well-recognized modality of treatment for benign tracheobronchial stenosis. However, in some benign disease groups, such as tuberculosis, sarcoidosis, war gas exposure, and inhalation burns, multiplicity of involvement or long length of stenosed segment heightens surgical challenge. We investigated the outcomes and long-term tolerability of the Natural stent (N-stent) in such patients with post-tuberculosis tracheobronchial stenosis. A retrospective review was done for 17 patients who underwent silicone stenting (N-stent) for post-tuberculosis tracheobronchial stenosis during January 2000-December 2003 but needed persistent stent placement and still require the stent. Significant increase in the ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC), expressed as FEV1%, as well as in forced percentual vital capacity (FVC%) (Δ24% and Δ11%, respectively) in the short term and sustained increase in the FEV1% and FVC% (Δ26.5% and Δ16.5%, respectively) in the long term were noted at a median (range) interval of 1 (0.5-72) month and 72 (12-114) months, respectively, along with symptomatic relief. No procedure-related death occurred. Stent-related late complications included granulation tissue formation (76%), migration (70%), and mucostasis (17%). The median duration for which N-stents were tolerated was 7.9 (range, 3-11) years. N-stents are well-tolerated for a prolonged period. Stent-related complications occur, but are easily managed. These results might carry medical implications for those who have airway lesions difficult to correct surgically.

Assessment of the long-term safety for SFR

Energy Technology Data Exchange (ETDEWEB)

Greis Dahlberg, Christina; Vahlund, Frederik [Svensk Kaernbraenslehantering AB, Stockholm (Sweden)

2015-07-01

During operation and decommissioning of the Swedish nuclear facilities, radioactive waste is generated that must be disposed of. Besides waste from the nuclear facilities, some waste derives from other activities such as industry, research, medical care, etc. Short-lived low- and intermediate-level waste from these activities is disposed of in the final repository for short-lived radioactive waste, SFR, in Forsmark. The facility, which has been in operation since 1988, is owned and operated by Svensk Karnbranslehantering AB, SKB. The existing facility has neither sufficient space nor a license to receive decommissioning waste. SFR must therefore be extended so that shortlived low- and intermediate-level decommissioning waste from the nuclear facilities can also be received. The need for additional capacity has been accentuated by the closure of two reactors in Barseback. These reactors cannot be dismantled until the SFR facility has been extended. The existing repository is built to receive, and after closure serve as a passive repository for, low- and intermediate-level radioactive waste. The disposal rooms are situated in the bedrock beneath the sea floor, covered by about 60 metres of rock. The repository has been designed so that it can be abandoned after closure without requiring further measures to maintain its function. The extension of SFR, is done at the -120 m level immediately adjacent to, and within the same depth range as, the existing facility. The basic function of the existing SFR and of the extended one will be the same. However, a clear difference is the design of the tunnel and the rock vault that are required to permit transport and storage of whole reactor pressure vessels. The application for a license to build this extension includes an assessment of the long-term safety (post-closure safety) of the facility. The safety assessment also contains an updated assessment of the long-term safety of the existing facility. The safety assessment for

Revisiting the phenotypic and genetic profiling of anergic T cells mediating long-term transplant tolerance.

Science.gov (United States)

You, Sylvaine; Chatenoud, Lucienne

2018-02-01

Herein our focus will be to revisit peripheral tolerance mechanisms and in particular 'active' or 'dominant' tolerance as originally defined and mediated by regulatory CD4FoxP3 T lymphocytes (Treg) and also T-cell anergy that appears as a major mainstay to support long-term allograft survival. It is at the same time interesting and rewarding that the tool that recently guided our efforts along this path is the in-vivo use of CD3 antibody, the first monoclonal introduced in the clinic (Orthoclone OKT3) about 35 years ago to treat and prevent rejection of renal allografts. Beyond their immunosuppressive activity, whenever administered judiciously, CD3 antibodies promote robust allograft tolerance through selective purging of alloreactive effectors, resetting Treg-mediated active tolerance and promoting a unique subset of anergic CD8 T cells. The new findings discussed open up new perspectives from both a fundamental and a clinical point of view. In basic research, concrete molecular signaling paths are now spotted to finely dissect the conditions that lead to the establishment and maintenance of robust T-lymphocyte anergy mediating allograft tolerance. In the clinic, this may rapidly translate into novel biomarkers to be used in parallel to the ones already available, to better adapt posttransplant immunotherapy and monitor for long-term allograft acceptance.

Safety and performance indicators for the assessment of long-term safety of deep geological disposal of radioactive waste

International Nuclear Information System (INIS)

Hugi, M.; Schneider, J.W.; Dorp, F. van; Zuidema, P.

2005-01-01

The evaluation of the ability to isolate radioactive waste and the assessment of the long-term safety of a deep geological repository is usually done in terms of the calculated dose and/or risk for an average individual of the population which is potentially most affected by the potential impacts of the repository. At present, various countries and international organisations are developing so-called complementary indicators to supplement such calculations. These indicators are called ''safety indicators'' if they refer to the safety of the whole repository system; if they address the isolation capability of individual system components or the whole system from a more technical perspective, they are called ''performance indicators''. The need for complementary indicators follows from the long time frames which characterise the safety assessment of a geological repository, and the corresponding uncertainty of the calculated radiation dose. The main reason for these uncertainties is associated with the uncertain long-term prognosis of the surface environment and the related human behaviour. (orig.)

Long-term Hg pollution induced Hg tolerance in the terrestrial isopod Porcellio scaber (Isopoda, Crustacea)

International Nuclear Information System (INIS)

Lapanje, A.; Drobne, D.; Nolde, N.; Valant, J.; Muscet, B.; Leser, V.; Rupnik, M.

2008-01-01

The aim of our work was to assess the pollution-induced community tolerance (PICT) of isopod gut microbiota and pollution-induced isopod population tolerance (PIPT). Animals collected from a chronically Hg polluted and an unpolluted location were exposed for 14 days to 10 μg Hg/g dry food under laboratory conditions. The lysosomal membrane stability, hepatopancreas epithelium thickness, feeding activity and animal bacterial gut microbiota composition were determined. The results confirm the hypothesis that the response to short-term Hg exposure differs for animals from the Hg polluted and the unpolluted field locations. The animals and their gut microbiota from the Hg polluted location were less affected by Hg in a short-term feeding experiment than those from the unpolluted environment. We discuss the pollution-induced population tolerance of isopods and their gut microbiota as a measure of effects of long-term environmental pollution. The ecological consequences of such phenomena are also discussed. - Isopods (Porcellio scaber) as well as their bacterial gut community from a mercury-polluted site are mercury tolerant

Long-term Hg pollution induced Hg tolerance in the terrestrial isopod Porcellio scaber (Isopoda, Crustacea)

Energy Technology Data Exchange (ETDEWEB)

Lapanje, A. [University of Ljubljana, Biotechnical Faculty, Department of Biology, Vecna pot 111, 1000 Ljubljana (Slovenia); Institute of Physical Biology, Veliko Mlacevo 59, 1290 Grosuplje (Slovenia)], E-mail: ales.lapanje@bf.uni-lj.si; Drobne, D. [University of Ljubljana, Biotechnical Faculty, Department of Biology, Vecna pot 111, 1000 Ljubljana (Slovenia); Nolde, N. [Institute Jozef Stefan, Department of Environmental Sciences, Jamova 39, 1000 Ljubljana (Slovenia); Valant, J. [University of Ljubljana, Biotechnical Faculty, Department of Biology, Vecna pot 111, 1000 Ljubljana (Slovenia); Muscet, B. [Institute of Physical Biology, Veliko Mlacevo 59, 1290 Grosuplje (Slovenia); Leser, V. [University of Ljubljana, Biotechnical Faculty, Department of Biology, Vecna pot 111, 1000 Ljubljana (Slovenia); Rupnik, M. [Institute of Public Health, Prvomajska 1, 2000 Maribor (Slovenia); Faculty of Medicine, University of Maribor, Slomskov trg 15, 2000 Maribor (Slovenia)

2008-06-15

The aim of our work was to assess the pollution-induced community tolerance (PICT) of isopod gut microbiota and pollution-induced isopod population tolerance (PIPT). Animals collected from a chronically Hg polluted and an unpolluted location were exposed for 14 days to 10 {mu}g Hg/g dry food under laboratory conditions. The lysosomal membrane stability, hepatopancreas epithelium thickness, feeding activity and animal bacterial gut microbiota composition were determined. The results confirm the hypothesis that the response to short-term Hg exposure differs for animals from the Hg polluted and the unpolluted field locations. The animals and their gut microbiota from the Hg polluted location were less affected by Hg in a short-term feeding experiment than those from the unpolluted environment. We discuss the pollution-induced population tolerance of isopods and their gut microbiota as a measure of effects of long-term environmental pollution. The ecological consequences of such phenomena are also discussed. - Isopods (Porcellio scaber) as well as their bacterial gut community from a mercury-polluted site are mercury tolerant.

Long-term management of GERD in the elderly with pantoprazole

Directory of Open Access Journals (Sweden)

Carlo Calabrese

2007-04-01

Full Text Available Carlo Calabrese, Anna Fabbri, Giulio Di FeboDepartment of Internal Medicine and Gastroenterology, University of Bologna, ItalyAbstract: The prevalence of gastroesophageal reflux disease (GERD increases with age and elderly are more likely to develop severe disease. Older patients often complain of less severe or frequent heartburn than younger patients and they may present with atypical symptoms such as dysphagia, weight loss, or extraesophageal symptoms. Proton pump inhibitors (PPIs are central in the management of GERD and are unchallenged with regards to their efficacy. They are considered safe and more effective than histamine receptor antagonists for healing esophagitis and for preventing its recurrence using a long term maintenance treatment. PPI have minimal side effects and few slight drug interactions and are considered safe for long term treatment. Pantoprazole is significantly effective both for acute and long-term treatment with excellent control of relapse and symptoms. It is well tolerated even for long-term therapy and its tolerability is optimal. Pantoprazole shows to have minimal interactions with other drugs because of a lower affinity for cytocrome P450 than older PPIs. Although the majority of elderly has concomitant illnesses and receive other drugs, this does not adversely effect the efficacy of pantoprazole because of its pharmacokinetics, which are independent of patient age. Clinical practice suggests that a low dose maintenance of PPIs should be used in older patients with GERD.Keywords: GERD, long-term management, pantoprazole, safety, efficacy, tolerability

Long-term storage of radioactive waste: IAEA perspectives on safety and sustainability

International Nuclear Information System (INIS)

Rowat, J.H.; Louvat, D.; Metcalf, P.E.

2006-01-01

As the amounts of radioactive waste in surface storage have increased, concern has grown over the safety and sustainability of storage in the long term. In response to increasing concerns, the International Atomic Energy Agency (IAEA) has included an action to address the safety implications of the long-term storage (LTS) of radioactive waste in its action plan for waste safety; the action plan was endorsed by the IAEA's Member States in 2001. In 2003, the IAEA published a position paper on the safety and sustainability of LTS as part fulfilment of the action in question. A key theme of the position paper is the contrast of safety and sustainability implications of LTS with those of disposal. The present paper provides a summary of the position paper, describes current IAEA activities that deal with the subject of LTS, and discusses findings from the 2004 Cordoba symposium on disposal of low activity radioactive waste that pertain to LTS. (author)

Desensitization to Oxcarbazepine: Long-Term Efficacy and Tolerability

Science.gov (United States)

Lee, Jiwon; Park, Eu Gene; Lee, Munhyang

2017-01-01

Background and Purpose Antiepileptic drug (AED)-associated cutaneous adverse drug reactions can lead to the discontinuation of medications. The aim of this study was to determine the long-term efficacy and safety of performing desensitization to oxcarbazepine. Methods This study involved 20 patients who exhibited cutaneous adverse drug reactions associated with oxcarbazepine use between July 2009 and March 2016 at Samsung Medical Center. All of the participants had to discontinue oxcarbazepine despite presenting initially positive responses. Human leukocyte antigen genotyping was performed to detect the genetic predisposition to Stevens-Johnson syndrome. The desensitization to oxcarbazepine was performed with a starting dosage of 0.1 mg/day. Efficacy was evaluated by comparing the frequency of seizures before and at 1 and 3 years after desensitization. Adverse events occurring during desensitization and the retention rate after desensitization were also investigated. Results Nineteen patients (95%) safely completed the desensitization protocol. One withdrew owing to emotional problems that appeared to be associated with oxcarbazepine. The follow-up period was 4.6±1.2 years (mean±SD), and oxcarbazepine was maintained for more than 3 years after desensitization in 15 patients (83.3%). The response rates were 84.2% and 77.8% at 1 and 3 years after desensitization, respectively. Eight patients remained seizure-free for 3 years, and two discontinued all AEDs. Transient adverse reactions such as mild rash and itching were reported by five patients during desensitization. Conclusions This study has demonstrated the long-term efficacy and safety of desensitization to oxcarbazepine in patients exhibiting cutaneous adverse drug reactions. This favorable outcome should encourage the implementation of desensitization in patients presenting with hypersensitivity to oxcarbazepine as an alternative strategy in clinical practice. PMID:27730770

Long-term safety of the maintenance and decommissioning waste of the encapsulation plant

International Nuclear Information System (INIS)

Nummi, O.; Kylloenen, J.; Eurajoki, T.

2012-12-01

This report, Long-term safety of the maintenance and decommissioning waste of the encapsulation plant, presents the disposal concept for the low and intermediate level waste (L/ILW) that is generated during the operation and decommissioning of the encapsulation plant, and assesses the long-term safety of the disposal of the waste. Radioactive waste originates from the spent nuclear fuel transferred and dried in the encapsulation plant. Radioactive waste accumulates also in the maintenance of the components and systems of the encapsulation plant. The waste is collected, exempted from control if possible and treated for final disposal if necessary. The waste is disposed of in the L/ILW hall which is currently planned to be located at a depth of -180 meters along the access tunnel to the repository for spent fuel. The main engineered barrier in the L/ILW hall is a concrete basin that encases the dried liquid waste. The safety concept of L/ILW disposal is based on the slow release of radioactivity from the L/ILW hall and its limited transport through the bedrock into biosphere. The release and transport of the radioactivity is described by the assessment scenarios, which include expected evolution and unlikely events affecting the long-term safety. The scenarios act as guidelines according to which the conceptual and mathematical models are formed. The long-term safety of the L/ILW hall is assessed using deterministic and probabilistic modeling. Special issues such as human intrusion and radiation effects on other biota are also assessed. The most significant contributor to the dose rates is the short-lived radionuclide 90 Sr followed by long-lived nuclides 129 I and 108 mAg. The annual doses to the public, and release rates of radioactive substances stay below the regulatory constraints in all analyzed scenarios. (orig.)

An open-label, long-term study examining the safety and tolerability of pregabalin in Japanese patients with central neuropathic pain

Directory of Open Access Journals (Sweden)

Onouchi K

2014-07-01

Full Text Available Kenji Onouchi,1 Hiroaki Koga,2 Kazumasa Yokoyama,3 Tamotsu Yoshiyama4 1Aida Memorial Rehabilitation Hospital, Moriya, Japan; 2Kumamoto Rehabilitation Hospital, Kikuchi-Gun, Japan; 3Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan; 4Pfizer Japan Inc., Tokyo, Japan Purpose: Studies of pregabalin for the treatment of central neuropathic pain have been limited to double-blind trials of 4–17 weeks in duration. The purpose of this study was to assess the long-term safety and tolerability of pregabalin in Japanese patients with central neuropathic pain. The efficacy of pregabalin was also assessed as a secondary measure. Patients and methods: This was a 53-week, multicenter, open-label trial of pregabalin (150–600 mg/day in Japanese patients with central neuropathic pain due to spinal cord injury, multiple sclerosis, or cerebral stroke. Results: A total of 103 patients received pregabalin (post-stroke =60; spinal cord injury =38; and multiple sclerosis =5. A majority of patients (87.4% experienced one or more treatment-related adverse events, most commonly somnolence, weight gain, dizziness, or peripheral edema. The adverse event profile was similar to that seen in other indications of pregabalin. Most treatment-related adverse events were mild (89.1% or moderate (9.2% in intensity. Pregabalin treatment improved total score, sensory pain, affective pain, visual analog scale (VAS, and present pain intensity scores on the Short-Form McGill Pain Questionnaire (SF-MPQ and ten-item modified Brief Pain Inventory (mBPI-10 total score at endpoint compared with baseline. Improvements in SF-MPQ VAS and mBPI-10 total scores were evident in all patient subpopulations. Mean changes from baseline in SF-MPQ VAS and mBPI-10 scores at endpoint were –20.1 and –1.4, respectively. Conclusion: These findings demonstrate that pregabalin is generally well tolerated and provides sustained efficacy over a 53-week treatment period in

Enumeration and characterization of arsenic-tolerant diazotrophic bacteria in a long-term heavy-metal-contaminated soil

OpenAIRE

Oliveira, A.; Pampulha, M.E.; Neto, M.M.; Almeida, A.C.

2009-01-01

The abundance of arsenic-tolerant diazotrophic bacteria was compared in a long-term contaminated soil versus a non-contaminated one. In addition, the characterization of tolerant diazotrophic bacteria was carried out. Differences in the number of heterotrophic N2 fixers were found between soils. Contaminated soil showed a decrease in the microbial population size of about 80%, confirming the great sensitivity of this group of soil bacteria to metals. However, quantitat...

Long-term criticality safety concerns associated with surplus fissile material disposition

International Nuclear Information System (INIS)

Choi, J.S.

1995-01-01

A substantial inventory of surplus fissile material would result from ongoing and planned dismantlement of US and Russian nuclear weapons. This surplus fissile material could be dispositioned by irradiation in nuclear reactors, and the resulting spent MOx fuel would be similar in radiation characteristics to regular LWR spent UO2 fuel. The surplus fissile material could also be immobilized into high-level waste forms, such as borosilicate glass, synroc, or metal-alloy matrix. The MOx spent fuel, or the immobilized waste forms, could then be directly disposed of in a geologic repository. Long-term criticality safety concerns arise because the fissile contents (i.e., Pu-239 and its decay daughter U-235) in these waste forms are higher than in LWR spent UO2 fuel. MOx spent fuel could contain 3 to 4 wt% of reactor-grade plutonium, compared to only 0.9 wt% of plutonium in LWR spent UO2 fuel. At some future time (tens of thousand of years), when the waste forms had deteriorated due to intruding groundwater, the water could mix with the long-lived fissile materials to form into a critical system. If the critical system is self-sustaining, somewhat like the natural-occurring reactor in OKLO, fission products produced could readily be available for dissolution and release out to the accessible environment, adversely affecting public health and safety. This paper will address ongoing activities to evaluate long-term criticality safety concerns associated with disposition of fissile material in a geologic setting. Issues to be addressed include the identification of a worst-case water-intrusion scenario and waste-form geometries which present the most concern for long-term criticality safety; and suggests of technical solutions for such concerns

Nonsurgical Outpatient Therapies for the Management of Female Stress Urinary Incontinence: Long-Term Effectiveness and Durability

Directory of Open Access Journals (Sweden)

G. Willy Davila

2011-01-01

Results. Thirty-two clinical trial reports were included. Prospective long-term studies of pelvic floor rehabilitation were limited but indicated significant improvements with treatment adherence for at least 12 months. Poor initial tolerability with duloxetine resulted in substantial discontinuation. Most patients receiving transurethral radiofrequency collagen denaturation or urethral bulking agents reported significant long-term improvements, generally good tolerability, and safety. Conclusions. Conservative therapy is an appropriate initial approach for female SUI, but if therapy fails, radiofrequency collagen denaturation or bulking agents may be an attractive intermediate management step or alternative to surgery.

Long-term use of short- and long-acting nitrates in stable angina pectoris.

Science.gov (United States)

Kosmicki, Marek Antoni

2009-05-01

Long-acting nitrates are effective antianginal drugs during initial treatment. However, their therapeutic value is compromised by the rapid development of tolerance during sustained therapy, which means that their clinical efficacy is decreased during long-term use. Sublingual nitroglycerin (NTG), a short-acting nitrate, is suitable for the immediate relief of angina. In patients with stable angina treated with oral long-acting nitrates, NTG maintains its full anti-ischemic effect both after initial oral ingestion and after intermittent long-term oral administration. However, NTG attenuates this effect during continuous treatment, when tolerance to oral nitrates occurs, and this is called cross-tolerance. In stable angina long-acting nitrates are considered third-line therapy because a nitrate-free interval is required to avoid the development of tolerance. Nitrates vary in their potential to induce the development of tolerance. During long-lasting nitrate therapy, except pentaerythritol tetranitrate (PETN), one can observe the development of reactive oxygen species (ROS) inside the muscular cell of a vessel wall, and these bind with nitric oxide (NO). This leads to decreased NO activity, thus, nitrate tolerance. PETN has no tendency to form ROS, and therefore during long-term PETN therapy, there is probably no tolerance or cross-tolerance, as during treatment with other nitrates.

Significance of actinide chemistry for the long-term safety of waste disposal

International Nuclear Information System (INIS)

Kim, Jae Il

2006-01-01

A geochemical approach to the long-term safety of waste disposal is discussed in connection with the significance of actinides, which shall deliver the major radioactivity inventory subsequent to the relatively short-term decay of fission products. Every power reactor generates transuranic (TRU) elements: plutonium and minor actinides (Np, Am, Cm), which consist chiefly of long-lived nuclides emitting alpha radiation. The amount of TRU actinides generated in a fuel life period is found to be relatively small (about 1 wt% or less in spent fuel) but their radioactivity persists many hundred thousands years. Geological confinement of waste containing TRU actinides demands, as a result, fundamental knowledge on the geochemical behavior of actinides in the repository environment for a long period of time. Appraisal of the scientific progress in this subject area is the main objective of the present paper. Following the introductory discussion on natural radioactivities, the nuclear fuel cycle is briefly brought up with reference to actinide generation and waste disposal. As the long-term disposal safety concerns inevitably with actinides, the significance of the aquatic actinide chemistry is summarized in two parts: the fundamental properties relevant to their aquatic behavior and the geochemical reactions in nanoscopic scale. The constrained space of writing allows discussion on some examples only, for which topics of the primary concern are selected, e.g. apparent solubility and colloid generation, colloid-facilitated migration, notable speciation of such processes, etc. Discussion is summed up to end with how to make a geochemical approach available for the long-term disposal safety of nuclear waste or for the Performance Assessment (PA) as known generally

Long-Term Efficacy, Tolerability, and Renal Safety of Atazanavir/Ritonavir-based Antiretroviral Therapy in a Cohort of Treatment-Naïve Patients with HIV-1 Infection: the REMAIN Study.

Science.gov (United States)

Teófilo, Eugénio; Rocha-Pereira, Nuno; Kuhlmann, Birger; Antela, Antonio; Knechten, Heribert; Santos, Jesús; Jiménez-Expósito, Maria Jesús

2016-02-01

Boosted protease inhibitors (PIs), including ritonavir-boosted atazanavir (ATV/r), are a recommended option for the initial treatment of HIV-1 infection based upon clinical trial data; however, long-term real-life clinical data are limited. We evaluated the long-term use of ATV/r as a component of antiretroviral combination therapy in the real-life setting in the REMAIN study. This was an observational cohort study conducted at sites across Germany, Portugal, and Spain. Retrospective historical and prospective longitudinal follow-up data were extracted every six months from medical records of HIV-infected treatment-naïve patients aged ≥ 18 years initiating a first-line ATV/r-containing regimen. Eligible patients (n = 517) were followed up for a median of 3.4 years. The proportion remaining on ATV/r at 5 years was 51.5% with an estimated Kaplan-Meier median time to treatment discontinuation of 4.9 years. Principal reasons for discontinuation were adverse events (15.9%; 8.9% due to hyperbilirubinemia) and virologic failure (6.8%). The Kaplan-Meier probability of not having virologic failure (HIV-1 RNA treatment-emergent major PI resistance occurred. ATV/r was generally well tolerated during long-term treatment with no significant changes in estimated glomerular filtration rate over five years. In a real-life clinical setting over five years, treatment-naïve patients with HIV-1 infection initiating an ATV/r-based regimen showed sustained virologic suppression, an overall treatment persistence rate of 51.5%, an absence of treatment-emergent major PI resistance mutations at virologic failure, a long-term safety profile consistent with that observed in clinical trials, and no significant decline in renal function.

Considerations on long-term immuno-intervention in the treatment of multiple sclerosis: an expert opinion.

Science.gov (United States)

Grigoriadis, Nikolaos; Linnebank, Michael; Alexandri, Nektaria; Muehl, Sarah; Hofbauer, Günther F L

2016-10-01

As management of multiple sclerosis (MS) requires life-long treatment with disease-modifying agents, any risks associated with long-term use should be considered when evaluating therapeutic options. Immune cells of the innate and adaptive immune systems play various roles in the pathogenesis of MS. MS therapies affect the immune system, each with a unique mode of action, and consequently possess different long-term safety profiles. Rare, but serious safety concerns, including an increased risk of infection and cancer, have been associated with immunosuppressant use. The risks associated with newer immunosuppressive agents, which target specific elements of MS disease pathophysiology, are not yet fully established as the duration of clinical trials is relatively short and post-marketing experience is limited. Non-immunosuppressants used to treat MS have well-defined safety profiles established over a large number of patient-years demonstrating them to be well-tolerated long-term treatment options. When considering the long-term use of disease-modifying agents for treating MS, classification as immunosuppressants or non-immunosuppressants can be useful when evaluating potential risks associated with chronic use. A successful therapeutic strategy for any serious, chronic disease such as MS should weigh effectiveness versus long-term safety of available treatments.

Long-term gastrointestinal tolerance of NUTRIOSE FB in healthy men.

Science.gov (United States)

Pasman, W; Wils, D; Saniez, M-H; Kardinaal, A

2006-08-01

To determine the gastrointestinal (GI) tolerance of NUTRIOSE FB in men. A randomized, placebo-controlled, parallel, double-blind study. The metabolic ward of TNO Quality of Life. Forty-eight subjects started the study: 16 men participated in one of the three treatments. SUBJECTS consumed either 22.5 g of pure maltodextrin (Glucidex 6), or 30 or 45 g of the dextrin NUTRIOSE FB daily for 4-5 weeks. Forty-three subjects completed the study (age: 34.7 +/- 8.2 years; BMI 24.9 +/- 3.3 kg m2). Tolerance of NUTRIOSE FB was examined with a GI complaints questionnaire; effectiveness on colonic flora was examined by faecal analysis; fermentation by breath hydrogen excretion measurement. Furthermore, the effect on body weight (BW), energy intake and blood parameters were examined in the study. Both doses of NUTRIOSE FB were very well tolerated and GI complaints hardly differed from the placebo treatment. No diarrhoea was reported due to NUTRIOSE FB supplementation. In the course of the study, some habituation and adaptation of GI symptoms were found. Fermentation and faecal characteristics (pH and enzyme activity) were significantly positively affected with NUTRIOSE FB treatment. Body weight in both NUTRIOSE FB groups remained stable over time, although the placebo-treated group showed a small increase in BW (Deltaday35-1 0.8 +/- 1.0 kg) (P = 0.07). However, total food intake and macronutrient composition of the diet remained the same throughout the study. No significant differences were found between the three treatment groups in hunger and satiety scores and food preferences. Long-term supplementation of 30 or 45 g of the dextrin NUTRIOSE FB per day was well tolerated, and may act as a pre-biotic supplement. TNO Quality of Life was assigned by Roquette Frères to perform the study.

Safety and optimization aspects of radioactive waste long-term storage at the ''Vector'' site

International Nuclear Information System (INIS)

Tokarevs'kij, O.V.; Kondrat'jev, S.M.; Aleksjejeva, Z.M.; Ribalka, N.V.

2015-01-01

The paper analyzes links between the final disposal option and needs for long-term storage of radioactive waste taking into proposals on possible changes in radwaste classification as regards disposal. It considers the conceptual approach to design facilities for long-term storage of long-lived radioactive waste at the Vector site and approaches to apply requirements of regulatory documents, radiation safety principles and criteria for long-term storage of radwaste and safety assessment.

Team safety and innovation by learning from errors in long-term care settings.

Science.gov (United States)

Buljac-Samardžić, Martina; van Woerkom, Marianne; Paauwe, Jaap

2012-01-01

Team safety and team innovation are underexplored in the context of long-term care. Understanding the issues requires attention to how teams cope with error. Team managers could have an important role in developing a team's error orientation and managing team membership instabilities. The aim of this study was to examine the impact of team member stability, team coaching, and a team's error orientation on team safety and innovation. A cross-sectional survey method was employed within 2 long-term care organizations. Team members and team managers received a survey that measured safety and innovation. Team members assessed member stability, team coaching, and team error orientation (i.e., problem-solving and blaming approach). The final sample included 933 respondents from 152 teams. Stable teams and teams with managers who take on the role of coach are more likely to adopt a problem-solving approach and less likely to adopt a blaming approach toward errors. Both error orientations are related to team member ratings of safety and innovation, but only the blaming approach is (negatively) related to manager ratings of innovation. Differences between members' and managers' ratings of safety are greater in teams with relatively high scores for the blaming approach and relatively low scores for the problem-solving approach. Team coaching was found to be positively related to innovation, especially in unstable teams. Long-term care organizations that wish to enhance team safety and innovation should encourage a problem-solving approach and discourage a blaming approach. Team managers can play a crucial role in this by coaching team members to see errors as sources of learning and improvement and ensuring that individuals will not be blamed for errors.

Dienogest in long-term treatment of endometriosis

Directory of Open Access Journals (Sweden)

Schindler AE

2011-07-01

Full Text Available Adolf E SchindlerInstitute for Medical Research and Education, Essen, GermanyAbstract: Endometriosis is a chronic disease primarily affecting women of childbearing age, in which endometriotic lesions form outside the uterus, typically leading to painful symptoms, fatigue, and infertility. The symptoms of endometriosis may cause significant impairment in quality of life and represent a substantial economic burden to patients, families, and society. There is no cure for endometriosis; management consists of alleviating pain and other symptoms, reducing endometriotic lesions, and improving quality of life. Recurrence after surgical intervention is common, while the clinical evidence to support the efficacy and safety of many medications currently used in endometriosis is limited. Dienogest is an oral progestin that has been investigated extensively in the treatment of endometriosis in two clinical programs performed in Europe and Japan, including dose-ranging, placebo-controlled, active comparator-controlled, and long-term (up to 65 weeks studies. These studies demonstrated that dienogest 2 mg daily effectively alleviates the painful symptoms of endometriosis, reduces endometriotic lesions, and improves indices of quality of life. Dienogest showed a favorable safety and tolerability profile in these studies, with predictable adverse effects, high rates of patient compliance, and low withdrawal rates. This review article describes the clinical trial evidence that characterizes the efficacy and safety of dienogest in endometriosis, including two studies characterizing dienogest in long-term use. The relevance of these findings to the management of endometriosis in clinical practice is discussed.Keywords: dienogest, endometriosis, progestins, long-term treatment, quality of life, symptoms, pain

Safety related terms for advanced nuclear plants

International Nuclear Information System (INIS)

1995-12-01

The terms considered in this document are in widespread current use without a universal consensus as to their meaning. Other safety related terms are already defined in national or international codes and standards as well as in IAEA's Nuclear Safety Standards Series. Most of the terms in those codes and standards have been defined and used for regulatory purposes, generally for application to present reactor designs. There is no intention to duplicate the description of such regulatory terms here, but only to clarify the terms used for advanced nuclear plants. The following terms are described in this paper: Inherent safety characteristics, passive component, active component, passive systems, active system, fail-safe, grace period, foolproof, fault-/error-tolerant, simplified safety system, transparent safety

Safety related terms for advanced nuclear plants

International Nuclear Information System (INIS)

1991-09-01

The terms considered in this document are in widespread current use without a universal consensus as to their meaning. Other safety related terms are already defined in national or international codes and standards as well as in IAEA's Nuclear Safety Standards Series. Most of the terms in those codes and standards have been defined and used for regulatory purposes, generally for application to present reactor designs. There is no intention to duplicate the description of such regulatory terms here, but only to clarify the terms used for advanced nuclear plants. The following terms are described in this paper: Inherent safety characteristics, passive component, active component, passive systems, active system, fail-safe, grace period, foolproof, fault-/error-tolerant, simplified safety system, transparent safety

Statement on safety requirements concerning the long-term operation of the Muehleberg nuclear power station

International Nuclear Information System (INIS)

2012-12-01

This report published by the Swiss Federal Nuclear Safety Inspectorate ENSI investigates the safety requirements with respect to the long-term operation of the Muehleberg nuclear power station in Switzerland. Relevant international requirements and Swiss legal stipulations concerning the long-term operation of the power station are stated. The management of aging processes is looked at. The regular verification of the integrity of various plant components such as containments, piping, steam generation system, etc. is looked at in detail. The state-of-the-art concerning deterministic accident analyses and refitting technology are discussed, as are automated safety systems. The applicable laws, decrees and guidelines are listed in appendices

Long-term (52-week) safety and efficacy of Sacubitril/valsartan in Asian patients with hypertension.

Science.gov (United States)

Supasyndh, Ouppatham; Sun, Ningling; Kario, Kazuomi; Hafeez, Kudsia; Zhang, Jack

2017-05-01

Sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor-neprilysin inhibitor, demonstrated significant reductions in office and 24 h ambulatory blood pressure (BP) over 8 weeks in Asian patients with hypertension. This 52-week extension to the 8-week core study was aimed at evaluating the long-term safety, tolerability and efficacy of sacubitril/valsartan. Patients who completed an 8-week randomized study (the core study) were enrolled in this 52-week open-label study and received sacubitril/valsartan 200 mg QD. The sacubitril/valsartan dose was uptitrated to 400 mg QD if BP was uncontrolled (>140/90 mm Hg) after 4 weeks. Subsequently, in patients with uncontrolled BP, treatment was intensified every 4 weeks with amlodipine 5-10 mg followed by hydrochlorothiazide 6.25-25 mg. Of the 341 patients enrolled, 7 (2.1%) discontinued the study drug due to adverse events (AEs). The incidence of AEs and serious AEs were 63.9 and 3.8%, respectively, and no deaths were reported in this study. The most frequent AEs were nasopharyngitis (18.2%) and dizziness (8.8%). Events that were potentially indicative of low BP were infrequent. One patient reported mild transient angioedema (lasting 2.5 h) that resolved without treatment but led to study drug discontinuation. The sacubitril/valsartan-based regimen provided clinically significant mean sitting systolic BP (msSBP) and mean sitting diastolic BP (msDBP) reductions from baseline (-24.7/-16.2 mm Hg). The overall BP control, msSBP and msDBP response rates were 75.3, 90.6 and 87.6%, respectively. Long-term use of sacubitril/valsartan was generally safe and well-tolerated in patients with hypertension and provided significant BP reductions from baseline.

Safety aspects of long term operation of water moderated reactors. Recommendations on the scope and content of programmes for safe long term operation. Final report of the extrabudgetary programme on safety aspects long term operation of water moderated reactors

International Nuclear Information System (INIS)

2007-07-01

During the last two decades, the number of IAEA Member States giving high priority to continuing the operation of nuclear power plants beyond the time frame originally anticipated is increasing. This is related to the age of nuclear power plants connected to the grid worldwide. The IAEA started to develop guidance on the safety aspects of ageing management in the 1990s. Recognizing the development in a number of its Member States, the IAEA initiated this Extrabudgetary Programme on Safety Aspects of Long Term Operation of Water Moderated Reactors in 2003. The objective of the Programme was to establish recommendations on the scope and content of activities to ensure safe long term operation of water moderated reactors. The term long term operation is used to accommodate various approaches in Member States and is defined as operation beyond an initial time frame set forth in design, standards, licence, and/or regulations, that is justified by safety assessment, considering life limiting processes and features for systems, structures and components. The scope of the Programme included general long term operation framework, mechanical components and materials, electrical components and instrumentation and control, and structural components and structures. The scope of the Programme was limited to physical structures of the NPPs. Four working groups addressed the above indicated technical areas. The Programme steering committee provided coordination and guidance and served as a forum for the exchange of information. The Programme implementation relied on voluntary in kind and financial contributions from the Czech Republic, Hungary, Slovakia, Sweden, the United Kingdom and the USA as well as in kind contributions from Bulgaria, Finland, the Netherlands, the Russian Federation, Spain, the Ukraine, and the European Commission. This report summarizes the main results, conclusions and recommendations of this Programme and provides in the Appendices I-IV detailed

Safety I and C system platforms - State-of-the-art and long-term available - A contradiction in terms?

International Nuclear Information System (INIS)

Richter, Steffen; Martin, Michael

2006-01-01

Automation systems, particularly in the field of safety I and C, are subject to conflict between three challenges. Customers' requests for state-of-the-art technology, ever shorter innovation cycles in the electronics industry and computer business and the requirement for long-term spare parts supply demand thorough and sustainable concepts from the supply market. The TELEPERM XS digital safety I and C platform has been applied successfully since 1998 for the modernization of safety I and C systems in over 30 NPP units from different reactor suppliers as well as for new plant construction. The platform is subject to a forward-looking life cycle management program combining an evolutionary and future-oriented approach to platform development with measures for ensuring the long-term support of the installed base. Driven by ever shorter innovation cycles in the electronics and automation industry, the platform is continuously evolved with state-of-the-art technology and enhanced safety features. The continuous innovation process is combined with maximum compatibility of the I and C components that make up the TELEPERM XS system platform. This makes the system future-oriented and simultaneously assures long-term availability of replacement parts. In this way TELEPERM XS meets the customer requirements for up-to-date but proven technology suitable to ensure an operating life of safety I and C equipment spanning several decades. As a matter of course, the platform and component development adheres to the robust and proven architecture of TELEPERM XS, thereby limiting risks for equipment qualification and project licensing to a minimum. (authors)

Safety I and C system platforms - State-of-the-art and long-term available - A contradiction in terms?

Energy Technology Data Exchange (ETDEWEB)

Richter, Steffen; Martin, Michael [Framatome ANP GmbH, P.O. Box 3220, Freyeslebenstrasse 1, D-91050 Erlangen (Germany)

2006-07-01

Automation systems, particularly in the field of safety I and C, are subject to conflict between three challenges. Customers' requests for state-of-the-art technology, ever shorter innovation cycles in the electronics industry and computer business and the requirement for long-term spare parts supply demand thorough and sustainable concepts from the supply market. The TELEPERM XS digital safety I and C platform has been applied successfully since 1998 for the modernization of safety I and C systems in over 30 NPP units from different reactor suppliers as well as for new plant construction. The platform is subject to a forward-looking life cycle management program combining an evolutionary and future-oriented approach to platform development with measures for ensuring the long-term support of the installed base. Driven by ever shorter innovation cycles in the electronics and automation industry, the platform is continuously evolved with state-of-the-art technology and enhanced safety features. The continuous innovation process is combined with maximum compatibility of the I and C components that make up the TELEPERM XS system platform. This makes the system future-oriented and simultaneously assures long-term availability of replacement parts. In this way TELEPERM XS meets the customer requirements for up-to-date but proven technology suitable to ensure an operating life of safety I and C equipment spanning several decades. As a matter of course, the platform and component development adheres to the robust and proven architecture of TELEPERM XS, thereby limiting risks for equipment qualification and project licensing to a minimum. (authors)

Patient-reported safety incidents in older patients with long-term conditions: a large cross-sectional study.

Science.gov (United States)

Panagioti, Maria; Blakeman, Thomas; Hann, Mark; Bower, Peter

2017-05-30

Increasing evidence suggests that patient safety is a serious concern for older patients with long-term conditions. Despite this, there is a lack of research on safety incidents encountered by this patient group. In this study, we sought to examine patient reports of safety incidents and factors associated with reports of safety incidents in older patients with long-term conditions. The baseline cross-sectional data from a longitudinal cohort study were analysed. Older patients (n=3378 aged 65 years and over) with a long-term condition registered in general practices were included in the study. The main outcome was patient-reported safety incidents including availability and appropriateness of medical tests and prescription of wrong types or doses of medication. Binary univariate and multivariate logistic regression analyses were undertaken to examine factors associated with patient-reported safety incidents. Safety incidents were reported by 11% of the patients. Four factors were significantly associated with patient-reported safety incidents in multivariate analyses. The experience of multiple long-term conditions (OR=1.09, 95% CI 1.05 to 1.13), a probable diagnosis of depression (OR=1.36, 95% CI 1.06 to 1.74) and greater relational continuity of care (OR=1.28, 95% CI 1.08 to 1.52) were associated with increased odds for patient-reported safety incidents. Perceived greater support and involvement in self-management was associated with lower odds for patient-reported safety incidents (OR=0.95, 95% CI 0.93 to 0.97). We found that older patients with multimorbidity and depression are more likely to report experiences of patient safety incidents. Improving perceived support and involvement of patients in their care may help prevent patient-reported safety incidents. © 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.

Long term safety requirements and safety indicators for the assessment of underground radioactive waste repositories

International Nuclear Information System (INIS)

Vovk, Ivan

1998-01-01

This presentation defines: waste disposal, safety issues, risk estimation; describes the integrated waste disposal process including quality assurance program. Related to actinides inventory it shows the main results of calculated activity obtained by deterministic estimation. It includes the Radioactive Waste Safety Standards and requirements; features related to site, design and waste package characteristics, as technical long term safety criteria for radioactive waste disposal facilities. Fundamental concern regarding the safety of radioactive waste disposal systems is their radiological impact on human beings and the environment. Safety requirements and criteria for judging the level of safety of such systems have been developed and there is a consensus among the international community on their basis within the well-established system of radiological protection. So far, however, little experience has been gained in applying long term safety criteria to actual disposal systems; consequently, there is an international debate on the most appropriate nature and form of the criteria to be used, taking into account the uncertainties involved. Emerging from the debate is the increasing conviction that the combined use of a variety of indicators would be advantageous in addressing the issue of reasonable assurance in the different time frames involved and in supporting the safety case for any particular repository concept. Indicators including risk, dose, radionuclide concentration, transit time, toxicity indices, fluxes at different points within the system, and barrier performance have all been identified as potentially relevant. Dose and risk are the indicators generally seen as most fundamental, as they seek directly to describe the radiological impact of a disposal system, and these are the ones that have been incorporated into most national standards to date. There are, however, certain problems in applying them. Application of a variety of different indicators

Long-Term Safety Analysis of Baldone Radioactive Waste Repository and Updating of Waste Acceptance Criteria

International Nuclear Information System (INIS)

2001-12-01

The main objective of the project was to provide advice to the Latvian authorities on the safety enhancements and waste acceptance criteria for near surface radioactive waste disposal facilities of the Baldone repository. The project included the following main activities: Analysis of the current status of the management of radioactive waste in Latvia in general and, at the Baldone repository in particular Development of the short and long-term safety analysis of the Baldone repository, including: the planned increasing of capacity for disposal and long term storage, the radiological analysis for the post-closure period Development of the Environment Impact Statement, for the new foreseen installations, considering the non radiological components Proposal of recommendations for future updating of radioactive waste acceptance criteria Proposal of recommendations for safety upgrades to the facility. The work programme has been developed in phases and main tasks as follows. Phase 0: Project inception, Phase 1: Establishment of current status, plans and practices (Legislation, regulation and standards, Radioactive waste management, Waste acceptance criteria), Phase 2: Development of future strategies for long-term safety management and recommendations for safety enhancements. The project team found the general approach use at the installation, the basic design and the operating practices appropriate to international standards. Nevertheless, a number of items subject to potential improvements were also identified. These upgrading recommendations deal with general aspects of the management (mainly storage versus disposal of long-lived sources), site and environmental surveillance, packaging (qualification of containers, waste characterization requirements), the design of an engineered cap and strategies for capping. (author)

Resilience Engineering in Critical Long Term Aerospace Software Systems: A New Approach to Spacecraft Software Safety

Science.gov (United States)

Dulo, D. A.

Safety critical software systems permeate spacecraft, and in a long term venture like a starship would be pervasive in every system of the spacecraft. Yet software failure today continues to plague both the systems and the organizations that develop them resulting in the loss of life, time, money, and valuable system platforms. A starship cannot afford this type of software failure in long journeys away from home. A single software failure could have catastrophic results for the spaceship and the crew onboard. This paper will offer a new approach to developing safe reliable software systems through focusing not on the traditional safety/reliability engineering paradigms but rather by focusing on a new paradigm: Resilience and Failure Obviation Engineering. The foremost objective of this approach is the obviation of failure, coupled with the ability of a software system to prevent or adapt to complex changing conditions in real time as a safety valve should failure occur to ensure safe system continuity. Through this approach, safety is ensured through foresight to anticipate failure and to adapt to risk in real time before failure occurs. In a starship, this type of software engineering is vital. Through software developed in a resilient manner, a starship would have reduced or eliminated software failure, and would have the ability to rapidly adapt should a software system become unstable or unsafe. As a result, long term software safety, reliability, and resilience would be present for a successful long term starship mission.

Evolution of safety standards for the long-term management of nuclear waste, and their application in Ontario Power Generation

International Nuclear Information System (INIS)

Kempe, T.F.

2006-01-01

This paper examines the need to develop current radiation protection methodologies further in order to take account of the special features of long-term waste management. The need to expand the scope and nature of regulatory submissions is also addressed. It is concluded that an international consensus is emerging as to requirements for a safety case for long-term waste management, and on safety assessment approaches and criteria to be applied in the regulation of long-term waste management facilities. The application of some of this methodology in preliminary concept assessments carried out by OPG for long-term waste management facilities is described. (author)

Understanding the differences amongst national regulatory criteria for the long-term safety of radioactive waste disposal

International Nuclear Information System (INIS)

Larsson, C.M.; Ferch, R.; Pescatore, C.

2008-01-01

Carl-Magnus Larsson detailed then the work of the Regulators' Forum and the origin of the LTSC initiative. He explained that one of the objectives of the LTSC was to identify a set of issues on long-term protection criteria and collate findings in a report. He explained why the idea of a 'collective opinion' was abandoned and why it should be replaced by a common understanding where differences between countries ought to be explained and understood. C.-M. Larsson detailed the different types of approaches to regulating long-term safety and the different approaches for numerical targets. He gave some explanations of the reasons for the differences in regulatory targets between countries (level of conservatism, progress in the safety case methodology, etc.). The regulatory function takes into account the nature of the demonstration (illustrations and societal demands). C.-M. Larsson referred to the evolution of IAEA safety fundamentals and stressed that the 'sustainability' concept, introduced by the Joint Convention, is not mentioned in the new safety standard. The term 'adequately protected' is now preferred in relation to future generations. The ICRP recommends that less emphasis be placed on assessment of doses in the long term. C.-M. Larsson concluded that one of the challenges for the regulator is not to promise nor require the impossible. (authors)

Tolerability and safety of antifungal drugs

Directory of Open Access Journals (Sweden)

Francesco Scaglione

2013-08-01

Full Text Available When treating critically ill patients, as those with fungal infections, attention should be focused on the appropriate use of drugs, especially in terms of dose, safety, and tolerability. The fungal infection itself and the concomitant physiological disorders concur to increase the risk of mortality in these patients, therefore the use of any antifungal agent should be carefully evaluated, considering both the direct action on the target fungus and the adverse effects eventually caused. Among antifungal drugs, echinocandins have the greatest tolerability. In fact, unlike amphotericin B, showing nephrotoxicity, and azoles, which are hepatotoxic, the use of echinocandins doesn’t result in major adverse events.http://dx.doi.org/10.7175/rhc.v4i2s.873

A long-term, open-label safety study of single-entity hydrocodone bitartrate extended release for the treatment of moderate to severe chronic pain

Directory of Open Access Journals (Sweden)

Nalamachu S

2014-11-01

Full Text Available Srinivas Nalamachu,1,2 Richard L Rauck,3 Martin E Hale,4 Orlando G Florete Jr,5 Cynthia Y Robinson,6 Stephen J Farr,6 1International Clinical Research Institute, Overland Park, KS, USA; 2Kansas University Medical Center, Kansas City, KS, USA; 3Carolinas Pain Institute, Center for Clinical Research, Wake Forest University School of Medicine, Winston-Salem, NC, USA; 4Gold Coast Research, LLC, Weston, FL, USA; 5Institute of Pain Management, Jacksonville, FL, USA; 6Zogenix, Inc., Emeryville, CA, USA Objective: To evaluate the long-term safety, tolerability, and effectiveness of single-entity extended-release hydrocodone in opioid-experienced subjects with moderate to severe chronic pain not receiving adequate pain relief or experiencing intolerable side effects from their current opioid. Methods: This multicenter, open-label study started with a conversion/titration phase (≤6 weeks where subjects (n=638 were converted to individualized doses (range 20–300 mg of extended-release hydrocodone dosed every 12 hours, followed by a 48-week maintenance phase (n=424. The primary objective (safety and tolerability and the secondary objective (long-term efficacy as measured by change in average pain score; 0= no pain, 10= worst imaginable pain were monitored throughout the study. Results: Subjects were treated for a range of chronic pain etiologies, including osteoarthritis, low back pain, and neuropathic and musculoskeletal conditions. The mean hydrocodone equivalent dose at screening was 68.9±62.2 mg/day and increased to 139.5±81.7 mg/day at the start of the maintenance phase. Unlimited dose adjustments were permitted at the investigator's discretion during the maintenance phase, reflecting typical clinical practice. No unexpected safety issues were reported. Common adverse events during the conversion/titration and maintenance phases, respectively, were constipation (11.3% and 12.5%, nausea (10.7% and 9.9%, vomiting (4.1% and 9.7%, and somnolence (7

Tolerance of Ruppia sinensis Seeds to Desiccation, Low Temperature, and High Salinity With Special Reference to Long-Term Seed Storage

Directory of Open Access Journals (Sweden)

Ruiting Gu

2018-03-01

Full Text Available Seeds are important materials for the restoration of globally-threatened marine angiosperm (seagrass populations. In this study, we investigated the differences between different Ruppia sinensis seed types and developed two feasible long-term R. sinensis seed storage methods. The ability of R. sinensis seeds to tolerate the short-term desiccation and extreme cold had been investigated. The tolerance of R. sinensis seeds to long-term exposure of high salinity, cold temperature, and desiccation had been considered as potential methods for long-term seed storage. Also, three morphological and nine physiological indices were measured and compared between two types of seeds: Shape L and Shape S. We found that: (1 wet storage at a salinity of 30–40 psu and 0°C were the optimal long-term storage conditions, and the proportion of viable seeds reached over 90% after a storage period of 11 months since the seeds were collected from the reproductive shoots; (2 dry condition was not the optimal choice for long-term storage of R. sinensis seeds; however, storing seeds in a dry condition at 5°C and 33 ± 10% relative humidity for 9 months had a relatively high percentage (74.44 ± 2.22% of viable seeds, consequently desiccation exposure could also be an acceptable seed storage method; (3 R. sinensis seeds would lose vigor in the interaction of extreme cold (-27°C and desiccation; (4 there were significant differences in seed weight, seed curvature, and endocarp thickness between the two types of seeds. These findings provided fundamental physiological information for R. sinensis seeds and supported the long-term storage of its seeds. Our results may also serve as useful reference for seed storage of other threatened seagrass species and facilitate their ex situ conservation and habitat restoration.

Tolerance of Ruppia sinensis Seeds to Desiccation, Low Temperature, and High Salinity With Special Reference to Long-Term Seed Storage.

Science.gov (United States)

Gu, Ruiting; Zhou, Yi; Song, Xiaoyue; Xu, Shaochun; Zhang, Xiaomei; Lin, Haiying; Xu, Shuai; Yue, Shidong; Zhu, Shuyu

2018-01-01

Seeds are important materials for the restoration of globally-threatened marine angiosperm (seagrass) populations. In this study, we investigated the differences between different Ruppia sinensis seed types and developed two feasible long-term R. sinensis seed storage methods. The ability of R. sinensis seeds to tolerate the short-term desiccation and extreme cold had been investigated. The tolerance of R. sinensis seeds to long-term exposure of high salinity, cold temperature, and desiccation had been considered as potential methods for long-term seed storage. Also, three morphological and nine physiological indices were measured and compared between two types of seeds: Shape L and Shape S. We found that: (1) wet storage at a salinity of 30-40 psu and 0°C were the optimal long-term storage conditions, and the proportion of viable seeds reached over 90% after a storage period of 11 months since the seeds were collected from the reproductive shoots; (2) dry condition was not the optimal choice for long-term storage of R. sinensis seeds; however, storing seeds in a dry condition at 5°C and 33 ± 10% relative humidity for 9 months had a relatively high percentage (74.44 ± 2.22%) of viable seeds, consequently desiccation exposure could also be an acceptable seed storage method; (3) R. sinensis seeds would lose vigor in the interaction of extreme cold (-27°C) and desiccation; (4) there were significant differences in seed weight, seed curvature, and endocarp thickness between the two types of seeds. These findings provided fundamental physiological information for R. sinensis seeds and supported the long-term storage of its seeds. Our results may also serve as useful reference for seed storage of other threatened seagrass species and facilitate their ex situ conservation and habitat restoration.

Testosterone Replacement Therapy: Long-Term Safety and Efficacy

Directory of Open Access Journals (Sweden)

Giovanni Corona

2017-08-01

Full Text Available Recent position statements and guidelines have raised the distinction between a true and false, age-related hypogonadism (HG or late-onset hypogonadism (LOH. The former is the consequence of congenital or acquired “organic” damage of the brain centers or of the testis. The latter is mainly secondary to age-related comorbidities and does not require testosterone (T therapy (TTh. In addition, concerns related to cardiovascular (CV safety have further increased the scepticism related to TTh. In this paper, we reviewed the available evidence supporting the efficacy of TTh in non-organic HG and its long term safety. A large amount of evidence has documented that sexual symptoms are the most specific correlates of T deficiency. TTh is able to improve all aspects of sexual function independent of the pathogenetic origin of the disease supporting the scientific demonstration that LOH does exist according to an “ex-juvantibus” criterion. Although the presence of metabolic derangements could mitigate the efficacy of TTh on erectile dysfunction, the positive effect of TTh on body composition and insulin sensitivity might counterbalance the lower efficacy. CV safety concerns related to TTh are essentially based on a limited number of observational and randomized controlled trials which present important methodological flaws. When HG is properly diagnosed and TTh correctly performed no CV and prostate risk have been documented.

Long-term tolerability of inhaled human insulin (Exubera) in patients with poorly controlled type 2 diabetes

DEFF Research Database (Denmark)

Barnett, A H; Lange, P; Dreyer, M

2007-01-01

or metformin (study 1) and patients poorly controlled on metformin were randomised to adjunctive EXU or the sulphonylurea, glibenclamide (study 2). PATIENTS: The studies included 446 (study 1) and 476 (study 2) patients with type 2 diabetes, no clinically significant respiratory disease and glycosylated....... There was no discernable effect of long-term EXU therapy on pulmonary gas exchange. Insulin antibody binding reached a plateau at 6 months and did not correlate with HbA(1c) or lung function changes. Glycaemic control was maintained over 2 years. CONCLUSIONS: Exubera was well tolerated during long-term use. Pulmonary...... function changes compared with comparator groups were small, non-progressive and reversed upon treatment discontinuation. Importantly, rates of lung function change were indistinguishable between EXU and comparator after 6 months of therapy. Udgivelsesdato: 2007-Oct...

Long-term safety and efficacy of twice-daily aclidinium bromide in patients with COPD.

Science.gov (United States)

Gelb, Arthur F; Tashkin, Donald P; Make, Barry J; Zhong, Xiaoyun; Garcia Gil, Esther; Caracta, Cynthia

2013-12-01

Aclidinium is a novel, long-acting muscarinic antagonist indicated for maintenance treatment of COPD. In this 52-week, parallel-group, double-blind study, patients with moderate-to-severe COPD were randomized (1:1) to receive aclidinium twice-daily (BID) 200 μg or 400 μg via a novel, dry powder inhaler (Genuair(®)/Pressair(®)) [Registered trademarks of Almirall, SA, Barcelona, Spain for use within the European Union, Iceland, Norway, and Switzerland as Genuair(®) and within the United States as Pressair(®)]. Safety, the primary objective, was assessed via adverse events (AEs), clinical laboratory tests, vital signs, and 12-lead electrocardiograms. Efficacy was evaluated using spirometry, SGRQ, and rescue medication use. A total of 605 patients were randomized in the study. The percentage of patients reporting any treatment-emergent AE (TEAE) was comparable between groups; most TEAEs were mild or moderate. Anticholinergic TEAEs were reported by low percentages of patients in either treatment group (dry mouth: 200 μg, 1.3%; 400 μg, 2.7%; constipation: 200 μg, 2.9%; 400 μg, 1.7%). Cardiac TEAEs were also reported by a low percentage of patients (<2% for any event in any group) and did not appear to be dose dependent. There were no clinically relevant abnormalities in other safety outcomes. Both aclidinium 200 μg and 400 μg resulted in improvements from baseline to Week 52 in FEV1, with numerically greater increases observed with the higher dose. Clinically important improvements in SGRQ scores and a reduction in rescue medication use were observed throughout the study for both doses. Long-term treatment with aclidinium 200 μg or 400 μg BID was well tolerated, with sustained benefits in lung function and health status in patients with COPD throughout the 1-year study. Copyright © 2013 Elsevier Ltd. All rights reserved.

Project Alternative Systems Study - PASS. Analysis of performance and long-term safety of repository concepts

International Nuclear Information System (INIS)

Birgersson, L.; Skagius, K.; Wiborgh, M.; Widen, H.

1992-09-01

This study is part of the Project on Alternative Systems Study, PASS, with the overall aim to perform a technical/economical ranking of alternative repository concepts and canisters for the final storage of spent nuclear fuel. The comparison should in the first stage separately assess technology in construction and operation, long-term performance and safety, and costs. Three of the repository concepts are assumed to be located at a depth of approximately 500 m in the host rock, KBS-3, Very Long Holes (VLH) and Medium Long Holes (MLH). In the KBS-3 concept the canisters are deposited in vertical deposition holes in a system of parallel storage tunnels. In the VLH concept larger canisters are deposited in long horizontal tunnels. The MLH concept, is an evolution of the two other concepts, with KBS-3 type canisters deposited in horizontal tunnels. Smaller canisters are to be deposited in deep bore holes at a depth between 2000 to 4000 m in the Very Deep Holes (VDH) concept. In all concepts the canisters will be surrounded by a bentonite buffer. The aim of the present study is to analyze and compare the performance and long-term safety of the repository concepts. Only a qualitative comparison of the concepts is made as no calculations of radionuclide releases or dose to man have been performed. The ranking of the repository concepts was carried out by comparing the VDH, VLH and MLH concept with the KBS-3 concept. The performance and long-term safety of the repositories located at 500 m level will be based on a multiple barrier system and the predictions for the concepts will involve similar uncertainties. (54 refs.)

Long-term safety evaluation of bimatoprost ophthalmic solution 0.03%: a pooled analysis of six double-masked, randomized, active-controlled clinical trials

Directory of Open Access Journals (Sweden)

Wirta D

2011-06-01

Full Text Available David Wirta1, Amanda M VanDenburgh2, Emily Weng3, Scott M Whitcup4, Sef Kurstjens5, Frederick C Beddingfield III4,61Private Practice, Newport Beach, CA, USA; 2Clinical Development, 3Biostatistics, 4Research and Development, 5Global Drug Development, Allergan, Inc, Irvine, CA, USA; 6Department of Medicine, Division of Dermatology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USABackground: Bimatoprost ophthalmic solution 0.03% was approved in the US for reducing intraoccular pressure (IOP based on two double-masked, active-controlled clinical trials. Four additional long-term studies (≥ 12months were conducted; however, the aggregate safety profile of the six studies has not been reported.Methods: Adverse events (AEs were pooled from six double-masked, active-controlled, long-term clinical trials in which subjects received bimatoprost 0.03% once daily (QD or twice daily (BID as an eyedrop. AE terms were converted to MedDRA (V.11.0 Preferred Terms and analyzed.Results: In total, 1409 patients received more than one dose of bimatoprost 0.03% QD or BID. Most AEs were mild in severity and reported by 86.7% (QD and 94.8% (BID of subjects (≤ 12 months of treatment. AEs reported through month 12 (aggregate incidence of ≥ 5% were conjunctival hyperemia, increased eyelash growth, eye pruritus, periocular skin hyperpigmentation, eye irritation, dry eye, and hypertrichosis. AE onset was generally reported within four months of treatment. The cumulative incidence of common AEs in the QD treatment group at 24–48 months was similar to that measured at 12 months of treatment.Conclusion: Bimatoprost 0.03% has a favorable safety and tolerability profile as characterized by six long-term studies. Common AEs were due to the known pharmacological activity of bimatoprost and reversible with treatment cessation.Keywords: intraocular pressure, eyelids, pharmacology, clinical trial, medical treatment

Influence of the design temperature on long-term safety of a salt dome repository

International Nuclear Information System (INIS)

Buhmann, D.; Brenner, J.; Storck, R.

1993-03-01

All studies made so far within the framwork of the mixed concept system analysis proceeded from a design temperature of the mine structure of 200 C. The concept based on a design temperature of 150 C was aimed at studying whether it made sense to maintain lower temperatures, if necessary. Deterministic and probabilistic calculations were made in order to determine the influence of the lower design temperature on long-term safety. The calculations were based on concept A of Joint Borehole and Gallery Storage. Assuming reference values of the input parameters, the deterministic calculations do not produce any radionuclide release from the mine structure. If, however, one assumes a lower rate for rock convergence, radionuclides are released at maximum dose rates of about 3.10 -5 Sv/a. Even a larger volume of limited brine inclusions may lead to radionuclide releases, in that case with dose commitments of the order of magnitude of 1.10 -5 Sv/a. The probabilistic calculations show that a design temperature of 150 C for long-term safety is less favourable than a higher design temperature. The share of simulations in the probabilistic calculations with a radionuclide release, and the expected value of dose commitment, are almost double as high as in the concept based on 200 C design temperature. Thus a higher design temperature is preferable with regard to the long-term safety of a salt repository. The most important parameters concerning dose commitment are the volume of limited brine inclusions, the convergence rate, and the permeability of barriers and backfilling rock. (orig./HP) [de

Topical nonsteroidal anti-inflammatory drugs for management of osteoarthritis in long-term care patients

Directory of Open Access Journals (Sweden)

Argoff CE

2011-09-01

Full Text Available Charles E Argoff1, F Michael Gloth2 1Albany Medical College and Comprehensive Pain Center, Albany Medical Center, Albany, NY, USA; 2Johns Hopkins University School of Medicine, Baltimore, MD, USA Abstract: Osteoarthritis is common in patients ≥65 years of age. Although nonsteroidal anti-inflammatory drugs (NSAIDs are often prescribed for osteoarthritis pain, they pose age-related cardiovascular, renal, and gastrointestinal risks. Two topical NSAIDs, diclofenac sodium 1% gel (DSG and diclofenac sodium 1.5% in 45.5% dimethylsulfoxide solution (D-DMSO, are approved in the US for the treatment of osteoarthritis pain. Topical NSAIDs have shown efficacy and safety in knee (DSG, D-DMSO and hand (DSG osteoarthritis. Analyses of data from randomized controlled trials of DSG in hand and knee osteoarthritis demonstrate significant improvement of pain and function in both younger patients (<65 years and older patients (≥65 years and suggest good safety and tolerability. However, long-term safety data in older patients are limited. Topical NSAIDs can ease medication administration and help address barriers to pain management in older patients, such as taking multiple medications and inability to swallow, and are a valuable option for long-term care providers. Keywords: nonsteroidal anti-inflammatory drugs, long-term care, nursing homes, chronic pain, topical analgesics

Long-Term Effectiveness and Safety of Dexmethylphenidate Extended-Release Capsules in Adult ADHD

Science.gov (United States)

Adler, Lenard A.; Spencer, Thomas; McGough, James J.; Jiang, Hai; Muniz, Rafael

2009-01-01

Objective: This study evaluates dexmethylphenidate extended release (d-MPH-ER) in adults with ADHD. Method: Following a 5-week, randomized, controlled, fixed-dose study of d-MPH-ER 20 to 40 mg/d, 170 adults entered a 6-month open-label extension (OLE) to assess long-term safety, with flexible dosing of 20 to 40 mg/d. Exploratory effectiveness…

Short-term safety, tolerability and efficacy of a very low-calorie-ketogenic diet interventional weight loss program versus hypocaloric diet in patients with type 2 diabetes mellitus.

Science.gov (United States)

Goday, A; Bellido, D; Sajoux, I; Crujeiras, A B; Burguera, B; García-Luna, P P; Oleaga, A; Moreno, B; Casanueva, F F

2016-09-19

Brackground:The safety and tolerability of very low-calorie-ketogenic (VLCK) diets are a current concern in the treatment of obese type 2 diabetes mellitus (T2DM) patients. Evaluating the short-term safety and tolerability of a VLCK diet (diet), and 44 to the standard low-calorie diet. No significant differences in the laboratory safety parameters were found between the two study groups. Changes in the urine albumin-to-creatinine ratio in VLCK diet were not significant and were comparable to control group. Creatinine and blood urea nitrogen did not change significantly relative to baseline nor between groups. Weight loss and reduction in waist circumference in the VLCK diet group were significantly larger than in control subjects (both Pdiet group (Pdiet group declined at last follow-up. The interventional weight loss program based on a VLCK diet is most effective in reducing body weight and improvement of glycemic control than a standard hypocaloric diet with safety and good tolerance for T2DM patients.

Safety and tolerability of aripiprazole for irritability in pediatric patients with autistic disorder: a 52-week, open-label, multicenter study.

Science.gov (United States)

Marcus, Ronald N; Owen, Randall; Manos, George; Mankoski, Raymond; Kamen, Lisa; McQuade, Robert D; Carson, William H; Findling, Robert L

2011-09-01

Evaluate the long-term safety and tolerability of aripiprazole in the treatment of irritability in pediatric subjects (6-17 years) with autistic disorder. A 52-week, open-label, flexibly dosed (2-15 mg/d) study of the safety and tolerability of aripiprazole in outpatients with a DSM-IV-TR diagnosis of autistic disorder who either had completed 1 of 2 antecedent, 8-week randomized trials or were enrolled de novo (ie, not treated in the randomized trials). Safety and tolerability measures included incidences of adverse events, extrapyramidal symptoms, weight, metabolic measures, vital signs, and other clinical assessments. Subjects were enrolled between September 2006 and June 2009. Three hundred thirty subjects entered the treatment phase: 86 de novo, 174 prior aripiprazole, and 70 prior placebo. A total of 199 (60.3%) subjects completed 52 weeks of treatment. Adverse events were experienced by 286/330 subjects (86.7%). Common adverse events included weight increase, vomiting, nasopharyngitis, increased appetite, pyrexia, upper respiratory tract infection, and insomnia. Discontinuations due to adverse events occurred in 35/330 randomized subjects (10.6%)-most commonly aggression and weight increase. One patient discontinued from the study due to a laboratory-related adverse event (moderately increased alanine transaminase and aspartate transaminase). Nine subjects experienced serious adverse events-most frequently aggression. Extrapyramidal symptoms-related adverse events occurred in 48/330 subjects (14.5%)-most commonly tremor (3.0%), psychomotor hyperactivity (2.7%), akathisia (2.4%), and dyskinesia (not tardive, 2.4%). At > 9 months' aripiprazole exposure (n = 220), mean change in body weight z score was 0.33 and body mass index z score was 0.31. The percentages of subjects with clinically significant fasting metabolic abnormalities at > 9 months were 2% for glucose, 5% for total cholesterol, 7% for low-density lipoprotein cholesterol, 30% for high

Long-term safety of etanercept and adalimumab compared to methotrexate in patients with juvenile idiopathic arthritis (JIA).

Science.gov (United States)

Klotsche, Jens; Niewerth, Martina; Haas, Johannes-Peter; Huppertz, Hans-Iko; Zink, Angela; Horneff, Gerd; Minden, Kirsten

2016-05-01

Published evidence on the long-term safety of etanercept (ETA) and adalimumab (ADA) in patients with polyarticular juvenile idiopathic arthritis (pJIA) is still limited. To investigate the rates of serious adverse events (SAE) and of events of special interest (ESI) under ETA and ADA treatment. Patients with pJIA were prospectively observed in the national JIA biological register, Biologika in der Kinderrheumatologie, and its follow-up register, Juvenile arthritis Methotrexate/Biologics long-term Observation. We calculated the relative risks of SAE and ESI for ETA and ADA compared with methotrexate (MTX). Among the 1414 patients treated with ETA (n=1414; 4461 exposure years (EY)) and ADA (n=320; 493 EY), significantly more SAE, infections and medically important infections were observed (ETA: 4.5, 5.7, 0.9; ADA: 4.7, 11.4, 0.4 per 100 EY) compared with those treated with MTX alone (n=1455; 2.907 EY; 2.6, 5.5, 0.5 per 100 EY). The risk for malignancies was not significantly increased for ETA and ADA compared with MTX (0.09, 0.27 and 0.07/100 person-years). Patients under ETA monotherapy developed more frequently incident inflammatory bowel disease (IBD) and incident uveitis (0.5 and 0.8/100 EY) than patients treated by ETA in combination with MTX (0.1 and 0.2/100 EY) or MTX alone (0.03 and 0.1/100 EY). Our data confirm the acceptable long-term tolerability of ETA and ADA in pJIA. However, whether the onset of IBD and uveitis during ETA monotherapy is a paradoxical effect or an inadequate response to therapy remains unclear and requires further investigation in this growing cohort. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Tolerability and safety of Souvenaid in patients with mild Alzheimer's disease: results of multi-center, 24-week, open-label extension study.

Science.gov (United States)

Olde Rikkert, Marcel G M; Verhey, Frans R; Blesa, Rafael; von Arnim, Christine A F; Bongers, Anke; Harrison, John; Sijben, John; Scarpini, Elio; Vandewoude, Maurits F J; Vellas, Bruno; Witkamp, Renger; Kamphuis, Patrick J G H; Scheltens, Philip

2015-01-01

The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to improve synapse formation and function in patients with Alzheimer's disease (AD). Two double-blind randomized controlled trials (RCT) with Souvenaid of 12 and 24 week duration (Souvenir I and Souvenir II) showed that memory performance was improved in drug-naïve mild AD patients, whereas no effects on cognition were observed in a 24-week RCT (S-Connect) in mild to moderate AD patients using AD medication. Souvenaid was well-tolerated in all RCTs. In this 24-week open-label extension (OLE) study to the 24-week Souvenir II RCT, long-term safety and intake adherence of the medical food Souvenaid was evaluated. Patients with mild AD (n = 201) received Souvenaid once-daily during the OLE. Main outcome parameters were safety and product intake adherence. The memory domain z-score from a revised neuropsychological test battery was continued as exploratory parameter. Compared to the RCT, a similar (low) incidence and type of adverse events was observed, being mainly (68.3%) of mild intensity. Pooled data (RCT and OLE) showed that 48-week use of Souvenaid was well tolerated with high intake adherence (96.1%). Furthermore, a significant increase in the exploratory memory outcome was observed in both the active-active and control-active groups during Souvenaid intervention. Souvenaid use for up to 48-weeks was well tolerated with a favorable safety profile and high intake adherence. The findings in this OLE study warrant further investigation toward the long-term safety and efficacy of Souvenaid in a well-controlled, double-blind RCT.

Long-term safety for the final repository for spent nuclear fuel at Forsmark. Main report of the SR-Site project

Energy Technology Data Exchange (ETDEWEB)

2011-03-15

The central conclusion of the safety assessment SR-Site is that a KBS-3 repository that fulfils long-term safety requirements can be built at the Forsmark site. This conclusion is reached because the favourable properties of the Forsmark site ensure the required long-term durability of the barriers of the KBS-3 repository. In particular, the copper canisters with their cast iron inserts have been demonstrated to provide a sufficient resistance to the mechanical and chemical loads to which they may be subjected in the repository environment. The conclusion is underpinned by: - The reliance of the KBS-3 repository on i) a geological environment that exhibits long-term stability with respect to properties of importance for long-term safety, i.e. mechanical stability, low groundwater flow rates at repository depth and the absence of high concentrations of detrimental components in the groundwater, and ii) the choice of naturally occurring materials (copper and bentonite clay) for the engineered barriers that are sufficiently durable in the repository environment to provide the barrier longevity required for safety. - The understanding, through decades of research at SKB and in international collaboration, of the phenomena that affect long-term safety, resulting in a mature knowledge base for the safety assessment. - The understanding of the characteristics of the site through several years of surface-based investigations of the conditions at depth and of scientific interpretation of the data emerging from the investigations, resulting in a mature model of the site, adequate for use in the safety assessment. - The detailed specifications of the engineered parts of the repository and the demonstration of how components fulfilling the specifications are to be produced in a quality assured manner, thereby providing a quality assured initial state for the safety assessment. The detailed analyses demonstrate that canister failures in a one million year perspective are rare

Long-term safety for the final repository for spent nuclear fuel at Forsmark. Main report of the SR-Site project

International Nuclear Information System (INIS)

2011-03-01

The central conclusion of the safety assessment SR-Site is that a KBS-3 repository that fulfils long-term safety requirements can be built at the Forsmark site. This conclusion is reached because the favourable properties of the Forsmark site ensure the required long-term durability of the barriers of the KBS-3 repository. In particular, the copper canisters with their cast iron inserts have been demonstrated to provide a sufficient resistance to the mechanical and chemical loads to which they may be subjected in the repository environment. The conclusion is underpinned by: - The reliance of the KBS-3 repository on i) a geological environment that exhibits long-term stability with respect to properties of importance for long-term safety, i.e. mechanical stability, low groundwater flow rates at repository depth and the absence of high concentrations of detrimental components in the groundwater, and ii) the choice of naturally occurring materials (copper and bentonite clay) for the engineered barriers that are sufficiently durable in the repository environment to provide the barrier longevity required for safety. - The understanding, through decades of research at SKB and in international collaboration, of the phenomena that affect long-term safety, resulting in a mature knowledge base for the safety assessment. - The understanding of the characteristics of the site through several years of surface-based investigations of the conditions at depth and of scientific interpretation of the data emerging from the investigations, resulting in a mature model of the site, adequate for use in the safety assessment. - The detailed specifications of the engineered parts of the repository and the demonstration of how components fulfilling the specifications are to be produced in a quality assured manner, thereby providing a quality assured initial state for the safety assessment. The detailed analyses demonstrate that canister failures in a one million year perspective are rare

Long-term safety issues associated with mixer pump operation

International Nuclear Information System (INIS)

Kubic, W.L. Jr.

1994-01-01

In this report, we examine several long-term issues: the effect of pump operation on future gas release events (GREs), uncontrolled chemical reactions, chronic toxic gas releases, foaming, and erosion and corrosion. Heat load in excess of the design limit, uncontrolled chemical reactions, chronic toxic gas releases, foaming, and erosion and corrosion have been shown not to be safety concerns. The effect of pump operation on future GREs could not be quantified. The problem with evaluating the long-term effects of pump operation on GREs is a lack of knowledge and uncertainty. In particular, the phenomena governing gas retention, particle size distribution, and settling are not well understood, nor are the interactions among these factors understood. There is a possibility that changes in these factors could increase the size of future GREs. Bounding estimates of the potential increase in size of GREs are not possible because of a lack of engineering data. Proper management of the hazards can reduce, but not eliminate, the possibility of undesirable changes. Maintaining temperature within the historical limits can reduce the possibility of undesirable changes. A monitoring program to detect changes in the gas composition and crust thickness will help detect slowly occurring changes. Because pump operation has be shown to eliminate GREs, continued pump operation can eliminate the hazards associated with future GREs

Risk-based approach to long-term safety assessment for near surface disposal of radioactive waste in Korea

International Nuclear Information System (INIS)

Jeong, C.W.; Kim, K.I.; Lee, J.I.

2000-01-01

This paper presents the Korean regulatory approach to safety assessment consistent with probabilistic, risk-based long-term safety requirements for near surface disposal facilities. The approach is based on: (1) From the standpoint of risk limitation, normal processes and probabilistic disruptive events should be integrated in a similar manner in terms of potential exposures; and (2) The uncertainties inherent in the safety assessment should be reduced using appropriate exposure scenarios. In addition, this paper emphasizes the necessity of international guidance for quantifying potential exposures and the corresponding risks from radioactive waste disposal. (author)

Monitoring the Long-Term Effectiveness of Integrated Safety Management System (ISMS) Implementation Through Use of a Performance Dashboard Process

International Nuclear Information System (INIS)

Kinney, Michael D.; Barrick, William D.

2008-01-01

This session will examine a method developed by Federal and Contractor personnel at the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office (NNSA/NSO) to examine long-term maintenance of DOE Integrated Safety Management System (ISMS) criteria, including safety culture attributes, as well as identification of process improvement opportunities. This process was initially developed in the summer of 2000 and has since been expanded to recognize the importance of safety culture attributes, and associated safety culture elements, as defined in DOE M 450.4-1, 'Integrated Safety Management System Manual'. This process has proven to significantly enhance collective awareness of the importance of long-term ISMS implementation as well as support commitments by NNSA/NSO personnel to examine the continued effectiveness of ISMS processes

Radioactive waste disposal system for Cuba. Safety assessment for the long term

International Nuclear Information System (INIS)

Peralta Vital, J.L.; Gil Castillo, R.; Mirta Torrez, B.

1998-01-01

The present work is performed within the frame of evaluating the radiological impact of the post-closure stage of the facility for disposal of the radioactive wastes generated in Cuba, including a description of the waste disposal systems defined in the country, and taking account of significant elements of their long term safety. The Methodology for Safety Assessment includes: the definition of possible scenarios for evaluation, the identification of principal present uncertainties, the model simulating the release of the radionuclides of the facility, their transport through the geosphere, and their final access to man, evaluating ultimately the radiological impact of the disposal system considering the dose for a critical group. The results obtained allow to demonstrate the radiological safety of the nominative barrier in the design of the system for the particular conditions of Cuba. (author)

FP7 project LONGLIFE: Treatment of long-term irradiation embrittlement effects in RPV safety assessment

International Nuclear Information System (INIS)

May, J.; Hein, H.; Altstadt, E.; Bergner, F.; Viehrig, H.W.; Ulbricht, A.; Chaouadi, R.; Radiguet, B.; Cammelli, S.; Huang, H.; Wilford, K.

2012-01-01

The increasing age of European Nuclear Power Plants (NPPs) and envisaged extensions of plant lifetimes from 40 up to 80 years require an improved understanding of ageing phenomena of RPV components. The Network of Excellence NULIFE (Nuclear Plant Life Prediction) has been established to advance the safe and economic long-term operation (LTO) of NPPs by facilitating increased co-operation for applied R and D amongst members of the European nuclear community. The accurate prediction and management of RPV neutron irradiation embrittlement connected with long-term operation is an important aspect of this co-operation. Phenomena that might become important at high neutron fluences (such as flux effects and late blooming effects) have to be considered adequately in safety assessments. However, the surveillance database for prolonged irradiation times and low neutron fluxes is sparse. Consequently, there are significant uncertainties in the treatment of long-term irradiation effects. Therefore, the project LONGLIFE (Treatment of long-term irradiation embrittlement effects in RPV safety assessment) was initiated under the Euratom 7th Framework Programme of the European Commission as an umbrella project of NULIFE. LONGLIFE aims at 1) improved understanding of long-term irradiation phenomena that might compromise RPV integrity, and thereby the LTO of European NPPs, and 2) assessment of the adequacy of current prediction tools, codes, standards and surveillance guidelines for supporting long-term RPV operation. The scope of the work comprises the analysis of LTO boundary conditions; microstructural investigations and supplementary mechanical tests on RPV steels, including RPV steels from decommissioned plants; training activities; and elaboration of recommendations for RPV materials assessment and embrittlement surveillance under LTO conditions. A key part of the technical work is the selection of relevant materials for examination, e.g. which contain different weld and base

Fulfillment of the long-term safety functions by the different barriers during the main time frames after repository closure

International Nuclear Information System (INIS)

Preter, P. de; Lalieux, Ph.

2002-01-01

In general terms the basis long-term safety functions of a disposal system (i.e. the engineered barrier system, including the waste forms and the host rock) are the functions that the system as a whole or its constituents must fulfill in order to assure an adequate level of long-term radiological safety. The long-term safety functions of a disposal system constitute a generic and methodological tool that can be used in a double sense. In the first place these functions provide an a priori instrument for designing the system: the implementer must ensure that these safety functions are fulfilled by a series of robust system barriers and components. These functions can also be used as an a posteriori means to describe and assess in general terms the functioning of the system. In this way they are an important qualitative element to help to support the safety case and to identify further R and D priorities. By providing a general description of system functioning they are also a communication tool to stakeholders who are less familiar with the details of a safety case. Instead of limiting the description to a multi-barrier system, the safety functions enable to better explain how the different barriers contribute to one or more safety functions and by which processes this is performed. By doing so the system description moves from multi-barrier to multi-function. The aim of this paper is to provide such a general description of the system functioning for the Belgian case of deep disposal of high-level waste (mainly spent fuel or vitrified waste from fuel reprocessing) in the Boom Clay, o poorly-indurated argillaceous formation. From the detailed safety and performance evaluations the main time frames after repository closure are identified. Each time frame relates to a period during which the successive safety functions play a key role. Also, in each time frame the radiological impact on the environment is distinctly different. (authors)

Atrial fibrillation detection and R-wave synchronization by Metrix implantable atrial defibrillator - Implications for long-term efficacy and safety

NARCIS (Netherlands)

Tse, HF; Lau, CP; Sra, JS; Crijns, HJGM; Edvardsson, N; Kacet, S; Wyse, DG

1999-01-01

Background-The long-term efficacy of atrial fibrillation (AF) detection and R-wave synchronization are critical safety requirements for the development of an implantable atrial defibrillator (LAD) for treatment of AF. Methods and Results The long-term efficacy of the Metrix IAD for AF detection and

Long-Term Safety of Drug-Eluting and Bare-Metal Stents

DEFF Research Database (Denmark)

Palmerini, Tullio; Benedetto, Umberto; Biondi-Zoccai, Giuseppe

2015-01-01

BACKGROUND: Previous meta-analyses have investigated the relative safety and efficacy profiles of different types of drug-eluting stents (DES) and bare-metal stents (BMS); however, most prior trials in these meta-analyses reported follow-up to only 1 year, and as such, the relative long-term safety....... RESULTS: Fifty-one trials that included a total of 52,158 randomized patients with follow-up duration ≥3 years were analyzed. At a median follow-up of 3.8 years, cobalt-chromium everolimus-eluting stents (EES) were associated with lower rates of mortality, definite stent thrombosis (ST), and myocardial...... infarction than BMS, paclitaxel-eluting stents (PES), and sirolimus-eluting stents (SES) and less ST than BES. Phosphorylcholine-based zotarolimus-eluting stents had lower rates of definite ST than SES and lower rates of myocardial infarction than BMS and PES. The late rates of target...

Safety and efficacy of ipragliflozin in Japanese patients with type 2 diabetes in real-world clinical practice: interim results of the STELLA-LONG TERM post-marketing surveillance study.

Science.gov (United States)

Nakamura, Ichiro; Maegawa, Hiroshi; Tobe, Kazuyuki; Tabuchi, Hiromi; Uno, Satoshi

2018-02-01

Data regarding the efficacy and safety of sodium-glucose cotransporter 2 inhibitors in the real-world setting in Japan are limited. The STELLA-LONG TERM study is an ongoing 3-year post-marketing surveillance study of ipragliflozin in type 2 diabetes (T2D) patients. Here, we report the interim results (including 3-, 12-, and 24-month data). All Japanese patients with T2D who were first prescribed ipragliflozin between 17 July 2014 and 16 October 2015 at participating centers in Japan were registered in STELLA-LONG TERM. At 3, 12, and 24 months, the safety analysis set comprised 11,053, 5475, and 138 patients, respectively; the efficacy analysis set comprised 8757 patients. Ipragliflozin treatment resulted in statistically significant improvements versus baseline in hemoglobin A1c, fasting plasma glucose concentration, body weight, blood pressure, heart rate, and serum concentrations of low-density lipoprotein cholesterol and triglycerides. The adverse drug reaction incidence rate was 10.71%, the most common reactions being renal and urinary disorders (5.06%), infections and infestations (1.24%), and skin and subcutaneous tissue disorders (1.14%). Ipragliflozin was well tolerated and effective in Japanese patients with T2D; no new safety issues were identified.

Evaluation of safety of excessive intake and efficacy of long-term intake of beverages containing apple polyphenols.

Science.gov (United States)

Akazome, Yoko; Kametani, Norihiro; Kanda, Tomomasa; Shimasaki, Hiroyuki; Kobayashi, Shuhei

2010-01-01

In the present study, a randomized, double-blind, placebo-controlled study was performed to evaluate the safety of an excessive intake and the efficacy of a long-term intake of polyphenols derived from apples for moderately underweight to moderately obese subjects (long-term intake: 94 subjects; excessive intake: 30 subjects). For each trial, the subjects were divided into the following two groups: a group that drank beverages with apple polyphenols (600 mg) (hereinafter referred to as the apple group) and a group that drank beverages without apple polyphenols (hereinafter referred to as the placebo group). For the long-term intake trial, the subjects were given a regular amount of the beverage (340 g) each day for 12 weeks. For the excessive intake trial, the subjects were given three times the regular amount of the beverage each day for 4 weeks. It is noteworthy that the visceral fat area (VFA) of subjects in the apple group for the long-term intake trial had decreased significantly by the 8- and 12-week marks (week 8: p or = 100 cm(2)) had decreased significantly by the 8- and 12-week marks compared to the baseline (week 8: p safety of the beverage with apple polyphenols.

Case Reports Showing a Long-Term Effect of Subanesthetic Ketamine Infusion in Reducing L-DOPA-Induced Dyskinesias

Directory of Open Access Journals (Sweden)

Scott J. Sherman

2016-02-01

Full Text Available Ketamine is an FDA-approved drug with a known safety profile. Low-dose subanesthetic intravenous ketamine infusion treatment has led to long-term reduction of treatment-resistant depression and of chronic pain states. We report on low-dose subanesthetic intravenous ketamine infusion treatment in Parkinson's disease (PD patients by 5 case studies and show a long-lasting therapeutic benefit to reduce L-DOPA-induced dyskinesia (LID, improve on time, and reduce depression. Based on the literature we hypothesize that low-dose ketamine may act as a ‘chemical deep brain stimulation', by desynchronizing hypersynchronous oscillatory brain activity, including in the basal ganglia and the motor cortex. The presented PD case reports indicate tolerability, safety and long-term beneficial effects of low-dose ketamine infusion that should be further investigated in a properly controlled prospective clinical trial for treatment of LID, as well as the prevalent nonmotor features pain and depression in PD patients.

Outages 1999 and 2000, investments in safety and long-term operation of NE Krsko

International Nuclear Information System (INIS)

Sirola, P.; Krajnc, J.; Androjna, F.

1999-01-01

Plant outage is an important part of nuclear power plant operation. During that time the conditions are established for the performance of specific activities, such as refueling, tests, inspections, preventive and corrective maintenance and modifications, that are intended to confirm proper condition and availability of safety and other important components and improve overall plant safety and reliability. It is well know that in Nuclear Power Plant Krsko (Nuklearna elektrarna Krsko NEK) during Outage 2000 new Steam Generators (SGs) will be placed in service, while Outage '99 was used for preparatory works. But the importance of those two outages is even greater, because they are implementing a broad number of improvements and establishing a basis for long-term plant operation. Outage '99 required very detailed planning to assure a good control over the outage activities and operational plant systems necessary for safe shutdown. Numerous activities took place in a relatively narrow space in the Reactor Building. Some of these activities will have a big significance for the future. The article treats the status update and summarizes the specifics and importance of the mentioned activities to long-term plant safe and reliable operation.(author)

Geoscientific long-term prognosis. Preliminary safety analysis for the site Gorleben

International Nuclear Information System (INIS)

Mrugalla, Sabine

2011-07-01

The preliminary safety analysis of the site Gorleben includes the following chapters: (1) Introduction; (2) Aim and content of the geoscientific long-term prognosis for the site Gorleben; (3) Boundary conditions at the site Gorleben: climate; geomorphology; overlying rocks and adjoining rocks; hydrogeology; salt deposit Gorleben. (4) Probable future geological developments at the site Gorleben: supraregional developments with effects on the site Gorleben; glacial period developments; developments of the geomorphology, overlying and adjoining rocks; future developments of the hydrological systems at the site Gorleben; future saliniferous specific developments of the salt deposit Gorleben. (5) Commentary on the unlikely or excludable developments of the site Gorleben.

Prolonged-release melatonin for insomnia – an open-label long-term study of efficacy, safety, and withdrawal

Directory of Open Access Journals (Sweden)

Lemoine P

2011-07-01

Full Text Available Patrick Lemoine1, Doron Garfinkel2, Moshe Laudon3, Tali Nir3, Nava Zisapel3,41The Clinique Lyon-Lumière, Meyzieu, France; 2Geriatric-Palliative Department, Shoham Geriatric Medical Center, Pardes Hanna, Israel; 3Neurim Pharmaceuticals Ltd, Tel-Aviv, Israel; 4Department of Neurobiology Faculty of Life Sciences, Tel Aviv University, Tel Aviv, IsraelBackground: Prolonged-release melatonin (PRM 2 mg is indicated for insomnia in patients aged 55 years and older. A recent double-blind placebo-controlled study demonstrated 6-month efficacy and safety of PRM in insomnia patients aged 18–80 and lack of withdrawal and rebound symptoms upon discontinuation.Objective: To investigate the efficacy, safety, and withdrawal phenomena associated with 6–12 months PRM treatment.Methods: Data from a prospective 6–12-month open-label study of 244 community dwelling adults with primary insomnia, who had participated in a placebo-controlled, double-blind dose-ranging trial of PRM. Patients received PRM nightly, followed by a 2-week withdrawal period. Main outcome measures were patient-reported sleep quality ratings (diary, adverse events, vital signs, and laboratory tests recorded at each visit, and withdrawal symptoms (CHESS-84 [Check-list Evaluation of Somatic Symptoms]. Nocturnal urinary 6-sulfatoxymelatonin excretion, a measure of the endogenous melatonin production, was assessed upon discontinuing long-term PRM.Results: Of the 244 patients, 36 dropped out, 112 completed 6 months of treatment, and the other 96 completed 12 months of treatment. The mean number of nights by which patients reported sleep quality as "good" or "very good" was significantly higher during PRM than before treatment. There was no evidence of tolerance to PRM. Discontinuation of PRM was not associated with rebound insomnia or withdrawal symptoms; on the contrary, residual benefit was observed. PRM was well tolerated, and there was no suppression of endogenous melatonin production

Efficacy and safety of laxatives for chronic constipation in long-term care settings: A systematic review.

Science.gov (United States)

Alsalimy, N; Madi, L; Awaisu, A

2018-06-09

Constipation is a common disorder among long-term care (LTC) patients due to several factors. However, there are no systematic reviews investigating the use of laxatives for chronic constipation in LTC settings. This study aims to explore the safety and efficacy of laxatives in LTC patients. A systematic review of randomized controlled trials (RCTs) describing the efficacy and safety of laxatives for chronic constipation in LTC patients was conducted using the following databases and search engines: MEDLINE, Cochrane Database of Systematic Reviews, ScienceDirect, ProQuest and Google Scholar. Two of the investigators independently performed the searches, and the data were extracted using a standardized data abstraction tool. Seven RCTs involving 444 patients were included in the review. These studies included senna (with or without fibre, ie Plantago ovata), lactulose, sodium picosulphate, docusate sodium, docusate calcium, isotonic and hypotonic polyethylene glycol and Chinese herbal medicine. Senna and lactulose were the most studied laxatives in LTC patients, and senna was found to be superior to or as effective as other laxatives. Generally, the frequency and severity of adverse drug reactions (ADRs) were similar between the arms of the studies, and no serious ADRs were reported. Considering the short duration of the trials, the lack of trials including newer laxatives and the low quality of some of the included trials, the long-term efficacy and safety of these laxatives are not conclusive. There is a need to conduct more robust RCTs that include newer agents to evaluate long-term outcomes. © 2018 John Wiley & Sons Ltd.

The basis for confidence in the long-term safety of nuclear waste disposal

International Nuclear Information System (INIS)

Allen, C.J.; Whitaker, S.H.

1993-07-01

Confidence in the acceptability and the long-term safety of deep geological disposal draws strength from a number of sources: the technical approach, i.e., the use of multiple barriers for redundancy and defence in depth; the adoption of the observational approach to site characterization and to disposal vault design, construction, operation and, eventually, closure; the overall approach, which is based on ongoing review and incremental decision making; and, active and effective involvement of the public in this process

Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia.

Science.gov (United States)

Spaeth, Michael; Alegre, Cayetano; Perrot, Serge; Wang, Youyu; Guinta, Diane R; Alvarez-Horine, Sarah; Russell, Irwin

2013-11-11

The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM. This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ≥ 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures. Responder analyses showed that 68.8% of patients achieved ≥ 30% reduction in pain VAS and 69.7% achieved ≥ 30% reduction in FIQ total score at study endpoint. The long-term safety profile of SXB in FM patients was similar to that in the previously reported controlled clinical trials. Improvement in pain and other FM clinical domains was maintained during long-term use. ClinicalTrials.gov NCT00423605.

Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia

Science.gov (United States)

2013-01-01

Introduction The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM. Methods This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ≥ 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures. Responder analyses showed that 68.8% of patients achieved ≥ 30% reduction in pain VAS and 69.7% achieved ≥ 30% reduction in FIQ total score at study endpoint. Conclusions The long-term safety profile of SXB in FM patients was similar to that in the previously reported controlled clinical trials. Improvement in pain and other FM clinical domains was maintained during long-term use. Trial registration ClinicalTrials.gov NCT00423605. PMID:24286114

Long-term use of neonatal helmet-CPAP: a case report.

Science.gov (United States)

Doglioni, N; Micaglio, M; Zanardo, V; Trevisanuto, D

2009-12-01

In a recent short-term physiological study, we demonstrated a new continuous positive airway pressure (CPAP) system (neonatal helmet-CPAP) that could be a feasible device for managing preterm infants needing continuous distending pressure with better tolerability than nasal-CPAP. However, its application for a long-term period has never been reported in neonates. Here, we describe the use of neonatal helmet-CPAP in a neonate with persistent pulmonary hypertension of the newborn. Twenty minutes after neonatal helmet-CPAP placement, the baseline post-ductal tcSaO2 (66%) and alveolar-arterial gradient O2 improved from 66% and 648 mmHg to 100% and 465 mmHg, respectively. The neonatal helmet-CPAP was applied for 48 hours and was well-tolerated by the patient without complications. Long-term use of neonatal helmet-CPAP appears feasible and well-tolerated. Comparative trials are needed.

An open-label, multicenter evaluation of the long-term safety and efficacy of risperidone in adolescents with schizophrenia

Directory of Open Access Journals (Sweden)

Pandina Gahan

2012-06-01

Full Text Available Abstract Background Data on the long-term efficacy, safety, and tolerability of risperidone in adolescents with schizophrenia are limited. The objective of this study was to evaluate the efficacy and safety of maintenance risperidone treatment in adolescents with schizophrenia. Methods This open-label study of adolescents aged 13 to 17 years with schizophrenia was a single extension study of two short-term double-blind risperidone studies and also enrolled subjects directly in open-label risperidone treatment. The risperidone dose was flexible and ranged from 2 to 6 mg/day. Most subjects enrolled for 6 months; a subset enrolled for 12 months. Assessment tools included the Positive and Negative Syndrome Scale total and factor scores, Clinical Global Impressions, Children’s Global Assessment Scale, adverse event (AE monitoring, vital signs, laboratory testing, and extrapyramidal symptom rating scales. Results A total of 390 subjects were enrolled; 48 subjects had received placebo in a previous double-blind study; 292 subjects had received risperidone as part of their participation in one of two previous controlled studies; and 50 subjects were enrolled directly for this study. A total of 279 subjects enrolled for 6 months of treatment, and 111 subjects enrolled for 12 months of treatment. Overall, 264 (67.7% subjects completed this study: 209 of the 279 subjects (75% in the 6-month group and 55 of the 111 subjects (50% in the 12-month group. The median mode dose was 3.8 mg/day. At 6 months, all three groups experienced improvement from open-label baseline in symptoms of schizophrenia as well as general assessments of global functioning. Improvements were generally maintained for the duration of treatment. The most common AEs (≥10% of subjects were somnolence, headache, weight increase, hypertonia, insomnia, tremor, and psychosis. Potentially prolactin-related AEs (PPAEs were reported by 36 (9% subjects. The AE profile in this study was

Long-term efficacy and safety of anastrozole for adjuvant treatment of early breast cancer in postmenopausal women

Directory of Open Access Journals (Sweden)

Sharath Gangadhara

2009-04-01

Full Text Available Sharath Gangadhara, Gianfilippo BertelliSouth West Wales Cancer Institute, Singleton Hospital, Swansea, UKAbstract: For more than 20 years, tamoxifen has been the gold standard for the adjuvant treatment of postmenopausal women with hormone-responsive early breast cancer. However, recent randomized trials have shown efficacy and tolerability benefits with the third-generation aromatase inhibitor anastrozole, resulting in an increased use of this agent in the adjuvant setting. Data on anastrozole’s long-term efficacy and tolerability are therefore of interest in clinical practice and will be reviewed here, especially in the light of the 100-month analysis of the ATAC (Anastrozole, Tamoxifen Alone or in Combination trial.Keywords: anastrozole, aromatase inhibitors, breast cancer, adjuvant therapy 

The long-term safety and performance analyses of the surface disposal facility for the Belgian category a waste at Dessel

Energy Technology Data Exchange (ETDEWEB)

Cool, Wim; Vermarien, Elise; Wacquier, William [ONDRAF/NIRAS Avenue des Arts 14, BE-1210 Bruxelles (Belgium); Perko, Janez [SCK-CEN Boeretang 200, BE-2400 Mol (Belgium)

2013-07-01

ONDRAF/NIRAS, the Belgian Agency for Radioactive Waste and Enriched Fissile Materials, and its partners have developed long-term safety and performance analyses in the framework of the license application for a surface disposal facility for low level radioactive waste (category A waste) at Dessel, Belgium. This paper focusses on the methodology of the safety assessments and on key results from the application of this methodology. An overview is given (1) of the performance analyses for the containment safety function of the disposal system and (2) of the radiological impact analyses confirming that radiological impacts are below applicable reference values and constraints and leading to radiological criteria for the waste and the facility. In this discussion, multiple indicators for performance and safety are used to illustrate the multi-faceted nature of long-term performance and safety of the surface disposal. This contributes to the multiple lines of reasoning for confidence building that a positive decision to proceed to the next stage of construction is justified. (authors)

Safety of long-term PPI therapy

DEFF Research Database (Denmark)

Reimer, Christina

2013-01-01

Proton pump inhibitors have become the mainstay of medical treatment of acid-related disorders. Long-term use is becoming increasingly common, in some cases without a proper indication. A large number of mainly observational studies on a very wide range of possible associations have been publishe...... to a careful evaluation of the indication for PPI treatment....

Requirements for a long-term safety certification for chemotoxic substances stored in a final storage facility for high radioactive and heat-generating radioactive waste in rock salt formations

International Nuclear Information System (INIS)

Tholen, M.; Hippler, J.; Herzog, C.

2007-01-01

Within the scope of a project funded by the German Federal Ministry of Economics and Technology (Bundesministerium fuer Wirtschaft und Technologie, BMWi), a safety certification concept for a future permanent final storage for high radioactive and heat-generating radioactive waste (HAW disposal facility) in rock salt formations is being prepared. For a reference concept, compliance with safety requirements in regard to operational safety as well as radiological and non-radiological protection objectives related to long-term safety, including ground water protection, will be evaluated. This paper deals with the requirements for a long-term safety certification for the purpose of protecting ground water from chemotoxic substances. In particular, longterm safety certifications for the permanent disposal of radioactive waste in a HAW disposal facility in rock salt formations and for the dumping of hazardous waste in underground storage facilities in rock salt formations are first discussed, followed by an evaluation as to whether these methods can be applied to the long-term safety certification for chemotoxic substances. The authors find it advisable to apply the long-term safety certification for underground storage facilities to the long-term safety certification for chemotoxic substances stored in a HAW disposal facility in rock salt formations. In conclusion, a corresponding certification concept is introduced. (orig.)

The Safety Assessment of Long term Interim Storage at Sellafield

International Nuclear Information System (INIS)

Buchan, Andrew B.

2014-01-01

that are most significant in terms of frequency and unmitigated potential consequences PSA looks at the full range of fault sequences and allows full incorporation of the reliability and failure probability of the safety measures and other features of the design and operations SAA considers significant but unlikely accidents where off-site consequences are likely to significantly affect the critical group and provides information on their progression, within the facility and also beyond the site boundary. The paper will illustrate how these techniques have been utilised to facilitate design, operation, resilience evaluation and accident management of facilities supporting long term interim storage at Sellafield. (author)

In Vivo Transplantation of Enteric Neural Crest Cells into Mouse Gut; Engraftment, Functional Integration and Long-Term Safety.

Directory of Open Access Journals (Sweden)

Julie E Cooper

Full Text Available Enteric neuropathies are severe gastrointestinal disorders with unsatisfactory outcomes. We aimed to investigate the potential of enteric neural stem cell therapy approaches for such disorders by transplanting mouse enteric neural crest cells (ENCCs into ganglionic and aganglionic mouse gut in vivo and analysing functional integration and long-term safety.Neurospheres generated from yellow fluorescent protein (YFP expressing ENCCs selected from postnatal Wnt1-cre;R26R-YFP/YFP murine gut were transplanted into ganglionic hindgut of wild-type littermates or aganglionic hindgut of Ednrbtm1Ywa mice (lacking functional endothelin receptor type-B. Intestines were then assessed for ENCC integration and differentiation using immunohistochemistry, cell function using calcium imaging, and long-term safety using PCR to detect off-target YFP expression.YFP+ ENCCs engrafted, proliferated and differentiated into enteric neurons and glia within recipient ganglionic gut. Transplanted cells and their projections spread along the endogenous myenteric plexus to form branching networks. Electrical point stimulation of endogenous nerve fibres resulted in calcium transients (F/F0 = 1.16 ± 0.01;43 cells, n = 6 in YFP+ transplanted ENCCs (abolished with TTX. Long-term follow-up (24 months showed transplanted ENCCs did not give rise to tumours or spread to other organs (PCR negative in extraintestinal sites. In aganglionic gut ENCCs similarly spread and differentiated to form neuronal and glial networks with projections closely associated with endogenous neural networks of the transition zone.Transplanted ENCCs successfully engrafted into recipient ganglionic and aganglionic gut showing appropriate spread, localisation and, importantly, functional integration without any long-term safety issues. This study provides key support for the development and use of enteric neural stem cell therapies.

Eurosafe 2006 radioactive waste management: long term safety requirements and societal expectations

International Nuclear Information System (INIS)

2006-01-01

The EUROSAFE Forum is part of the EUROSAFE approach, which consists of two further elements: the EUROSAFE Tribune and the EUROSAFE web site. The general aim of EUROSAFE is to contribute to fostering the convergence of technical nuclear safety practices in a broad European context. This is done by providing technical safety and research organisations, safety authorities, power utilities, the rest of the industry and non-governmental organisations mainly from the European Union and East-European countries, and international organisations with a platform for the presentation of recent analyses and R and D in the field of nuclear safety, to share experiences, exchange technical and scientific opinions, and conduct debates on key issues in the fields of nuclear safety and radiation protection. The EUROSAFE Forum 2006 focuses on 'Radioactive Waste Management: Long Term Safety Requirements and Societal Expectations' from the point of view of the authorities, TSOs and industry and presents the latest work in nuclear installation safety and research, waste management, radiation safety as well as nuclear material and nuclear facilities security carried out by GRS, IRSN, AVN and their partners in the European Union, Switzerland and Eastern Europe. A high level of nuclear safety is a priority for Europe. The technical safety organisations play an important role in contributing to that objective through appropriate approaches to major safety issues as part of their assessments and research activities. The challenges to nuclear safety are international. Changes in underlying technologies such as instrumentation and control, the impact of electricity market deregulation, demands for improved safety and safety management, the ageing of nuclear facilities, waste management, maintaining and improving scientific and technical knowledge, and the need for greater transparency - these are all issues where the value of an international approach is gaining increasing recognition. This

Eurosafe 2006 radioactive waste management: long term safety requirements and societal expectations

Energy Technology Data Exchange (ETDEWEB)

NONE

2006-07-01

The EUROSAFE Forum is part of the EUROSAFE approach, which consists of two further elements: the EUROSAFE Tribune and the EUROSAFE web site. The general aim of EUROSAFE is to contribute to fostering the convergence of technical nuclear safety practices in a broad European context. This is done by providing technical safety and research organisations, safety authorities, power utilities, the rest of the industry and non-governmental organisations mainly from the European Union and East-European countries, and international organisations with a platform for the presentation of recent analyses and R and D in the field of nuclear safety, to share experiences, exchange technical and scientific opinions, and conduct debates on key issues in the fields of nuclear safety and radiation protection. The EUROSAFE Forum 2006 focuses on 'Radioactive Waste Management: Long Term Safety Requirements and Societal Expectations' from the point of view of the authorities, TSOs and industry and presents the latest work in nuclear installation safety and research, waste management, radiation safety as well as nuclear material and nuclear facilities security carried out by GRS, IRSN, AVN and their partners in the European Union, Switzerland and Eastern Europe. A high level of nuclear safety is a priority for Europe. The technical safety organisations play an important role in contributing to that objective through appropriate approaches to major safety issues as part of their assessments and research activities. The challenges to nuclear safety are international. Changes in underlying technologies such as instrumentation and control, the impact of electricity market deregulation, demands for improved safety and safety management, the ageing of nuclear facilities, waste management, maintaining and improving scientific and technical knowledge, and the need for greater transparency - these are all issues where the value of an international approach is gaining increasing recognition. This

Eurosafe 2006 radioactive waste management: long term safety requirements and societal expectations

Energy Technology Data Exchange (ETDEWEB)

NONE

2006-07-01

The EUROSAFE Forum is part of the EUROSAFE approach, which consists of two further elements: the EUROSAFE Tribune and the EUROSAFE web site. The general aim of EUROSAFE is to contribute to fostering the convergence of technical nuclear safety practices in a broad European context. This is done by providing technical safety and research organisations, safety authorities, power utilities, the rest of the industry and non-governmental organisations mainly from the European Union and East-European countries, and international organisations with a platform for the presentation of recent analyses and R and D in the field of nuclear safety, to share experiences, exchange technical and scientific opinions, and conduct debates on key issues in the fields of nuclear safety and radiation protection. The EUROSAFE Forum 2006 focuses on 'Radioactive Waste Management: Long Term Safety Requirements and Societal Expectations' from the point of view of the authorities, TSOs and industry and presents the latest work in nuclear installation safety and research, waste management, radiation safety as well as nuclear material and nuclear facilities security carried out by GRS, IRSN, AVN and their partners in the European Union, Switzerland and Eastern Europe. A high level of nuclear safety is a priority for Europe. The technical safety organisations play an important role in contributing to that objective through appropriate approaches to major safety issues as part of their assessments and research activities. The challenges to nuclear safety are international. Changes in underlying technologies such as instrumentation and control, the impact of electricity market deregulation, demands for improved safety and safety management, the ageing of nuclear facilities, waste management, maintaining and improving scientific and technical knowledge, and the need for greater transparency - these are all issues where the value of an international approach is gaining increasing recognition

Development and implementation of setpoint tolerances for special safety systems

International Nuclear Information System (INIS)

Oliva, A.F.; Balog, G.; Parkinson, D.G.; Archinoff, G.H.

1991-01-01

The establishment of tolerances and impairment limits for special safety system setpoints is part of the process whereby the plant operator demonstrates to the regulatory authority that the plant operates safely and within the defined plant licensing envelope. The licensing envelope represents the set of limits and plant operating state and for which acceptably safe plant operation has been demonstrated by the safety analysis. By definition, operation beyond this envelope contributes to overall safety system unavailability. Definition of the licensing envelope is provided in a wide range of documents including the plant operating licence, the safety report, and the plant operating policies and principles documents. As part of the safety analysis, limits are derived for each special safety system initiating parameter such that the relevant safety design objectives are achieved for all design basis events. If initiation on a given parameter occurs at a level beyond its limit, there is a potential reduction in safety system effectiveness relative to the performance credited in the plant safety analysis. These safety system parameter limits, when corrected for random and systematic instrument errors and other errors inherent in the process of periodic testing or calibration, are then used to derive parameter impairment levels and setpoint tolerances. This paper describes the methodology that has evolved at Ontario Hydro for developing and implementing tolerances for special safety system parameters (i.e., the shutdown systems, emergency coolant injection system and containment system). Tolerances for special safety system initiation setpoints are addressed specifically, although many of the considerations discussed here will apply to performance limits for other safety system components. The first part of the paper deals with the approach that has been adopted for defining and establishing setpoint limits and tolerances. The remainder of the paper addresses operational

RADIATION SAFETY JUSTIFICATION FOR THE LONG-TERM STORAGE OF GAS CONDENSATE IN THE UNDERGROUND RESERVOURS FORMED BY THE NUCLEAR EXPLOSION TECHNOLOGY

Directory of Open Access Journals (Sweden)

I. K. Romanovich

2010-01-01

Full Text Available The paper presents approaches to the safety justification of the gas condensate and brine long-term storage in the underground reservoirs formed by the nuclear explosion technology. Gas condensate and brine are the intermediate level liquid radioactive waste containing isotopes: 3Н, 137Cs and 90Sr, in traces - 239Pu, 235U, 241Am.Safety of the gas condensate and brine long-term storage in the underground reservoirs is assessed on the base of the multi-barrier principle implementation, used during radioactive waste disposal. It is shown that the gas condensate and brine long-term storage in the sealed underground reservoirs formed by nuclear explosion technologies in salt domes does not lead to the surface radioactive contamination and population exposure.

Project JADE. Long-term function and safety. Comparison of repository systems

International Nuclear Information System (INIS)

Birgersson, Lars; Pers, K.; Wiborgh, M.

2001-12-01

A comparison of the KBS-3 V(ertical deposition), KBS-3 H(orizontal deposition) and MLH repository systems with regard to the long-term repository performance and the radionuclide migration is presented in the report. Several differences between the repository systems have been identified. The differences are mainly related to the: distance between canister and backfilled tunnels, excavated rock volumes, deposition hole direction. The overall conclusion is that the differences are in general quite small with regard to the repository function and safety. None of the differences are of such importance for the long-term repository performance and radionuclide migration that they discriminate any of the repository systems. The differences between the two KBS-3 systems are small. Based on this study, there is no reason to change from the reference system KBS-3 V to KBS-3 H. MLH has the potential to be a very robust system, especially in a long-term perspective. However, the MLH system will require extensive research, development, and analysis before it will be as confident as the reference repository system, KBS-3 V. Although the MLH and KBS-3 H systems are in some ways favourable compared to the reference system KBS-3 V, the overall conclusion is that the KBS-3 V system is still a very attractive system. A major advantage with KBS-3 V is that it is by far the most investigated and developed system. The JADE-project was initiated in 1996, and the main part of the study was carried out during 1997 and 1998. The JADE study is consequently based on presumptions that were valid a few years ago. Some of these presumptions have been modified since then. The new presumptions are however not judged to change the overall conclusions

Long-Term Safety and Effectiveness of the “OptEase” Vena Cava Filter

International Nuclear Information System (INIS)

Kalva, Sanjeeva P.; Marentis, Theodore C.; Yeddula, Kalpana; Somarouthu, Bhanusupriya; Wicky, Stephan; Stecker, Michael S.

2011-01-01

Purpose: To assess the long-term safety and effectiveness of the OptEase inferior vena cava (IVC) filter. Materials and Methods: In this Institutional Review Board-approved, retrospective study, we reviewed data of 71 patients who received an OptEase filter at our institution from 2002 to 2007. Thirty-nine (55%) patients had symptoms of venous thromboembolism before filter placement. The indications for filter included contraindication to anticoagulation in 31 (44%) patients, prophylaxis against pulmonary embolism (PE) in 29 (41%) patients, and failure of anticoagulation in 11 (15%) patients. Procedure-related complications, such as symptomatic post-filter PE, deep venous thrombosis (DVT), IVC occlusion, and incidental imaging-evident filter-related complications, were recorded. Safety was assessed by the occurrence of filter-related complications during placement and follow-up. Effectiveness was assessed by the occurrence of post-filter PE. Results: Sixty-five (92%) filters were placed under fluoroscopy, and 6 (8%) were placed using intravascular ultrasound guidance. Seventy (99%) filters were placed successfully. Seven (10%) filters were placed in the suprarenal cava. Retrieval was attempted in 14 (20%) patients, and 12 filters were successfully retrieved. Clinical follow-up was available for 20 ± 21 months. Symptoms of postfilter PE and DVT occurred in 15% (n = 11) and 10% (n = 7) patients, respectively. None of these patients had computed tomography (CT)-proven PE, and only one had ultrasound-proven new DVT. One patient had symptomatic IVC occlusion. Follow-up abdominal CT in 20 patients showed thrombus in the filter in two of them. There were no instances of filter migration, filter tilt, or caval wall penetration. Conclusion: The OptEase filter appears to have an acceptable long-term safety profile. The filter was effective against PE.

Long-term efficacy and safety of ramosetron in the treatment of diarrhea-predominant irritable bowel syndrome

Directory of Open Access Journals (Sweden)

Chiba T

2013-07-01

Full Text Available Toshimi Chiba, Kazunari Yamamoto, Shoko Sato, Kazuyuki Suzuki Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Iwate, Japan Abstract: Irritable bowel syndrome (IBS is a functional disease with persisting gastrointestinal symptoms that has been classified into four subtypes. Serotonin (5-hydroxytryptamine [5-HT] plays important physiological roles in the contraction and relaxation of smooth muscle. Intraluminal distension of the intestine is known to stimulate the release of endogenous 5-HT from enterochromaffin cells, activating 5-HT3 receptors located on primary afferent neurons and leading to increases in intestinal secretions and peristaltic activity. Ramosetron, a potent and selective 5-HT3-receptor antagonist, has been in development for use in patients suffering from diarrhea-predominant IBS. In a double-blind, placebo-controlled, parallel-group study of 418 patients with diarrhea-predominant IBS-D, once-daily 5 µg and 10 µg doses of ramosetron increased the monthly responder rates of IBS symptoms compared to placebo. In a 12-week randomized controlled trial of 539 patients, a positive response to treatment was reported by 47% of a once-daily 5 µg dose of ramosetron-treated individuals compared to 27% of patients receiving placebo (P<0.001. Furthermore, the responder rate was increased in the oral administration of 5 µg of ramosetron for at least 28 weeks (up to 52 weeks, and long-term efficacy for overall improvement of IBS symptoms was also demonstrated. The rate was further increased subsequently. Adverse events were reported by 7% in ramosetron treatment. No serious adverse events, eg, severe constipation or ischemic colitis, were reported for long-term treatment with ramosetron. In conclusion, further studies to evaluate the long-term efficacy and safety of ramosetron are warranted in the form of randomized controlled trials. Keywords: long-term

Efficacy, tolerability, and safety of aripiprazole once-monthly versus other long-acting injectable antipsychotic therapies in the maintenance treatment of schizophrenia: a mixed treatment comparison of double-blind randomized clinical trials.

Science.gov (United States)

Majer, Istvan M; Gaughran, Fiona; Sapin, Christophe; Beillat, Maud; Treur, Maarten

2015-01-01

Treatment with long-acting injectable (LAI) antipsychotic medication is an important element of relapse prevention in schizophrenia. Recently, the intramuscular once-monthly formulation of aripiprazole received marketing approval in Europe and the United States for schizophrenia. This study aimed to compare aripiprazole once-monthly with other LAI antipsychotics in terms of efficacy, tolerability, and safety. A systematic literature review was conducted to identify relevant double-blind randomized clinical trials of LAIs conducted in the maintenance treatment of schizophrenia. MEDLINE, MEDLINE In-Process, Embase, the Cochrane Library, PsycINFO, conference proceedings, clinical trial registries, and the reference lists of key review articles were searched. The literature search covered studies dating from January 2002 to May 2013. Studies were required to have ≥24 weeks of follow-up. Patients had to be stable at randomization. Studies were not eligible for inclusion if efficacy of acute and maintenance phase treatment was not reported separately. Six trials were identified (0.5% of initially identified studies), allowing comparisons of aripiprazole once-monthly, risperidone LAI, paliperidone palmitate, olanzapine pamoate, haloperidol depot, and placebo. Data extracted included study details, study duration, the total number of patients in each treatment arm, efficacy, tolerability, and safety outcomes. The efficacy outcome contained the number of patients that experienced a relapse, tolerability outcomes included the number of patients that discontinued treatment due to treatment-related adverse events (AEs), and that discontinued treatment due to reasons other than AEs (e.g., loss to follow-up). Safety outcomes included the incidence of clinically relevant weight gain and extrapyramidal symptoms. Data were analyzed by applying a mixed treatment comparison competing risks model (efficacy) and using binary models (safety). There was no statistically significant

Long-term safety and feasibility of three-vessel multimodality intravascular imaging in patients with ST-elevation myocardial infarction

DEFF Research Database (Denmark)

Taniwaki, Masanori; Radu, Maria D; Garcia-Garcia, Hector M

2015-01-01

We assessed the feasibility and the procedural and long-term safety of intracoronary (i.c) imaging for documentary purposes with optical coherence tomography (OCT) and intravascular ultrasound (IVUS) in patients with acute ST-elevation myocardial infarction (STEMI) undergoing primary PCI in the s......We assessed the feasibility and the procedural and long-term safety of intracoronary (i.c) imaging for documentary purposes with optical coherence tomography (OCT) and intravascular ultrasound (IVUS) in patients with acute ST-elevation myocardial infarction (STEMI) undergoing primary PCI...... in the setting of IBIS-4 study. IBIS4 (NCT00962416) is a prospective cohort study conducted at five European centers including 103 STEMI patients who underwent serial three-vessel coronary imaging during primary PCI and at 13 months. The feasibility parameter was successful imaging, defined as the number...... of pullbacks suitable for analysis. Safety parameters included the frequency of peri-procedural complications, and major adverse cardiac events (MACE), a composite of cardiac death, myocardial infarction (MI) and any clinically-indicated revascularization at 2 years. Clinical outcomes were compared...

Open-label, randomized, multicenter, phase III study to evaluate the safety and efficacy of benzoyl peroxide gel in long-term use in patients with acne vulgaris: A secondary publication.

Science.gov (United States)

Kawashima, Makoto; Nagare, Toshitaka; Katsuramaki, Tsuneo

2017-06-01

An open-label, randomized, multicenter study was conducted to evaluate the safety and efficacy of long-term use of 2.5% and 5% benzoyl peroxide (BPO) gels administrated once daily for 52 weeks to Japanese patients with acne vulgaris. The efficacy of the study drugs was evaluated by counting inflammatory lesions and non-inflammatory lesions. Safety was evaluated based on adverse events, local skin tolerability scores and laboratory test values. In total, 458 subjects were included in the efficacy and safety analyses. The total lesion count, the efficacy end-point, was similarly changed both in the 2.5% and 5% BPO groups over the course of the study. The median rates of reduction from baseline to week 12 were approximately 65%. Thereafter, the counts were maintained at a reduced level without increasing until week 52. The median rates at week 52 were approximately 80%. Similar trends were observed for inflammatory and non-inflammatory lesion counts. Bacteriological evaluation indicated similar distribution of the minimum inhibitory concentration of each of the antibacterial drugs against Propionibacterium acnes between the values at baseline and at week 52, suggesting that long-term use did not result in changes in the drug sensitivity. The incidence of adverse events was 84.0% in the 2.5% BPO group and 87.2% in the 5% BPO group. Many of the adverse events occurred within the first month and were mild or moderate in severity and transient. The results suggest that both 2.5% and 5% BPO gels are effective and safe for long-term treatment of patients with acne vulgaris. © 2017 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

Regulating the long-term safety of geological disposal of radioactive waste: practical issues and challenges

International Nuclear Information System (INIS)

2008-01-01

Regulating the long-term safety of geological disposal of radioactive waste is a key part of making progress on the radioactive waste management issue. A survey of member countries has shown that differences exist both in the protection criteria being applied and in the methods for demonstrating compliance, reflecting historical and cultural differences between countries which in turn result in a diversity of decision-making approaches and frameworks. At the same time, however, these differences in criteria are unlikely to result in significant differences in long-term protection, as all the standards being proposed are well below levels at which actual effects of radiological exposure can be observed and a range of complementary requirements is foreseen. In order to enable experts from a wide range of backgrounds to debate the various aspects of these findings, the NEA organised an international workshop in November 2006 in Paris, France. Discussions focused on diversity in regulatory processes; the basis and tools for assuring long-term protection; ethical responsibilities of one generation to later generations and how these can be discharged; and adapting regulatory processes to the long time frames involved in implementing geological disposal. These proceedings include a summary of the viewpoints expressed as well as the 22 papers presented at the workshop. (author)

Methodology of fuel cycles long-term safety assessment of SNF/HLW geological disposal

International Nuclear Information System (INIS)

Pritrsky, J.

2008-01-01

Methodology for the long-term safety assessment of nuclear fuel cycles is given in the presented doctoral thesis. The aim of work was to develop a geological repository model for disposal of spent nuclear fuel (SNF) and high level waste (HLW) using an appropriate software code able to calculate the influence of partitioning and transmutation in advanced fuel cycles. The first step in this process was specifying of indicators which can be used to quantify the radiological impact of each fuel cycle. Indicators such as annual effective dose and radiotoxicity of inventory have been quantitatively analysed to determine the potential risk and radiological consequences associated with production of SNF/HLW. Advanced fuel types bring a number of advantages in comparison to uranium oxide fuel UO 2 used worldwide nowadays in terms of safety improvement due to minor actinides transmutation and non-proliferation aspects as well. Within the scope of work, three different fuel cycles are compared from the point of view of long-term safety of deep geological repository. The first considered fuel cycle is the currently used open fuel cycle (UOX) which uses only U-FA (Uranium Fuel Assembly). The second assessed cycle is a closed fuel cycle (MOX) with MOX-FA (Mixed OXides Fuel Assembly) and the third considered one is a partially closed fuel cycle (IMF) with IMC-FA (Inert Matrix Combined Fuel Assembly). Description and input data of advanced fuel cycles have been gained by participation in the EC project RED-IMPACT. Results were calculated using code AMBER, which is a flexible software tool that allows building dynamic compartmental models to represent the migration and fate of contaminants in a system, for example in the surface and sub-surface environment. Contaminants in solid, liquid and gaseous phases can be considered. AMBER gives the user the flexibility to define any number of compartments; any number of contaminants and associated decays; deterministic, probabilistic and

Methodology of fuel cycles long-term safety assessment of SNF/HLW geological disposal

International Nuclear Information System (INIS)

Pritrsky, J.

2008-02-01

Methodology for the long-term safety assessment of nuclear fuel cycles is given in the presented doctoral thesis. The aim of work was to develop a geological repository model for disposal of spent nuclear fuel (SNF) and high level waste (HLW) using an appropriate software code able to calculate the influence of partitioning and transmutation in advanced fuel cycles. The first step in this process was specifying of indicators which can be used to quantify the radiological impact of each fuel cycle. Indicators such as annual effective dose and radiotoxicity of inventory have been quantitatively analysed to determine the potential risk and radiological consequences associated with production of SNF/HLW. Advanced fuel types bring a number of advantages in comparison to uranium oxide fuel UO 2 used worldwide nowadays in terms of safety improvement due to minor actinides transmutation and non-proliferation aspects as well. Within the scope of work, three different fuel cycles are compared from the point of view of long-term safety of deep geological repository. The first considered fuel cycle is the currently used open fuel cycle (UOX) which uses only U-FA (Uranium Fuel Assembly). The second assessed cycle is a closed fuel cycle (MOX) with MOX-FA (Mixed OXides Fuel Assembly) and the third considered one is a partially closed fuel cycle (IMF) with IMC-FA (Inert Matrix Combined Fuel Assembly). Description and input data of advanced fuel cycles have been gained by participation in the EC project RED-IMPACT. Results were calculated using code AMBER, which is a flexible software tool that allows building dynamic compartmental models to represent the migration and fate of contaminants in a system, for example in the surface and sub-surface environment. Contaminants in solid, liquid and gaseous phases can be considered. AMBER gives the user the flexibility to define any number of compartments; any number of contaminants and associated decays; deterministic, probabilistic and

Deep geological repositories. Safe operation and long-term safety in the prism of reversibility

Energy Technology Data Exchange (ETDEWEB)

Espivent, Camille; Tichauer, Michael [IRSN, Fontenay-aux-Roses (France)

2015-07-01

A deep geological repository is the reference solution enshrined in the French law for the long-term management of high-level radioactive waste. The current project is led by Andra, the French radioactive waste management organization. As a technical support organization, IRSN's mission is, on the basis of the safety case produced by Andra, to assess the safety of such a facility at its various stages of development, that is to say the design, construction, operation and post-closure phases of the facility. Such a facility will have to meet specific requirements, within different time frames as stated above. One of the requirements is ''reversibility'': in fact, French law poses that the geological disposal will have to be ''reversible'' for a certain time, yet not fully defined. Reversibility is nevertheless believed encompassing both the decision making process related to the waste emplacement process during operational phase and the ability to retrieve waste, should such a decision be made. Thus, underground structures have to be designed and operated to allow both waste emplacement and removal. Moreover, future decision making about the disposal process will have to rely on a sound technical basis. This implies a data collection scheme and a monitoring program of the facility to check if the disposal process is bound by limits, controls and conditions compatible with (i) a safe operation of the facility and (ii) the state of the facility that the operator wants to achieve at the time of its closure, so that long-term safety is guaranteed. Therefore, technical criteria and key parameters have to be selected and monitored during construction and operation, that is to say for decades. Then, reversibility have to make room for corrective actions, including the retrieval of waste, if something goes wrong and especially if the facility is not seen as safe anymore, especially in the perspective of long-term safety. To

Deep geological repositories. Safe operation and long-term safety in the prism of reversibility

International Nuclear Information System (INIS)

Espivent, Camille; Tichauer, Michael

2015-01-01

A deep geological repository is the reference solution enshrined in the French law for the long-term management of high-level radioactive waste. The current project is led by Andra, the French radioactive waste management organization. As a technical support organization, IRSN's mission is, on the basis of the safety case produced by Andra, to assess the safety of such a facility at its various stages of development, that is to say the design, construction, operation and post-closure phases of the facility. Such a facility will have to meet specific requirements, within different time frames as stated above. One of the requirements is ''reversibility'': in fact, French law poses that the geological disposal will have to be ''reversible'' for a certain time, yet not fully defined. Reversibility is nevertheless believed encompassing both the decision making process related to the waste emplacement process during operational phase and the ability to retrieve waste, should such a decision be made. Thus, underground structures have to be designed and operated to allow both waste emplacement and removal. Moreover, future decision making about the disposal process will have to rely on a sound technical basis. This implies a data collection scheme and a monitoring program of the facility to check if the disposal process is bound by limits, controls and conditions compatible with (i) a safe operation of the facility and (ii) the state of the facility that the operator wants to achieve at the time of its closure, so that long-term safety is guaranteed. Therefore, technical criteria and key parameters have to be selected and monitored during construction and operation, that is to say for decades. Then, reversibility have to make room for corrective actions, including the retrieval of waste, if something goes wrong and especially if the facility is not seen as safe anymore, especially in the perspective of long-term safety. To

Comparative Evaluation of the Safety and Efficacy of Long-Term Use of Imidafenacin and Solifenacin in Patients with Overactive Bladder: A Prospective, Open, Randomized, Parallel-Group Trial (the LIST Study

Directory of Open Access Journals (Sweden)

Masayoshi Zaitsu

2011-01-01

Full Text Available Objectives. Overactive bladder (OAB is a chronic disease, but comparative trials of anticholinergics, which are commonly used for treatment of OAB, have generally been performed for up to 12 weeks only. There is no comparative study of a long-term intervention. Methods. We conducted a 52-week prospective randomized comparative study to evaluate the efficacy and tolerability of two anticholinergics. Results. Forty-one Japanese patients with untreated OAB were randomly assigned to imidafenacin and solifenacin groups. There was no difference in OABSS and KHQ scores between the two groups, but the severity and incidence of adverse events caused by the anticholinergics showed increased differences between the groups with time. The severity of dry mouth and the incidence of constipation were significantly lower in the imidafenacin group (=0.0092 and =0.0013, resp.. Conclusions. This study is the first long-term trial to show differences in the properties of anticholinergics that were not detected in short-term studies. Since OAB is a chronic disease, we conclude that imidafenacin is preferable to solifenacin from a perspective of safety.

Workplace Violence and Safety Issues in Long-Term Medical Care Facilities: Nurses' Perspectives.

Science.gov (United States)

Fasanya, Bankole K; Dada, Emmanuel A

2016-06-01

Workplace violence (WPV) is becoming an issue that needs immediate attention in the United States, especially during this period as more states are adopting the "stand your ground laws to promote worker protection." This study was conducted to investigate how WPV has contributed to an unsafe environment for nurses and nursing assistants who work in long-term medical care facilities. A structure questionnaire was used to collect data for the study. Three facilities were sampled and 80 nurses and certified nursing assistants participated in the study. Ninety-two percent (n = 74) were female and 8% (n = 6) were male. Approximately 62% were black or African American, approximately 33% were Caucasians, and only 2% were from other ethnicities. We found that 65% of the participants had experienced WPV while 41% believed that management shows little or no concern for their safety. Approximately 23% of respondents believed that reporting supervisor's WPV act is an unsafe action. In addition, 22% of those who reported that they have experienced WPV believed that the work environment is not safe to perform their duties. This significant difference in perception of workplace safety between those who had experienced WPV and those who had not was significant (t = 3.95, df = 158, p < 0.0001). WPV is an epidemic problem that affects all health-care professionals. The findings of this study could help long-term medical care facilities' management identify the areas to focus on mitigating, controlling, and/or eliminating incidents of WPV.

Radiation effects after low dose chronic long-term exposure

International Nuclear Information System (INIS)

Fliedner, T.M.; Friesecke, I.

1997-01-01

This document approaches the radiation effects after low dose chronic long-term exposure, presenting examples occurred, the pathophysiologic mechanisms for cell system tolerance in elevated radiation fields, and the diagnostic and therapeutic possibilities

Long-term efficacy and safety of ExPress implantation for treatment of open angle glaucoma

OpenAIRE

Lee, Geun Young; Lee, Chong Eun; Lee, Kyoo Won; Seo, Sam

2017-01-01

AIM: To compare the long-term efficacy and safety of ExPress implantation and standard trabeculectomy in patients with primary open angle glaucoma (POAG). METHODS: In this retrospective study, we compared 17 eyes treated by ExPress implantation with 23 eyes treated by trabeculectomy. Efficacy was assessed according to the relevant intraocular pressure (IOP) values and success rates during the first year of follow-up. Postoperative corneal endothelial cell loss was also compared. RESULTS...

Design analysis of various transportation package options for BN-350 SNF in terms of nuclear radiation safety in planning for long-terms dry storage

International Nuclear Information System (INIS)

Aisabekov, A.Z.; Mukenova, S.A.; Tur, E.S.; Tsyngaev, V.M.

2004-01-01

Full text: This effort is performed under the BN-350 reactor facility decommissioning project. One of the project tasks - spent nuclear fuel handling - includes the following: fuel packaging into sealed canisters, transportation of the canisters in multi-seat metallo-concrete containers and placement of the containers for a long-term dry storage. The goal of this effort is to computationally validate nuclear and radiation safety of the SNF containers placed for storage both under normal storage conditions and probable accident situations. The basic unit structure and design configurations are presented: assemblies, canisters, transportation containers. The major factors influencing nuclear and radiation safety are presented: fuel burn-up, enrichment, fabrication tolerance, types of fuel assemblies, configuration of assemblies in the canister and canisters in the container, background of assemblies placed in the reactor and cooling pool. Conditions under which the SNF containers will be stored are described and probable accident situations are listed. Proceeding from the conservatism principle, selection of the assemblies posing the greatest nuclear hazard is validated. A neutron effective multiplication factor is calculated for the SNF containers under the normal storage conditions and for the case of emergency. The effective multiplication factor is shown to be within a standard value of 0.95 in any situation. Based on the experimental data on assembly and canister dose rates, canisters posing the highest radiation threat are selected. Activities of sources and gamma-radiation spectral composition are calculated. Distribution of the dose rate outside the containers both under the normal storage conditions and accident situations are calculated. The results obtained are analyzed

Parametric Analysis of PWR Spent Fuel Depletion Parameters for Long-Term-Disposal Criticality Safety

International Nuclear Information System (INIS)

DeHart, M.D.

1999-01-01

Utilization of burnup credit in criticality safety analysis for long-term disposal of spent nuclear fuel allows improved design efficiency and reduced cost due to the large mass of fissile material that will be present in the repository. Burnup-credit calculations are based on depletion calculations that provide a conservative estimate of spent fuel contents (in terms of criticality potential), followed by criticality calculations to assess the value of the effective neutron multiplication factor (k(sub)eff) for the a spent fuel cask or a fuel configuration under a variety of probabilistically derived events. In order to ensure that the depletion calculation is conservative, it is necessary to both qualify and quantify assumptions that can be made in depletion models

Realistic integration of sorption processes in transport codes for long-term safety assessments

Energy Technology Data Exchange (ETDEWEB)

Noseck, Ulrich; Fluegge, Judith; Britz, Susan; Schneider, Anke [Gesellschaft fuer Anlagen- und Reaktorsicherheit mbH (GRS), Koeln (Germany); Brendler, Vinzenz; Stockmann, Madlen; Schikora, Johannes [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany); Lampe, Michael [Frankfurt Univ. (Germany). Goethe Center for Scientific Computing

2012-09-15

One important aspect in long-term safety assessment is related to radionuclide transport in geologic formations. In order to assess its consequences over assessment periods of one million years numerical models describing flow and transport are applied. Sorption on mineral surfaces is the most relevant process retarding radionuclide transport. On the one hand an increased transport time might cause a decrease in radionuclide concentration by radioactive decay. On the other hand it might increase concentrations of dose-relevant daughter nuclides in decay chains. In order to treat the radionuclide sorption processes in natural systems close to reality the so-called smart K{sub d}-concept is implemented into the transport program r{sup 3}t, which is applied to large model areas and very long time scales in long-term safety assessment. In the first stage this approach is developed for a typical sedimentary system covering rock salt and clay formations in Northern Germany. The smart K{sub d}-values are based on mechanistic surface complexation models (SCM), varying in time and space and de-pending on the actual geochemical conditions, which might change in the future e. g. due to the impact of climate changes. The concept developed and introduced here is based on a feasible treatment of the most relevant geochemical parameters in the transport code as well as on a matrix of smart K{sub d}-values calculated in dependence on these parameters. The implementation of the concept comprises the selection of relevant elements and minerals to be considered, an experimental program to fill data gaps of the thermody-namic sorption database, an uncertainty and sensitivity analysis to identify the most important environmental parameters influencing sorption of long-term relevant radionu-clides, the creation of a matrix with K{sub d}-values dependent on the selected environmental parameters, and the development and realisation of the conceptual model for treatment of temporal and

Safety related terms for advanced nuclear plants; Terminos relacionados con la seguridad para centrales nucleares avanzadas

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-12-01

The terms considered in this document are in widespread current use without a universal consensus as to their meaning. Other safety related terms are already defined in national or international codes and standards as well as in IAEA's Nuclear Safety Standards Series. Most of the terms in those codes and standards have been defined and used for regulatory purposes, generally for application to present reactor designs. There is no intention to duplicate the description of such regulatory terms here, but only to clarify the terms used for advanced nuclear plants. The following terms are described in this paper: Inherent safety characteristics, passive component, active component, passive systems, active system, fail-safe, grace period, foolproof, fault-/error-tolerant, simplified safety system, transparent safety.

Long-term Safety of a Geologic Repository: What does the public want to know?

International Nuclear Information System (INIS)

Kotra, Janet

2008-01-01

Janet Kotra of the U.S. NRC recounted the questions most frequently asked of the Commission's staff, concerning the long-term safety of the planned Yucca Mountain repository. The first question was related to who would decide whether the facility is safe enough. The next question linked to it is if regulatory staff is sufficiently qualified, and if they have access to independent sources of information or depend merely on the information provided by the implementer. The subsequent questions were about what criteria the regulator used and whether they were comprehensive enough. A separate group of questions addressed the safety of the technology, including the geologic features of the site, the engineered structures and the packaging of waste. Issues of documentation, operational control, long-term monitoring, oversight, and enforcement were also raised, along with the transparency of such processes and the accessibility of documents to the public. In addition, several questions were related to the fairness of decision making, public involvement, and the flexibility of the implementation process with regard to future knowledge and RD and D. Ms Kotra propounded that a single question was behind those cited above, namely whether one could rely on the regulator or not. Since it is not realistic to expect an overall consensus on the decision of the regulator agency, the goal should rather be to build confidence in the decision-making process. Key factors of confidence include openness on the part of the regulator and other decision-making institutions, and access to trustworthy representatives of these organisations

Long-term safety and efficacy of a cholesterol-lowering diet in children with elevated low-density lipoprotein cholesterol : Seven-year results of the Dietary Intervention Study in Children (DISC)

NARCIS (Netherlands)

Obarzanek, E; Kimm, SYS; Barton, BA; Van Horn, L; Kwiterovich, PO; Simons-Morton, DG; Hunsberger, SA; Lasser, NL; Robson, AM; Franklin, FA; Lauer, RM; Stevens, VJ; Friedman, LA; Dorgan, JF; Greenlick, MR

Objective. Diets reduced in fat and cholesterol are recommended for children over 2 years of age, yet long-term safety and efficacy are unknown. This study tests the long-term efficacy and safety of a cholesterol-lowering dietary intervention in children. Methods. Six hundred sixty-three children 8

Safety aspects in the dry storage of spent nuclear fuel in long term operation

Energy Technology Data Exchange (ETDEWEB)

Nodarim, Claudir J.; Silva, Viviane B. da; Fontes, Gladson S. [Instituto Militar de Engenharia (IME), Rio de Janeiro, RJ (Brazil); Saldanha, Pedro L.C., E-mail: claudirnodari@gmail.com, E-mail: vivisborges@gmail.com, E-mail: gsfontes@hotmail.com, E-mail: Saldanha@cnen.gov.br [Comissão Nacional de Energia Nuclear (CNEN), Rio de Janeiro, RJ (Brazil)

2017-07-01

The purpose of the present paper is to discuss the safety assessment of the Dry Storage Unit (DSU), taking into account the long term operation and the operational experience already evidenced in similar facilities. In this sense, the RIDM (Risk-Informed Decision-Making) concept will be adopted for the regulatory decision-making process. Potential technical issues associated with the aging of materials from the dry storage unit will be considered. The work will be done using the rules and requirements of 10 CFR Part 72 and the U.S. NRC (United States Nuclear Regulatory Commission) regulatory guides. (author)

Consideration of environmental change in the safety evaluation: Long-term climate scenarios in the Iberian Peninsula

International Nuclear Information System (INIS)

Recreo Jimenez, F.; Ruiz Rivas, C.

1997-01-01

The main objective of this report is twofold. On the one hand, to define the most likely sequences of climate states in the Iberian Peninsula for a period of 125 Ka into the future, to the next interglacial stage, 125 Ka AP; on the other hand, to establish potential climate scenarios during such a period of time determining also the variability ranges of primary climate and climate-related variables of interest to the post-closure performance assessment and underground repository safety evaluations. The report reviews the potential effects of environmental changes on the performance of underground radioactive waste repositories, emphasizing the consideration given to long-term climatic changes in radioactive waste disposal system safety evaluations. (Author)

IGSC Experience: Links Between RD and D and Stakeholder Confidence: The Aspect of Long-Term Safety

International Nuclear Information System (INIS)

Stroemberg, Bo

2008-01-01

Bo Stroemberg from the IGSC Core Group (SKI, Sweden) reported on the International Symposium on the Safety Case organised in 2007 by IGSC. Participants of a session focusing on the role of the safety case in societal dialogue pointed out that in the technical community there is a shared understanding of the issues of long-term safety, which the SC should address. They observed, however, that public concerns may be quite different from these issues. For example, the extremely long timescales are not easily understood by the broader public. Also, technical experts' focus on quantitative indicators is incompatible with the perceptions of non-experts, who tend to give heavier weight to qualitative characteristics of risks. Therefore, conducting a dialogue with the public in which their safety concerns are explored is of key importance. It is not only the technical content but also the presentation of the SC which should be adapted to stakeholders' concerns. At the same time, stakeholder input can improve both the technical basis and the presentation of the SC. Mr Stroemberg went on to present IGSC Core Group answers to questions addressed to them by the FSC: 1. What are the questions about safety and the safety case you feel the public is asking? What kind of reply? Or approach to replying? Do they require? What weight should they be given? 2. How has dialogue with stakeholders improved your safety case? What lessons may be drawn for the technical community to improve on its capability to respond to questions from the general public and other stakeholders? 3. What is the role of RD and D when arguing safety or confidence in safety? Anecdotal experience was received from Europe, Japan and the United States. Common concerns expressed by the public focus on how scientists can 'know they are right' when making safety predictions for the long term, and whether unexpected events can be addressed. Because some concerns fall beyond the topics typically covered by a safety case

Long-term risks of kidney living donation

DEFF Research Database (Denmark)

Maggiore, Umberto; Budde, Klemens; Heemann, Uwe

2017-01-01

Two recent matched cohort studies from the USA and Norway published in 2014 have raised some concerns related to the long-term safety of kidney living donation. Further studies on the long-term risks of living donation have since been published. In this position paper, Developing Education Science...... and Care for Renal Transplantation in European States (DESCARTES) board members critically review the literature in an effort to summarize the current knowledge concerning long-term risks of kidney living donation to help physicians for decision-making purposes and for providing information...... to the prospective live donors. Long-term risk of end-stage renal disease (ESRD) can be partially foreseen by trying to identify donors at risk of developing ‘de novo’ kidney diseases during life post-donation and by predicting lifetime ESRD risk. However, lifetime risk may be difficult to assess in young donors...

Long-term efficacy and tolerability of quetiapine in patients with schizophrenia who switched from other antipsychotics because of inadequate therapeutic response-a prospective open-label study.

Science.gov (United States)

Hashimoto, Naoki; Toyomaki, Atsuhito; Honda, Minoru; Miyano, Satoru; Nitta, Nobuyuki; Sawayama, Hiroyuki; Sugawara, Yasufumi; Uemura, Keiichi; Tsukamoto, Noriko; Koyama, Tsukasa; Kusumi, Ichiro

2015-01-01

While the frequency and importance of antipsychotic switching in patients with schizophrenia, there is insufficient evidence with regard to switching strategy. Quetiapine is one of the drugs of choice for switch because of its unique receptor profile. However, there were no data on the long-term clinical and neurocognitive effect of quetiapine in patients who had responded inadequately to prior antipsychotics. The purpose of this study is to examine the long-term efficacy and tolerability of quetiapine in patients with schizophrenia who switched from other antipsychotics because of inadequate therapeutic response. We hypothesized that quetiapine would show long-term effectiveness in broad symptom dimensions including negative and neurocognitive symptoms while having good tolerability. Twenty-nine subjects with schizophrenia who did not respond to their current monotherapy of antipsychotic or who could not tolerate the treatment were switched to quetiapine and assessed at baseline and at 3, 6, and 12 months. The outcome measures included the brief assessment of cognition in schizophrenia (BACS), the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions Scale (CGI), the Schizophrenia Quality of Life Scale Japanese version (JSQLS), the Athens Insomnia Scale (AIS), and the Drug Attitude Inventory with 30 items (DAI-30). The Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS), HbA1c, prolactin (PRL), and body weight were also evaluated. Statistically significant improvements were observed in all subscores of the PANSS, the GAF, and the symptoms and side effects subscale of the JSQLS, the DIEPSS, the AIS, and the PRL level, and nearly significant improvements were observed in the DAI-30. Quetiapine monotherapy was associated with significant improvement in the verbal memory test, even after controlling for the practice effect. Although quetiapine was well tolerated, three subjects dropped out because of the worsening of the psychotic symptoms and

Evaluation of the leucine incorporation technique for detection of pollution-induced community tolerance to copper in a long-term agricultural field trial with urban waste fertilizers

DEFF Research Database (Denmark)

Lekfeldt, Jonas Duus Stevens; Magid, Jakob; Holm, Peter Engelund

2014-01-01

increased bacterial community tolerance to Cu was observed for soils amended with organic waste fertilizers and was positively correlated with total soil Cu. However, metal speciation and whole-cell bacterial biosensor analysis demonstrated that the observed PICT responses could be explained entirely by Cu......Copper (Cu) is known to accumulate in agricultural soils receiving urban waste products as fertilizers. We here report the use of the leucine incorporation technique to determine pollution-induced community tolerance (Leu-PICT) to Cu in a long-term agricultural field trial. A significantly...

Safety and tolerability of once-daily tiotropium Respimat(®) as add-on to at least inhaled corticosteroids in adult patients with symptomatic asthma

DEFF Research Database (Denmark)

Dahl, Ronald; Engel, Michael; Dusser, Daniel

2016-01-01

BACKGROUND: Tiotropium, a long-acting anticholinergic bronchodilator, has demonstrated efficacy and safety as add-on therapy to inhaled corticosteroids (ICS), with or without other maintenance therapies, in patients with symptomatic asthma. OBJECTIVE: To evaluate safety and tolerability of tiotro...

Long-term tolerance and outcomes for dose escalation in early salvage post-prostatectomy radiation therapy

International Nuclear Information System (INIS)

Safdieh, Joseph; Schwartz, David; Weiner, Joseph; Weiss, Jeffrey P.; Madeb, Isaac; Rotman, Marvin; Schreiber, David; Rineer, Justin

2014-01-01

To study the long-term outcomes and tolerance in our patients who received dose escalated radiotherapy in the early salvage post-prostatectomy setting. The medical records of 54 consecutive patients who underwent radical prostatectomy subsequently followed by salvage radiation therapy (SRT) to the prostate bed between 2003-2010 were analyzed. Patients included were required to have a pre-radiation prostate specific antigen level (PSA) of 2 ng/mL or less. The median SRT dose was 70.2 Gy. Biochemical failure after salvage radiation was defined as a PSA level >0.2 ng/mL. Biochemical control and survival endpoints were analyzed using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis were used to identify the potential impact of confounding factors on outcomes. The median pre-SRT PSA was 0.45 ng/mL and the median follow-up time was 71 months. The 4- and 7-year actuarial biochemical control rates were 75.7% and 63.2%, respectively. The actuarial 4- and 7-year distant metastasis-free survival was 93.7% and 87.0%, respectively, and the actuarial 7-year prostate cancer specific survival was 94.9%. Grade 3 late genitourinary toxicity developed in 14 patients (25.9%), while grade 4 late genitourinary toxicity developed in 2 patients (3.7%). Grade 3 late gastrointestinal toxicity developed in 1 patient (1.9%), and grade 4 late gastrointestinal toxicity developed in 1 patient (1.9%). In this series with long-term follow-up, early SRT provided outcomes and toxicity profiles similar to those reported from the three major randomized trials studying adjuvant radiation therapy.

Long-Term Effects of Adderall XR in ADHD

Directory of Open Access Journals (Sweden)

J Gordon Millichap

2005-06-01

Full Text Available The long-term tolerability and effectiveness of extended release mixed amphetamine salts (Adderall XR in children with attention deficit hyperactivity disorder (ADHD were evaluated in a 24-month, multicenter, open-label extension of 2 placebo-controlled studies at UCLA, Massachusetts General Hospital, UC-Irvine, Maitland, FL, and Shire Pharmaceutical, Wayne, PA.

Safety case methodology for decommissioning of research reactors. Assessment of the long term impact of a flooding scenario

International Nuclear Information System (INIS)

Vladescu, G.; Banciu, O.

1999-01-01

The paper contains the assessment methodology of a Safety Case fuel decommissioning of research reactors, taking into account the international approach principles. The paper also includes the assessment of a flooding scenario for a decommissioned research reactor (stage 1 of decommissioning). The scenario presents the flooding of reactor basement, radionuclide migration through environment and long term radiological impact for public. (authors)

Long-term safety and efficacy of adalimumab for intestinal Behçet's disease in the open label study following a phase 3 clinical trial

Directory of Open Access Journals (Sweden)

Nagamu Inoue

2017-07-01

Full Text Available Background/Aims: Intestinal Behçet's disease (BD is an immune-mediated inflammatory disorder. We followed up the patients and evaluated safety profile and effectiveness of adalimumab for the treatment of intestinal BD through 100 weeks rolled over from the 52 week clinical trial (NCT01243671.Methods: Patients initiated adalimumab therapy at 160 mg at week 0, followed by 80 mg at week 2, followed by 40 mg every other week until the end of the study. Long-term safety and all adverse events (AEs were examined. The efficacy was assessed on the basis of marked improvement (MI and complete remission (CR using a composite efficacy index, which combined global gastrointestinal symptoms and endoscopic assessments.Results: Twenty patients were enrolled in this study; 15 patients received adalimumab treatment until study completion. The incidence of AEs through week 100 was 544.4 events/100 person-years, which was comparable to the incidence through week 52 (560.4 events/100 person-years. No unexpected trend was observed and adalimumab was well tolerated. At weeks 52 and 100, 60.0% and 40.0% of patients showed MI, respectively, and 20.0% and 15.0% of patients showed CR, respectively.Conclusions: This report demonstrates 2 years safety and effectiveness of adalimumab in intestinal BD patients. Patients with intestinal BD refractory to conventional treatment receiving up to 2 years of adalimumab treatment demonstrated safety outcomes consistent with the known profile of adalimumab, and the treatment led to sustained reduction of clinical and endoscopic disease activity.

Reference biospheres for the long term safety assessment of radioactive waste disposal facilities

International Nuclear Information System (INIS)

Crossland, I.G.; Torres, C.

2002-01-01

Regulatory guidance on the safety assessment of radioactive waste disposals usually requires the consequences of any radionuclide releases to be considered in terms of their potential impact on human health. This requires consideration of the prevailing biosphere and the habits of the potentially exposed humans within it. However, it could take many thousands of years for migrating radionuclides to reach the surface environment. In these circumstances, an assessment model that was based on the present-day biosphere could be inappropriate while future biospheres would be unpredictable. These and other considerations suggest that a standardised, or reference biosphere, approach may be useful. Theme 1 of the IAEA BIOMASS project was established to develop the concept of reference biospheres into a practical system that can be applied to the assessment of the long term safety of geological disposal facilities for radioactive waste. The technical phase of the project lasted for four years until November 2000 and brought together disparate interests from many countries including waste disposal agencies, regulators and technical experts. Building on the experience from earlier BIOMOVS projects, a methodology was constructed for the logical and defensible construction of mathematical biosphere models that can be used in the total system performance assessment of radioactive waste disposal. The methodology was then further developed through the creation of a series of BIOMASS Example Reference Biospheres ('Examples'). These are stylised biosphere models that, in addition to illustrating the methodology, are intended to be useful assessment tools in their own right. (author)

Long-term safety and efficacy of single-tablet combinations of solifenacin and tamsulosin oral controlled absorption system in men with storage and voiding lower urinary tract symptoms: results from the NEPTUNE Study and NEPTUNE II open-label extension.

Science.gov (United States)

Drake, Marcus J; Chapple, Christopher; Sokol, Roman; Oelke, Matthias; Traudtner, Klaudia; Klaver, Monique; Drogendijk, Ted; Van Kerrebroeck, Philip

2015-02-01

Short-term trials have demonstrated the efficacy and safety of combination therapy using antimuscarinics and α-blockers in men with lower urinary tract symptoms (LUTS). The Study of Solifenacin Succinate and Tamsulosin Hydrochloride OCAS (oral controlled absorption system) in Males with Lower Urinary Tract Symptoms (NEPTUNE) II is the first long-term study using solifenacin (Soli) and the oral controlled absorption system formulation of tamsulosin (TOCAS). To evaluate long-term (up to 52 wk) safety and efficacy of flexible dosing of two fixed-dose combinations (FDC) of Soli plus TOCAS in men with moderate to severe storage symptoms and voiding symptoms. Patients with both storage and voiding LUTS, maximum urinary flow rate of 4.0-12.0 ml/s, prostate size storage and voiding subscores, micturition diary variables, and quality of life parameters. In all, 1066 men completed NEPTUNE and received one dose or more of study medication in NEPTUNE II. Treatment-emergent adverse events were reported in 499 (46.8%) patients who participated in NEPTUNE II; most were mild or moderate. Urinary retention occurred in 13 of 1208 (1.1%) patients receiving one or more FDCs in NEPTUNE and/or NEPTUNE II; 8 (0.7%) required catheterisation (acute urinary retention [AUR]). Reductions in total IPSS and TUFS during NEPTUNE were maintained for up to 52 wk of FDC treatment, with mean reductions of 9.0 (standard deviation [SD]: 5.7) and 10.1 (SD: 9.2), respectively, from baseline to end of treatment. Clinically relevant improvements were also observed for secondary efficacy end points. Long-term treatment with FDC Soli plus TOCAS was well tolerated and efficacious in men with storage and voiding LUTS, with a low incidence of AUR. Treatment with solifenacin plus tamsulosin in a fixed-dose combination tablet was well tolerated by men with lower urinary tract symptoms. Improvements in symptoms were achieved after 4 wk of treatment, with further improvements at week 16 maintained for up to 52 wk

Longitudinal study to assess the safety and efficacy of a live-attenuated SHIV vaccine in long term immunized rhesus macaques

International Nuclear Information System (INIS)

Yankee, Thomas M.; Sheffer, Darlene; Liu Zhengian; Dhillon, Sukhbir; Jia Fenglan; Chebloune, Yahia; Stephens, Edward B.; Narayan, Opendra

2009-01-01

Live-attenuated viruses derived from SIV and SHIV have provided the most consistent protection against challenge with pathogenic viruses, but concerns regarding their long-term safety and efficacy have hampered their clinical usefulness. We report a longitudinal study in which we evaluated the long-term safety and efficacy of ΔvpuSHIV PPC , a live virus vaccine derived from SHIV PPC . Macaques were administered two inoculations of ΔvpuSHIV PPC , three years apart, and followed for eight years. None of the five vaccinated macaques developed an AIDS-like disease from the vaccine. At eight years, macaques were challenged with pathogenic SIV and SHIV. None of the four macaques with detectable cellular-mediated immunity prior to challenge had detectable viral RNA in the plasma. This study demonstrates that multiple inoculations of a live vaccine virus can be used safely and can significantly extend the efficacy of the vaccine, as compared to a single inoculation, which is efficacious for approximately three years

The Long-Term Safety of S-Flurbiprofen Plaster for Osteoarthritis Patients: An Open-Label, 52-Week Study.

Science.gov (United States)

Yataba, Ikuko; Otsuka, Noboru; Matsushita, Isao; Matsumoto, Hideo; Hoshino, Yuichi

2016-08-01

The newly developed S-flurbiprofen plaster (SFPP) is a tape-type patch that shows innovative percutaneous absorption. This study was designed to evaluate the safety of a long-term 52-week SFPP application to osteoarthritis (OA) patients. This was a multi-center, open-label, uncontrolled prospective study that included 201 OA patients. SFPP at 40 mg/day was applied to the site of pain in 101 patients and at 80 mg/day (2 patches) in 100 patients at a total of 301 sites for 52 weeks. The affected sites assessed included the knee (192), lumbar spine (66), cervical spine (26), and others (17). Drug safety was evaluated by medical examination, laboratory tests, and examination of vital signs. Efficacy was evaluated by the patient's and clinician's global assessments and clinical symptoms. Most patients (80.1 %) completed the 52-week SFPP application. The majority of drug-related adverse events (AEs) included mild dermatitis at the application sites and occurred in 46.8 % of the sites. No photosensitive dermatitis was observed. Systemic AEs occurred in 9.0 % of the patients; a serious AE (gastric ulcer hemorrhage) occurred in one patient. No clinically significant changes in the laboratory tests and vital signs were observed. The efficacy evaluation showed an improvement from 2 weeks after the SFPP application, which continued during the 52 weeks' treatment. No apparent safety concerns were observed, even during the long-term SFPP application. Therefore, SFPP could be an additional pharmacotherapy in OA treatment.

Lithium safety and tolerability in mood disorders: a critical review

Directory of Open Access Journals (Sweden)

Ivan Aprahamian

2014-04-01

Full Text Available Background : Lithium is a first-line treatment for bipolar disorder in all phases, also indicated as add-on drug for unipolar depression and suicide prevention. This study encompasses a broad critical review on the safety and tolerability of lithium for mood disorders. Methods : A computerized search for English written human studies was made in MEDLINE, using the keywords “lithium” and “mood disorders”, starting from July 1993 through July 2013 (n = 416. This initial search aimed to select clinical trials, prospective data, and controlled design studies of lithium treatment for mood disorders reporting adverse effects (n = 36. The final selection yielded 91 studies. Results : The most common general side effects in patients on lithium treatment were thirst, frequent urination, dry mouth, weight gain, fatigue and cognitive complaints. Lithium users showed a high prevalence of hypothyroidism, hyperparathyroidism, and decrease in urinary concentration ability. Reduction of glomerular filtration rate in patients using lithium was also observed, but in a lesser extent. The evidence of teratogenicity associated with lithium use is not well established. Anti-inflammatory non-steroidal drugs, thiazide diuretics, angiotensin-converting enzyme inhibitors, and alprazolam may increase serum lithium and the consequent risk for intoxication. Discussion : Short-term lithium treatment is associated with mild side effects. Medium and long-term lithium treatment, however, might have effects on target organs which may be prevented by periodical monitoring. Overall, lithium is still a safe option for the treatment of mood disorders.

Long-Term Results of Targeted Intraoperative Radiotherapy (Targit) Boost During Breast-Conserving Surgery

Energy Technology Data Exchange (ETDEWEB)

Vaidya, Jayant S., E-mail: jayant.vaidya@ucl.ac.uk [Research Department of Surgery, Division of Surgery and Interventional Science, University College London, London (United Kingdom); Baum, Michael [Research Department of Surgery, Division of Surgery and Interventional Science, University College London, London (United Kingdom); Tobias, Jeffrey S. [Department of Radiation Oncology, University College London Hospitals, London (United Kingdom); Wenz, Frederik [Radiation Oncology and Gynaecology, University Medical Centre of Mannheim (Germany); Massarut, Samuele [Surgery and Radiation Oncology, Centro di Riferimento Oncologico (CRO), Aviano (Italy); Keshtgar, Mohammed [Research Department of Surgery, Division of Surgery and Interventional Science, University College London, London (United Kingdom); Hilaris, Basil [Radiation Oncology, Our Lady of Mercy, New York Medical College, New York (United States); Saunders, Christobel [Institute of Health and Rehabilitation Research, University of Notre Dame, Fremantle, Western Australia (Australia); Williams, Norman R.; Brew-Graves, Chris [Research Department of Surgery, Division of Surgery and Interventional Science, University College London, London (United Kingdom); Corica, Tammy [Institute of Health and Rehabilitation Research, University of Notre Dame, Fremantle, Western Australia (Australia); Roncadin, Mario [Surgery and Radiation Oncology, Centro di Riferimento Oncologico (CRO), Aviano (Italy); Kraus-Tiefenbacher, Uta; Suetterlin, Marc [Radiation Oncology and Gynaecology, University Medical Centre of Mannheim (Germany); Bulsara, Max [Institute of Health and Rehabilitation Research, University of Notre Dame, Fremantle, Western Australia (Australia); Joseph, David [Radiation Oncology, Sir Charles Gairdner Hospital and School of Surgery, University of Western Australia, Perth (Australia)

2011-11-15

Purpose: We have previously shown that delivering targeted radiotherapy to the tumour bed intraoperatively is feasible and desirable. In this study, we report on the feasibility, safety, and long-term efficacy of TARGeted Intraoperative radioTherapy (Targit), using the Intrabeam system. Methods and Materials: A total of 300 cancers in 299 unselected patients underwent breast-conserving surgery and Targit as a boost to the tumor bed. After lumpectomy, a single dose of 20 Gy was delivered intraoperatively. Postoperative external beam whole-breast radiotherapy excluded the usual boost. We also performed a novel individualized case control (ICC) analysis that computed the expected recurrences for the cohort by estimating the risk of recurrence for each patient using their characteristics and follow-up period. Results: The treatment was well tolerated. The median follow up was 60.5 months (range, 10-122 months). Eight patients have had ipsilateral recurrence: 5-year Kaplan Meier estimate for ipsilateral recurrence is 1.73% (SE 0.77), which compares well with that seen in the boosted patients in the European Organization for Research and Treatment of Cancer study (4.3%) and the UK STAndardisation of breast RadioTherapy study (2.8%). In a novel ICC analysis of 242 of the patients, we estimated that there should be 11.4 recurrences; in this group, only 6 recurrences were observed. Conclusions: Lumpectomy and Targit boost combined with external beam radiotherapy results in a low local recurrence rate in a standard risk patient population. Accurate localization and the immediacy of the treatment that has a favorable effect on tumour microenvironment may contribute to this effect. These long-term data establish the long-term safety and efficacy of the Targit technique and generate the hypothesis that Targit boost might be superior to an external beam boost in its efficacy and justifies a randomized trial.

Developmental Hypoxia Has Negligible Effects on Long-Term Hypoxia Tolerance and Aerobic Metabolism of Atlantic Salmon (Salmo salar).

Science.gov (United States)

Wood, Andrew T; Clark, Timothy D; Andrewartha, Sarah J; Elliott, Nicholas G; Frappell, Peter B

Exposure to developmental hypoxia can have long-term impacts on the physiological performance of fish because of irreversible plasticity. Wild and captive-reared Atlantic salmon (Salmo salar) can be exposed to hypoxic conditions during development and continue to experience fluctuating oxygen levels as juveniles and adults. Here, we examine whether developmental hypoxia impacts subsequent hypoxia tolerance and aerobic performance of Atlantic salmon. Individuals at 8°C were exposed to 50% (hypoxia) or 100% (normoxia) dissolved oxygen (DO) saturation (as percent of air saturation) from fertilization for ∼100 d (800 degree days) and then raised in normoxic conditions for a further 15 mo. At 18 mo after fertilization, aerobic scope was calculated in normoxia (100% DO) and acute (18 h) hypoxia (50% DO) from the difference between the minimum and maximum oxygen consumption rates ([Formula: see text] and [Formula: see text], respectively) at 10°C. Hypoxia tolerance was determined as the DO at which loss of equilibrium (LOE) occurred in a constantly decreasing DO environment. There was no difference in [Formula: see text], [Formula: see text], or aerobic scope between fish raised in hypoxia or normoxia. There was some evidence that hypoxia tolerance was lower (higher DO at LOE) in hypoxia-raised fish compared with those raised in normoxia, but the magnitude of the effect was small (12.52% DO vs. 11.73% DO at LOE). Acute hypoxia significantly reduced aerobic scope by reducing [Formula: see text], while [Formula: see text] remained unchanged. Interestingly, acute hypoxia uncovered individual-level relationships between DO at LOE and [Formula: see text], [Formula: see text], and aerobic scope. We discuss our findings in the context of developmental trajectories and the role of aerobic performance in hypoxia tolerance.

Dungeness 'A' Nuclear Power Station. The findings of NII's assessment of Nuclear Electric's long term safety review

International Nuclear Information System (INIS)

1994-01-01

The assessment is reported of Nuclear Electrics' Long Term Safety Reviews (LTSR) of the Dungeness A magnox reactors. The assessment was undertaken by the Health and Safety Executive's Nuclear Installations Inspectorate (NII) which is responsible for regulating the safety of nuclear installations in the United Kingdom. This was one of a programme of LTSRs for all the UK magnox reactors. The LTSR for each plant was proceeded by a Generic Issues programme. The results of both the LTSR and the Generic Issues programme have been used by NII in forming the conclusions of this assessment. Overall the safety case for Dungeness A is satisfactory for continued operation. A programme of additional modifications and inspections has been put in place which further enhances the safety justification. Reactor operations will continue to be monitored and regulated in accordance with the inspections required under the licensing arrangements. Provided these requirements and the agreed further analysis, improvements and inspections give satisfactory results it is expected that the station will be able to operate safely till each reactor is at least 30 years old. Beyond this point a further Periodic Safety Review will be required. (UK)

Nuclear Energy, Long Term Requirements

International Nuclear Information System (INIS)

Knapp, V.

2006-01-01

There are serious warnings about depletion of oil and gas and even more serious warnings about dangers of climate change caused by emission of carbon dioxide. Should developed countries be called to replace CO2 emitting energy sources as soon as possible, and the time available may not be longer then few decades, can nuclear energy answer the call and what are the requirements? Assuming optimistic contribution of renewable energy sources, can nuclear energy expand to several times present level in order to replace large part of fossil fuels use? Paper considers intermediate and long-term requirements. Future of nuclear power depends on satisfactory answers on several questions. First group of questions are those important for near and intermediate future. They deal with economics and safety of nuclear power stations in the first place. On the same time scale a generally accepted concept for radioactive waste disposal is also required. All these issues are in the focus of present research and development. Safer and more economical reactors are targets of international efforts in Generation IV and INPRO projects, but aiming further ahead these innovative projects are also addressing issues such as waste reduction and proliferation resistance. However, even assuming successful technical development of these projects, and there is no reason to doubt it, long term and large-scale nuclear power use is thereby not yet secured. If nuclear power is to play an essential role in the long-term future energy production and in reduction of CO2 emission, than several additional questions must be replied. These questions will deal with long-term nuclear fuel sufficiency, with necessary contribution of nuclear power in sectors of transport and industrial processes and with nuclear proliferation safety. This last issue is more political then technical, thus sometimes neglected by nuclear engineers, yet it will have essential role for the long-term prospects of nuclear power. The

Long-term (5 years), high daily dosage of dietary agmatine--evidence of safety: a case report.

Science.gov (United States)

Gilad, Gad M; Gilad, Varda H

2014-11-01

There is presently a great interest in the therapeutic potential of agmatine, decarboxylated arginine, for various diseases. Recent clinical studies have already shown that oral agmatine sulfate given for up to 3 weeks provides a safe and, as compared with current therapeutics, more effective treatment for neuropathic pain. These studies have ushered in the use of dietary agmatine as a nutraceutical. However, in view of information paucity, assessment of long-term safety of oral agmatine treatment is now clearly required. The authors of this report undertook to assess their own health status during ongoing consumption of a high daily dosage of oral agmatine over a period of 4-5 years. A daily dose of 2.67 g agmatine sulfate was encapsulated in gelatin capsules; the regimen consists of six capsules daily, each containing 445 mg, three in the morning and three in the evening after meals. Clinical follow-up consists of periodic physical examinations and laboratory blood and urine analyses. All measurements thus far remain within normal values and good general health status is sustained throughout the study period, up to 5 years. This case study shows for the first time that the recommended high dosage of agmatine may be consumed for at least 5 years without evidence of any adverse effects. These initial findings are highly important as they provide significant evidence for the extended long-term safety of a high daily dosage of dietary agmatine--a cardinal advantage for its utility as a nutraceutical.

Data and methods for studying commercial motor vehicle driver fatigue, highway safety and long-term driver health.

Science.gov (United States)

Stern, Hal S; Blower, Daniel; Cohen, Michael L; Czeisler, Charles A; Dinges, David F; Greenhouse, Joel B; Guo, Feng; Hanowski, Richard J; Hartenbaum, Natalie P; Krueger, Gerald P; Mallis, Melissa M; Pain, Richard F; Rizzo, Matthew; Sinha, Esha; Small, Dylan S; Stuart, Elizabeth A; Wegman, David H

2018-03-09

This article summarizes the recommendations on data and methodology issues for studying commercial motor vehicle driver fatigue of a National Academies of Sciences, Engineering, and Medicine study. A framework is provided that identifies the various factors affecting driver fatigue and relating driver fatigue to crash risk and long-term driver health. The relevant factors include characteristics of the driver, vehicle, carrier and environment. Limitations of existing data are considered and potential sources of additional data described. Statistical methods that can be used to improve understanding of the relevant relationships from observational data are also described. The recommendations for enhanced data collection and the use of modern statistical methods for causal inference have the potential to enhance our understanding of the relationship of fatigue to highway safety and to long-term driver health. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Challenges in long-term operation of nuclear power plants - Implications for regulatory bodies

International Nuclear Information System (INIS)

Soda, Kunihisa; Van Wonterghem, Frederik; Khouaja, Hatem; Vilpas, Martti; Osouf, Nicolas; Harikumar, S.; Ishigaki, Hiroki; Osaki, Toru; Yamada, Tomoho; Carlsson, Lennart; Shepherd, David; Galloway, Melanie; Liszka, Ervin; Svab, Miroslav; Pereira, Ken; Huerta, Alejandro

2012-01-01

Nuclear power reactors have become a major source of electricity supply in many countries in the past half a century. Based on this experience, many operators have sought and have received authorisation for long-term operation, whereby plant operation continues beyond the period considered in the design of the plant. Acceptance of a nuclear power plant for extended service should be based on assurance of the fitness of the plant and the operator for safe and reliable operation over the entire period considered for long-term operation. This assurance may be obtained by establishment of appropriate regulatory requirements, specification of goals and safety levels and regulatory assessment and oversight of the operator's programme for long-term operation. The operators and regulators should ensure that operating experience continues to be evaluated during long-term operation to ensure that any relevant lessons are effectively applied. Other considerations for assurance of safe operation are effective management of ageing, possible need for safety improvements, application of lessons learnt from operating experience, evaluation of environmental impacts, adequate staff resources and performance, review of security at the plant, action in response to emerging issues, and openness and transparency in the transition to long-term operation. Even though most of these considerations are addressed under the regulatory framework that applies to the initial operating period, additional regulatory activities in these areas may be necessary for long-term operation. Although there can be significant differences in regulatory approaches used by different countries for evaluating acceptability of long-term operation, there is general agreement on the purposes and goals of the regulatory reviews. An authorisation of long-term operation could involve a licence renewal or a periodic safety review or an approach that melds elements of both. This report presents guidance that is intended

Safety and tolerability of Bifidobacterium longum subspecies infantis EVC001 supplementation in healthy term breastfed infants: a phase I clinical trial.

Science.gov (United States)

Smilowitz, Jennifer T; Moya, Jackelyn; Breck, Melissa A; Cook, Chelsea; Fineberg, Annette; Angkustsiri, Kathleen; Underwood, Mark A

2017-05-30

Historically, bifidobacteria were the dominant intestinal bacteria in breastfed infants. Still abundant in infants in developing nations, levels of intestinal bifidobacteria are low among infants in developed nations. Recent studies have described an intimate relationship between human milk and a specific subspecies of Bifidobacterium, B. longum subsp. infantis (B. infantis), yet supplementation of breastfed, healthy, term infants with this organism, has not been reported. The IMPRINT Study, a Phase I clinical trial, was initiated to determine the safety and tolerability of supplementing breastfed infants with B. infantis (EVC001). Eighty mother-infant dyads were enrolled in either lactation support plus B. infantis supplementation (BiLS) or lactation support alone (LS). Starting with Day 7 postnatal, BiLS infants were fed 1.8-2.8 × 10 10  CFU B. infantis EVC001 daily in breast milk for 21 days. Mothers collected fecal samples, filled out health questionnaires, and kept daily logs about their infants' feeding and gastrointestinal symptoms from birth until Day 61 postnatal. Safety and tolerability were determined from maternal reports. There were no differences in the mean gestational age at birth, weight 1 and 2 months postnatal, and breast milk intake between groups. The mean Log 10 change in fecal Bifidobacterium from Day 6 to Day 28 was higher (p = 0.0002) for BiLS (6.6 ± 2.8 SD) than for LS infants (3.5 ± 3.5 SD). Daily stool number was higher (p jaundice, number of illnesses, sick doctor visits, or diagnoses of eczema were different for the groups at any point. The B. infantis EVC001 supplement was safely consumed and well-tolerated. Stools were fewer and better formed in infants in the BiLS group compared with LS group. Adverse events were those expected in healthy infants and not different between groups. ClinicalTrials.gov NCT02457338 . Registered May 27, 2015.

Development of the international status of science and technology concerning methods and tools for operational and long-term safety cases

International Nuclear Information System (INIS)

Seher, Holger; Beuth, Thomas; Bracke, Guido; Kock, Ingo; Mayer, Kim-Marisa; Moog, Helge C.; Uhlmann, Stephan; Weyand, Torben

2016-09-01

The project ''development of the international status of science and technology concerning methods and tools for operational and long-term safety cases'' covers the following key aspects: global aspects of the methodology for scenario assumption for the operational phase following closure, potential analysis of the derives safety cases for the project Gorleben, determination of the solid phase composition of high-level radioactive wastes using geochemical modeling calculations, search for an adequate approach for the calculation of density and viscosity of saline solutions for the future use in GRS computer codes, international approaches for an integral analysis for the host rocks clay and granite in relation to the safety requirements of BMUB.

Long-term health status of Danish women with silicone breast implants

DEFF Research Database (Denmark)

Breiting, Vibeke B; Hölmich, Lisbet R; Brandt, Bodil

2004-01-01

Long-term safety data are important in the evaluation of possible adverse health outcomes related to silicone breast implants. The authors evaluated long-term symptoms and conditions and medication use among 190 Danish women with cosmetic silicone breast implants compared with 186 women who had u...

Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab.

Science.gov (United States)

Topalian, Suzanne L; Sznol, Mario; McDermott, David F; Kluger, Harriet M; Carvajal, Richard D; Sharfman, William H; Brahmer, Julie R; Lawrence, Donald P; Atkins, Michael B; Powderly, John D; Leming, Philip D; Lipson, Evan J; Puzanov, Igor; Smith, David C; Taube, Janis M; Wigginton, Jon M; Kollia, Georgia D; Gupta, Ashok; Pardoll, Drew M; Sosman, Jeffrey A; Hodi, F Stephen

2014-04-01

Programmed cell death 1 (PD-1) is an inhibitory receptor expressed by activated T cells that downmodulates effector functions and limits the generation of immune memory. PD-1 blockade can mediate tumor regression in a substantial proportion of patients with melanoma, but it is not known whether this is associated with extended survival or maintenance of response after treatment is discontinued. Patients with advanced melanoma (N = 107) enrolled between 2008 and 2012 received intravenous nivolumab in an outpatient setting every 2 weeks for up to 96 weeks and were observed for overall survival, long-term safety, and response duration after treatment discontinuation. Median overall survival in nivolumab-treated patients (62% with two to five prior systemic therapies) was 16.8 months, and 1- and 2-year survival rates were 62% and 43%, respectively. Among 33 patients with objective tumor regressions (31%), the Kaplan-Meier estimated median response duration was 2 years. Seventeen patients discontinued therapy for reasons other than disease progression, and 12 (71%) of 17 maintained responses off-therapy for at least 16 weeks (range, 16 to 56+ weeks). Objective response and toxicity rates were similar to those reported previously; in an extended analysis of all 306 patients treated on this trial (including those with other cancer types), exposure-adjusted toxicity rates were not cumulative. Overall survival following nivolumab treatment in patients with advanced treatment-refractory melanoma compares favorably with that in literature studies of similar patient populations. Responses were durable and persisted after drug discontinuation. Long-term safety was acceptable. Ongoing randomized clinical trials will further assess the impact of nivolumab therapy on overall survival in patients with metastatic melanoma.

SALTO Peer Review Guidelines. Guidelines for Peer Review of Safety Aspects of Long Term Operation of Nuclear Power Plants

International Nuclear Information System (INIS)

2014-01-01

International peer review is a useful tool for Member States to exchange experiences, learn from each other and apply good practices in the long term operation (LTO) of nuclear power plants (NPPs). The peer review is also an important mechanism through which the IAEA supports Member States in enhancing the safety of NPPs. The IAEA has conducted various types of safety review that indirectly address aspects of LTO, including safety reviews for design, engineering, operation and external hazards. Operational Safety Review Team (OSART) services include review of ageing management programmes. In addition, several Member States have requested Ageing Management Assessment Team (AMAT) missions. Through these experiences, it was recognized that a comprehensive peer review on LTO would be very useful to Member States. The Safety Aspects of Long Term Operation (SALTO) peer review addresses strategy and key elements for the safe LTO of NPPs, which includes AMAT objectives and complements OSART reviews. The SALTO peer review is designed to assist operating organizations in adopting a proper approach to LTP including implementing appropriate activities to ensure that plant safety will be maintained during the LTO period. The SALTO peer review can be tailored to focus on ageing management programmes (AMPs) or on other activities related to LTO to support the Member State in enhancing the safety of its NPPs. The SALTO peer review can also support regulators in establishing or improving regulatory and licensing strategies for the LTO of NPPs. The guidelines in this publication are primarily intended for members of a SALTO review team and provide a basic structure and common reference for peer reviews of LTO. Additionally, the guidelines also provide useful information to the operating organizations of NPPs (or technical support organizations) for carrying out their own self-assessments or comprehensive programme reviews. The guidelines are intended to be generic, as there are

GEOSAF Part II. Demonstration of the operational and long-term safety of geological disposal facilities for radioactive waste. IAEA international intercomparison and harmonization project

Energy Technology Data Exchange (ETDEWEB)

Kumano, Yumiko; Bruno, Gerard [International Atomic Energy Agency, Vienna (Austria). Vienna International Centre; Tichauer, Michael [IRSN, Institut de Radioprotection et de Surete Nucleaire, Fontenay-aux-Roses (France); Hedberg, Bengt [Swedish Radiation Safety Authority, Stockholm (Sweden)

2015-07-01

International intercomparison and harmonization projects are one of the mechanisms developed by the IAEA for examining the application and use of safety standards, with a view to ensuring their effectiveness and working towards harmonization of approaches to the safety of radioactive waste management. The IAEA has organized a number of international projects on the safety of radioactive waste management; in particular on the issues related to safety demonstration for radioactive waste management facilities. In 2008, GEOSAF, Demonstration of The Operational and Long-Term Safety of Geological Disposal Facilities for Radioactive Waste, project was initiated. This project was completed in 2011 by delivering a project report focusing on the safety case for geological disposal facilities, a concept that has gained in recent years considerable prominence in the waste management area and is addressed in several international safety standards. During the course of the project, it was recognized that little work was undertaken internationally to develop a common view on the safety approach related to the operational phase of a geological disposal although long-term safety of disposal facility has been discussed for several decades. Upon completion of the first part of the GEOSAF project, it was decided to commence a follow-up project aiming at harmonizing approaches on the safety of geological disposal facilities for radioactive waste through the development of an integrated safety case covering both operational and long-term safety. The new project was named as GEOSAF Part II, which was initiated in 2012 initially as 2-year project, involving regulators and operators. GEOSAF Part II provides a forum to exchange ideas and experience on the development and review of an integrated operational and post-closure safety case for geological disposal facilities. It also aims at providing a platform for knowledge transfer. The project is of particular interest to regulatory

Evaluation of long-term safety and efficacy of omalizumab in elderly patients with uncontrolled allergic asthma.

Science.gov (United States)

Tat, Tugba Songul; Cilli, Aykut

2016-11-01

Severe asthma management in elderly patients may be difficult because of increased comorbid conditions, polypharmacy, physiologic changes that occur with aging, incorrect use of inhaler devices, and poor adherence. To evaluate the long-term safety and efficacy of the anti-IgE antibody omalizumab in elderly (aged ≥65 years) patients with uncontrolled allergic asthma. The efficiency and adverse effects of omalizumab treatment were evaluated based on data extracted from medical records. Patients were evaluated monthly for efficacy and adverse reactions. Treatment efficacy was evaluated by level of asthma symptom control, using the Global Initiative for Asthma guideline. Nineteen consecutive elderly patients with asthma (female to male ratio, 14:5) formed our cohort. The mean (SD) age, disease duration, and total IgE level were 69.3 (5.8) years, 19.4 (8.6) years, and 299.1 (197.2) IU/mL, respectively. The mean (SD) duration of omalizumab treatment was 35.6 (17.8) months (range, 9-66 months). All the patients had at least 1 perennial inhalant allergen sensitivity and had uncontrolled allergic asthma. Elderly patients experienced no significantly important adverse reaction considered to be related to omalizumab treatment. Only 1 patient had a local adverse reaction and 1 had myalgia that was considered to be drug related. After omalizumab treatment, asthma symptoms were well controlled in 9 patients (47.4%) and partly controlled in 8 patients (42.1%). Two of the patients (10.5%) still had uncontrolled asthma. Our study found that omalizumab is a well-tolerated and effective therapy for elderly patients with uncontrolled asthma. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Long term safety assessment of geological waste disposal systems: issues on release scenarios

International Nuclear Information System (INIS)

Khan, S.A.; Qureshi, A.A.

1995-01-01

Geological insolation of high level nuclear waste is an attractive waste disposal concept. However, long term safety demonstration of this concept is a major challenge to the operators, regulators and the scientific community. Identification of the factors responsible for the release of radionuclides from geosphere to biosphere,is first step in this regard. Current understanding of the release scenarios indicates that faulting, ground after percolation, seismicity, volcanism and human intrusion are the dominating release factors for most of the candidate rock formations. The major source of uncertainties is the probability values of various release events due to random nature of catastrophic geological events and past poor historical records of the frequencies of such events. There is consensus among the experts that the waste release via human intrusion is the most unpredictable scenario at present state of the knowledge. (author)

Cross matching observations on toxicological and clinical data for the assessment of tolerability and safety of Ginkgo biloba leaf extract

International Nuclear Information System (INIS)

Heinonen, Tuula; Gaus, Wilhelm

2015-01-01

Highlights: • Cross-matching of toxicological, clinical and other data improves risk analysis. • Induction of drug metabolism is linked to increased cell proliferation. • Rodents and man have differences in metabolism of Ginkgo biloba. • Controlled clinical data did not reveal any serious or specific adverse drug reaction. • Cross-matching of various sources gives strong evidence that G. biloba is safe. - Abstract: Ginkgo biloba is one of the most widely used herbal remedies in Europe and the US. It may be purchased in different types of formulations, but most of the clinical studies have been performed with the controlled G. biloba extract EGb761 ® . Indications include Alzheimers disease, cardiovascular disease, dementia, memory loss, and cerebral ischemia. The pharmacological modes of action cover antioxidant effects, radical scavenging, inhibition of platelet activating factor, alterations in membrane fluidity (signal transduction), and inhibition of glucocorticoid synthesis. Due to the widespread and long-term use of G. biloba – about a million doses of EGb761 ® are sold per day – tolerability and safety are a crucial issue. Based on broad and long-term clinical use of G. biloba extracts, it is regarded as well tolerated in man. Cross matching, a tool we introduced, combines different fields of knowledge and types of data to a consolidated result. In this article, we combine toxicological and clinical data and utilize other sources of information to assess tolerability and safety of G. biloba. It is well known that because of biological differences between animals and man or even between animal species, animal experiments do not necessarily mimic the effects in humans. Therefore, for adequate risk assessment, the relevance of non-clinical toxicological findings should be correlated with human data. The cross matching of toxicological data and results from clinical studies is possible because many toxicological and clinical studies are available

Criticality safety evaluation for long term storage of FFTF fuel in interim storage casks

International Nuclear Information System (INIS)

Richard, R.F.

1995-01-01

It has been postulated that a degradation phenomenon, referred to as ''hot cell rot'', may affect irradiated FFTF mixed plutonium-uranium oxide (MOX) fuel during dry interim storage. ''Hot cell rot'' refers to a variety of phenomena that degrade fuel pin cladding during exposure to air and inert gas environments. It is thought to be a form of caustic stress corrosion cracking or environmentally assisted cracking. Here, a criticality safety analysis was performed to address the effect of the ''hot cell rot'' phenomenon on the long term storage of irradiated FFTF fuel in core component containers. The results show that seven FFTF fuel assemblies or six Ident-69 pin containers stored in core component containers within interim storage casks will remain safely subcritical

Long-term safety and efficacy of a novel once-weekly oral trelagliptin as monotherapy or in combination with an existing oral antidiabetic drug in patients with type 2 diabetes mellitus: A 52-week open-label, phase 3 study.

Science.gov (United States)

Inagaki, Nobuya; Sano, Hiroki; Seki, Yoshifumi; Kuroda, Shingo; Kaku, Kohei

2016-09-01

Trelagliptin is a novel once-weekly oral dipeptidyl peptidase-4 inhibitor for type 2 diabetes mellitus that was first approved in Japan. We evaluated long-term safety and efficacy of trelagliptin in Japanese patients with type 2 diabetes mellitus. This was a phase 3, multicenter, open-label study to evaluate long-term safety and efficacy of trelagliptin. Patients with type 2 diabetes mellitus inadequately controlled despite diet/exercise or treatment with one of the existing oral antidiabetic drugs along with diet/exercise received trelagliptin 100 mg orally once weekly for 52 weeks as monotherapy or combination therapies. The primary end-points were the safety variables, and the secondary end-points were glycosylated hemoglobin and fasting plasma glucose. A total of 680 patients received the following antidiabetic therapies: trelagliptin monotherapy (n = 248), combination with a sulfonylurea (n = 158), a glinide (n = 67), an α-glucosidase inhibitor (n = 65), a biguanide (n = 70), or a thiazolidinedione (n = 72). During the study, 79.8% of the patients experienced at least one adverse event for monotherapy, 87.3% for combination with a sulfonylurea, 77.6% for a glinide, 81.5% for an α-glucosidase inhibitor, 64.3% for a biguanide, and 84.7% for a thiazolidinedione, respectively. Most of the adverse events were mild or moderate. The change in glycosylated hemoglobin from baseline at the end of the treatment period was -0.74 to -0.25% for each therapy. Once-weekly oral trelagliptin provides well-tolerated long-term safety and efficacy in both monotherapy and combination therapies in Japanese patients with type 2 diabetes mellitus. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Efficacy, tolerability, and safety of hypnosis in adult irritable bowel syndrome: systematic review and meta-analysis.

Science.gov (United States)

Schaefert, Rainer; Klose, Petra; Moser, Gabriele; Häuser, Winfried

2014-06-01

To assess the efficacy, tolerability, and safety of hypnosis in adult irritable bowel syndrome by a meta-analysis of randomized controlled trials. Studies were identified by a literature search of the databases Allied and Complementary Medicine Database, Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, PubMed, PsycINFO, and Scopus (from inception to June 30, 2013). Primary outcomes were adequate symptom relief, global gastrointestinal score, and safety. Summary relative risks (RRs) with number needed to treat (NNT) and standardized mean differences (SMDs) with 95% confidence intervals (95% CIs) were calculated using random-effects models. Eight randomized controlled trials with a total of 464 patients and a median of 8.5 (7-12) hypnosis sessions over a median of 12 (5-12) weeks were included into the analysis. At the end of therapy, hypnosis was superior to control conditions in producing adequate symptom relief (RR, 1.69 [95% CI = 1.14-2.51]; NNT, 5 [3-10]) and in reducing global gastrointestinal score (SMD, 0.32 [95% CI = -0.56 to -0.08]). At long-term follow-up, hypnosis was superior to controls in adequate symptom relief (RR, 2.17 [95% CI = 1.22-3.87]; NNT, 3 [2-10]), but not in reducing global gastrointestinal score (SMD, -0.57 [-1.40 to 0.26]). One (0.4%) of 238 patients in the hypnosis group dropped out due to an adverse event (panic attack). This meta-analysis demonstrated that hypnosis was safe and provided long-term adequate symptom relief in 54% of patients with irritable bowel syndrome refractory to conventional therapy.

Long-term follow-up of kidney transplant patients with posttransplant lymphoproliferative disorder

DEFF Research Database (Denmark)

Birkeland, S A; Hamilton-Dutoit, Stephen Jacques; Bendtzen, K

2003-01-01

Posttransplant lymphoproliferative disorder (PTLD) can be resolved in many transplant patients by the reduction or cessation of immunosuppression, after which many grafts continue to function as the result of a form of operational tolerance. When graft function deteriorates, retransplantation may...... be an option. Cytokines such as interleukin (IL)-10 and IL-18 may play a role in PTLD tolerance induction and tumor regression. We report long-term follow-up on the duration of graft tolerance and the course of retransplantation in a series of patients who underwent kidney transplantation and demonstrated PTLD...

[Requirements for long-term follow-up on efficacy and safety of advanced therapy medicinal products. Risk management and traceability].

Science.gov (United States)

Klug, B; Reinhardt, J; Schröder, C

2010-01-01

Advanced therapy medicinal products (ATMPs) are an innovative treatment option. To promote timely access of the innovative medicinal product and to safeguard public health, new elements have been introduced into legislation. A key element of the ATMP regulation is the requirement for long-term follow-up on safety and efficacy of patients enrolled in clinical trials with ATMPs, which is beyond the routine requirements on pharmacovigilance. For gene therapy medicinal products, a guideline on long-term follow-up, which lays down the technical requirements, is available. A further key element of the ATMP regulation is the traceability of the starting materials used to manufacture the ATMP. A common European coding system is imperative to ensure the traceability of starting materials, especially across the borders of European Member States.

Long-term post-marketing surveillance of mizoribine for the treatment of lupus nephritis: Safety and efficacy during a 3-year follow-up

Directory of Open Access Journals (Sweden)

Nobuyuki Yagi

2014-05-01

Full Text Available Objective: To determine the safety and efficacy of long-term use of mizoribine by undertaking a 3-year post-marketing surveillance study. Methods: Subjects were all lupus nephritis patients newly treated with mizoribine between 1 October 2003 and 30 September 2005 at contracted study sites. Results: Mizoribine was administered to 881 lupus nephritis patients in the safety analysis set consisting of 946 patients recruited from 281 contracted study sites after satisfying the eligibility criteria. There were 301 events of adverse drug reactions that were observed in 196 (20.7% of the 946 subjects. There were 34 events of serious adverse drug reactions in 31 patients (3.2%. No deterioration in hematological and biochemical test values was observed, but immunological testing showed significant improvements in C3, CH50, and anti-DNA antibody titers. The negative rate of proteinuria also increased over time. The median steroid dosage was 15 mg/day at the commencement of treatment, but was reduced to 10 mg/day at 12 months and 8 mg/day at 36 months. Conclusion: The findings of the 3-year long-term drug use surveillance study indicated that mizoribine can be used over the long term with relatively few adverse drug reactions, suggesting its suitability for use in maintenance drug therapy.

Safety and tolerability of denosumab for the treatment of postmenopausal osteoporosis

Directory of Open Access Journals (Sweden)

Lewiecki EM

2011-12-01

Full Text Available E Michael LewieckiNew Mexico Clinical Research & Osteoporosis Center, Albuquerque, New Mexico, USAAbstract: Denosumab is a fully human monoclonal antibody to receptor activator of nuclear factor kappa-B ligand (RANKL, a cytokine member of the tumor necrosis factor family that is the principal regulator of osteoclastic bone resorption. Postmenopausal osteoporosis (PMO is a systemic skeletal disease associated with high levels of RANKL, resulting in a high rate of bone remodeling and an imbalance of bone resorption over bone formation. By inhibiting RANKL in women with PMO, denosumab reduces the rate of bone remodeling, thereby increasing bone mineral density, improving bone strength, and reducing the risk of fractures. In clinical trials of women with osteoporosis and low bone mineral density, denosumab has been well tolerated, with overall rates of adverse events and serious adverse events in women treated with denosumab similar to those receiving placebo. In the largest clinical trial of denosumab for the treatment of women with PMO, there was a significantly greater incidence of cellulitis reported as a serious adverse event, with no difference in the overall incidence of cellulitis, and a significantly lower incidence of the serious adverse event of concussions with denosumab compared with placebo. The evidence supports a favorable balance of benefits versus risks of denosumab for the treatment of PMO. Assessments of the long-term safety of denosumab are ongoing. Denosumab 60 mg subcutaneously every 6 months is an approved treatment for women with PMO who are at high risk for fracture.Keywords: denosumab, osteoporosis, safety, risk, benefit, FDA

Long-term safety and efficacy of deferasirox (Exjade) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease.

Science.gov (United States)

Vichinsky, Elliott; Bernaudin, Françoise; Forni, Gian Luca; Gardner, Renee; Hassell, Kathryn; Heeney, Matthew M; Inusa, Baba; Kutlar, Abdullah; Lane, Peter; Mathias, Liesl; Porter, John; Tebbi, Cameron; Wilson, Felicia; Griffel, Louis; Deng, Wei; Giannone, Vanessa; Coates, Thomas

2011-08-01

To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, deferoxamine (DFO)-controlled study entered a 4-year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4 ± 6·3 mg/kg per d. Of 185 patients who received at least one deferasirox dose, 33·5% completed the 5-year study. The most common reasons for discontinuation were withdrawal of consent (23·8%), lost to follow-up (9·2%) and adverse events (AEs) (7·6%). Investigator-assessed drug-related AEs were predominantly gastrointestinal [including nausea (14·6%), diarrhoea (10·8%)], mild-to-moderate and transient in nature. Creatinine clearance remained within the normal range throughout the study. Despite conservative initial dosing, serum ferritin levels in patients with ≥ 4 years deferasirox exposure significantly decreased by -591 μg/l (95% confidence intervals, -1411, -280 μg/l; P = 0·027; n = 67). Long-term deferasirox treatment for up to 5 years had a clinically acceptable safety profile, including maintenance of normal renal function, in patients with SCD. Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4 years. © 2011 Blackwell Publishing Ltd.

Key Performance Criteria Affecting the Most the Safety of a Nuclear Waste Long Term Storage : A Case Study Commissioned by CEA

Energy Technology Data Exchange (ETDEWEB)

Marvy, A.; Lioure, A; Heriard-Dubreuil, G.; Gadbois, S.; Schneider, T.; Schieber, C.

2003-02-24

As part of the work scope set in the French law on high level long lived waste R&D passed in 1991, CEA is conducting a research program to establish the scientific basis and assess the feasibility of long term storage as an option for the safe management of nuclear waste for periods as long as centuries. This goal is a significant departure from the current industrial practice where storage facilities are usually built to last only a few decades. From a technical viewpoint such an extension in time seems feasible provided care and maintenance is exercised. Considering such long periods of time, the risk for Society of loosing oversight and control of such a facility is real, which triggers the question of whether and how long term storage safety can be actually achieved. Therefore CEA commissioned a study (1) in which MUTADIS Consultants (2) and CEPN (3) were both involved. The case study looks into several past and actual human enterprises conducted over significant periods o f time, one of them dating back to the end of the 18th century, and all identified out of the nuclear field. Then-prevailing societal behavior and organizational structures are screened out to show how they were or are still able to cope with similar oversight and control goals. As a result, the study group formulated a set of performance criteria relating to issues like responsibility, securing funds, legal and legislative implications, economic sustainable development, all being areas which are not traditionally considered as far as technical studies are concerned. These criteria can be most useful from the design stage onward, first in an attempt to define the facility construction and operating guiding principles, and thereafter to substantiate the safety case for long term storage and get geared to the public dialogue on that undertaking should it become a reality.

Key Performance Criteria Affecting the Most the Safety of a Nuclear Waste Long Term Storage : A Case Study Commissioned by CEA

International Nuclear Information System (INIS)

Marvy, A.; Lioure, A; Heriard-Dubreuil, G.; Gadbois, S.; Schneider, T.; Schieber, C.

2003-01-01

As part of the work scope set in the French law on high level long lived waste R and D passed in 1991, CEA is conducting a research program to establish the scientific basis and assess the feasibility of long term storage as an option for the safe management of nuclear waste for periods as long as centuries. This goal is a significant departure from the current industrial practice where storage facilities are usually built to last only a few decades. From a technical viewpoint such an extension in time seems feasible provided care and maintenance is exercised. Considering such long periods of time, the risk for Society of loosing oversight and control of such a facility is real, which triggers the question of whether and how long term storage safety can be actually achieved. Therefore CEA commissioned a study (1) in which MUTADIS Consultants (2) and CEPN (3) were both involved. The case study looks into several past and actual human enterprises conducted over significant periods o f time, one of them dating back to the end of the 18th century, and all identified out of the nuclear field. Then-prevailing societal behavior and organizational structures are screened out to show how they were or are still able to cope with similar oversight and control goals. As a result, the study group formulated a set of performance criteria relating to issues like responsibility, securing funds, legal and legislative implications, economic sustainable development, all being areas which are not traditionally considered as far as technical studies are concerned. These criteria can be most useful from the design stage onward, first in an attempt to define the facility construction and operating guiding principles, and thereafter to substantiate the safety case for long term storage and get geared to the public dialogue on that undertaking should it become a reality

Comparison of two humidification systems for long-term noninvasive mechanical ventilation.

Science.gov (United States)

Nava, S; Cirio, S; Fanfulla, F; Carlucci, A; Navarra, A; Negri, A; Ceriana, P

2008-08-01

There is no consensus concerning the best system of humidification during long-term noninvasive mechanical ventilation (NIMV). In a technical pilot randomised crossover 12-month study, 16 patients with stable chronic hypercapnic respiratory failure received either heated humidification or heat and moisture exchanger. Compliance with long-term NIMV, airway symptoms, side-effects and number of severe acute pulmonary exacerbations requiring hospitalisation were recorded. Two patients died. Intention-to-treat statistical analysis was performed on 14 patients. No significant differences were observed in compliance with long-term NIMV, but 10 out of 14 patients decided to continue long-term NIMV with heated humidification at the end of the trial. The incidence of side-effects, except for dry throat (significantly more often present using heat and moisture exchanger), hospitalisations and pneumonia were not significantly different. In the present pilot study, the use heated humidification and heat and moisture exchanger showed similar tolerance and side-effects, but a higher number of patients decided to continue long-term noninvasive mechanical ventilation with heated humidification. Further larger studies are required in order to confirm these findings.

Transplantation Tolerance through Hematopoietic Chimerism: Progress and Challenges for Clinical Translation

Directory of Open Access Journals (Sweden)

Benedikt Mahr

2017-12-01

Full Text Available The perception that transplantation of hematopoietic stem cells can confer tolerance to any tissue or organ from the same donor is widely accepted but it has not yet become a treatment option in clinical routine. The reasons for this are multifaceted but can generally be classified into safety and efficacy concerns that also became evident from the results of the first clinical pilot trials. In comparison to standard immunosuppressive therapies, the infection risk associated with the cytotoxic pre-conditioning necessary to allow allogeneic bone marrow engraftment and the risk of developing graft-vs.-host disease (GVHD constitute the most prohibitive hurdles. However, several approaches have recently been developed at the experimental level to reduce or even overcome the necessity for cytoreductive conditioning, such as costimulation blockade, pro-apoptotic drugs, or Treg therapy. But even in the absence of any hazardous pretreatment, the recipients are exposed to the risk of developing GVHD as long as non-tolerant donor T cells are present. Total lymphoid irradiation and enriching the stem cell graft with facilitating cells emerged as potential strategies to reduce this peril. On the other hand, the long-lasting survival of kidney allografts, seen with transient chimerism in some clinical series, questions the need for durable chimerism for robust tolerance. From a safety point of view, loss of chimerism would indeed be favorable as it eliminates the risk of GVHD, but also complicates the assessment of tolerance. Therefore, other biomarkers are warranted to monitor tolerance and to identify those patients who can safely be weaned off immunosuppression. In addition to these safety concerns, the limited efficacy of the current pilot trials with approximately 40–60% patients becoming tolerant remains an important issue that needs to be resolved. Overall, the road ahead to clinical routine may still be rocky but the first successful long-term

Long-term opioid treatment of chronic nonmalignant pain: unproven efficacy and neglected safety?

Directory of Open Access Journals (Sweden)

Kissin I

2013-07-01

Full Text Available Igor Kissin Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Background: For the past 30 years, opioids have been used to treat chronic nonmalignant pain. This study tests the following hypotheses: (1 there is no strong evidence-based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective; and (2 the main problem associated with the safety of such treatment – assessment of the risk of addiction – has been neglected. Methods: Scientometric analysis of the articles representing clinical research in this area was performed to assess (1 the quality of presented evidence (type of study; and (2 the duration of the treatment phase. The sufficiency of representation of addiction was assessed by counting the number of articles that represent (1 editorials; (2 articles in the top specialty journals; and (3 articles with titles clearly indicating that the addiction-related safety is involved (topic-in-title articles. Results: Not a single randomized controlled trial with opioid treatment lasting >3 months was found. All studies with a duration of opioid treatment ≥6 months (n = 16 were conducted without a proper control group. Such studies cannot provide the consistent good-quality evidence necessary for a strong clinical recommendation. There were profound differences in the number of addiction articles related specifically to chronic nonmalignant pain patients and to opioid addiction in general. An inadequate number of chronic pain-related publications were observed with all three types of counted articles: editorials, articles in the top specialty journals, and topic-in-title articles. Conclusion: There is no strong evidence-based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective. The above identified signs indicating neglect of addiction associated with the

Life-long diseases need life-long treatment: long-term safety of ciclosporin in canine atopic dermatitis

Science.gov (United States)

Nuttall, Tim; Reece, Douglas; Roberts, Elizabeth

2014-01-01

Ciclosporin (Atopica; Novartis Animal Health) has been licensed for canine atopic dermatitis (AD) since 2002. Adverse events (AEs) have been reported in 55 per cent of 759 dogs in 15 clinical trials, but are rare in pharmacovigilance data (71.81 AEs/million capsules sold). Gastrointestinal reactions were most common, but were mild and rarely required intervention. Other AEs were rare (≤1 per cent in clinical trials; metabolism is not clinically significant for normal dogs. Concomitant treatment with most drugs is safe. Effects on cytochrome P450 and MDR1 P-glycoprotein activity may elevate plasma ciclosporin concentrations, but short-term changes are not clinically significant. Monitoring of complete blood counts, urinalysis or ciclosporin levels is not justified except with higher than recommended doses and/or long-term concurrent immunosuppressive drugs. Ciclosporin is not a contraindication for killed (including rabies) vaccines, but the licensed recommendation is that live vaccination is avoided during treatment. In conclusion, ciclosporin has a positive risk-benefit profile for the long-term management of canine AD. PMID:24682696

Ethics and Intimate Sexual Activity in Long-Term Care.

Science.gov (United States)

Metzger, Eran

2017-07-01

A case is presented in which the staff of a long-term care facility discovers that the husband of a resident with dementia is engaged in sexual activity with her. The case illustrates a dilemma for long-term care facilities that create a home-like environment with a goal of maximizing residents' autonomy while ensuring their safety. An approach to assessing capacity to consent to intimate sexual activity is described, followed by guidelines that nursing homes can implement to support residents who wish to engage in sexual activity. Recommendations are also offered for supporting long-term care staff and family members of residents who are interested in intimate sexual activity. © 2017 American Medical Association. All Rights Reserved.

Long-Term Marine Traffic Monitoring for Environmental Safety in the Aegean Sea

Science.gov (United States)

Giannakopoulos, T.; Gyftakis, S.; Charou, E.; Perantonis, S.; Nivolianitou, Z.; Koromila, I.; Makrygiorgos, A.

2015-04-01

The Aegean Sea is characterized by an extremely high marine safety risk, mainly due to the significant increase of the traffic of tankers from and to the Black Sea that pass through narrow straits formed by the 1600 Greek islands. Reducing the risk of a ship accident is therefore vital to all socio-economic and environmental sectors. This paper presents an online long-term marine traffic monitoring work-flow that focuses on extracting aggregated vessel risks using spatiotemporal analysis of multilayer information: vessel trajectories, vessel data, meteorological data, bathymetric / hydrographic data as well as information regarding environmentally important areas (e.g. protected high-risk areas, etc.). A web interface that enables user-friendly spatiotemporal queries is implemented at the frontend, while a series of data mining functionalities extracts aggregated statistics regarding: (a) marine risks and accident probabilities for particular areas (b) trajectories clustering information (c) general marine statistics (cargo types, etc.) and (d) correlation between spatial environmental importance and marine traffic risk. Towards this end, a set of data clustering and probabilistic graphical modelling techniques has been adopted.

Changes in glucose-elicited blood metabolite responses following weight loss and long term weight maintenance in obese individuals with impaired glucose tolerance.

Science.gov (United States)

Geidenstam, Nina; Danielsson, Anders P H; Spégel, Peter; Ridderstråle, Martin

2016-03-01

Weight loss improves insulin sensitivity and glucose tolerance in obese subjects with impaired glucose tolerance (IGT), but the long term dynamic effects on blood metabolites other than glucose during an oral glucose tolerance test (OGTT), are largely unknown. Here, we studied changes in OGTT-elicited metabolite patterns in obese subjects during a diet-induced weight loss study. Blood samples from 14 obese individuals with IGT were collected at 0, 30 and 120 min during a standard 75 g OGTT at baseline (BMI 44 ± 2 kg/m(2)), after weight loss (BMI 36 ± 2 kg/m(2)) and after weight maintenance (BMI 35 ± 2 kg/m(2)). Serum metabolite levels were analyzed by gas chromatography/mass spectrometry and compared to a lean glucose tolerant group. Changes in the OGTT-elicited metabolite patterns occurred differentially during weight loss and weight maintenance. Enhanced suppression of aromatic amino acids were associated with decreased insulinogenic index observed after weight loss (tyrosine: r=0.72, p=0.013; phenylalanine: r=0.63, p=0.039). The OGTT-elicited suppression and/or lack of increase in levels of glutamate, glutamine, isoleucine, leucine, and the fatty acids laurate, oleate and palmitate, improved towards the lean profile after weight maintenance, paralleling an improvement in glucose tolerance. The greater heterogeneity in the response before and after weight loss in the obese, compared to lean subjects, was markedly reduced after weight maintenance. Diet-induced weight loss followed by weight maintenance results in changes in metabolite profiles associated with either hepatic insulin sensitivity or peripheral glucose tolerance. Our results highlight the importance of evaluating the effects of weight loss and weight maintenance separately. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Long-term efficacy and safety of otilonium bromide in the management of irritable bowel syndrome: a literature review

Directory of Open Access Journals (Sweden)

Triantafillidis JK

2014-04-01

Full Text Available John K Triantafillidis, George Malgarinos Inflammatory Bowel Disease Unit, IASO General Hospital, Athens, Greece Abstract: Irritable bowel syndrome (IBS is a very common functional gastrointestinal disorder characterized by abdominal pain or discomfort and altered bowel habits. The disease affects a large part of the world population. The clinical course is mostly characterized by a cyclic recurrence of symptoms. Therefore, IBS patients should receive, as an initial therapeutic approach, a short course of treatment, and long-term treatment should be reserved for those patients with recurrent symptoms. The available clinical trials show that significant improvement of the symptoms over placebo could be achieved with various drugs, although this improvement is frequently time dependent and with high relapse rates after the cessation of the treatment. In a proportion of patients, clinically obvious relapse could appear long after stopping the treatment. Some of the available pharmacologic agents, including otilonium bromide (OB, are able to significantly prolong the time to the appearance of relapse, compared with placebo. As a consequence, some authors suggest that a cyclic treatment could be of benefit. Antispasmodic drugs have been used for many years in an effort to control the symptoms of IBS. OB is a poorly absorbed spasmolytic drug, exerting significantly greater control of the symptoms of IBS compared with placebo. Recent data suggest that the drug could effectively be used for the long-term management of patients with IBS. The aim of this review is to provide the reader with an evidence-based overview of the efficacy and tolerability of OB in the long-term management of IBS patients, based on the results of the clinical trials published so far. Keywords: irritable bowel syndrome, IBS, treatment, otilonium bromide

Preclinical rodent toxicity studies for long term use of ceftriaxone

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Elena Ratti

2015-01-01

Ceftriaxone showed rapid absorption with half-life values ranging between 1 and 1.5 h. Additionally, there was no evidence of accumulation and a virtually complete elimination by 16 h after the last dose. Overall there were no toxicologically meaningful drug-related animal findings associated with the long-term administration (6 months of ceftriaxone. These results support safety of long-term use of ceftriaxone in human clinical trials.

Long-term follow-up observation of the safety, immunogenicity, and effectiveness of Gardasil™ in adult women.

Directory of Open Access Journals (Sweden)

Joaquin Luna

Full Text Available Previous analyses from a randomized trial in women aged 24-45 have shown the quadrivalent HPV vaccine to be efficacious in the prevention of infection, cervical intraepithelial neoplasia (CIN and external genital lesions (EGL related to HPV 6/11/16/18 through 4 years. In this report we present long term follow-up data on the efficacy, safety and immunogenicity of the quadrivalent HPV vaccine in adult women.Follow-up data are from a study being conducted in 5 sites in Colombia designed to evaluate the long-term immunogenicity, effectiveness, and safety of the qHPV vaccine in women who were vaccinated at 24 to 45 years of age (in the original vaccine group during the base study [n = 684] or 29 to 50 years of age (in the original placebo group during the base study [n = 651]. This analysis summarizes data collected as of the year 6 post-vaccination visit relative to day 1 of the base study (median follow-up of 6.26 years from both the original base study and the Colombian follow-up.There were no cases of HPV 6/11/16/18-related CIN or EGL during the extended follow-up phase in the per-protocol population. Immunogenicity persists against vaccine-related HPV types, and no evidence of HPV type replacement has been observed. No new serious adverse experiences have been reported.Vaccination with qHPV vaccine provides generally safe and effective protection from HPV 6-, 11-, 16-, and 18-related genital warts and cervical dysplasia through 6 years following administration to 24-45 year-old women.Clinicaltrials.govNCT00090220.

High-level Waste Long-term management technology development

International Nuclear Information System (INIS)

Choi, Jong Won; Kang, C. H.; Ko, Y. K.

2012-02-01

The purpose of this project is to develop a long-term management system(A-KRS) which deals with spent fuels from domestic nuclear power stations, HLW from advanced fuel cycle and other wastes that are not admitted to LILW disposal site. Also, this project demonstrate the feasibility and reliability of the key technologies applied in the A-KRS by evaluating them under in-situ condition such as underground research laboratory and provide important information to establish the safety assessment and long-term management plan. To develop the technologies for the high level radioactive wastes disposal, demonstrate their reliability under in-situ condition and establish safety assessment of disposal system, The major objects of this project are the following: Ο An advanced disposal system including waste containers for HLW from advanced fuel cycle and pyroprocess has been developed. Ο Quantitative assessment tools for long-term safety and performance assessment of a radwaste disposal system has been developed. Ο Hydrological and geochemical investigation and interpretation methods has been developed to evaluate deep geological environments. Ο The THMC characteristics of the engineered barrier system and near-field has been evaluated by in-situ experiments. Ο The migration and retardation of radionuclides and colloid materials in a deep geological environment has been investigated. The results from this project will provide important information to show HLW disposal plan safe and reliable. The knowledge from this project can also contribute to environmental conservation by applying them to the field of oil and gas industries to store their wastes safe

An open-label extension long-term study of the safety and efficacy of aripiprazole for irritability in children and adolescents with autistic disorder in Japan.

Science.gov (United States)

Ichikawa, Hironobu; Hiratani, Michio; Yasuhara, Akihiro; Tsujii, Noa; Oshimo, Takashi; Ono, Hiroaki; Tadori, Yoshihiro

2018-02-01

The purpose of this study was to evaluate the long-term safety and efficacy of aripiprazole in treating irritability in pediatric patients (6-17 years) with autistic disorder (AD) in Japan. In this open-label extension study, patients who had completed a previous randomized, double-blind, placebo-controlled 8-week study were enrolled and were flexibly dosed with aripiprazole (1-15 mg/day) until the new indication of irritability in pediatric autism spectrum disorder was approved in Japan. Seventy (81%) out of 86 enrolled patients completed week-48 assessments. The mean duration of treatment was 694.9 days. The mean daily dose of aripiprazole over the treatment period was 7.2 mg and the mean of the final dose was 8.5 mg. The most common treatment-emergent adverse events (TEAE; ≥20%) included nasopharyngitis, somnolence, influenza, and increased weight. The majority of these TEAE were mild or moderate in severity, and there were no deaths, and no clinically relevant findings in laboratory values except prolactin decrease, vital signs, height, or ECG parameters. At week 48 (observed case), the mean change from baseline in the Irritability subscale score for the Aberrant Behavior Checklist Japanese Version was -6.3 in prior placebo patients and -2.6 in prior aripiprazole patients. Aripiprazole was generally safe, well tolerated, and effective in the long-term treatment of irritability associated with AD in Japanese pediatric patients. © 2017 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.

Safety and Tolerability Profile of Artemisinin-Based Antimalarial ...

African Journals Online (AJOL)

The WHO in 2001 advocated artemisinin- based antimalarial combination therapy (ACT), which was adopted by Nigeria in 2005. The objective of this study was to characterize the safety and tolerability profile of the ACTs in adult patients with uncomplicated malaria. A descriptive longitudinal study was conducted in the ...

Prevalence of Long-Term Opioid Use in Long-Stay Nursing Home Residents.

Science.gov (United States)

Hunnicutt, Jacob N; Chrysanthopoulou, Stavroula A; Ulbricht, Christine M; Hume, Anne L; Tjia, Jennifer; Lapane, Kate L

2018-01-01

Overall and long-term opioid use among older adults have increased since 1999. Less is known about opioid use in older adults in nursing homes (NHs). Cross-sectional. U.S. NHs (N = 13,522). Long-stay NH resident Medicare beneficiaries with a Minimum Data Set 3.0 (MDS) assessment between April 1, 2012, and June 30, 2012, and 120 days of follow-up (N = 315,949). We used Medicare Part D claims to measure length of opioid use in the 120 days from the index assessment (short-term: ≤30 days, medium-term: >30-89 days, long-term: ≥90 days), adjuvants (e.g., anticonvulsants), and other pain medications (e.g., corticosteroids). MDS assessments in the follow-up period were used to measure nonpharmacological pain management use. Modified Poisson models were used to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for age, gender, race and ethnicity, cognitive and physical impairment, and long-term opioid use. Of all long-stay residents, 32.4% were prescribed any opioid, and 15.5% were prescribed opioids long-term. Opioid users (versus nonusers) were more commonly prescribed pain adjuvants (32.9% vs 14.9%), other pain medications (25.5% vs 11.0%), and nonpharmacological pain management (24.5% vs 9.3%). Long-term opioid use was higher in women (aPR = 1.21, 95% CI = 1.18-1.23) and lower in racial and ethnic minorities (non-Hispanic blacks vs whites: APR = 0.93, 95% CI = 0.90-0.94) and those with severe cognitive impairment (vs no or mild impairment, aPR = 0.82, 95% CI = 0.79-0.83). One in seven NH residents was prescribed opioids long-term. Recent guidelines on opioid prescribing for pain recommend reducing long-term opioid use, but this is challenging in NHs because residents may not benefit from nonpharmacological and nonopioid interventions. Studies to address concerns about opioid safety and effectiveness (e.g., on pain and functional status) in NHs are needed. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics

Comparison of Plant Life Management Approaches for Long Term Operations

International Nuclear Information System (INIS)

Kang, Kisig

2012-01-01

Plant life management can be defined as the integration of ageing and economic planning to maintain a high level of safety and optimize operations. Many Member States have given high priority to long term operation of nuclear power plants beyond the time frame originally anticipated (e. g. 30 or 40 years). Out of a total of 445 (369 GWe) operating nuclear power plants, 349 units (297 GWe) have been in operation for more than 20 years (as of November 2011). The need for engineering support to operation, maintenance, safety review and life management for long term operation as well as education and training in the field is increasingly evident. In addition the Fukushima accident has rendered all stake holders even more attentive to safety concerns and to the provision of beyond safety measures in the preparation and scrutiny of applications for operational design life extensions. In many countries, the safety performance of NPPs is periodically followed and characterized via the periodic safety review (PSR) approach. The regulatory The regulatory review and acceptance of the PSR gives the licensee the permission to operate the plant for up to the end of the next PSR cycle (usually 10 years). In the USA and other countries operating US designed plants, the license renewal application is based on the five pre-requisite requirements and ageing management programme for passive long life system structure and components(SSCs) and active systems is adequately addressed by the maintenance rule (MR) requirements and other established regulatory processes. Other Member States have adopted a combined approach that incorporates elements of both PSR and additional LRA specific requirements primarily focused on time limited ageing analysis. Taking into account this variety of approaches, the international atomic energy agency (IAEA) initiated work for collecting and sharing information among Member States about good practices on plant life management for long term operation in

Long-term surveillance plan for the South Clive disposal site Clive, Utah

International Nuclear Information System (INIS)

1997-09-01

This long-term surveillance plan (LTSP) describes the U.S. Department of Energy's (DOE) long-term care program for the Uranium Mill Tailings Remedial Action (UMTRA) Project South Clive disposal site in Clive, Utah. This LSTP describes the long-term surveillance program the DOE will implement to ensure the South Clive disposal site performs as designed and is cared for in a manner that protects the public health and safety and the environment. Before each disposal site is licensed for custody and long-term care, the Nuclear Regulatory Commission (NRC) requires the DOE to submit such a site-specific LTSP

Long-term safety and efficacy of deferasirox (Exjade®) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease

Science.gov (United States)

Vichinsky, Elliott; Bernaudin, Françoise; Forni, Gian Luca; Gardner, Renee; Hassell, Kathryn; Heeney, Matthew M; Inusa, Baba; Kutlar, Abdullah; Lane, Peter; Mathias, Liesl; Porter, John; Tebbi, Cameron; Wilson, Felicia; Griffel, Louis; Deng, Wei; Giannone, Vanessa; Coates, Thomas

2011-01-01

To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, deferoxamine (DFO)-controlled study entered a 4-year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4 ± 6·3 mg/kg per d. Of 185 patients who received at least one deferasirox dose, 33·5% completed the 5-year study. The most common reasons for discontinuation were withdrawal of consent (23·8%), lost to follow-up (9·2%) and adverse events (AEs) (7·6%). Investigator-assessed drug-related AEs were predominantly gastrointestinal [including nausea (14·6%), diarrhoea (10·8%)], mild-to-moderate and transient in nature. Creatinine clearance remained within the normal range throughout the study. Despite conservative initial dosing, serum ferritin levels in patients with ≥4 years deferasirox exposure significantly decreased by −591 μg/l (95% confidence intervals, −1411, −280 μg/l; P=0·027; n=67). Long-term deferasirox treatment for up to 5 years had a clinically acceptable safety profile, including maintenance of normal renal function, in patients with SCD. Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4 years. PMID:21592110

Long-term safety and efficacy of perinatal probiotic intervention: Evidence from a follow-up study of four randomized, double-blind, placebo-controlled trials.

Science.gov (United States)

Lundelin, Krista; Poussa, Tuija; Salminen, Seppo; Isolauri, Erika

2017-03-01

Societies worldwide are faced with a progressive increase in immune-mediated health problems such as allergic, autoimmune, and inflammatory diseases, as well as obesity. Perinatal administration of specific probiotic bacteria is an attractive approach in reducing the risk of these conditions, but long-term efficacy and safety data are lacking. The aim here was to evaluate the clinical benefit and long-term safety of specific probiotics administered during the perinatal period. The probiotic strains used were Lactobacillus rhamnosus GG, Bifidobacterium lactis Bb-12, Lactobacillus paracasei ST11, and Bifidobacterium longum BL999. The children involved have subsequently undergone prospective long-term follow-up. In addition to physical examination, data were collected by structured questionnaires on non-communicable diseases and continued probiotic use, and growth data from welfare clinics and school nurses. Altogether 303 mother-infant pairs were included in the analysis. Seventy-six of 163 (47%) children receiving perinatal probiotics had developed allergic disease compared with 79 of 140 (56%) receiving placebo (OR 0.67, 95% confidence intervals [CI] 0.43-1.06, p = 0.09). Fifty-nine of 133 (44%) children receiving L. rhamnosus GG perinatally had developed allergic disease, OR 0.62, 95% CI 0.38-0.99, p = 0.047, as compared to placebo. We found no differences in growth or non-communicable disease prevalence between children receiving perinatally probiotics or placebo. Perinatal probiotic administration is safe in long-term follow-up. Children receiving L. rhamnosus GG perinatally tended to have decreased allergy prevalence. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effectiveness and tolerance of long-term malaria prophylaxis with mefloquine. Need for a better dosing regimen.

Science.gov (United States)

Lobel, H O; Bernard, K W; Williams, S L; Hightower, A W; Patchen, L C; Campbell, C C

1991-01-16

To measure the effectiveness and tolerance of long-term malaria prophylaxis with mefloquine, the incidence of Plasmodium falciparum malaria and of adverse reactions was compared in Peace Corps volunteers in West Africa who took mefloquine every 2 weeks and in volunteers who took chloroquine phosphate weekly. Mefloquine was only 63% more effective than chloroquine; the monthly incidence of P falciparum infections was one case per 100 volunteers who took mefloquine and 2.7 cases per 100 volunteers who took chloroquine. Using daily proguanil (chloroguanide) hydrochloride in addition to chloroquine did not provide additional protection. All mefloquine prophylaxis failures occurred during the second week of the every-2-weeks dosing regimen in volunteers who had used mefloquine for more than 2 months. Blood concentrations of mefloquine were lower during the second week of the alternate-week regimen than during the first week, suggesting that blood levels are too low during the second week to suppress parasitemia. No serious adverse reactions were observed. The results indicate that a dosing regimen of 250 mg of mefloquine weekly should be considered for travelers to areas with chloroquine-resistant P falciparum malaria.

School-based prevention program associated with increased short- and long-term retention of safety knowledge.

Science.gov (United States)

Klas, Karla S; Vlahos, Peter G; McCully, Michael J; Piche, David R; Wang, Stewart C

2015-01-01

Validation of program effectiveness is essential in justifying school-based injury prevention education. Although Risk Watch (RW) targets burn, fire, and life safety, its effectiveness has not been previously evaluated in the medical literature. Between 2007 and 2012, a trained fire service public educator (FSPE) taught RW to all second grade students in one public school district. The curriculum was delivered in 30-minute segments for 9 consecutive weeks via presentations, a safety smoke house trailer, a model-sized hazard house, a student workbook, and parent letters. A written pre-test (PT) was given before RW started, a post-test (PT#1) was given immediately after RW, and a second post-test (PT#2) was administered to the same students the following school year (ranging from 12 to 13 months after PT). Students who did not complete the PT or at least one post-test were excluded. Comparisons were made by paired t-test, analysis of variance, and regression analysis. After 183 (8.7%) were excluded for missing tests, 1,926 remaining students scored significantly higher (P = .0001) on PT#1 (mean 14.8) and PT#2 (mean 14.7) than the PT (mean 12.1). There was 1 FSPE and 36 school teachers with class size ranging from 10 to 27 (mean 21.4). Class size was not predictive of test score improvement (R = 0%), while analysis of variance showed that individual teachers trended toward some influence. This 6-year prospective study demonstrated that the RW program delivered by an FSPE effectively increased short-term knowledge and long-term retention of fire/life safety in early elementary students. Collaborative partnerships are critical to preserving community injury prevention education programs.

Tolerability of risk, safety assessment principles and their implications for probabilistic safety analysis

International Nuclear Information System (INIS)

Ewing, D.J.F.; Campbell, J.F.

1994-01-01

This paper gives a regulatory view of probabilistic safety assessment as seen by the Nuclear Installations Inspectorate (NII) and in the light of the general regulatory risk aims set out in the Health and Safety Executive's (HSE) The tolerability of risk from nuclear power stations (TOR) and in Safety assessment principles for nuclear plants (SAPs), prepared by NII on behalf of the HSE. Both of these publications were revised and republished in 1992. This paper describes the SAPs, together with the historical background, the motivation for review, the effects of the Sizewell and Hinkley Point C public inquiries, changes since the original versions, comparison with international standards and use in assessment. For new plant, probabilistic safety analysis (PSA) is seen as an essential tool in balancing the safety of the design and in demonstrating compliance with TOR and the SAPs. (Author)

Short and long-term safety of the 2009 AS03-adjuvanted pandemic vaccine.

Directory of Open Access Journals (Sweden)

Gaston De Serres

Full Text Available This study assessed the short and the long term safety of the 2009 AS03 adjuvanted monovalent pandemic vaccine through an active web-based electronic surveillance. We compared its safety profile to that of the seasonal trivalent inactivated influenza vaccine (TIV for 2010-2011.Health care workers (HCW vaccinated in 2009 with the pandemic vaccine (Arepanrix ® from GSK or HCW vaccinated in 2010 with the 2010-2011 TIV were invited to participate in a web-based active surveillance of vaccine safety. They completed two surveys the day-8 survey covered the first 7 days post-vaccination and the day-29 survey covered events occurring 8 to 28 days after vaccination. Those who reported a problem were called by a nurse to obtain details. The main outcome was the occurrence of a new health problem or the worsening of an existing health condition that resulted in a medical consultation or work absenteeism. For the pandemic vaccine, a six-month follow-up for the occurrence of serious adverse events (SAE was conducted. Among the 6242 HCW who received the pandemic vaccine, 440 (7% reported 468 events compared to 328 of the 7645 HCW (4.3% who reported 339 events after the seasonal vaccine. The 2009 pandemic vaccine was associated with significantly more local reactions than the 2010-2011 seasonal vaccine (1% vs. 0.03%, p<0.001. Paresthesia was reported by 7 HCW (0.1% after the pandemic vaccine but by none after the seasonal vaccine. For the pandemic vaccine, no clustering of SAE was found in the 6 month follow-up.The 2009 pandemic vaccine seems to have a good safety profile, similar to the 2010-2011 TIV, with the exception of local reactions. This surveillance was adequately powered to identify AE associated with an excess risk ≥1 per 1000 vaccinations but is insufficient to detect rare AE.ClinicalTrials.gov NCT01289418, NCT01318876.

THEREDA - a contribution to long-term safety of repositories of nuclear and non-nuclear wastes

International Nuclear Information System (INIS)

Altmaier, M.; Kienzler, B.; Marquardt, C.M.; Neck, V.; Voigt, W.; Wilhelm, S.

2008-01-01

Long-term safety analyses of German repositories of radioactive waste as well as underground repositories for chemical toxic waste and other uses (contaminated site remediation) urgently require a standardized, comprehensive thermodynamic reference database. The former 'Thermodynamic Standard Database Working Party' was set up to establish such a database. The activities of that group have been supported within the integrated 'THEREDA' (Thermodynamic Reference Database) project since July 2006 for an initial period of 3 years by the German Federal Ministries of Education and Research, of Economics, and by the Federal Office of Radiation Protection. THEREDA at present is composed of 5 partner institutions essentially representing the key German research institutions in the field of repository safety research. THEREDA is to improve the transparency and validity of safety analyses in Germany and, for the first time, provides consistent thermodynamic datasets for the repository options discussed in Germany. Quality levels are indicated for each thermodynamic quantity on the basis of unambiguously defined evaluation criteria, which allow users to either include or exclude data in accordance with the specific problems at hand. Missing thermodynamic data are substituted in THEREDA by well-founded estimates, thus permitting future model calculations for safety analysis to be carried out on a clearly broader basis of data. The data are managed centrally in a database and will be available to users free of charge on the Internet. Import formats allowing THEREDA to be transferred into the most common modeling codes (EQ3/6, PHREEQC, Geochemist's Workbench, CHEMAPP, etc.) are also made available free of charge. (orig.)

Long-term health benefits of appetite suppressants remain unproven

Directory of Open Access Journals (Sweden)

Francisco José Roma Paumgartten

2011-12-01

Full Text Available Because of the increasing prevalence of obesity, prevention and treatment of overweight has become a major public health concern. In addition to diet and exercise, drugs are needed for patients who failed to lose weight with behavioral treatment. The current article aimed to summarize recent concerns on the safety and efficacy of appetite suppressants. Several appetite suppressants have been banned for safety reasons. In 2010, sibutramine was withdrawn from the market because a long-term study showed it increased the risks of cardiovascular events. So far no study with a sufficiently large sample size has demonstrated that appetite suppressants can reduce morbidity and mortality associated with overweight. The withdrawal of sibutramine highlights that guidelines for the evaluation of weight control drugs must be more stringent, and studies on their long-term health benefits are needed prior to their marketing.

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.

Rodent model for assessing the long term safety and performance of peripheral nerve recording electrodes

Science.gov (United States)

Vasudevan, Srikanth; Patel, Kunal; Welle, Cristin

2017-02-01

Objective. In the US alone, there are approximately 185 000 cases of limb amputation annually, which can reduce the quality of life for those individuals. Current prosthesis technology could be improved by access to signals from the nervous system for intuitive prosthesis control. After amputation, residual peripheral nerves continue to convey motor signals and electrical stimulation of these nerves can elicit sensory percepts. However, current technology for extracting information directly from peripheral nerves has limited chronic reliability, and novel approaches must be vetted to ensure safe long-term use. The present study aims to optimize methods to establish a test platform using rodent model to assess the long term safety and performance of electrode interfaces implanted in the peripheral nerves. Approach. Floating Microelectrode Arrays (FMA, Microprobes for Life Sciences) were implanted into the rodent sciatic nerve. Weekly in vivo recordings and impedance measurements were performed in animals to assess performance and physical integrity of electrodes. Motor (walking track analysis) and sensory (Von Frey) function tests were used to assess change in nerve function due to the implant. Following the terminal recording session, the nerve was explanted and the health of axons, myelin and surrounding tissues were assessed using immunohistochemistry (IHC). The explanted electrodes were visualized under high magnification using scanning electrode microscopy (SEM) to observe any physical damage. Main results. Recordings of axonal action potentials demonstrated notable session-to-session variability. Impedance of the electrodes increased upon implantation and displayed relative stability until electrode failure. Initial deficits in motor function recovered by 2 weeks, while sensory deficits persisted through 6 weeks of assessment. The primary cause of failure was identified as lead wire breakage in all of animals. IHC indicated myelinated and unmyelinated axons

Beyond post-marketing research and MedWatch: Long-term studies of drug risks.

Science.gov (United States)

Resnik, David B

2007-10-01

Critics of the drug safety system have discussed many different potential reforms, ranging from mandatory registration of clinical trials to increasing the power of regulatory agencies, but few have discussed one of the most important ways of enhancing safety: increasing the number of long-term studies of medications. Long-term studies of the risks and benefits of drugs can provide useful information for regulators, healthcare professionals, and patients. Government funding agencies should lead the effort to conduct long-term studies of drugs, but private companies should also be required to lend financial support. Because cost-effectiveness is likely to be an important consideration in conducting this research, funding agencies should focus, at first, on drugs that are used to treat common, chronic conditions.

Multicentric cohort study on the long-term efficacy and safety of electronic cigarettes: study design and methodology.

Science.gov (United States)

Manzoli, Lamberto; La Vecchia, Carlo; Flacco, Maria Elena; Capasso, Lorenzo; Simonetti, Valentina; Boccia, Stefania; Di Baldassarre, Angela; Villari, Paolo; Mezzetti, Andrea; Cicolini, Giancarlo

2013-09-24

While electronic cigarettes are forbidden in several countries, their sales are exploding in many others. Although e-cigarettes have been proposed as long-term substitutes for traditional smoking or as a tool for smoking cessation, very scarce data are available on their efficacy and safety.We describe the protocol of a 5-year multicentric prospective study aimed to evaluate short- and long-term adherence to e-cigarette smoking and the efficacy of e-cigarettes in reducing and/or quitting traditional cigarette smoking. The study will also compare the health effects of electronic vs traditional vs mixed cigarette smoking. From June to December 2013, we will enroll adult smokers of: (EC) e-cigarettes (self-reported inhaling ≥ 50 puffs per week since ≥ 6 months); (TC) traditional cigarettes (≥ 1 per day since ≥ 6 m); (Mixed) both electronic and traditional cigarettes (≥ 1 per day since ≥ 6 m). Eligible subjects will be requested participation through newspaper advertisements and direct contact at the shops. Each subject will have to compile a structured questionnaire at enrolment and after 6, 12, 24, 36 and 60 months. The level of carbon monoxide in expired after breath will be evaluated in all subjects declaring no traditional cigarette smoking in any follow-up phase, using portable carbon monoxide analyzers. The primary outcomes are traditional smoking cessation rates and number of smoked cigarettes. Secondary outcomes include adherence to e-cigarettes, self-reported adverse events, quality of life, and time to hospital admission for one among cardiovascular diseases, chronic obstructive pulmonary diseases, cancer of the lung, esophagus, larynx, oral cavity, bladder, pancreas, kidney, stomach, cervix, and myeloid leukemia. Admissions will be checked using official discharge data of the Abruzzo Region. A minimum of 500 subjects in each group will be enrolled, for a total of 1500 participants. Cox proportional hazards analysis will be used to calculate

Long-term safety and efficacy of dasatinib in the treatment of chronic-phase chronic myeloid leukemia patients resistant or intolerant to imatinib

Directory of Open Access Journals (Sweden)

Shoumariyeh K

2014-09-01

Full Text Available Khalid Shoumariyeh, Nikolas von BubnoffDepartment of Hematology, Oncology and Stem Cell Transplantation, University Hospital Freiburg, Freiburg, Germany Abstract: Treatment of chronic myeloid leukemia (CML has undergone dramatic changes in the last decade. Dissecting the molecular pathways that lead to the development of this disease resulted in the development of targeted therapy against the molecular driver of CML, namely the aberrantly activated tyrosine kinase BCR-ABL1. By introducing the tyrosine kinase inhibitor imatinib to the treatment repertoire, the natural course of the disease has been dramatically altered and overall survival of patients with CML prolonged substantially. Nevertheless, a significant number of patients are primarily resistant, acquire resistance during the course of their disease, or do not tolerate the intake of imatinib due to adverse effects. Second-generation tyrosine kinase inhibitors were developed in an attempt to overcome these problems. Dasatinib is a potent oral kinase inhibitor that was originally developed as an Src-kinase inhibitor but exhibited promising potency against BCR-ABL1 as well. Phase I and II trials demonstrated efficacy in patients failing imatinib, and thus dasatanib was approved in 2006 for the treatment of imatinib-resistant or -intolerant patients with chronic-phase CML harboring the BCR-ABL1 fusion protein. It has since shown promising efficacy and good overall tolerability in subsequent clinical trials, including the Phase III first-line DASISION trial that led to the extension of its approval for first-line treatment of chronic-phase CML. The following review summarizes the available data on the long-term efficacy and safety of dasatinib as a second-line therapy in chronic-phase CML. Keywords: BCR-ABL1, TKI, CML-CP, second-line treatment

Study on improvement in reliability of inventory assessment in vitrified waste for long-term safety of geological disposal

International Nuclear Information System (INIS)

Ishikawa, Masumi; Kaneko, Satoru; Kitayama, Kazumi; Ishiguro, Katsuhiko; Ueda, Hiroyoshi; Wakasugi, Keiichiro; Shinohara, Nobuo; Okumura, Keisuke; Chino, Masamichi; Moriya, Noriyasu

2009-01-01

Since quality control issues for vitrified waste are defined mainly with the focus on the transport and interim storage of the waste rather than the long-term safety of geological disposal, they do not cover inventories of long-lived nuclides that are of most interest in the safety assessment of geological disposal. Therefore, we suggest a flow chart for the assessment of inventories of long-lived nuclides in the vitrified waste focusing on the measured values. This includes an indirect assessment with indicative nuclides that have been already measured in the returned vitrified wastes from abroad. In order to apply this flow chart for commercial operation, its applicability should be examined for cases with a variation in burn-up history and with an uncertainty associated with carry-over fraction at reprocessing. We started an R and D program to examine the applicability as well as to improve the reliability of the nuclide generation/decay code and the nuclear data library using liquid waste from spent fuel with a clear irradiation history. To solve the issue of quality control for vitrified waste, a comprehensive study is needed in aspects not only of geological disposal field but also of operation of a nuclear power plant, reprocessing of spent fuel and vitrification of liquid waste. This study is a pioneering study conducted to integrate them. (author)

LISA package user guide. Part II: LISA (Long Term Isolation Safety Assessment) program description and user guide

International Nuclear Information System (INIS)

Prado, P.; Saltelli, A.; Homma, T.

1992-01-01

This manual is subdivided into three parts. In this second part, this document describes the LISA (Long term Isolation Safety Assessment) Code and its submodels. LISA is a tool for analysis of the safety of an underground disposal of nuclear waste. It has the capability to handle nuclide chain of arbitrary length and to evaluate the migration of nuclide through a geosphere medium composed of an arbitrary number of segments. LISA makes use of Monte Carlo methodology to evaluate the uncertainty in the quantity being assessed (eg dose) arising from the uncertainty in the model input parameters. In the present version LISA is equipped with a very simple source term submodel, a relatively complex geosphere and a simplified biosphere. The code is closely associated with its statistical pre-processor code (PREP), which generates the input Monte Carlo sample from the assigned parameter probability density functions and with its post-processor code (SPOP) which provides useful statistics on the output sample (uncertainty and sensitivity analysis). This report describes the general structure of LISA, its subroutines and submodels, the code input ant output files. It is intended to provide the user with enough information to know and run the code as well as the capacity to incorporate different submodels. 15 refs., 6 figs

A Systematic Review of the Safety of Lisdexamfetamine Dimesylate

OpenAIRE

Coghill, David R.; Caballero, Beatriz; Sorooshian, Shaw; Civil, Richard

2014-01-01

Background Here we review the safety and tolerability profile of lisdexamfetamine dimesylate (LDX), the first long-acting prodrug stimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD). Methods A PubMed search was conducted for English-language articles published up to 16 September 2013 using the following search terms: (lisdexamfetamine OR lisdexamphetamine OR SPD489 OR Vyvanse OR Venvanse OR NRP104 NOT review [publication type]). Results In short-term, parallel-group...

Long-term real-time structural health monitoring using wireless smart sensor

Science.gov (United States)

Jang, Shinae; Mensah-Bonsu, Priscilla O.; Li, Jingcheng; Dahal, Sushil

2013-04-01

Improving the safety and security of civil infrastructure has become a critical issue for decades since it plays a central role in the economics and politics of a modern society. Structural health monitoring of civil infrastructure using wireless smart sensor network has emerged as a promising solution recently to increase structural reliability, enhance inspection quality, and reduce maintenance costs. Though hardware and software framework are well prepared for wireless smart sensors, the long-term real-time health monitoring strategy are still not available due to the lack of systematic interface. In this paper, the Imote2 smart sensor platform is employed, and a graphical user interface for the long-term real-time structural health monitoring has been developed based on Matlab for the Imote2 platform. This computer-aided engineering platform enables the control, visualization of measured data as well as safety alarm feature based on modal property fluctuation. A new decision making strategy to check the safety is also developed and integrated in this software. Laboratory validation of the computer aided engineering platform for the Imote2 on a truss bridge and a building structure has shown the potential of the interface for long-term real-time structural health monitoring.

Newly detected abnormal glucose regulation and long-term prognosis after acute myocardial infarction

DEFF Research Database (Denmark)

Pararajasingam, Gokulan; Høfsten, Dan Eik; Løgstrup, Brian Bridal

2016-01-01

BACKGROUND: An oral glucose tolerance test (OGTT) and/or glycosylated haemoglobin A1c (HbA1c) in patients with acute myocardial infarction (AMI) identify patients with increased mortality risk, but no comparison of the long-term prognostic values has yet been investigated. METHODS: This study...... to patients categorized as normal/impaired fasting glycaemia/impaired glucose tolerance by OGTT and HbA1c values. CONCLUSION: An OGTT is recommended in AMI patients without known DM...

Long-term efficacy and safety of vildagliptin add-on therapy in type 2 diabetes mellitus with insulin treatment.

Science.gov (United States)

Kanazawa, Ippei; Tanaka, Ken-Ichiro; Notsu, Masakazu; Tanaka, Sayuri; Kiyohara, Nobuaki; Koike, Sayo; Yamane, Yuko; Tada, Yuko; Sasaki, Motofumi; Yamauchi, Mika; Sugimoto, Toshitsugu

2017-01-01

The use of dipeptidyl peptidase (DPP)-4 inhibitors in patients with type 2 diabetes treated with insulin may be beneficial. However, the long-term efficacy and safety of vildagliptin add-on therapy in these patients remains unclear. A total of 73 patients with type 2 diabetes treated with insulin were randomly assigned to receive either add-on therapy of vildagliptin (n=37) or conventional therapy without DPP-4 inhibitors (n=36) for glucose control. Hemoglobin A1c (HbA1c) levels, dose and number of insulin injections, number of hypoglycemia episodes, and liver and renal function were monitored for 2years. The baseline characteristics of subjects, including age, dose of insulin injections, or HbA1c levels, did not differ between the two groups. In the vildagliptin group, HbA1c levels significantly decreased and the significance of HbA1c reduction was maintained for 24months (from 8.0±1.2% to 7.4±1.0%, pinsulin injections significantly reduced (-5.6units, p1, and -0.9 times, p1). However, these parameters were unchanged in the control group. The number of patients who experienced three or more episodes of hypoglycemia per year was significantly lower in the vildagliptin group (n=4) than in the control group (n=11) (odds ratio, 0.28; 95% confidence interval, 0.08-0.97; pinsulin treatment for 24months was well tolerated and led to sustained reductions in HbA1c, the dose and number of insulin injections, and the risk of hypoglycemia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Overview of waste isoltaion safety assessment program and description of source term characterization task at PNL

International Nuclear Information System (INIS)

Bradley, D.

1977-01-01

A project is being conducted to develop and illustrate the methods and obtain the data necessary to assess the safety of long-term disposal of high-level radioactive waste in geologic formations. The methods and data will initially focus on generic geologic isolation systems but will ultimately be applied to the long-term safety assessment of specific candidate sites that are selected in the NWTS Program. The activities of waste isolation safety assessment (WISAP) are divided into six tasks: (1) Safety Assessment Concepts and Methods, (2) Disruptive Event Analysis, (3) Source Characterization, (4) Transport Modeling, (5) Transport Data and (6) Societal Acceptance

Development of nuclear fuel cycle technologies - bases of long-term provision of fuel and environmental safety of nuclear power

International Nuclear Information System (INIS)

Solonin, M.I.; Polyakov, A.S.; Zakharkin, B.S.; Smelov, V.S.; Nenarokomov, E.A.; Mukhin, I.V.

2000-01-01

To-day nuclear power is one of the options, however, to-morrow it may become the main source of the energy, thus, providing for the stable economic development for the long time to come. The availability of the large-scale nuclear power in the foreseeable future is governed by not only the safe operation of nuclear power plants (NPP) but also by the environmentally safe management of spent nuclear fuel, radioactive waste conditioning and long-term storage. More emphasis is to be placed to the closing of the fuel cycle in view of substantial quantities of spent nuclear fuel arisings. The once-through fuel cycle that is cost effective at the moment cannot be considered to be environmentally safe even for the middle term since the substantial build-up of spent nuclear fuel containing thousands of tons Pu will require the resolution of the safe management problem in the nearest future and is absolutely unjustified in terms of moral ethics as a transfer of the responsibility to future generations. The minimization of radioactive waste arisings and its radioactivity is only feasible with the closed fuel cycle put into practice and some actinides and long-lived fission radionuclides burnt out. The key issues in providing the environmentally safe fuel cycle are efficient processes of producing fuel for NPP, radionuclide after-burning included, a long-term spent nuclear fuel storage and reprocessing as well as radioactive waste management. The paper deals with the problems inherent in producing fuel for NPP with a view for the closed fuel cycle. Also discussed are options of the fuel cycle, its effectiveness and environmental safety with improvements in technologies of spent nuclear fuel reprocessing and long-lived radionuclide partitioning. (authors)

Development of nuclear fuel cycle technologies - bases of long-term provision of fuel and environmental safety of nuclear power

Energy Technology Data Exchange (ETDEWEB)

Solonin, M I; Polyakov, A S; Zakharkin, B S; Smelov, V S; Nenarokomov, E A; Mukhin, I V [SSC, RF, A.A. Bochvar ALL-Russia Research Institute of Inorganic Materials, Moscow (Russian Federation)

2000-07-01

To-day nuclear power is one of the options, however, to-morrow it may become the main source of the energy, thus, providing for the stable economic development for the long time to come. The availability of the large-scale nuclear power in the foreseeable future is governed by not only the safe operation of nuclear power plants (NPP) but also by the environmentally safe management of spent nuclear fuel, radioactive waste conditioning and long-term storage. More emphasis is to be placed to the closing of the fuel cycle in view of substantial quantities of spent nuclear fuel arisings. The once-through fuel cycle that is cost effective at the moment cannot be considered to be environmentally safe even for the middle term since the substantial build-up of spent nuclear fuel containing thousands of tons Pu will require the resolution of the safe management problem in the nearest future and is absolutely unjustified in terms of moral ethics as a transfer of the responsibility to future generations. The minimization of radioactive waste arisings and its radioactivity is only feasible with the closed fuel cycle put into practice and some actinides and long-lived fission radionuclides burnt out. The key issues in providing the environmentally safe fuel cycle are efficient processes of producing fuel for NPP, radionuclide after-burning included, a long-term spent nuclear fuel storage and reprocessing as well as radioactive waste management. The paper deals with the problems inherent in producing fuel for NPP with a view for the closed fuel cycle. Also discussed are options of the fuel cycle, its effectiveness and environmental safety with improvements in technologies of spent nuclear fuel reprocessing and long-lived radionuclide partitioning. (authors)

Long-term surveillance plan for the Mexican Hat disposal site Mexican Hat, Utah

International Nuclear Information System (INIS)

1997-06-01

This long-term surveillance plan (LTSP) describes the U.S. Department of Energy's (DOE) long-term care program for the Uranium Mill Tailings Remedial Action (UMTRA) Project Mexican Hat, Utah, disposal site. This LSTP describes the long-term surveillance program the DOE will implement to ensure the Mexican Hat disposal site performs as designed and is cared for in a manner that protects the public health and safety and the environment. Before each disposal site is licensed for custody and long-term care, the Nuclear Regulatory Commission (NRC) requires the DOE to submit such a site-specific LTSP

Long-term surveillance plan for the Estes Gulch disposal site near Rifle, Colorado

International Nuclear Information System (INIS)

1997-07-01

This long-term surveillance plan (LTSP) describes the U.S. Department of Energy's (DOE) long-term care program for the Uranium Mill Tailings Remedial Action (UMTRA) Project Estes Gulch disposal site near Rifle, Colorado. This LSTP describes the long-term surveillance program the DOE will implement to ensure the Estes Gulch disposal site performs as designed and is cared for in a manner that protects the public health and safety and the environment. Before each disposal site is licensed for custody and long-term care, the Nuclear Regulatory Commission (NRC) requires the DOE to submit such a site-specific LTSP

Long-term surveillance plan for the Cheney disposal site near Grand Junction, Colorado

International Nuclear Information System (INIS)

1997-07-01

This long-term surveillance plan (LTSP) describes the U.S. Department of Energy's (DOE) long-term care program for the Uranium Mill Tailings Remedial Action (UMTRA) Project Cheney Disposal Site near Grand Junction, Colorado. This LSTP describes the long-term surveillance program the DOE will implement to ensure the Cheney Disposal Site performs as designed and is cared for in a manner that protects the public health and safety and the environment. Before each disposal site is licensed for custody and long-term care, the Nuclear Regulatory Commission (NRC) requires the DOE to submit such a site-specific LTSP

Long term operation of nuclear power plants in the U.S

International Nuclear Information System (INIS)

Young, G.G.

2015-01-01

This series of slides shows that safety, performance, cost, environmental and public opinion factors are favorable for long term operation of U.S. nuclear power plants. In the U.S. 1 reactor has an operating life ranging between 10 and 19 years, 37 reactors have an operating life ranging between 20 and 29 years, 42 reactors between 30 and 39 years and 20 reactors have an operating life over 40 years. The original license term is 40 years and it can be extended by 20 years for each renewal. The application for renewal must be at least 5 years before expiration of the current license. 3 main areas are reviewed by NRC to get the renewal: safety, environmental and adjudicatory. A slide describes the NRC license renewal process and another slide lists the regulatory and industry guidance documents based on lessons learned and operating experience. Research and development efforts around materials aging and safety margin characterization by EPRI, DOE, NRC and industry groups are essential to support and maintain the option of long term operation of nuclear reactors. (A.C.)

Long-Term Hydrologic Monitoring Program, Amchitka Island, Alaska

International Nuclear Information System (INIS)

1982-01-01

The purpose of the Long-Term Hydrologic Monitoring Program for Amchitka Island, Alaska, is to obtain data that will assure the public safety, inform the public, the news media, and the scientific community relative to radiological contamination, and to document compliance with federal, state, and local antipollution requirements. Amchitka's geographical setting, climate, geology, hydrology, and ecology are described. Site history including event information for LONG SHOT in 1965, MILROW in 1969, and CANNIKIN in 1971 is described. Event related contamination has been observed only at the LONG SHOT site. At this site, tritium in concentrations below the drinking water standards has been observed in mud pits and wells in the area adjacent to surface ground zero. The Long-Term Hydrologic Monitoring Program for Amchitka is described. No radioactive venting, significant radioactive leakage, or bioenvironmental damage resulted from any of the nuclear tests on Amchitka

Clinical trials with rasagiline: evidence for short-term and long-term effects.

Science.gov (United States)

Siderowf, Andrew; Stern, Matthew

2006-05-23

Rasagiline (N-propargyl-1 (R)-aminoindan) is a selective, potent irreversible inhibitor of MAO-B that possesses neuroprotective and anti-apoptotic properties in a variety of in vitro and in vivo animal models relevant to Parkinson's disease (PD). Several randomized controlled clinical trials have demonstrated the safety and efficacy of rasagiline as monotherapy in PD and as adjunctive therapy for patients receiving levodopa. In addition, the 1-year randomized, delayed-start analysis of the TEMPO study suggests that rasagiline may slow the rate of progression of PD. The randomized delayed-start paradigm has potential to differentiate short-term symptomatic effects from long-term effects of anti-parkinsonian agents. In the future, long-term trials to examine the potential disease-modifying effects of rasagiline, which incorporate biological markers as well as clinical endpoints, may further elucidate the role of rasagiline in the treatment of both early and advanced PD.

Long-term salinity tolerance is accompanied by major restructuring of the coral bacterial microbiome

KAUST Repository

Röthig, Till

2016-02-03

Scleractinian corals are assumed to be stenohaline osmoconformers, although they are frequently subjected to variations in seawater salinity due to precipitation, freshwater runoff, and other processes. Observed responses to altered salinity levels include differences in photosynthetic performance, respiration, and increased bleaching and mortality of the coral host and its algal symbiont, but a study looking at bacterial community changes is lacking. Here we exposed the coral Fungia granulosa to strongly increased salinity levels in short- and long-term experiments to disentangle temporal and compartment effects of the coral holobiont (i.e. coral host, symbiotic algae, and associated bacteria). Our results show a significant reduction in calcification and photosynthesis, but a stable microbiome after short-term exposure to high salinity levels. By comparison, long-term exposure yielded unchanged photosynthesis levels and visually healthy coral colonies indicating long-term acclimation to high salinity levels that were accompanied by a major coral microbiome restructuring. Importantly, a bacterium in the family Rhodobacteraceae was succeeded by Pseudomonas veronii as the numerically most abundant taxon. Further, taxonomy-based functional profiling indicates a shift in the bacterial community towards increased osmolyte production, sulfur oxidation, and nitrogen fixation. Our study highlights that bacterial community composition in corals can change within days to weeks under altered environmental conditions, where shifts in the microbiome may enable adjustment of the coral to a more advantageous holobiont composition.

Rolls-Royce I and C long term support a dedicated solution to manage plant condition, optimize operating life and maximize plant value while improving safety

International Nuclear Information System (INIS)

Baillonmartos, F.

2010-01-01

Rolls-Royce supplied safety I and C equipment as Original Equipment Manufacturer (OEM) for 200 reactors in operation from 1970', including various technological steps (analog to digital hardware). The hardware scope covers various systems, either more than 500 hardware references, either more than 150000 parts in operation. Rolls-Royce contributes to life time extension ensuring system availability and reliability on long term basis by determining the optimum solution between different maintenance approaches: maintenance and repair with limited retrofit or major system retrofit. Based on Long Term Support (LTS) agreement with customers, Rolls-Royce commits to maintain the capability to manufacture, modify, repair, test, at board, rack and systems level over a long time period. This means finding solution to hardware ageing, technology evolution, skills and tools maintenance. This paper describes how Rolls-Royce has built a global process based on delivering a package of services and developing long term support engineering solutions and tools. Our main experience on EDF partnership will serve to illustrate Rolls-Royce I and C Long Term Support activity. (authors)

Symptoms and Character Traits in Patients Selected for Long-term Psychodynamic Psychotherapy

Science.gov (United States)

Wilczek, Alexander; Weinryb, Robert M.; Gustavsson, Petter J.; Barber, Jacques P.; Schubert, Johan; ÅSBERG, Marie

1998-01-01

In this naturalistic study of 55 outpatients selected for long-term psychodynamic psychotherapy, two Swedish assessment instruments are presented (the Karolinska Psychodynamic Profile and the Karolinska Scales of Personality), and the significance of psychodynamic criteria for the selection of patients is discussed. Thirty patients (55%) fulfilled criteria for a DSM-III-R diagnosis. The most prominent psychodynamically defined character pathology was found in the areas of coping with aggressive affects; dependency and separation; frustration tolerance; and impulse control. Some psychodynamically defined character traits, particularly poor frustration tolerance, were related to symptomatic suffering. PMID:9407473

Risk Assessment and Control through Countermeasure System Iplementation for Long-term Crew Exposure to Microgravity

Science.gov (United States)

Gernand, Jeremy M.

2004-01-01

Experience with the International Space Station (ISS) program demonstrates the degree to which engineering design and operational solutions must protect crewmembers from health risks due to long-term exposure to the microgravity environment. Risks to safety and health due to degradation in the microgravity environment include crew inability to complete emergency or nominal activities, increased risk of injury, and inability to complete safe return to the ground due to reduced strength or embrittled bones. These risks without controls slowly increase in probability for the length of the mission and become more significant for increasing mission durations. Countermeasures to microgravity include hardware systems that place a crewmember s body under elevated stress to produce an effect similar to daily exposure to gravity. The ISS countermeasure system is predominately composed of customized exercise machines. Historical treatment of microgravity countermeasure systems as medical research experiments unintentionally reduced the foreseen importance and therefore the capability of the systems to function in a long-term operational role. Long-term hazardous effects and steadily increasing operational risks due to non-functional countermeasure equipment require a more rigorous design approach and incorporation of redundancy into seemingly non- mission-critical hardware systems. Variations in the rate of health degradation and responsiveness to countermeasures among the crew population drastically increase the challenge for design requirements development and verification of the appropriate risk control strategy. The long-term nature of the hazards and severe limits on logistical re-supply mass, volume and frequency complicates assessment of hardware availability and verification of an adequate maintenance and sparing plan. Design achievement of medically defined performance requirements by microgravity countermeasure systems and incorporation of adequate failure tolerance

Development of Long-term Cooling Operation Strategy with H-SIT

International Nuclear Information System (INIS)

Jeon, In Seop; Kang, Hyun Gook

2016-01-01

In the current nuclear power plants (NPPs), most of the critical safety functions are provided by many active safety systems. Long-term cooling of core is an ultimate goal of all mitigation actions for plant safety and feed and bleed (F and B) operation strategy is one of long-term cooling strategies in conventional pressurized water reactor (PWR). The important point of F and B operation is that, in conventional mitigation strategy, injection for feed operation is performed by only high pressure injection (HPSI) pump. Low pressure injection (LPSI) pump such as shut down cooling pump (SCP) cannot be used for F and B operation. Thus, when F and B operation is needed, if high-pressure injection pump fails, core should be damaged. In this study, F and B operation strategy with LPSI and H-SIT is developed. This is a new concept for the long-term cooling operation. If this strategy is applied, low pressure injection pump can be successfully used for F and B operation thus operator has the additional mitigation way. As this strategy make plant safe even though HPSI and PAFS are both failed, it can effectively enhance the plant safety. For this strategy two RCGVSs and two POSRVs are needed as a depressurization system for bleed operation and only one LPSI is enough for feed operation. H-SIT operation is also needed to make up core inventory during bleed operation. For this operation, four H-SITs have to be used to make up core safely. Based on the risk analysis using PSA method, if this strategy is applied, core damage frequency is 1.868e-6 which declined 7 percent from original model.

A double-blind study evaluating the long-term safety of varenicline for smoking cessation.

Science.gov (United States)

Williams, Kathryn E; Reeves, Karen R; Billing, Clare B; Pennington, Ann M; Gong, Jason

2007-04-01

We assessed the safety of long-term varenicline administration for smoking cessation. In this randomized, double-blind, multicenter trial, eligible adult smokers (18-75 years) who smoked an average of > or =10 cigarettes/day were randomized to either varenicline 1 mg twice daily (BID) or placebo for 52 weeks. Subjects made weekly clinic visits until week 8, and then every 4 weeks until week 52, with a follow-up visit at week 53. The target quit date was the morning of the week 1 clinic visit. Brief counseling was provided at each visit, and vital signs, adverse events (AEs), and smoking status were documented. Other laboratory measures were collected at specified visits. A total of 251 subjects were randomized to varenicline and 126 to placebo. Approximately half of the subjects in each arm completed the study (53.8% varenicline; 46.8% placebo). Treatment-emergent AEs were observed in 96.4% of varenicline- and 82.5% of placebo-treated subjects during the study. Common varenicline-associated AEs were nausea (40.2%), abnormal dreams (22.7%), and insomnia (19.1%). Most AEs were considered mild or moderate in intensity. AEs leading to discontinuation of varenicline treatment included nausea (7.6%), insomnia (3.2%), and abnormal dreams (2.4%). A single varenicline-related serious AE, bilateral subcapsular cataracts, was observed. At week 52, 7-day point prevalence abstinence rates were 36.7% (varenicline) and 7.9% (placebo). Varenicline 1 mg BID can be safely administered for up to 1 year. Varenicline was also a more effective smoking cessation aid than placebo throughout the study, supporting both its short- (12-week) and long-term (52-week) efficacy.

Long-term gastrointestinal tolerance of NUTRIOSE®FB in healthy men

NARCIS (Netherlands)

Pasman, W.; Wils, D.; Saniez, M.H.; Kardinaal, A.

2006-01-01

Objective: To determine the gastrointestinal (GI) tolerance of NUTRIOSE®FB in men. Design: A randomized, placebo-contro lled, parallel, double-blind study. Setting: The metabolic ward of TNO Quality of Life. Subjects: Forty-eight subjects started the study: 16 men participated in one of the three

Long-term safety and efficacy of autologous platelet lysate drops for treatment of ocular GvHD.

Science.gov (United States)

Pezzotta, S; Del Fante, C; Scudeller, L; Rossi, G C; Perotti, C; Bianchi, P E; Antoniazzi, E

2017-01-01

Current ocular GvHD (oGvHD) treatments are suboptimal. We investigated the safety and efficacy of long-term continuous treatment with autologous platelet lysate (PL) drops in patients with oGvHD Dry Eye Syndrome (DES) score 2-3 refractory to topical conventional therapy. Ophthalmic evaluation was performed at 6 month intervals. Symptoms were assessed using the Glaucoma Symptom Scale (GSS). Patients were defined 'responders' when showing a reduction at least one grade on National Institutes of Health Eye Score from baseline at the 6 month visit. Thirty-one patients were included, and 16 (51%) completed 36 months of follow-up (range 6.5-72.7). At 6 months all patients were classified as responders: median GSS symptom score decreased from 70 to 41 (33 at 36 months), median GSS function score reduced from 68 to 46 (33 at 36 months) (all P<0.001). Median Tear Break Up Time improved from 3 to 6 s after 6 months and was maintained over time. All signs improved at 6 and 36 months (clinical and statistical significance). No severe adverse events occurred. Long-term treatment with PL drops is secure and effective for oGvHD and can be an efficient therapy option from initial stages of oGvHD to prevent permanent ocular impairment and improving quality of life.

Long-term stable, long-term safe storage of residues and radioactive waste. Contribution to discussion to the storage (final storage); Langzeitstabile, langzeitsichere Verwahrung von Rueckstaenden und radioaktiven Abfaellen. Beitrag zur Diskussion um Lagerung (Endlagerung)

Energy Technology Data Exchange (ETDEWEB)

Lersow, Michael [DGGT e.V., Breitenbrunn/Erzgeb. (Germany). Ak 5.5 Tailings; Gellermann, Rainer [Nuclear Control and Consulting GmbH, Braunschweig (Germany)

2015-09-15

In this paper it is presented, where radioactive waste and residues occur, how these materials can be classified, which rules and regulations have to be complied with regarding the disposal and which geotechnical environmental constructions (final repositories) are suitable to guarantee a safe long-term disposal of these materials. Primary protection objective is ''to permanently prevent the transfer of toxic, radioactive contaminations into the biosphere by air, water or rock path or to keep the amount of contamination within a commonly accepted range''. Radionuclide inventories and the given time period considered for long-term safety are compared with. It is shown, that the site-specific disposal solutions cannot be justified by the radioactive inventory deposited there. The given period of 10{sup 6} years is critically evaluated. Based on this it is suggested to subdivide this period into two time periods with different prognosis reliabilities. Results of a specially designed long-term monitoring as part of the site-specific waste disposal solution should be considered for the long-term safety proof. A modular concept for the final storage of High Active Waste (HAW) is derived based on the critical evaluation of the long-term safety, including transmutation, provisional storage and monitoring module. A foundation model is proposed to guarantee the financial resources required for the disposal of HAW.

Long-Term Safety and Effectiveness of Adalimumab for Moderate to Severe Psoriasis: Results from 7-Year Interim Analysis of the ESPRIT Registry.

Science.gov (United States)

Menter, Alan; Thaçi, Diamant; Wu, Jashin J; Abramovits, William; Kerdel, Francisco; Arikan, Dilek; Guo, Dianlin; Ganguli, Arijit; Bereswill, Mareike; Camez, Anne; Valdecantos, Wendell C

2017-09-01

ESPRIT (NCT00799877) is an ongoing 10-year international prospective observational registry evaluating the long-term safety and effectiveness of originator adalimumab in routine clinical practice for adult patients with chronic plaque psoriasis. Herein, we report the long-term safety, effectiveness, and patient-reported outcomes (PROs) following adalimumab treatment over the first 7 years of the ESPRIT registry. All treatment-emergent (All-TE) adverse events (AE) since the initial (first ever) dose of adalimumab were assessed. Physician Global Assessment (PGA) and PROs (PROs for US patients only) were evaluated during registry participation. As of 30 November 2015, 6051 patients in the ESPRIT registry were analyzed, representing 23,660.1 patient-years (PY) of overall adalimumab exposure. The incidence rates for All-TE serious AEs, serious infections, and malignancies were 4.4, 1.0, and 1.0 events per 100 PY (E/100PY), respectively. The standardized mortality ratio for TE deaths in the registry was 0.27 (95% CI 0.18-0.38). During the registry's first 7 years, PGA "clear" or "minimal" was achieved by >50% of patients at each annual visit, and among US patients, the mean improvement from baseline in different PROs was maintained. No new safety signals were identified during the first 7 years of the registry, and safety was consistent with the known safety profile of adalimumab. The number of TE deaths was below the expected rate. During the registry's first 7 years, most of the patients remained free of All-TE cardiovascular events, serious infections, and malignancy. As-observed effectiveness of adalimumab and improvements from baseline in PROs were maintained through 7 years of registry participation. Abbvie. ClinicalTrials.gov identifier, NCT00799877.

Long-term salinity tolerance is accompanied by major restructuring of the coral bacterial microbiome.

Science.gov (United States)

Röthig, Till; Ochsenkühn, Michael A; Roik, Anna; van der Merwe, Riaan; Voolstra, Christian R

2016-03-01

Scleractinian corals are assumed to be stenohaline osmoconformers, although they are frequently subjected to variations in seawater salinity due to precipitation, freshwater run-off and other processes. Observed responses to altered salinity levels include differences in photosynthetic performance, respiration and increased bleaching and mortality of the coral host and its algal symbiont, but a study looking at bacterial community changes is lacking. Here, we exposed the coral Fungia granulosa to strongly increased salinity levels in short- and long-term experiments to disentangle temporal and compartment effects of the coral holobiont (i.e. coral host, symbiotic algae and associated bacteria). Our results show a significant reduction in calcification and photosynthesis, but a stable microbiome after short-term exposure to high-salinity levels. By comparison, long-term exposure yielded unchanged photosynthesis levels and visually healthy coral colonies indicating long-term acclimation to high-salinity levels that were accompanied by a major coral microbiome restructuring. Importantly, a bacterium in the family Rhodobacteraceae was succeeded by Pseudomonas veronii as the numerically most abundant taxon. Further, taxonomy-based functional profiling indicates a shift in the bacterial community towards increased osmolyte production, sulphur oxidation and nitrogen fixation. Our study highlights that bacterial community composition in corals can change within days to weeks under altered environmental conditions, where shifts in the microbiome may enable adjustment of the coral to a more advantageous holobiont composition. © 2016 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

PSA modeling of long-term accident sequences

International Nuclear Information System (INIS)

Georgescu, Gabriel; Corenwinder, Francois; Lanore, Jeanne-Marie

2014-01-01

In the context of the extension of PSA scope to include external hazards, in France, both operator (EDF) and IRSN work for the improvement of methods to better take into account in the PSA the accident sequences induced by initiators which affect a whole site containing several nuclear units (reactors, fuel pools,...). These methodological improvements represent an essential prerequisite for the development of external hazards PSA. However, it has to be noted that in French PSA, even before Fukushima, long term accident sequences were taken into account: many insight were therefore used, as complementary information, to enhance the safety level of the plants. IRSN proposed an external events PSA development program. One of the first steps of the program is the development of methods to model in the PSA the long term accident sequences, based on the experience gained. At short term IRSN intends to enhance the modeling of the 'long term' accident sequences induced by the loss of the heat sink or/and the loss of external power supply. The experience gained by IRSN and EDF from the development of several probabilistic studies treating long term accident sequences shows that the simple extension of the mission time of the mitigation systems from 24 hours to longer times is not sufficient to realistically quantify the risk and to obtain a correct ranking of the risk contributions and that treatment of recoveries is also necessary. IRSN intends to develop a generic study which can be used as a general methodology for the assessment of the long term accident sequences, mainly generated by external hazards and their combinations. This first attempt to develop this generic study allowed identifying some aspects, which may be hazard (or combinations of hazards) or related to initial boundary conditions, which should be taken into account for further developments. (authors)

Prevention of fall-related injuries in long-term care: a randomized controlled trial of staff education.

Science.gov (United States)

Ray, Wayne A; Taylor, Jo A; Brown, Anne K; Gideon, Patricia; Hall, Kathi; Arbogast, Patrick; Meredith, Sarah

2005-10-24

Fall-related injuries, a major public health problem in long-term care, may be reduced by interventions that improve safety practices. Previous studies have shown that safety practice interventions can reduce falls; however, in long-term care these have relied heavily on external funding and staff. The aim of this study was to test whether a training program in safety practices for staff could reduce fall-related injuries in long-term care facilities. A cluster randomization clinical trial with 112 qualifying facilities and 10,558 study residents 65 years or older and not bedridden. The intervention was an intensive 2-day safety training program with 12-month follow-up. The training program targeted living space and personal safety; wheelchairs, canes, and walkers; psychotropic medication use; and transferring and ambulation. The main outcome measure was serious fall-related injuries during the follow-up period. There was no difference in injury occurrence between the intervention and control facilities (adjusted rate ratio, 0.98; 95% confidence interval, 0.83-1.16). For residents with a prior fall in facilities with the best program compliance, there was a nonsignificant trend toward fewer injuries in the intervention group (adjusted rate ratio, 0.79; 95% confidence interval, 0.57-1.10). More intensive interventions are required to prevent fall-related injuries in long-term care facilities.

Successful long-term preservation of rat sperm by freeze-drying.

Directory of Open Access Journals (Sweden)

Takehito Kaneko

Full Text Available BACKGROUND: Freeze-drying sperm has been developed as a new preservation method where liquid nitrogen is no longer necessary. An advantage of freeze-drying sperm is that it can be stored at 4 °C and transported at room temperature. Although the successful freeze-drying of sperm has been reported in a number of animals, the possibility of long-term preservation using this method has not yet been studied. METHODOLOGY/PRINCIPAL FINDINGS: Offspring were obtained from oocytes fertilized with rat epididymal sperm freeze-dried using a solution containing 10 mM Tris and 1 mM EDTA adjusted to pH 8.0. Tolerance of testicular sperm to freeze-drying was increased by pre-treatment with diamide. Offspring with normal fertility were obtained from oocytes fertilized with freeze-dried epididymal sperm stored at 4 °C for 5 years. CONCLUSIONS AND SIGNIFICANCE: Sperm with -SS- cross-linking in the thiol-disulfide of their protamine were highly tolerant to freeze-drying, and the fertility of freeze-dried sperm was maintained for 5 years without deterioration. This is the first report to demonstrate the successful freeze-drying of sperm using a new and simple method for long-term preservation.

Long-term exposure and safety of lacosamide monotherapy for the treatment of partial-onset (focal) seizures: Results from a multicenter, open-label trial.

Science.gov (United States)

Vossler, David G; Wechsler, Robert T; Williams, Paulette; Byrnes, William; Therriault, Sheila

2016-10-01

To assess long-term use and safety of lacosamide (LCM) ≤800 mg/day monotherapy in patients with partial-onset seizures (POS) enrolled previously in a historical-controlled, conversion-to-monotherapy study (SP902; NCT00520741). Patients completing or exiting SP902 with LCM as monotherapy or as adjunctive therapy were eligible to enter this 2-year open-label extension (OLE) trial (SP904; NCT00530855) at a starting dose ±100 mg/day of their final SP902 dose. Investigators could adjust the LCM dose to 100-800 mg/day and add up to two antiepileptic drugs to optimize tolerability and seizure reduction. Three hundred twenty-two patients received LCM: 210 patients (65.2%) completed and 112 (34.8%) discontinued, most commonly owing to withdrawal of consent (9.3%). Two hundred fifty-eight patients (80.1%) had ≥1 year of and 216 (67.1%) had ≥2 years of LCM exposure, of whom 179/258 (69.4%) achieved LCM monotherapy lasting for any 12-month period, and 126/216 (58.3%) patients exposed for ≥24 months achieved LCM monotherapy for any 24-month period. Total exposure = 525.5 patient-years. The median modal dose was 500 mg/day. Two hundred ninety-two patients (90.7%) achieved LCM monotherapy at some point during the study. Sixty-five of 87 patients who exited and 193/235 who completed SP902 were exposed for ≥12 months, and 43.1% and 78.2%, respectively, achieved LCM monotherapy for ≥12 months. Median LCM monotherapy duration was 587.0 days (2-791 days); 91.0% of patients reported treatment-emergent adverse events, of which the most common were dizziness (27.3%), headache (17.1%), and nausea (14.3%). Compared with the SP902 study baseline, 74.2% of patients had a ≥50% seizure reduction and 5.6% were seizure-free at 24 months. The majority of patients were receiving LCM monotherapy at 0, 12, and 24 months in this OLE. Lacosamide monotherapy (median dose of 500 mg/day) had a safety profile similar to that of adjunctive therapy studies. These results support the use of

Immune response at birth, long-term immune memory and 2 years follow-up after in-utero anti-HBV DNA immunization.

Science.gov (United States)

Fazio, V M; Ria, F; Franco, E; Rosati, P; Cannelli, G; Signori, E; Parrella, P; Zaratti, L; Iannace, E; Monego, G; Blogna, S; Fioretti, D; Iurescia, S; Filippetti, R; Rinaldi, M

2004-03-01

Infections occurring at the end of pregnancy, during birth or by breastfeeding are responsible for the high toll of death among first-week infants. In-utero DNA immunization has demonstrated the effectiveness in inducing specific immunity in newborns. A major contribution to infant immunization would be achieved if a vaccine proved able to be protective as early as at the birth, preventing the typical 'first-week infections'. To establish its potential for use in humans, in-utero DNA vaccination efficiency has to be evaluated for short- and long-term safety, protection at delivery, efficacy of boosts in adults and effective window/s for modulation of immune response during pregnancy, in an animal model suitable with human development. Here we show that a single intramuscular in-utero anti-HBV DNA immunization at two-thirds of pig gestation produces, at birth, antibody titers considered protective in humans. The boost of antibody titers in every animal following recall at 4 and 10 months demonstrates the establishment of immune memory. The safety of in-utero fetus manipulation is guaranteed by short-term (no fetus loss, lack of local alterations, at-term spontaneous delivery, breastfeeding) and long-term (2 years) monitoring. Treatment of fetuses closer to delivery results in immune ignorance without induction of tolerance. This result highlights the repercussion of selecting the appropriate time point when this approach is used to deliver therapeutic genes. All these findings illustrate the relevance of naked DNA-based vaccination technology in therapeutic efforts aimed to prevent the high toll of death among first-week infants.

Interim long-term surveillance plan for the Cheney disposal site near, Grand Junction, Colorado

International Nuclear Information System (INIS)

1997-08-01

This interim long-term surveillance plan (LTSP) describes the U.S. Department of Energy's (DOE) long-term care program for the Uranium Mill Tailings Remedial Action (UMTRA) Project Cheney Disposal Site in Mesa County near Grand Junction, Colorado. This LSTP describes the long-term surveillance program the DOE will implement to ensure the Cheney disposal site performs as designed and is cared for in a manner that protects the public health and safety and the environment. Before each disposal site is licensed for custody and long-term care, the Nuclear Regulatory Commission (NRC) requires the DOE to submit such a site-specific LTSP

Sustained weight loss in patients treated with mifepristone for Cushing's syndrome: a follow-up analysis of the SEISMIC study and long-term extension.

Science.gov (United States)

Fein, Henry G; Vaughan, T Brooks; Kushner, Harvey; Cram, David; Nguyen, Dat

2015-10-27

Overweight and obesity are common among patients with Cushing's syndrome (CS) and may persist in some patients even after ostensibly curative surgery, contributing to cardiometabolic dysfunction and increased cardiovascular risk. Mifepristone, a selective glucocorticoid receptor antagonist, was effective in controlling hyperglycemia in a 24-week trial of adults (N = 50) with endogenous CS and associated type 2 diabetes mellitus/impaired glucose tolerance or hypertension who had failed or were not candidates for surgery (SEISMIC, Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing's Syndrome). This analysis examines long-term weight change among patients who received mifepristone in SEISMIC and enrolled in a long-term safety extension (LTE) study. Patients completing the 24-week SEISMIC study and subsequent 6-week off-drug safety evaluation were invited to enroll in the LTE study. Mifepristone doses at the end of SEISMIC were the LTE starting doses. Body weight measures were reviewed at baseline and week 24 of SEISMIC and at LTE month 6, 12, 18, 24, and final visit (last observation collected during the LTE study). Of the 30 patients enrolled in the LTE, evaluable weight data were available for 29 (20/29 female; mean age of 44.7 ± 11.2 years). These patients received mifepristone for a median of 29.2 months (range 8.4-41.9). Mean ± SD weight from SEISMIC baseline to LTE final visit decreased by 10.3 ± 16.3 kg (mean 105.4 ± 34.3 kg to 95.1 ± 32.9 kg), a 9.3 % decrease from baseline weight (P = 0.0008). Of the 29 LTE patients, 18 (62.1 %) lost ≥ 5 % of body weight by the end of the initial 24-week treatment period; this ≥5 % weight loss persisted in 83.3 % (15/18) at LTE final visit. Ten patients (34.5 %) lost ≥ 10 % of initial body weight by week 24 of SEISMIC, which persisted in 80 % at LTE final visit. No new safety signals were detected with long-term mifepristone use. Clinically meaningful weight loss achieved during

Ways of ensuring short/long term safety

International Nuclear Information System (INIS)

Boeck, B. de; Baltes, B.; Besnus, F.

2006-01-01

Various strategies have been adopted among countries to manage radioactive waste. The present publication gives to this respect a broad overview of the policies and strategies adopted by Germany, Belgium and France. It appears that these may show remarkable differences, but motivated mainly by political and societal considerations. With regard to safety, practices for waste management are consistent and reflect the broad international consensus that has been progressively established. As an illustration, safety practices and possible specificities for the storage and geological disposal of spent fuel and high level radioactive waste from reprocessing are shortly described. (authors)

Safety, Efficacy, and Persistence of Long-Term Mirabegron Treatment for Overactive Bladder in the Daily Clinical Setting: Interim (1-Year) Report from a Japanese Post-Marketing Surveillance Study.

Science.gov (United States)

Kato, Daisuke; Tabuchi, Hiromi; Uno, Satoshi

2017-08-01

To report interim 1-year results from a 3-year surveillance study evaluating safety, efficacy, and persistence of long-term mirabegron for overactive bladder (OAB). Patients starting treatment with mirabegron for urinary urgency, daytime frequency, and urgency incontinence associated with OAB were registered and followed up for 3 years. Data were collected on adverse drug reactions (ADR), changes in OAB symptoms, changes in Overactive Bladder Symptom Score (OABSS), and treatment discontinuations. Treatment persistence rates were calculated by Kaplan-Meier analysis. Eighty-one ADR were observed in 72/1139 patients (6.3%) through 1 year of mirabegron treatment, with the incidence highest during the first month. No significant change in residual urine volume was observed at any observation point up to 1 year of mirabegron treatment. Mirabegron was deemed "effective" in 883/1091 patients (80.9%) at 1 year/discontinuation. Total OABSS was decreased with statistical significance at 3 months, 6 months, and 1 year, or at discontinuation (P similar for male and female patients but significantly higher for patients aged ≥65 years (67.3%; n = 908) compared with those aged <65 years (59.8%; n = 231; log-rank test: P = 0.032). Long-term OAB treatment with mirabegron was well-tolerated, with effectiveness maintained through 1 year. Mirabegron treatment persistence was higher than has been previously reported, and was greater in patients aged ≥65 years compared with those aged <65 years. © 2017 John Wiley & Sons Australia, Ltd.

Mark I containment, short term program. Safety evaluation report

International Nuclear Information System (INIS)

1977-12-01

Presented is a Safety Evaluation Report (SER) prepared by the Office of Nuclear Reactor Regulation addressing the Short Term Program (STP) reassessment of the containment systems of operating Boiler Water Reactor (BWR) facilities with the Mark I containment system design. The information presented in this SER establishes the basis for the NRC staff's conclusion that licensed Mark I BWR facilities can continue to operate safely, without undue risk to the health and safety of the public, during an interim period of approximately two years while a methodical, comprehensive Long Term Program (LTP) is conducted. This SER also provides one of the basic foundations for the NRC staff review of the Mark I containment systems for facilities not yet licensed for operation

Non-intrusive long-term monitoring approaches

International Nuclear Information System (INIS)

Smathers, D.; Mangan, D.

1998-01-01

In order to promote internatinal confidence that the US and Russia are disarming per their commitments under Article 6 of the Non-Proliferation Treaty, an international verification regime may be applied to US and Russian excess fissile materials. Initially, it is envisioned that this verification regime would be applied at storage facilities; however, it should be anticipated that the verification regime would continue throughout any material disposition activities, should such activities be pursued. once the materials are accepted into the verification regime, it is assumed that long term monitoring will be used to maintain continuity of knowledge. The requirements for long term storage monitoring include unattended operation for extended periods of time, minimal intrusiveness on the host nation's safety and security activities, data collection incorporating data authentication, and monitoring redundancy to allow resolution of anomalies and to continue coverage in the event of equipment failures. Additional requirements include effective data review and analysis processes, operation during storage facility loading, procedure for removal of inventory items for safety-related surveillance, and low cost, reliable equipment. A monitoring system might include both continuous monitoring of storagecontainers and continuous area monitoring. These would be complemented with periodic on-site inspections. A fissile material storage facility is not a static operation. The initial studies have shown there are a number of valid reasons why a host nation may need them to remove material from the storage facility. A practical monitoring system must be able to accommodate necessary material movements

Maximum tolerable radiation doses recommended by the Israel Advisory Committee on nuclear safety

International Nuclear Information System (INIS)

Tadmor, J.; Litai, D.; Lubin, E.

1978-01-01

Maximum tolerable doses have been recommended by the Israel Advisory Committee on Nuclear Safety. The recommendations which are based on a comparison with risks tolerated in other human activities, are for doses to radiation workers, for individual members of the population at the fence of a nuclear installation, and for the population at large, for both normal operating and accident conditions. Tolerable whole-body doses and doses to different critical organs are listed

Long-term surveillance plan for the Burro Canyon disposal cell Slick Rock, Colorado

International Nuclear Information System (INIS)

1997-08-01

This long-term surveillance plan (LTSP) describes the U.S. Department of Energy's (DOE) long-term care program for the Uranium Mill Tailings Remedial Action (UMTRA) Project Burro Canyon disposal cell in San Miguel County, Colorado. This LSTP describes the long-term surveillance program the DOE will implement to ensure the Burro Canyon disposal cell performs as designed and is cared for in a manner that protects the public health and safety and the environment. The program is based on site inspections to identify threats to disposal cell integrity. Before each disposal cell is licensed for custody and long-term care, the Nuclear Regulatory Commission (NRC) requires the DOE to submit such a site-specific LTSP

Application of geostatistical methods to long-term safety analyses for radioactive waste repositories

International Nuclear Information System (INIS)

Roehlig, K.J.

2001-01-01

Long-term safety analyses are an important part of the design and optimisation process as well as of the licensing procedure for final repositories for radioactive waste in deep geological formations. For selected scenarios describing possible evolutions of the repository system in the post-closure phase, quantitative consequence analyses are performed. Due to the complexity of the phenomena of concern and the large timeframes under consideration, several types of uncertainties have to be taken into account. The modelling work for the far-field (geosphere) surrounding or overlaying the repository is based on model calculations concerning the groundwater movement and the resulting migration of radionuclides which possibly will be released from the repository. In contrast to engineered systems, the geosphere shows a strong spatial variability of facies, materials and material properties. The paper presented here describes the first steps towards a quantitative approach for an uncertainty assessment taking into account this variability. Due to the availability of a large amount of data and information of several types, the Gorleben site (Germany) has been used for a case study in order to demonstrate the method. (orig.)

Morphological characteristic of purple long yard bean cultivars and their tolerance to drought stress

Directory of Open Access Journals (Sweden)

M W Lestari

2015-01-01

Full Text Available The cultivation of purple long yard bean which tolerance to drought stress and have high productivity can improve farming in arid area. The purpose of this study was to evaluate the mechanism of the tolerance purple long yard beans to drought stress based on morphologic characters, to get the hypothesis method of tolerance and to obtain tolerance cultivars to the drought stress. Eight cultivars of purple long yard beans, i.e. UBPHU1-41, UBPHU1-130, UBPU3-153, UBPU1-202, UBPU2-222, UBPU1-365, Brawijaya 4 and Bagong 2, were tested in two environmental conditions, 100% field capacity and 50% field capacity. The results showed that drought stress in purple long yard bean affected all morphological characters observed, except for root length and flowering time. Estimation of tolerance to drought stress using the Principles Component Analysis (PCA showed that the shoot fresh weight could be an indicator of purple pod bean tolerance to drought stress. However, the test using Stress Susceptibility Index (SSI was not able to classify the purple long yard bean tolerance to drought stress. The results of analysis using PCA followed by discriminant analysis and clustering dendrogram showed that the UBPU1-41, UBPU1-130, UBPU2-222, UBPU1-365, UB4 and Bagong 2 cultivars were medium cultivars that are tolerant to drought stress. Therefore, they can be planted in semiarid regions.

Computerised clinical decision support systems to improve medication safety in long-term care homes: a systematic review.

Science.gov (United States)

Marasinghe, Keshini Madara

2015-05-12

Computerised clinical decision support systems (CCDSS) are used to improve the quality of care in various healthcare settings. This systematic review evaluated the impact of CCDSS on improving medication safety in long-term care homes (LTC). Medication safety in older populations is an important health concern as inappropriate medication use can elevate the risk of potentially severe outcomes (ie, adverse drug reactions, ADR). With an increasing ageing population, greater use of LTC by the growing ageing population and increasing number of medication-related health issues in LTC, strategies to improve medication safety are essential. Databases searched included MEDLINE, EMBASE, Scopus and Cochrane Library. Three groups of keywords were combined: those relating to LTC, medication safety and CCDSS. One reviewer undertook screening and quality assessment. Overall findings suggest that CCDSS in LTC improved the quality of prescribing decisions (ie, appropriate medication orders), detected ADR, triggered warning messages (ie, related to central nervous system side effects, drug-associated constipation, renal insufficiency) and reduced injury risk among older adults. CCDSS have received little attention in LTC, as attested by the limited published literature. With an increasing ageing population, greater use of LTC by the ageing population and increased workload for health professionals, merely relying on physicians' judgement on medication safety would not be sufficient. CCDSS to improve medication safety and enhance the quality of prescribing decisions are essential. Analysis of review findings indicates that CCDSS are beneficial, effective and have potential to improve medication safety in LTC; however, the use of CCDSS in LTC is scarce. Careful assessment on the impact of CCDSS on medication safety and further modifications to existing CCDSS are recommended for wider acceptance. Due to scant evidence in the current literature, further research on implementation and

Safety relevant aspects of the long-term intermediate storage of spent fuel elements and vitrified high-level radioactive wastes; Sicherheitstechnische Aspekte der langfristigen Zwischenlagerung von bestrahlten Brennelementen und verglastem HAW

Energy Technology Data Exchange (ETDEWEB)

Ellinger, A.; Geupel, S.; Gewehr, K.; Gmal, B.; Hannstein, V.; Hummelsheim, K.; Kilger, R.; Wagner, M. [Gesellschaft fuer Anlagen- und Reaktorsicherheit mbH (GRS), Koeln (Germany); Schmidt, G.; Spieth-Achtnich, A. [Oeko-Institut e.V. - Institut fuer angewandte Oekolgie (Germany)

2010-04-15

The currently in Germany pursued concept for management of spent fuel from nuclear power plants provides intermediate dry cask storage at the NPP sites until direct disposal in a deep geologic repository. In addition the earlier commissioned centralized dry storage facilities are being used for storage of high level radioactive waste returned from foreign reprocessing of German spent fuel performed so far. The dry interim storage facilities are licensed for 40 years of operation time. According to the German regulations a full scope periodic safety review is not required so far, neither practical experience on dry storage for this period of time is available. With regard to this background the report at hand is dealing with long term effects, which may affect safety of the interim storage during the 40 years period or beyond if appropriate, and with the question, whether additional analyses or monitoring measures may be required. Therefore relevant publications have been evaluated, calculations have been performed as well as a systematic screening with regard to loads and possible ageing effects has been applied to structures and components important for safety of the storage, in order to identify relevant long term effects, which may not have been considered sufficiently so far and to provide proposals for an improved ageing management. The report firstly provides an overview on the current state of technology describing shortly the national and international practice and experience. In the following chapters safety aspects of interim storage with regard to time dependent effects and variations are being analyzed and discussed. Among this not only technical aspects like the long term behavior of fuel elements, canisters and storage systems are addressed, but also operational long term aspects regarding personnel planning, know how conservation, documentation and quality management are taken into account. A separate chapter is dedicated to developing and describing

Viral Infection: A Potent Barrier to Transplantation Tolerance

Directory of Open Access Journals (Sweden)

David M. Miller

2008-01-01

Full Text Available Transplantation of allogeneic organs has proven to be an effective therapeutic for a large variety of disease states, but the chronic immunosuppression that is required for organ allograft survival increases the risk for infection and neoplasia and has direct organ toxicity. The establishment of transplantation tolerance, which obviates the need for chronic immunosuppression, is the ultimate goal in the field of transplantation. Many experimental approaches have been developed in animal models that permit long-term allograft survival in the absence of chronic immunosuppression. These approaches function by inducing peripheral or central tolerance to the allograft. Emerging as some of the most promising approaches for the induction of tolerance are protocols based on costimulation blockade. However, as these protocols move into the clinic, there is recognition that little is known as to their safety and efficacy when confronted with environmental perturbants such as virus infection. In animal models, it has been reported that virus infection can prevent the induction of tolerance by costimulation blockade and, in at least one experimental protocol, can lead to significant morbidity and mortality. In this review, we discuss how viruses modulate the induction and maintenance of transplantation tolerance.

Long-Term Retardation of Uranium in the KURT Environment

International Nuclear Information System (INIS)

Baik, Min Hoon; Shin, Joo Do; Park, Tae Jin

2016-01-01

One of possibilities resolving this issue is to study the migration and retardation processes of radionuclides in the subsurface environments by using naturally occurring radionuclides as analogues of radioactive waste. To date, however, the long-term behavior of radionuclides in a granitic groundwater system is not yet fully understood. The ubiquitous presence of uranium (U) in rocks makes it an ideal natural analogue for studying the behaviors of radionuclides in a deep geological repository for the final disposal of HLW. In this study, long-term retardation behavior of natural uranium was investigated using granite rock samples taken from the KURT (KAERI Underground Research Tunnel), located in Daejeon city. The distribution of uranium and its binding mechanism in granite samples were investigated using the sequential chemical extraction (SCE) technique combined with X-ray diffraction (XRD) and ICP-MS methods. In this study, the long-term retardation of uranium in the KURT environment was investigated using SCE and EPMA techniques combined with ICP-MS and XRD. Results showed that long-term interaction of rock with groundwater can change U species and mineralize dissolved U, which can consequently contribute to the retardation of U in the fractured granitic rock environment. This study will help us to understand the long-term behavior of radionuclides migrating through the fractured granite rock and then enhance the reliability of the safety assessment for a HLW repository

Monitoring antimalarial safety and tolerability in clinical trials: A case study from Uganda

Directory of Open Access Journals (Sweden)

Mpimbaza Arthur

2008-06-01

Full Text Available Abstract Background New antimalarial regimens, including artemisinin-based combination therapies (ACTs, have been adopted widely as first-line treatment for uncomplicated malaria. Although these drugs appear to be safe and well-tolerated, experience with their use in Africa is limited and continued assessment of safety is a priority. However, no standardized guidelines for evaluating drug safety and tolerability in malaria studies exist. A system for monitoring adverse events in antimalarial trials conducted in Uganda was developed. Here the reporting system is described, and difficulties faced in analysing and interpreting the safety results are illustrated, using data from the trials. Case description Between 2002 and 2007, eleven randomized, controlled clinical trials were conducted to compare the efficacy, safety, and tolerability of different antimalarial regimens for treatment of uncomplicated malaria in Uganda. The approach to adverse event monitoring was similar in all studies. A total of 5,614 treatments were evaluated in 4,876 patients. Differences in baseline characteristics and patterns of adverse event reporting were noted between the sites, which limited the ability to pool and analyse data. Clinical failure following antimalarial treatment confounded associations between treatment and adverse events that were also common symptoms of malaria, particularly in areas of lower transmission intensity. Discussion and evaluation Despite prospectively evaluating for adverse events, limitations in the monitoring system were identified. New standardized guidelines for monitoring safety and tolerability in antimalarial trials are needed, which should address how to detect events of greatest importance, including serious events, those with a causal relationship to the treatment, those which impact on adherence, and events not previously reported. Conclusion Although the World Health Organization has supported the development of

Application of a Long Term Asset Management Strategy for HP Feedwater Heaters

International Nuclear Information System (INIS)

Won, Se Youl; Yun, Eun Sub; Park, Young Sheop

2008-01-01

As the commercial operating year of nuclear power plants is increased, it becomes imperative to develop integrated cost-effective asset management and to improve plans for degraded Structures, Systems, and Components (SSCs) in terms of safety and economical consideration. A long-term asset management (LTAM) strategy can improve the condition of nuclear plants, maximize their value, and optimize their operational life by maintaining their safety. This paper presents an optimized LTAM plan for HP feedwater heaters at a specific nuclear power plant

Audit of long-term and short-term liabilities

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Korinko M.D.

2017-03-01

Full Text Available The article determines the importance of long-term and short-term liabilities for the management of financial and material resources of an enterprise. It reviews the aim, objects and information generators for realization of audit of short-term and long-term obligations. The organizing and methodical providing of audit of long-term and short-term liabilities of an enterprise are generalized. The authors distinguish the stages of realization of audit of long-term and short-term liabilities, the aim of audit on each of the presented stages, and recommend methodical techniques. It is fixed that it is necessary to conduct the estimation of the systems of internal control and record-keeping of an enterprise by implementation of public accountant procedures for determination of volume and maintenance of selection realization. After estimating the indicated systems, a public accountant determines the methodology for realization of public accountant verification of long-term and short-term liabilities. The analytical procedures that public accountants are expedient to use for realization of audit of short-term and long-term obligations are determined. The authors suggest the classification of the educed defects on the results of the conducted public accountant verification of short-term and long-term obligations.

Short and long term maintenance strategy for reactor vessel head penetrations

International Nuclear Information System (INIS)

Teissier, A.; Heuze, A.

1995-01-01

This paper presents elements based on : surveys, operating inspection, theoretical studies, safety analysis, laboratory results, that enabled to determine maintenance options and short and long term strategies for processing on reactor vessel head leaks. (TEC). 1 tab

Long term efficacy and safety of etanercept in the treatment of psoriasis and psoriatic arthritis

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Kivelevitch D

2014-04-01

Full Text Available Dario Kivelevitch, Bobbak Mansouri, Alan Menter Department of Dermatology, Baylor University Medical Center, Dallas, TX, USA Abstract: Psoriasis is a chronic, immune-mediated inflammatory disease affecting both the skin and joints. Approximately 20% of patients suffer a moderate to severe form of skin disease and up to 30% have joint involvement. Standard therapies for psoriasis include topical medications, phototherapy, and both oral systemic and biological therapies whereas therapies for psoriatic arthritis include nonsteroidal anti-inflammatory drugs followed by disease modifying antirheumatic drugs and/or tumor necrosis factor (TNF-α inhibitors and interleukin-12/23p40 inhibitors. Treatment of both diseases is typically driven by disease severity. In the past decade, major advances in the understanding of the immunopathogenesis of psoriasis and psoriatic arthritis have led to the development of numerous biological therapies, which have revolutionized the treatment for moderate to severe plaque psoriasis and psoriatic arthritis. Anti-TNF-α agents are currently considered as first line biological therapies for the treatment of moderate to severe psoriasis and psoriatic arthritis. Currently approved anti-TNF-α agents include etanercept, adalimumab, and infliximab for psoriasis and psoriatic arthritis as well as golimumab and certolizumab for psoriatic arthritis. In this article, we aim to evaluate the long term safety and efficacy of etanercept in psoriasis and psoriatic arthritis. Keywords: psoriasis, psoriatic arthritis, etanercept, biological therapy, tumor necrosis factor, safety

China's current status and long-term outlook of nuclear power and radioactive waste disposal management

International Nuclear Information System (INIS)

Li, Zhidong

2015-01-01

This study identified the current status and long-term outlook of China's nuclear power development and radioactive waste disposal management after the 3.11 FUKUSHIMA accidents. China strengthened the actions for achieving nuclear power safety and cost efficiency as well as safety management of radioactive waste. It is a hard work to expand the capacity to 58 GW, the governmental target in 2020. The long-term development will strongly depend on the progress in safety management of nuclear power and radioactive waste and economic competitiveness. (author)

Unconventional cytokine profiles and development of T cell memory in long-term survivors after cancer vaccination

DEFF Research Database (Denmark)

Kyte, Jon Amund; Trachsel, Sissel; Risberg, Bente

2009-01-01

Cancer vaccine trials frequently report on immunological responses, without any clinical benefit. This paradox may reflect the challenge of discriminating between effective and pointless immune responses and sparse knowledge on their long-term development. Here, we have analyzed T cell responses...... in long-term survivors after peptide vaccination. There were three main study aims: (1) to characterize the immune response in patients with a possible clinical benefit. (2) To analyze the long-term development of responses and effects of booster vaccination. (3) To investigate whether the Th1/Th2...... display unconventional cytotoxicity and specifically kill tumor cells expressing mutated TGFbeta receptor II. Cytokine profiling on the long-term survivors demonstrates high IFN gamma/IL10-ratios, favoring immunity over tolerance, and secretion of multiple chemokines likely to mobilize the innate...

The challenges facing the long term interim storage

Energy Technology Data Exchange (ETDEWEB)

Iracane, D. [CEA Sacaly, Dir. de la Simulation et des Outils Experimentaux-DSOE, 91 - Gif sur Yvette (France); Marvy, A. [CEA Saclay, Dir. du Developpement et de l' Innovation Nucleares-DDIN, 91 - Gif Sur Yvette (France)

2001-07-01

In France electricity generation by means of commercial nuclear power plants has come to a point where it contributes to the national demand at a level of 80%. The safety performance of the production system has also reached a high level of both maturity and reliability taking advantage of the cumulative effect of a 30 years long learning experience and ever more stringent safety requirements. The policy to reprocess spent fuel has been overriding but no final decision has yet been made regarding the ultimate disposition of the waste streams. Although studies on deep geological disposal are ongoing, France is also looking at whether and under which conditions a long-term interim storage may provide an effective flexibility to the fuel cycle back-end. We discuss thereafter the needs and the paramount objectives of this latter R and D program. Results are being framed as potential guiding criteria for decision makers and various stakeholders. In first part, we propose a general analysis which emphasises that a long term interim storage is more than a classical nuclear facility because it explicitly requires long-lasting control and creates a burden for Society during many generations. Then, in second part, we offer an overview of the technical results from the R and D program as they stand at the time of writing. As an answer to the Government request, a strong emphasis has been put on this research for three years. Conclusion is an attempt to outline the societal context in which future decisions will have to be made. (author)

The challenges facing the long term interim storage

International Nuclear Information System (INIS)

Iracane, D.; Marvy, A.

2001-01-01

In France electricity generation by means of commercial nuclear power plants has come to a point where it contributes to the national demand at a level of 80%. The safety performance of the production system has also reached a high level of both maturity and reliability taking advantage of the cumulative effect of a 30 years long learning experience and ever more stringent safety requirements. The policy to reprocess spent fuel has been overriding but no final decision has yet been made regarding the ultimate disposition of the waste streams. Although studies on deep geological disposal are ongoing, France is also looking at whether and under which conditions a long-term interim storage may provide an effective flexibility to the fuel cycle back-end. We discuss thereafter the needs and the paramount objectives of this latter R and D program. Results are being framed as potential guiding criteria for decision makers and various stakeholders. In first part, we propose a general analysis which emphasises that a long term interim storage is more than a classical nuclear facility because it explicitly requires long-lasting control and creates a burden for Society during many generations. Then, in second part, we offer an overview of the technical results from the R and D program as they stand at the time of writing. As an answer to the Government request, a strong emphasis has been put on this research for three years. Conclusion is an attempt to outline the societal context in which future decisions will have to be made. (author)

Safety issues in construction of facilities for long-term storage of radioactive waste at vector site

Energy Technology Data Exchange (ETDEWEB)

Tokarevskyi, O.; Alekseeva, Z.; Kondratiev, S. [State Scientific and Technical Center for Nuclear and Radiation Safety, Kyiv (Ukraine); Rybalka, N. [State Nuclear Regulatory Inspectorate of Ukraine, Kyiv (Ukraine)

2013-07-01

In Ukraine, it is planned to create a number of near-surface facilities for disposal of short-lived RW and long-term (up to 100 years) storage of long-lived RW at the Vector site in the Chernobyl exclusion zone. The expected streams of long-lived RW are analyzed in the paper. According to the analysis of RW streams, in particular, issues are considered on development of RW acceptance criteria, admissible radiological impacts during preparation of RW for long-term storage, reliability of barriers (RW packages, modules and structures, etc.) during long-term storage of RW. (orig.)

Long-term follow-up study and long-term care of childhood cancer survivors

Directory of Open Access Journals (Sweden)

Hyeon Jin Park

2010-04-01

Full Text Available The number of long-term survivors is increasing in the western countries due to remarkable improvements in the treatment of childhood cancer. The long-term complications of childhood cancer survivors in these countries were brought to light by the childhood cancer survivor studies. In Korea, the 5-year survival rate of childhood cancer patients is approaching 70%; therefore, it is extremely important to undertake similar long-term follow-up studies and comprehensive long-term care for our population. On the basis of the experiences of childhood cancer survivorship care of the western countries and the current Korean status of childhood cancer survivors, long-term follow-up study and long-term care systems need to be established in Korea in the near future. This system might contribute to the improvement of the quality of life of childhood cancer survivors through effective intervention strategies.

Possible new roles for tolerable risk mediators

International Nuclear Information System (INIS)

O'Riordan, T.

1989-01-01

In his report on the Sizewell B Inquiry, the Inspector, Sir Frank Layfield, Q.C. introduced the term ''tolerable risk''. He regarded this as a better concept than the much abused and mis-interpreted phrase ''acceptable risk''. The application of tolerable risk implies that, even after regulation and incorporation of appropriate design safety criteria, there will always be a residual risk over which elements of the public will remain uneasy. They may tolerate, but they do not accept. They only tolerate because they have come to trust the process by which safety is assessed and delivered. This interpretation also implies that no safety target, the central theme of this meeting, should ever be regarded as stable or final. Such targets should continually be argued about and subject to regular searching review. Above all, such targets need to be re-justified to a doubting public so that they can be assured that the safety delivery process, namely the principles and management methods to ensure safety levels are actually met, is accountable and open for them to inspect. Thus the ''tolerable zone'' of nuclear plant safety is the product of procedures not simply assessments. These procedures need to be robust and adaptable. They need to be able to incorporate diversity of viewpoints and have a capacity to enable all who are involved to learn from each other's viewpoints and experience. In short the safety determination process needs to be more participatory and creative. (author)

Long-term storage or disposal of HLW-dilemma

International Nuclear Information System (INIS)

Ninkovic, M. M.; Raicevic, J.

1995-01-01

In this paper, a new concept approach to HLW management founded on deterministic safety philosophy - i.e. long-term storage with final objective of destroying was justified and proposed instead of multi barrier concept with final disposal in extra stable environmental conditions, which are founded on probabilistic safety approach model. As a support to this new concept some methods for destruction of waste which are now accessible, on scientific stage only, as transmutation in fast reactors and accelerators of heavy ions were briefly discussed . It is justified to believe that industrial technology for destruction of HLW would be developed in not so far future. (author).

PEBS. Long-term performance of engineered barrier systems

Energy Technology Data Exchange (ETDEWEB)

Wieczorek, Klaus; Czaikowski, Oliver; Miehe, Ruediger

2014-12-15

The evolution of the engineered barrier system (EBS) of geological repositories for radioactive waste has been the subject of many national and international research programmes. The emphasis of the research activities was on the elaboration of a detailed understanding of the complex THMC processes, which are expected to evolve in the early post closure period in the near field. From the perspective of radiological long-term safety, an in-depth understanding of these coupled processes is of great significance, because the evolution of the EBS during the early post-closure phase may have a non-negligible impact on the radiological safety functions at the time when the canisters breach. Unexpected process interactions during the resaturation phase could impair the safety-relevant parameters in the EBS (e. g. swelling pressure, hydraulic conductivity, diffusivity).

Long-term effects of radiotherapy on taste and salivary function in man

International Nuclear Information System (INIS)

Mossman, K.; Shatzman, A.; Chencharick, J.

1982-01-01

The long-term effects of radiotherapy on taste and salivary function were studied in 13 patients treated by radiation 1-7 years previously for tumors of the head and neck. Taste function was studied quantitatively using a standard forced choice, three-stimulus-drop technique for the determination of detection and recognition thresholds and a forced-scaling technique for the determination of taste intensity reponsiveness. Parotid salivary function was quantitatively evaluated by determination of flow rate and protein secretion rate. Nine of the 13 patients studied (69%) had measurable taste loss; every patient who had radiotherapy including the parotid glands had measurable salivary dysfunction. Our results demonstrate that curative courses of radiotherapy for tumors of the head and neck may result in long-term changes in taste and salivary function. From the present study, the maximum tolerance doses resulting in a 50% complication rate 5 years after treatment (TD 50/5) are estimated to be 40-65 Gy for xerostomia and 50-65 Gy for taste loss. Therefore, in a standard treatment regimen for tumors of the head and neck, with curative intent, gustatory and salivary gland tissues frequently sustain maximum tolerance injury

Safety profile and long-term engraftment of human CD31+ blood progenitors in bone tissue engineering.

Science.gov (United States)

Zigdon-Giladi, Hadar; Elimelech, Rina; Michaeli-Geller, Gal; Rudich, Utai; Machtei, Eli E

2017-07-01

Endothelial progenitor cells (EPCs) participate in angiogenesis and induce favorable micro-environments for tissue regeneration. The efficacy of EPCs in regenerative medicine is extensively studied; however, their safety profile remains unknown. Therefore, our aims were to evaluate the safety profile of human peripheral blood-derived EPCs (hEPCs) and to assess the long-term efficacy of hEPCs in bone tissue engineering. hEPCs were isolated from peripheral blood, cultured and characterized. β tricalcium phosphate scaffold (βTCP, control) or 10 6 hEPCs loaded onto βTCP were transplanted in a nude rat calvaria model. New bone formation and blood vessel density were analyzed using histomorphometry and micro-computed tomography (CT). Safety of hEPCs using karyotype analysis, tumorigenecity and biodistribution to target organs was evaluated. On the cellular level, hEPCs retained their karyotype during cell expansion (seven passages). Five months following local hEPC transplantation, on the tissue and organ level, no inflammatory reaction or dysplastic change was evident at the transplanted site or in distant organs. Direct engraftment was evident as CD31 human antigens were detected lining vessel walls in the transplanted site. In distant organs human antigens were absent, negating biodistribution. Bone area fraction and bone height were doubled by hEPC transplantation without affecting mineral density and bone architecture. Additionally, local transplantation of hEPCs increased blood vessel density by nine-fold. Local transplantation of hEPCs showed a positive safety profile. Furthermore, enhanced angiogenesis and osteogenesis without mineral density change was found. These results bring us one step closer to first-in-human trials using hEPCs for bone regeneration. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Long-term Exon Skipping Studies With 2′-O-Methyl Phosphorothioate Antisense Oligonucleotides in Dystrophic Mouse Models

Directory of Open Access Journals (Sweden)

Christa L Tanganyika-de Winter

2012-01-01

Full Text Available Antisense-mediated exon skipping for Duchenne muscular dystrophy (DMD is currently tested in phase 3 clinical trials. The aim of this approach is to modulate splicing by skipping a specific exon to reframe disrupted dystrophin transcripts, allowing the synthesis of a partly functional dystrophin protein. Studies in animal models allow detailed analysis of the pharmacokinetic and pharmacodynamic profile of antisense oligonucleotides (AONs. Here, we tested the safety and efficacy of subcutaneously administered 2′-O-methyl phosphorothioate AON at 200 mg/kg/week for up to 6 months in mouse models with varying levels of disease severity: mdx mice (mild phenotype and mdx mice with one utrophin allele (mdx/utrn+/−; more severe phenotype. Long-term treatment was well tolerated and exon skipping and dystrophin restoration confirmed for all animals. Notably, in the more severely affected mdx/utrn+/− mice the therapeutic effect was larger: creatine kinase (CK levels were more decreased and rotarod running time was more increased. This suggests that the mdx/utrn+/− model may be a more suitable model to test potential therapies than the regular mdx mouse. Our results also indicate that long-term subcutaneous treatment in dystrophic mouse models with these AONs is safe and beneficial.

Use of the live attenuated Japanese Encephalitis vaccine SA 14-14-2 in children: A review of safety and tolerability studies.

Science.gov (United States)

Ginsburg, Amy Sarah; Meghani, Ankita; Halstead, Scott B; Yaich, Mansour

2017-10-03

Japanese encephalitis (JE) is the leading cause of viral neurological disease and disability in Asia. Some 50-80% of children with clinical JE die or have long-term neurologic sequelae. Since there is no cure, human vaccination is the only effective long-term control measure, and the World Health Organization recommends that at-risk populations receive a safe and effective vaccine. Four different types of JE vaccines are currently available: inactivated mouse brain-derived vaccines, inactivated Vero cell vaccines, live attenuated SA 14-14-2 vaccines and a live recombinant (chimeric) vaccine. With the rapidly increasing demand for and availability and use of JE vaccines, countries face an important decision in the selection of a JE vaccine. This article provides a comprehensive review of the available safety literature for the live attenuated SA 14-14-2 JE vaccine (LAJEV), the most widely used new generation JE vaccine. With well-established effectiveness data, a single dose of LAJEV protects against clinical JE disease for at least 5 years, providing a long duration of protection compared with inactivated mouse brain-derived vaccines. Since 1988, about 700 million doses of the LAJEV have been distributed globally. Our review found that LAJEV is well tolerated across a wide age range and can safely be given to children as young as 8 months of age. While serious adverse events attributable to LAJEV have been reported, independent experts have not found sufficient evidence for causality based on the available data.

Long-term monitoring FBG-based cable load sensor

Science.gov (United States)

Zhang, Zhichun; Zhou, Zhi; Wang, Chuan; Ou, Jinping

2006-03-01

Stay cables are the main load-bearing components of stayed-cable bridges. The cables stress status is an important factor to the stayed-cable bridge structure safety evaluation. So it's very important not only to the bridge construction, but also to the long-term safety evaluation for the bridge structure in-service. The accurate measurement for cable load depends on an effective sensor, especially to meet the long time durability and measurement demand. FBG, for its great advantage of corrosion resistance, absolute measurement, high accuracy, electro-magnetic resistance, quasi-distribution sensing, absolute measurement and so on, is the most promising sensor, which can cater for the cable force monitoring. In this paper, a load sensor has been developed, which is made up of a bushing elastic supporting body, 4 FBGs uniformly-spaced attached outside of the bushing supporting body, and a temperature compensation FBG for other four FBGs, moreover a cover for protection of FBGs. Firstly, the sensor measuring principle is analyzed, and relationship equation of FBG wavelength shifts and extrinsic load has also been gotten. And then the sensor calibration experiments of a steel cable stretching test with the FBG load sensor and a reference electric pressure sensor is finished, and the results shows excellent linearity of extrinsic load and FBG wavelength shifts, and good repeatability, which indicates that such kind of FBG-based load sensor is suitable for load measurement, especially for long-term, real time monitoring of stay-cables.

A Framework for Estimating Long Term Driver Behavior

Directory of Open Access Journals (Sweden)

Vijay Gadepally

2017-01-01

Full Text Available We present a framework for estimation of long term driver behavior for autonomous vehicles and vehicle safety systems. The Hybrid State System and Hidden Markov Model (HSS+HMM system discussed in this article is capable of describing the hybrid characteristics of driver and vehicle coupling. In our model, driving observations follow a continuous trajectory that can be measured to create continuous state estimates. These continuous state estimates can then be used to estimate the most likely driver state using decision-behavior coupling inherent to the HSS+HMM system. The HSS+HMM system is encompassed in a HSS structure and intersystem connectivity is determined by using signal processing and pattern recognition techniques. The proposed method is suitable for a number of autonomous and vehicle safety scenarios such as estimating intent of other vehicles near intersections or avoiding hazardous driving events such as unexpected lane changes. The long term driver behavior estimation system involves an extended HSS+HMM structure that is capable of including external information in the estimation process. Through the grafting and pruning of metastates, the HSS+HMM system can be dynamically updated to best represent driver choices given external information. Three application examples are also provided to elucidate the theoretical system.

Adenovirus serotype 11 causes less long-term intraperitoneal inflammation than serotype 5: Implications for ovarian cancer therapy

International Nuclear Information System (INIS)

Thoma, Clemens; Bachy, Veronique; Seaton, Patricia; Green, Nicola K.; Greaves, David R.; Klavinskis, Linda; Seymour, Leonard W.; Morrison, Joanne

2013-01-01

In a phase II/III clinical trial intraperitoneal (i.p.) administration of a group C adenovirus vector (Ad5) caused bowel adhesion formation, perforation and obstruction. However, we had found that i.p. group B, in contrast to group C adenoviruses, did not cause adhesions in nude BALB/c ovarian cancer models, prompting further investigation. Ex vivo, group B Ad11 caused lower inflammatory responses than Ad5 on BALB/c peritoneal macrophages. In vivo, i.p. Ad11 triggered short-term cytokine and cellular responses equal to Ad5 in both human CD46-positive and -negative mice. In contrast, in a long-term study of repeated i.p. administration, Ad11 caused no/mild, whereas Ad5 induced moderate/severe adhesions and substantial liver toxicity accompanied by elevated levels of IFNγ and VEGF and loss of i.p. macrophages, regardless of CD46 expression. It appears that, although i.p. Ad11 evokes immediate inflammation similar to Ad5, repeated administration of Ad11 is better tolerated and long-term fibrotic tissue remodelling is reduced. - Highlights: • i.p. Ad11 causes less long-term intraperitoneal inflammation than Ad5 in CD46-transgenic mice. • Ex vivo BALB/c peritoneal macrophages express less RANTES after Ad11 than Ad3 or Ad5 treatment. • In vivo, cytokine and cellular responses 6 h after i.p. Ad11 are equal to Ad5. • In contrast, after repeated i.p. application, Ad5, but not Ad11, causes severe i.p. toxicity. • The use of Ad11 instead of Ad5 might increase patient safety in future virotherapy of ovarian cancer

Adenovirus serotype 11 causes less long-term intraperitoneal inflammation than serotype 5: Implications for ovarian cancer therapy

Energy Technology Data Exchange (ETDEWEB)

Thoma, Clemens, E-mail: c.thoma@oxfordalumni.org [Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU (United Kingdom); Bachy, Veronique [Peter Gorer Department of Immunobiology, Kings College London, Guys Hospital, Great Maze Pond, London SE1 9RT (United Kingdom); Seaton, Patricia [Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU (United Kingdom); Green, Nicola K. [Clinical Biomanufacturing Facility, University of Oxford, Old Road, Oxford OX3 7JT (United Kingdom); Greaves, David R. [Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE (United Kingdom); Klavinskis, Linda [Peter Gorer Department of Immunobiology, Kings College London, Guys Hospital, Great Maze Pond, London SE1 9RT (United Kingdom); Seymour, Leonard W. [Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ (United Kingdom); Morrison, Joanne [Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU (United Kingdom); Department of Obstetrics and Gynaecology, Musgrove Park Hospital, Taunton TA1 5DA (United Kingdom)

2013-12-15

In a phase II/III clinical trial intraperitoneal (i.p.) administration of a group C adenovirus vector (Ad5) caused bowel adhesion formation, perforation and obstruction. However, we had found that i.p. group B, in contrast to group C adenoviruses, did not cause adhesions in nude BALB/c ovarian cancer models, prompting further investigation. Ex vivo, group B Ad11 caused lower inflammatory responses than Ad5 on BALB/c peritoneal macrophages. In vivo, i.p. Ad11 triggered short-term cytokine and cellular responses equal to Ad5 in both human CD46-positive and -negative mice. In contrast, in a long-term study of repeated i.p. administration, Ad11 caused no/mild, whereas Ad5 induced moderate/severe adhesions and substantial liver toxicity accompanied by elevated levels of IFNγ and VEGF and loss of i.p. macrophages, regardless of CD46 expression. It appears that, although i.p. Ad11 evokes immediate inflammation similar to Ad5, repeated administration of Ad11 is better tolerated and long-term fibrotic tissue remodelling is reduced. - Highlights: • i.p. Ad11 causes less long-term intraperitoneal inflammation than Ad5 in CD46-transgenic mice. • Ex vivo BALB/c peritoneal macrophages express less RANTES after Ad11 than Ad3 or Ad5 treatment. • In vivo, cytokine and cellular responses 6 h after i.p. Ad11 are equal to Ad5. • In contrast, after repeated i.p. application, Ad5, but not Ad11, causes severe i.p. toxicity. • The use of Ad11 instead of Ad5 might increase patient safety in future virotherapy of ovarian cancer.

De Novo Transcriptome Assembly and Identification of Gene Candidates for Rapid Evolution of Soil Al Tolerance in Anthoxanthum odoratum at the Long-Term Park Grass Experiment.

Directory of Open Access Journals (Sweden)

Billie Gould

Full Text Available Studies of adaptation in the wild grass Anthoxanthum odoratum at the Park Grass Experiment (PGE provided one of the earliest examples of rapid evolution in plants. Anthoxanthum has become locally adapted to differences in soil Al toxicity, which have developed there due to soil acidification from long-term experimental fertilizer treatments. In this study, we used transcriptome sequencing to identify Al stress responsive genes in Anthoxanhum and identify candidates among them for further molecular study of rapid Al tolerance evolution at the PGE. We examined the Al content of Anthoxanthum tissues and conducted RNA-sequencing of root tips, the primary site of Al induced damage. We found that despite its high tolerance Anthoxanthum is not an Al accumulating species. Genes similar to those involved in organic acid exudation (TaALMT1, ZmMATE, cell wall modification (OsSTAR1, and internal Al detoxification (OsNRAT1 in cultivated grasses were responsive to Al exposure. Expression of a large suite of novel loci was also triggered by early exposure to Al stress in roots. Three-hundred forty five transcripts were significantly more up- or down-regulated in tolerant vs. sensitive Anthoxanthum genotypes, providing important targets for future study of rapid evolution at the PGE.

De Novo Transcriptome Assembly and Identification of Gene Candidates for Rapid Evolution of Soil Al Tolerance in Anthoxanthum odoratum at the Long-Term Park Grass Experiment.

Science.gov (United States)

Gould, Billie; McCouch, Susan; Geber, Monica

2015-01-01

Studies of adaptation in the wild grass Anthoxanthum odoratum at the Park Grass Experiment (PGE) provided one of the earliest examples of rapid evolution in plants. Anthoxanthum has become locally adapted to differences in soil Al toxicity, which have developed there due to soil acidification from long-term experimental fertilizer treatments. In this study, we used transcriptome sequencing to identify Al stress responsive genes in Anthoxanhum and identify candidates among them for further molecular study of rapid Al tolerance evolution at the PGE. We examined the Al content of Anthoxanthum tissues and conducted RNA-sequencing of root tips, the primary site of Al induced damage. We found that despite its high tolerance Anthoxanthum is not an Al accumulating species. Genes similar to those involved in organic acid exudation (TaALMT1, ZmMATE), cell wall modification (OsSTAR1), and internal Al detoxification (OsNRAT1) in cultivated grasses were responsive to Al exposure. Expression of a large suite of novel loci was also triggered by early exposure to Al stress in roots. Three-hundred forty five transcripts were significantly more up- or down-regulated in tolerant vs. sensitive Anthoxanthum genotypes, providing important targets for future study of rapid evolution at the PGE.

Long-term efficiency and safety of trans-catheter uterine artery embolization by lipiodol-pingyingmycin emulsion for uterine fibroids

International Nuclear Information System (INIS)

Du Juan; Zuo Yuewei; Hong Nanhua; Chen Xiaoming; Li Yong

2009-01-01

Objective: To investigate the long-term efficiency and safety of trans-catheter uterine artery embolization using lipiodol-pingyingmycin emulsion (LPE-TUAE) for uterine fibroids. Methods: Two hundred and forty-three patients with uterine fibroids were treated by LPE-TUAE. Fourteen of them underwent hysterectomy or myomectomy 3 days to 6 months after LPE-TUAE. The specimens were studied pathologically. Another 229 patients were followed up for 1 to 4 years to observe the long-term outcomes. Results: Menorrhagia became normal or improved markedly in 96.0% (193/201). Lumbago and lower abdominal pain disappeared or relieved markedly in 949% (94/99). Bulk-related symptoms disappeared or lessened markedly in 96.0% (48/50). Ultrasound revealed that the average decreased rate in the largest fibroid volume were 60.7% at 1 year, 63.3% at 2 year, 65.6% at 3 year and 67.4% at 4 year after embolization, and the average decreased rate in the largest uterine volume were 49.6% at 1 year, 54.3% at 2 year, 55.2% at 3 year and 57.1% at 4 year after embolization. Reoccurrence rate of myoma was 10.8% 3-4 year after embolization. No significant difference was found in hormone level between pre- and post-embolization. Pathological studies of specimens showed that lipiodol was only accumulated in fibroids and was not seen in myometrium. Spotty necrosis 2 weeks after embolization and extensive patchy necrosis 3 weeks after embolization were occurred in fibroids. Necrosis was not showed in myometrium. No serious complications occurred. Conclusion: LPE-TUAE possesses a good long-term effectiveness for uterine fibroids, which doesn't cause the damage on ovarian function and normal myometrium or serious complications. (authors)

Transuranic waste: long-term planning

International Nuclear Information System (INIS)

Young, K.C.

1985-07-01

Societal concerns for the safe handling and disposal of toxic waste are behind many of the regulations and the control measures in effect today. Transuranic waste, a specific category of toxic (radioactive) waste, serves as a good example of how regulations and controls impact changes in waste processing - and vice versa. As problems would arise with waste processing, changes would be instituted. These changes improved techniques for handling and disposal of transuranic waste, reduced the risk of breached containment, and were usually linked with regulatory changes. Today, however, we face a greater public awareness of and concern for toxic waste control; thus, we must anticipate potential problems and work on resolving them before they can become real problems. System safety analyses are valuable aids in long-term planning for operations involving transuranic as well as other toxic materials. Examples of specific system safety analytical methods demonstrate how problems can be anticipated and resolution initiated in a timely manner having minimal impacts upon allocation of resource and operational goals. 7 refs., 1 fig

Long term (>1 year) postpartum glucose tolerance status among Indian women with history of Gestational Diabetes Mellitus (GDM) diagnosed by IADPSG criteria.

Science.gov (United States)

Goyal, Alpesh; Gupta, Yashdeep; Kalaivani, Mani; Sankar, M Jeeva; Kachhawa, Garima; Bhatla, Neerja; Gupta, Nandita; Tandon, Nikhil

2018-05-24

To determine prevalence of long term dysglycemia and its risk factors among women with history of GDM diagnosed using IADPSG criteria at a tertiary care hospital in North India. Women with GDM diagnosed between 2012 and 2016 were invited. Socio-demographic, anthropometric, medical data were collected and 75 gm OGTT with serum insulin estimation, HbA1c and fasting lipid profile were done at the hospital visit. Women (N = 267) were tested at 32.5 (±4.6) years of age and at a median (q 25- q 75 ) of 20 (12-44) months following the index delivery. Dysglycemia was found in 57.7% by ADA criteria [Diabetes in 10.5% and prediabetes in 47.2%]. Risk factors for cardiovascular disease were significantly more prevalent among these women. On multivariable analysis, HOMA-IR correlated positively, while insulinogenic index correlated negatively with postpartum dysglycemia. This is possibly the first long term (>1 year) glucose tolerance outcome study in South Asian women with history of GDM diagnosed by IADPSG criteria, which demonstrates significantly elevated risk of postpartum dysglycemia. While the IADPSG criteria identify women with a lower future conversion to diabetes compared with previous criteria, prediabetes conversion remains high, thereby offering an opportunity to intervene early and prevent progression to future diabetes. Copyright © 2018 Elsevier B.V. All rights reserved.

Clinical Safety and Tolerability of Vildagliptin - Insights from Randomised Trials, Observational Studies and Post-marketing Surveillance.

Science.gov (United States)

Mathieu, Chantal; Kozlovski, Plamen; Paldánius, Päivi M; Foley, James E; Modgill, Vikas; Evans, Marc; Serban, Carmen

2017-08-01

Vildagliptin is one of the most extensively studied dipeptidyl peptidase-4 (DPP-4) inhibitors in terms of its clinical utility. Over the last decade, a vast panorama of evidence on the benefit-risk profile of vildagliptin has been generated in patients with type 2 diabetes mellitus (T2DM). In this article, we review the cumulative evidence on the safety of vildagliptin from the clinical development programme, as well as reports of rare adverse drug reactions detected during the post-marketing surveillance of the drug. Across clinical studies, the overall safety and tolerability profile of vildagliptin was similar to placebo, and it was supported by real-world data in a broad population of patients with T2DM, making DPP-4 inhibitors, like vildagliptin, a safe option for managing patients with T2DM.

Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

Science.gov (United States)

Solmi, Marco; Murru, Andrea; Pacchiarotti, Isabella; Undurraga, Juan; Veronese, Nicola; Fornaro, Michele; Stubbs, Brendon; Monaco, Francesco; Vieta, Eduard; Seeman, Mary V; Correll, Christoph U; Carvalho, André F

2017-01-01

Since the discovery of chlorpromazine (CPZ) in 1952, first-generation antipsychotics (FGAs) have revolutionized psychiatric care in terms of facilitating discharge from hospital and enabling large numbers of patients with severe mental illness (SMI) to be treated in the community. Second-generation antipsychotics (SGAs) ushered in a progressive shift from the paternalistic management of SMI symptoms to a patient-centered approach, which emphasized targets important to patients – psychosocial functioning, quality of life, and recovery. These drugs are no longer limited to specific Diagnostic and Statistical Manual of Mental Disorders (DSM) categories. Evidence indicates that SGAs show an improved safety and tolerability profile compared with FGAs. The incidence of treatment-emergent extrapyramidal side effects is lower, and there is less impairment of cognitive function and treatment-related negative symptoms. However, treatment with SGAs has been associated with a wide range of untoward effects, among which treatment-emergent weight gain and metabolic abnormalities are of notable concern. The present clinical review aims to summarize the safety and tolerability profile of selected FGAs and SGAs and to link treatment-related adverse effects to the pharmacodynamic profile of each drug. Evidence, predominantly derived from systematic reviews, meta-analyses, and clinical trials of the drugs amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, CPZ, haloperidol, loxapine, and perphenazine, is summarized. In addition, the safety and tolerability profiles of antipsychotics are discussed in the context of the “behavioral toxicity” conceptual framework, which considers the longitudinal course and the clinical and therapeutic consequences of treatment-emergent side effects. In SMI, SGAs with safer metabolic profiles should ideally be prescribed

A multicenter, open-label, long-term safety and tolerability study of DFN-02, an intranasal spray of sumatriptan 10 mg plus permeation enhancer DDM, for the acute treatment of episodic migraine.

Science.gov (United States)

Munjal, Sagar; Brand-Schieber, Elimor; Allenby, Kent; Spierings, Egilius L H; Cady, Roger K; Rapoport, Alan M

2017-12-01

DFN-02 is a novel intranasal spray formulation composed of sumatriptan 10 mg and a permeation-enhancing excipient comprised of 0.2% 1-O-n-Dodecyl-β-D-Maltopyranoside (DDM). This composition of DFN-02 allows sumatriptan to be rapidly absorbed into the systemic circulation and exhibit pharmacokinetics comparable to subcutaneously administered sumatriptan. Rapid rate of absorption is suggested to be important for optimal efficacy. The objective of this study was to evaluate the safety and tolerability of DFN-02 (10 mg) in the acute treatment of episodic migraine with and without aura over a 6-month period based on the incidence of treatment-emergent adverse events and the evaluation of results of clinical laboratory tests, vital signs, physical examination, and electrocardiograms. This was a multi-center, open-label, repeat-dose safety study in adults with episodic migraine with and without aura. Subjects diagnosed with migraine with or without aura according to the criteria set forth in the International Classification of Headache Disorders, 2nd edition, who experienced 2 to 6 attacks per month with fewer than 15 headache days per month and at least 48 headache-free hours between attacks, used DFN-02 to treat their migraine attacks acutely over the course of 6 months. A total of 173 subjects was enrolled, 167 (96.5%) subjects used at least 1 dose of study medication and were evaluable for safety, and 134 (77.5%) subjects completed the 6-month study. A total of 2211 migraine attacks was reported, and 3292 doses of DFN-02 were administered; mean per subject monthly use of DFN-02 was 3.6 doses. Adverse events were those expected for triptans, as well as for nasally administered compounds. No new safety signals emerged. Dysgeusia and application site pain were the most commonly reported treatment-emergent adverse events over 6 months (21% and 30.5%, respectively). Most of the treatment-emergent adverse events were mild. There were 5 serious adverse events, all

Long-term surveillance plan for the Maybell, Colorado Disposal Site

International Nuclear Information System (INIS)

1997-09-01

This long-term surveillance plan (LTSP) describes the U.S. Department of Energy's (DOE) long-term care program for the Uranium Mill Tailings Remedial Action (UMTRA) Project Maybell disposal site in Moffat County, Colorado. The U.S. Nuclear Regulatory Commission (NRC) has developed regulations for the issuance of a general license for the custody and long-term care of UMTRA Project disposal sites in 10 CFR Part 40. The purpose of this general license is to ensure that the UMTRA Project disposal sites are cared for in a manner that protects the public health and safety and the environment. Before each disposal site is licensed, the NRC requires the DOE to submit a site-specific LTSP. The DOE prepared this LTSP to meet this requirement for the Maybell disposal site. The general license becomes effective when the NRC concurs with the DOE's determination that remedial action is complete for the Maybell site and the NRC formally accepts this LTSP. This document describes the long-term surveillance program the DOE will implement to ensure the Maybell disposal site performs as designed. The program is based on site inspections to identify threats to disposal cell integrity. The LTSP is based on the UMTRA Project long-term surveillance program guidance document and meets the requirements of 10 CFR section 40.27(b) and 40 CFR section 192.03

Peptide-based anti-PCSK9 vaccines - an approach for long-term LDLc management.

Directory of Open Access Journals (Sweden)

Gergana Galabova

Full Text Available Low Density Lipoprotein (LDL hypercholesterolemia, and its associated cardiovascular diseases, are some of the leading causes of death worldwide. The ability of proprotein convertase subtilisin/kexin 9 (PCSK9 to modulate circulating LDL cholesterol (LDLc concentrations made it a very attractive target for LDLc management. To date, the most advanced approaches for PCSK9 inhibition are monoclonal antibody (mAb therapies. Although shown to lower LDLc significantly, mAbs face functional limitations because of their relatively short in vivo half-lives necessitating frequent administration. Here, we evaluated the long-term efficacy and safety of PCSK9-specific active vaccines in different preclinical models.PCSK9 peptide-based vaccines were successfully selected by our proprietary technology. To test their efficacy, wild-type (wt mice, Ldlr+/- mice, and rats were immunized with highly immunogenic vaccine candidates. Vaccines induced generation of high-affine PCSK9-specific antibodies in all species. Group mean total cholesterol (TC concentration was reduced by up to 30%, and LDLc up to 50% in treated animals. Moreover, the PCSK9 vaccine-induced humoral immune response persisted for up to one year in mice, and reduced cholesterol levels significantly throughout the study. Finally, the vaccines were well tolerated in all species tested.Peptide-based anti-PCSK9 vaccines induce the generation of antibodies that are persistent, high-affine, and functional for up to one year. They are powerful and safe tools for long-term LDLc management, and thus may represent a novel therapeutic approach for the prevention and/or treatment of LDL hypercholesterolemia-related cardiovascular diseases in humans.

Peripheral arteriovenous fistula as vascular access for long-term chemotherapy.

Science.gov (United States)

Kovalyov, Oleksiy O; Kostyuk, Oleksandr G; Tkachuk, Tetyana V

To provide long-term vascular access in clinical oncology peripheral forearm veins (up to 95% of patients in Ukraine), central venous access and "complete implanted vascular systems" are used most often. Many oncology patients have contraindications to catheterization of superior vena cava. Besides, exploitation of central veins is associated with potential technical and infectious complications. The aim - to study short-term and long-term results of arteriovenous fistula exploitation as vascular access for continuous anticancer therapy. Peripheral venous bed status in 41 oncology patients taking long-term chemotherapy treatment is analyzed in the article. Doppler sonography, morphologic and immune histochemical analyses were used in the study. Doppler sonography found qualitative and quantitative changes in forearm veins at different time periods after initiation of chemotherapy in the majority of patients. The major morphologic manifestations of venous wall damage were chemical phlebitis, local or extended hardening of venous wall, venous thrombosis and extravasations with necrosis and subsequent paravasal tissue sclerosis. Alternative vascular access created in 12 patients completely met the adequacy criteria (safety, multiple use, longevity, realization of the designed therapy program). The conclusion was made about inapplicability of forearm veins for long-term administration of cytostatic agents. If it is impossible to use central veins, arteriovenous fistula can become an alternative vascular access.

A look at new key performance criteria that could most affect the safety of long term storage of nuclear waste. A case study commissioned by CEA

International Nuclear Information System (INIS)

Marvy, A.; Lioure, A.; Heriard-Dubreuil, G.; Gadbois, S.; Schneider, T.; Schieber, C

2002-01-01

As part of the work scope set in the French law on high level long lived waste R and D passed in 1991, CEA is conducting research work to establish the scientific basis and assess the feasibility of long term storage as an option for the safe management of nuclear waste for periods as long as a few centuries. This goal is a significant departure from current industrial practice where storage facilities are usually built to last only a few decades. From a technical viewpoint such an extension in time seems feasible provided care and maintenance is exercised. Considering such long periods of time risk for Society of loosing oversight and control of such a facility is real which triggers the question of whether and how long term storage safety can be actually achieved. Therefore CEA commissioned a study in which MUTADIS Consultants and CEPN were both involved. The case study looks into several past and actual human enterprises conducted over significant periods of time - one dating back to the end of the 18th century - and identified off the nuclear field. Then-prevailing societal behaviour and organizational structures are screened out to show how they were and are still able to cope with similar oversight and control goals. As a result the study group obtained a set of performance criteria relating to issues like responsibility, securing funds, legal and legislative implications, economic sustainable development, all being areas which are not traditionally considered when technical studies are conducted. These criteria can be most useful from the design stage onward, first in an attempt to define the facility construction and operating guiding principles, and thereafter to substantiate the safety case for long term storage and get geared to the public dialogue on that undertaking should it become a reality. (author)

[Long-term psychiatric hospitalizations].

Science.gov (United States)

Plancke, L; Amariei, A

2017-02-01

Long-term hospitalizations in psychiatry raise the question of desocialisation of the patients and the inherent costs. Individual indicators were extracted from a medical administrative database containing full-time psychiatric hospitalizations for the period 2011-2013 of people over 16 years old living in the French region of Nord-Pas-de-Calais. We calculated the proportion of people who had experienced a hospitalization with a duration of 292 days or more during the study period. A bivariate analysis was conducted, then ecological data (level of health-care offer, the deprivation index and the size of the municipalities of residence) were included into a multilevel regression model in order to identify the factors significantly related to variability of long-term hospitalization rates. Among hospitalized individuals in psychiatry, 2.6% had had at least one hospitalization of 292 days or more during the observation period; the number of days in long-term hospitalization represented 22.5% of the total of days of full-time hospitalization in psychiatry. The bivariate analysis revealed that seniority in the psychiatric system was strongly correlated with long hospitalization rates. In the multivariate analysis, the individual indicators the most related to an increased risk of long-term hospitalization were: total lack of autonomy (OR=9.0; 95% CI: 6.7-12.2; P<001); diagnoses of psychological development disorders (OR=9.7; CI95%: 4.5-20.6; P<.001); mental retardation (OR=4.5; CI95%: 2.5-8.2; P<.001): schizophrenia (OR=3.0; CI95%: 1.7-5.2; P<.001); compulsory hospitalization (OR=1.7; CI95%: 1.4-2.1; P<.001); having experienced therapeutic isolation (OR=1.8; CI95%: 1.5-2.1; P<.001). Variations of long-term hospitalization rates depending on the type of establishment were very high, but the density of hospital beds or intensity of ambulatory activity services were not significantly linked to long-term hospitalization. The inhabitants of small urban units had

Long-term surveillance plan for the Gunnison, Colorado, disposal site

International Nuclear Information System (INIS)

1996-05-01

This long-term surveillance plan (LTSP) describes the US Department of Energy's (DOE) long-term care program for the Uranium Mill Tailings Remedial Action (UMTRA) Project Gunnison disposal site in Gunnison County, Colorado. The US Nuclear Regulatory Commission (NRC) has developed regulations for the issuance of a general license for the custody and long-term care of UMTRA Project disposal sites in 10 CFR Part 40. The purpose of this general license is to ensure that the UMTRA Project disposal sites will be cared for in a manner that protects the public health and safety and the environment.For each disposal site to be licensed, the NRC requires the DOE to submit a site-specific LTSP. The DOE prepared this LTSP to meet this requirement for the Gunnison disposal site. The general license becomes effective when the NRC concurs with the DOE's determination of completion of remedial action for the Gunnison site and the NRC formally accepts this LTSP

Quantitative evaluation of the fault tolerance of systems important to the safety of atomic power plants

International Nuclear Information System (INIS)

Malkin, S.D.; Sivokon, V.P.; Shmatkova, L.V.

1989-01-01

Fault tolerance is the property of a system to preserve its performance upon failures of its components. Thus, in nuclear-reactor technology one has only a qualitative evaluation of fault tolerance - the single-failure criterion, which does not enable one to compare and perform goal-directed design of fault-tolerant systems, and in the field of computer technology there are no generally accepted evaluations of fault tolerance that could be applied effectively to reactor systems. This paper considers alternative evaluations of fault tolerance and a method of comprehensive automated calculation of the reliability and fault tolerance of complex systems. The authors presented quantitative estimates of fault tolerance that develop the single-failure criterion. They have limiting processes that allow simple and graphical standardization. They worked out a method and a program for comprehensive calculation of the reliability and fault tolerance of systems of complex structure that are important to the safety of atomic power plants. The quantitative evaluation of the fault tolerance of these systems exhibits a degree of insensitivity to failures and shows to what extent their reliability is determined by a rigorously defined structure, and to what extent by the probabilistic reliability characteristics of the components. To increase safety, one must increase the fault tolerance of the most important systems of atomic power plants

Long-term effect of urethral dilatation and internal urethrotomy for urethral strictures.

Science.gov (United States)

Veeratterapillay, Rajan; Pickard, Rob S

2012-11-01

Urethral dilatation and direct visual internal urethrotomy (DVIU) are widely used minimally invasive options to manage men with urethral strictures. Advances in open urethroplasty with better long-term cure rates have fuelled the continuing debate as to which treatment is best for primary and recurrent urethral strictures. We reviewed recent literature to identify contemporary practice of urethral dilatation and DVIU and the long-term outcome of these procedures. Systematic literature search for the period January 2010 to December 2011 showed that urethral dilatation and DVIU remain frequently used treatment options as confirmed by surveys of urologists in the USA and the Netherlands. Multiple reports of laser DVIU confirm the safety of this approach but long-term data were lacking. Stricture free rates from urethra dilatation and DVIU vary from 10 to 90% at 12 months, although adjunctive intermittent self-dilatation can reduce time to recurrence. Although quality-of-life benefit appears good in the short term, repeated procedures may harm sexual function in the long-term. Urethral dilatation and DVIU remain widely used in urethral stricture management but high-level comparative evidence of benefit and harms against urethroplasty in the short and long-term is still lacking.

Long-term storage of Greater-Than-Class C Low-Level Waste

International Nuclear Information System (INIS)

Magleby, M.T.

1990-01-01

Under Federal law, the Department of Energy (DOE) is responsible for safe disposal of Greater-Than-Class C Low-Level Waste (GTCC LLW) generated by licenses of the Nuclear Regulatory commission (NRC) or Agreement States. Such waste must be disposed of in a facility licensed by the NRC. It is unlikely that licensed disposal of GTCC LLW will be available prior to the year 2010. Pending availability of disposal capacity, DOE is assessing the need for collective, long-term storage of GTCC LLW. Potential risks to public health and safety caused by long-term storage of GTCC LLW at the place of generation will be evaluated to determine if alternative facilities are warranted. If warranted, several options will be investigated to determine the preferred alternative for long-term storage. These options include modification of an existing DOE facility, development of a new DOE facility, or development of a facility by the private sector with or without DOE support. Reasonable costs for long-term storage would be borne by the waste generators. 5 refs., 1 fig

Minor Antigen Disparities Impede Induction of Long Lasting Chimerism and Tolerance through Bone Marrow Transplantation with Costimulation Blockade

Directory of Open Access Journals (Sweden)

Sinda Bigenzahn

2016-01-01

Full Text Available Mixed chimerism and tolerance can be successfully induced in rodents through allogeneic bone marrow transplantation (BMT with costimulation blockade (CB, but varying success rates have been reported with distinct models and protocols. We therefore investigated the impact of minor antigen disparities on the induction of mixed chimerism and tolerance. C57BL/6 (H2b mice received nonmyeloablative total body irradiation (3 Gy, costimulation blockade (anti-CD40L mAb and CTLA4Ig, and 2×107 bone marrow cells (BMC from either of three donor strains: Balb/c (H2d (MHC plus multiple minor histocompatibility antigen (mHAg mismatched, B10.D2 (H2d or B10.A (H2a (both MHC mismatched, but mHAg matched. Macrochimerism was followed over time by flow cytometry and tolerance was tested by skin grafting. 20 of 21 recipients of B10.D2 BMC but only 13 of 18 of Balb/c BMC and 13 of 20 of B10.A BMC developed stable long-term multilineage chimerism (p<0.05 for each donor strain versus B10.D2. Significantly superior donor skin graft survival was observed in successfully established long-term chimeras after mHAg matched BMT compared to mHAg mismatched BMT (p<0.05. Both minor and major antigen disparities pose a substantial barrier for the induction of chimerism while the maintenance of tolerance after nonmyeloablative BMT and costimulation blockade is negatively influenced by minor antigen disparities.

Data of long term atmospheric diffusion experiments (Winter, 1992)

Energy Technology Data Exchange (ETDEWEB)

Hayashi, Takashi; Chino, Masamichi; Yamazawa, Hiromi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment] [and others

1998-10-01

The data were obtained in the long-term atmospheric diffusion experiments in the Tokai area, autumn, 1991 which were a part of the Evaluation Safety Demonstration Experiments of Environmental Radiation entrusted with the Science and Technology Agency. The experiments were conducted by JAERI in cooperation with the Japan Weather Association. The report includes tracer concentration data of surface sampling points and meteorological data. (author)

Long-term behaviour of radioactive nuclides in the environment

International Nuclear Information System (INIS)

Brechignac, F.; Moberg, L.; Suomela, M.

1999-01-01

Report of recent advances in Europe, regarding the long-term development of radioactive nuclides in the environment. The corresponding scientific findings from three projects - Peace, Landscape and Epora (involving 18 European laboratories) - have been collected together. These projects were managed by the IPSN for the European Commission (DG XII) in the framework of the programme 'Surete de la fission nucleaire' (Nuclear fission safety programme). (author)

Long-term potentiation and long-term depression: a clinical perspective

Directory of Open Access Journals (Sweden)

Timothy V.P. Bliss

2011-01-01

Full Text Available Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.

Long-term surveillance plan for the Gunnison, Colorado disposal site. Revision 2

International Nuclear Information System (INIS)

1997-02-01

This long-term surveillance plan (LTSP) describes the US Department of Energy's (DOE) long-term care program for the Uranium Mill Tailings Remedial Action (UMTRA) Project Gunnison disposal site in Gunnison County, Colorado. The US Nuclear Regulatory Commission (NRC) has developed regulations for the issuance of a general license for the custody and long-term care of UMTRA Project disposal sites in 10 CFR Part 40. The purpose of this general license is to ensure that the UMTRA Project disposal sites will be cared for in a manner that protects the public health and safety and the environment. Before each disposal site is licensed, the NRC requires the DOE to submit a site-specific LTSP. This LTSP describes the long-term surveillance program the DOE will implement to ensure that the Gunnison disposal site performs as designed. The program is based on two distinct activities: (1) site inspections to identify threats to disposal cell integrity, and (2) ground water monitoring to demonstrate disposal cell performance

Emergency planning and long-term care: least paid, least powerful, most responsible.

Science.gov (United States)

Covan, Eleanor Krassen; Fugate-Whitlock, Elizabeth

2010-11-01

As disasters can occur anywhere, planning to avoid emergencies is an international concern. Our research specifically addresses planning for the needs and safety of a vulnerable population, long-term care residents. Our initial purposes in this evaluation research were to assess the utility of a template to gather emergency management information for individual long-term care communities, to report on how prepared they are to cope with emergencies that have occurred elsewhere in areas like ours, and to assess the effectiveness of employing gerontology students in the planning process. As we began analyzing our data, we realized that it is imperative to consider whether it is possible for long-term care communities to respond effectively to disasters. In our findings we focus on the impact of gender in the planning process, the importance of size with regard to template utility, the positive and negative consequences of student aid, and the fact that gathering plans for individual long-term care communities may have detracted from collaborative community planning.

Short-term and long-term effects of GDP on traffic deaths in 18 OECD countries, 1960-2011.

Science.gov (United States)

Dadgar, Iman; Norström, Thor

2017-02-01

Research suggests that increases in gross domestic product (GDP) lead to increases in traffic deaths plausibly due to the increased road traffic induced by an expanding economy. However, there also seems to exist a long-term effect of economic growth that is manifested in improved traffic safety and reduced rates of traffic deaths. Previous studies focus on either the short-term, procyclical effect, or the long-term, protective effect. The aim of the present study is to estimate the short-term and long-term effects jointly in order to assess the net impact of GDP on traffic mortality. We extracted traffic death rates for the period 1960-2011 from the WHO Mortality Database for 18 OECD countries. Data on GDP/capita were obtained from the Maddison Project. We performed error correction modelling to estimate the short-term and long-term effects of GDP on the traffic death rates. The estimates from the error correction modelling for the entire study period suggested that a one-unit increase (US$1000) in GDP/capita yields an instantaneous short-term increase in the traffic death rate by 0.58 (pGDP leads to an immediate increase in traffic deaths. However, after the mid-1970s this short-term effect is more than outweighed by a markedly stronger protective long-term effect, whereas the reverse is true for the period before the mid-1970s. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Polyaromatic hydrocarbon (PAH) degradation potential of a new acid tolerant, diazotrophic P-solubilizing and heavy metal resistant bacterium Cupriavidus sp. MTS-7 isolated from long-term mixed contaminated soil.

Science.gov (United States)

Kuppusamy, Saranya; Thavamani, Palanisami; Megharaj, Mallavarapu; Lee, Yong Bok; Naidu, Ravi

2016-11-01

An isolate of Cupriavidus (strain MTS-7) was identified from a long-term PAHs and heavy metals mixed contaminated soil with the potential to biodegrade both LMW and HMW PAHs with added unique traits of acid and alkali tolerance, heavy metal tolerance, self-nutrient assimilation by N fixation and P solubilization. This strain completely degraded the model 3 (150 mg L(-1) Phe), 4 (150 mg L(-1) Pyr) and 5 (50 mg L(-1) BaP) ring PAHs in 4, 20 and 30 days, respectively. It could mineralize 90-100% of PAHs (200 mg L(-1) of Phe and Pyr) within 15 days across pH ranging from 5 to 8 and even in the presence of toxic metal contaminations. During biodegradation, the minimum inhibitory concentrations were 5 (Cu(2+)) and 3 (Cd(2+), Pb(2+), Zn(2+)) mg L(-1) of the potentially bioavailable metal ions and over 17 mg L(-1) metal levels was lethal for the microbe. Further, it could fix 217-274 μg mL(-1) of N and solubilize 79-135 μg mL(-1) of P while PAHs degradation. MTS-7 as a superior candidate could be thus used in the enhanced bioaugmentation and/or phytoremediation of long-term mixed contaminated sites. Copyright © 2016 Elsevier Ltd. All rights reserved.

Long-Term Symbolic Learning

National Research Council Canada - National Science Library

Kennedy, William G; Trafton, J. G

2007-01-01

What are the characteristics of long-term learning? We investigated the characteristics of long-term, symbolic learning using the Soar and ACT-R cognitive architectures running cognitive models of two simple tasks...

Safety and long-term efficacy of transition from sildenafil to tadalafil due to side effects in patients with pulmonary arterial hypertension.

Science.gov (United States)

Lichtblau, Mona; Harzheim, Dominik; Ehlken, Nicola; Marra, Alberto; Pinado, Fabiola Pena; Grünig, Ekkehard; Egenlauf, Benjamin

2015-02-01

Two phosphodiesterase-type 5 (PDE-5) inhibitors, sildenafil and tadalafil, are approved for treatment of pulmonary arterial hypertension (PAH). It has not yet been observed if transition from sildenafil to tadalafil is beneficial in patients suffering from adverse reactions. Aim of this study was to analyze safety and long-term effects in PAH patients whose treatment was transitioned from sildenafil to tadalafil due to intolerable side-effects. A retrospective analysis of PAH-patients who were stable on sildenafil for >3 months and transitioned to tadalafil due to adverse events was performed. Data collected included demographics, PAH-etiology, WHO-functional class, 6 min walking distance (6MWD), echocardiography, lung function tests, and NTproBNP pre-transition and 3, 6, and 12 months post-transition. Included were 13 PAH patients (8 females mean age 64 ± 10 years) who had been on sildenafil for a mean of 12 ± 8.4 months. In six patients (46.1 %) a switch to tadalafil was feasible and resulted in tolerable side effects and a stable clinical course with improvement of symptoms, 6MWD, stable echocardiographic findings, and NTproBNP-levels during a follow-up of 11 ± 3 months. In 5 out of 13 patients (38.5 %) adverse events occurred under tadalafil as well and therapy with PDE-5 inhibitors was discontinued. In two patients (15.4 %) sildenafil-treatment could be successfully restarted after an intermittent switch to tadalafil. The observations of this study indicate that a transition of sildenafil to tadalafil in case of intolerable side effects is a reasonable therapy option in about 50 % of the patients. These results should be verified by a larger prospective study.

Pediatric polytrauma : Short-term and long-term outcomes

NARCIS (Netherlands)

vanderSluis, CK; Kingma, J; Eisma, WH; tenDuis, HJ

Objective: To assess the short-term and long-term outcomes of pediatric polytrauma patients and to analyze the extent to which short-term outcomes can predict long-term outcomes. Materials and Methods: Ail pediatric polytrauma patients (Injury Severity Score of greater than or equal to 16, less than

Mark I containment long-term program safety evaluation report, resolution of generic technical activity A-7. Report for February 1977-December 1979

International Nuclear Information System (INIS)

1980-07-01

During testing for an advanced Boiling Water Reactor (BWR) containment system design (Mark III), suppression pool hydrodynamic loads were identified which had not been considered in the original design of the Mark I containment system. To address this issue, a Mark I Owners Group was formed and the assessment was divided into a short-term and long-term program. The results of the NRC staff's review of the Mark I Containment Short Term Program are described in NUREG-0408. This report describes the results of the NRC staff's review of the generic Mark I Containment Long Term Program (LTP). The LTP was conducted to provide a generic basis to define suppression pool hydrodynamic loads and the related structural acceptance criteria, such that a comprehensive reassessment of each Mark I containment system would be performed. A series of experimental and analytical programs were conducted by the Mark I Owners Group to provide the necessary bases for the generic load definition and structural assessment techniques. The generic methods proposed by the Mark I Owners Group, as modified by the NRC staff's requirements, will be used to perform plant-unique analyses, which will identify the plant modifications, if any, that will be needed to restore the originally intended margin of safety in the Mark I containment designs

Safety and tolerability of prolonged-release nicotinic acid in statin-treated patients

NARCIS (Netherlands)

Birjmohun, R. S.; Kastelein, J. J. P.; Poldermans, D.; Stroes, E. S. G.; Hostalek, U.; Assmann, G.

2007-01-01

Objective: To evaluate the safety and tolerability of prolonged -release nicotinic acid (Niaspan*) added to statin therapy in patients at increased cardiovascular risk. Methods: This was a 6-month, prospective, observational, multicentre, open-label evaluation of prolonged-release nicotinic acid

Long-term performance of motor-operated valves

Energy Technology Data Exchange (ETDEWEB)

Scarbrough, T.G.

1996-12-01

The U.S. Nuclear Regulatory Commission (NRC) requires that motor-operated valves (MOVs) important to safety be designed, fabricated, erected, and tested to quality standards commensurate with the importance of the safety functions to be performed. Despite these requirements, operating experience and research revealed problems with the performance of MOVs in operating nuclear power plants. In response to the concerns about MOV performance, the NRC issued Generic Letter (GL) 89-10, {open_quotes}Safety-Related Motor-Operated Valve Testing and Surveillance,{close_quotes} and its supplements. Most licensees have completed the aspects of their GL 89-10 programs associated with the review of MOV design bases, verification of MOV switch settings initially, testing of MOVs under design-basis conditions where practicable, and improvement of evaluations of MOV failures and necessary corrective action. Licensees are establishing processes to ensure that the long-term aspects of their MOV programs, such as periodic verification of MOV capability and the trending of MOV problems, are maintained. The NRC staff is developing a generic letter to address periodic verification of MOV design-basis capability.

Long-term performance of motor-operated valves

International Nuclear Information System (INIS)

Scarbrough, T.G.

1996-01-01

The U.S. Nuclear Regulatory Commission (NRC) requires that motor-operated valves (MOVs) important to safety be designed, fabricated, erected, and tested to quality standards commensurate with the importance of the safety functions to be performed. Despite these requirements, operating experience and research revealed problems with the performance of MOVs in operating nuclear power plants. In response to the concerns about MOV performance, the NRC issued Generic Letter (GL) 89-10, open-quotes Safety-Related Motor-Operated Valve Testing and Surveillance,close quotes and its supplements. Most licensees have completed the aspects of their GL 89-10 programs associated with the review of MOV design bases, verification of MOV switch settings initially, testing of MOVs under design-basis conditions where practicable, and improvement of evaluations of MOV failures and necessary corrective action. Licensees are establishing processes to ensure that the long-term aspects of their MOV programs, such as periodic verification of MOV capability and the trending of MOV problems, are maintained. The NRC staff is developing a generic letter to address periodic verification of MOV design-basis capability

Long-term surveillance plan for the Gunnison, Colorado disposal site

International Nuclear Information System (INIS)

1996-04-01

This long-term surveillance plan (LTSP) describes the U.S. Department of Energy's (DOE) long-term care program for the Uranium Mill Tailings Remedial Action (UMTRA) Project Gunnison disposal site in Gunnison County, Colorado. The U.S. Nuclear Regulatory Commission (NRC) has developed regulations for the issuance of a general license for the custody and long-term care of UMTRA Project disposal sites in 10 CFR Part 40. The purpose of this general license is to ensure that the UMTRA Project disposal sites will be cared for in a manner that protects the public health and safety and the environment. For each disposal site to be licensed, the NRC requires the DOE to submit a site-specific LTSP. The DOE prepared this LTSP to meet this requirement for the Gunnison disposal site. The general license becomes effective when the NRC concurs with the DOE's determination of completion of remedial action for the Gunnison site and the NRC formally accepts this LTSP. This LTSP describes the long-term surveillance program the DOE will implement to ensure that the Gunnison disposal site performs as designed. The program is based on two distinct activities: (1) site inspections to identify threats to disposal cell integrity, and (2) ground water monitoring to demonstrate disposal cell performance. The LTSP is based on the UMTRA Project long-term surveillance program guidance and meets the requirements of 10 CFR section 40.27(b) and 40 CFR section 192.03

Long-term surveillance plan for the Gunnison, Colorado, disposal site

International Nuclear Information System (INIS)

1997-04-01

This long-term surveillance plan (LTSP) describes the U.S. Department of Energy's (DOE) long-term care program for the Uranium Mill Tailings Remedial Action (UMTRA) Project Gunnison disposal site in Gunnison County, Colorado. The U.S. Nuclear Regulatory Commission (NRC) has developed regulations for the issuance of a general license for the custody and long-term care of UMTRA Project disposal sites in 10 CFR Part 40. The purpose of this general license is to ensure that the UMTRA Project disposal sites will be cared for in a manner that protects the public health and safety and the environment. Before each disposal site is licensed, the NRC requires the DOE to submit a site-specific LTSP. The DOE prepared this LTSP to meet this requirement for the Gunnison disposal site. The general license becomes effective when the NRC concurs with the DOE's determination of completion of remedial action for the Gunnison site and the NRC formally accepts this LTSP. This LTSP describes the long-term surveillance program the DOE will implement to ensure that the Gunnison disposal site performs as designed. The program is based on two distinct activities: (1) site inspections to identify threats to disposal cell integrity, and (2) ground water monitoring to demonstrate disposal cell performance. The LTSP is based on the UMTRA Project long-term surveillance program guidance and meets the requirements of 10 CFR section 40.27(b) and 40 CFR section 192.03

Long-term surveillance plan for the Gunnison, Colorado disposal site

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-04-01

This long-term surveillance plan (LTSP) describes the U.S. Department of Energy`s (DOE) long-term care program for the Uranium Mill Tailings Remedial Action (UMTRA) Project Gunnison disposal site in Gunnison County, Colorado. The U.S. Nuclear Regulatory Commission (NRC) has developed regulations for the issuance of a general license for the custody and long-term care of UMTRA Project disposal sites in 10 CFR Part 40. The purpose of this general license is to ensure that the UMTRA Project disposal sites will be cared for in a manner that protects the public health and safety and the environment. For each disposal site to be licensed, the NRC requires the DOE to submit a site-specific LTSP. The DOE prepared this LTSP to meet this requirement for the Gunnison disposal site. The general license becomes effective when the NRC concurs with the DOE`s determination of completion of remedial action for the Gunnison site and the NRC formally accepts this LTSP. This LTSP describes the long-term surveillance program the DOE will implement to ensure that the Gunnison disposal site performs as designed. The program is based on two distinct activities: (1) site inspections to identify threats to disposal cell integrity, and (2) ground water monitoring to demonstrate disposal cell performance. The LTSP is based on the UMTRA Project long-term surveillance program guidance and meets the requirements of 10 CFR {section}40.27(b) and 40 CFR {section}192.03.

Long-term surveillance plan for the Gunnison, Colorado, disposal site

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-04-01

This long-term surveillance plan (LTSP) describes the U.S. Department of Energy`s (DOE) long-term care program for the Uranium Mill Tailings Remedial Action (UMTRA) Project Gunnison disposal site in Gunnison County, Colorado. The U.S. Nuclear Regulatory Commission (NRC) has developed regulations for the issuance of a general license for the custody and long-term care of UMTRA Project disposal sites in 10 CFR Part 40. The purpose of this general license is to ensure that the UMTRA Project disposal sites will be cared for in a manner that protects the public health and safety and the environment. Before each disposal site is licensed, the NRC requires the DOE to submit a site-specific LTSP. The DOE prepared this LTSP to meet this requirement for the Gunnison disposal site. The general license becomes effective when the NRC concurs with the DOE`s determination of completion of remedial action for the Gunnison site and the NRC formally accepts this LTSP. This LTSP describes the long-term surveillance program the DOE will implement to ensure that the Gunnison disposal site performs as designed. The program is based on two distinct activities: (1) site inspections to identify threats to disposal cell integrity, and (2) ground water monitoring to demonstrate disposal cell performance. The LTSP is based on the UMTRA Project long-term surveillance program guidance and meets the requirements of 10 CFR {section}40.27(b) and 40 CFR {section}192.03.

Long-term surveillance plan for the Gunnison, Colorado, disposal site

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-05-01

This long-term surveillance plan (LTSP) describes the U.S. Department of Energy`s (DOE) long-term care program for the Uranium Mill Tailings Remedial Action (UMTRA) Project Gunnison disposal site in Gunnison County, Colorado. The U.S. Nuclear Regulatory Commission (NRC) has developed regulations for the issuance of a general license for the custody and long-term care of UMTRA Project disposal sites in 10 CFR Part 40. The purpose of this general license is to ensure that the UMTRA Project disposal sites will be cared for in a manner that protects the public health and safety and the environment. For each disposal site to be licensed, the NRC requires the DOE to submit a site-specific LTSP. The DOE prepared this LTSP to meet this requirement for the Gunnison disposal site. The general license becomes effective when the NRC concurs with the DOE`s determination of completion of remedial action for the Gunnison site and the NRC formally accepts this LTSP. This LTSP describes the long-term surveillance program the DOE will implement to ensure that the Gunnison disposal site performs as designed. The program is based on two distinct activities: (1) site inspections to identify threats to disposal cell integrity, and (2) ground water monitoring to demonstrate disposal cell performance. The LTSP is based on the UMTRA Project long-term surveillance program guidance and meets the requirements of 10 CFR {section}40.27(b) and 40 CFR {section}192.03.

Long-term surveillance plan for the Gunnison, Colorado, disposal site

International Nuclear Information System (INIS)

1996-05-01

This long-term surveillance plan (LTSP) describes the U.S. Department of Energy's (DOE) long-term care program for the Uranium Mill Tailings Remedial Action (UMTRA) Project Gunnison disposal site in Gunnison County, Colorado. The U.S. Nuclear Regulatory Commission (NRC) has developed regulations for the issuance of a general license for the custody and long-term care of UMTRA Project disposal sites in 10 CFR Part 40. The purpose of this general license is to ensure that the UMTRA Project disposal sites will be cared for in a manner that protects the public health and safety and the environment. For each disposal site to be licensed, the NRC requires the DOE to submit a site-specific LTSP. The DOE prepared this LTSP to meet this requirement for the Gunnison disposal site. The general license becomes effective when the NRC concurs with the DOE's determination of completion of remedial action for the Gunnison site and the NRC formally accepts this LTSP. This LTSP describes the long-term surveillance program the DOE will implement to ensure that the Gunnison disposal site performs as designed. The program is based on two distinct activities: (1) site inspections to identify threats to disposal cell integrity, and (2) ground water monitoring to demonstrate disposal cell performance. The LTSP is based on the UMTRA Project long-term surveillance program guidance and meets the requirements of 10 CFR section 40.27(b) and 40 CFR section 192.03

Measuring client experiences in long-term care in the Netherlands: a pilot study with the Consumer Quality Index Long-term Care

Directory of Open Access Journals (Sweden)

Kool Rudolf B

2010-04-01

Full Text Available Abstract Background This study aims to describe the development, testing and optimization of a new standard instrument, the Consumer Quality Index (CQ-index® Long-term Care, for measuring client experiences with long-term care in the Netherlands. Methods Three versions of the CQ-index questionnaires and protocols for study sampling and data collection were developed, designed for interviews with residents of nursing or residential care homes and postal surveys among representatives of psychogeriatric residents and homecare clients. From July to November 2006 a pilot study was conducted among 2,697 clients of 68 nursing or residential care homes, 2,164 representatives of clients in 57 psychogeriatric care institutions, and 1,462 clients of 19 homecare organizations. We performed psychometric analyses and descriptive analyses, and evaluated the pilot study. Results The pilot study showed the feasibility and usability of the instruments, supported the multidimensionality of the questionnaires and showed first findings on client experiences and possibilities for quality improvement. Nine scales applied to all care settings: shared decision making, attitude and courtesy, information, body care, competence and safety of care, activities, autonomy, mental well-being, and availability of personnel. The pilot resulted in three optimized questionnaires and recommendations for nationwide implementation. Conclusions The CQ-index® Long-term Care provides a good basis to investigate the quality of nursing homes, residential care homes and homecare from the clients' perspective. This standardized instrument enables a nationwide comparison of the quality of long-term care for the purpose of transparency and quality assurance.

Evolution of sorption properties in large-scale concrete structures accounting for long-term physical-chemical concrete degradation - 59297

International Nuclear Information System (INIS)

Perko, Janez; Jacques, Diederik; Mallants, Dirk; Seetharam, Suresh

2012-01-01

Long-term safety of radioactive waste disposal facilities relies on the longevity of natural or engineered barriers designed to minimize the migration of contaminants from the facility into the environment. Especially near surface disposal facilities, such as planned by ONDRAF/NIRAS for the Dessel site in Belgium, long-term safety relies almost exclusively on the containment ability of the engineered barriers (EB) with concrete being the most important EB material used. Concrete is preferred over other materials mainly due to its favourable chemical properties resulting in a high chemical retention capacity, and owing to its good hydraulic isolation properties. However, due to the long time frames typically involved in safety assessment, the chemical, physical and mechanical properties of concrete evolve in time. The alterations in concrete mineralogy also cause changes in pH and sorption behaviour for many radionuclides during chemical degradation processes. Application of dynamic sorption of concrete requires an adequate knowledge of long-term concrete degradation processes, knowledge of the effect of changing mineralogy to sorption of radionuclides and knowledge of large-scale system behaviour over time. Moreover, when applied to safety assessment models, special attention is required to assure robustness and transparency of the implementation. The discussion in this paper focuses on the sorption properties of concrete; selection of data, rescaling issues and on the hypotheses used to build a robust and yet transparent dynamic model for large-scale concrete structures for assessing the long-term performance. In this paper we summarize the steps required for the appropriate use of sorption values for large-scale cementitious components accounting for long-term concrete degradation in safety assessment studies. Four steps were recognized through the safety assessment in the framework of the license application for the near-surface disposal facility in Dessel

Long-term safety assessment of trench-type surface repository at Chernobyl, Ukraine - computer model and comparison with results from simplified models

International Nuclear Information System (INIS)

Haverkamp, B.; Krone, J.; Shybetskyi, I.

2013-01-01

The Radioactive Waste Disposal Facility (RWDF) Buryakovka was constructed in 1986 as part of the intervention measures after the accident at Chernobyl NPP (ChNPP). Today, the surface repository for solid low and intermediate level waste (LILW) is still being operated but its maximum capacity is nearly reached. Long-existing plans for increasing the capacity of the facility shall be implemented in the framework of the European Commission INSC Programme (Instrument for Nuclear Safety Co-operation). Within the first phase of this project, DBE Technology GmbH prepared a safety analysis report of the facility in its current state (SAR) and a preliminary safety analysis report (PSAR) for a future extended facility based on the planned enlargement. In addition to a detailed mathematical model, also simplified models have been developed to verify results of the former one and enhance confidence in the results. Comparison of the results show that - depending on the boundary conditions - simplifications like modeling the multi trench repository as one generic trench might have very limited influence on the overall results compared to the general uncertainties associated with respective long-term calculations. In addition to their value in regard to verification of more complex models which is important to increase confidence in the overall results, such simplified models can also offer the possibility to carry out time consuming calculations like probabilistic calculations or detailed sensitivity analysis in an economic manner. (authors)

Risk assessment in long-term storage of spent nuclear fuel

International Nuclear Information System (INIS)

Ahn, T.; Guttmann, J.; Mohseni, A.

2013-01-01

This paper presents probabilistic risk-informed approaches that the Nuclear Regulatory Commission (NRC) staff is planning to consider in preparing regulatory bases for long-term storage of spent nuclear fuel (SNF) for up to 300 years. Due to uncertainties associated with long-term SNF storage, the NRC is considering a probabilistic risk-informed approach as well as a deterministic design-based approach. The uncertainties considered here are primarily associated with materials aging of the canister and SNF in the cask system during long-term storage of SNF. This paper discusses some potential risk contributors involved in long-term SNF storage. Methods of performance evaluation are presented that assess the various types of risks involved. They include deterministic evaluation, probabilistic evaluation, and consequence assessment under normal conditions and the conditions of accidents and natural hazards. Some potentially important technical issues resulting from the consideration of a probabilistic risk-informed evaluation of the cask system performance are discussed for the canister and SNF integrity. These issues are also discussed in comparison with the deterministic approach for comparison purposes, as appropriate. Probabilistic risk-informed methods can provide insights that deterministic methods may not capture. Two specific examples include stress corrosion cracking of the canister and hydrogen-induced cladding failure. These examples are discussed in more detail, in terms of their effects on radionuclide release and nuclear subcriticality associated with the failure. The plan to consider the probabilistic risk-informed approaches is anticipated to provide helpful regulatory insights for long-term storage of SNF that provide reasonable assurance for public health and safety. (authors)

Selection of tolerable risk criteria for dam safety decision making

International Nuclear Information System (INIS)

Nielsen, N.M.; Hartford, D.N.D.; MacDonald, T.F.

1994-01-01

Risk assessment has received increasing attention in recent years as a means of aiding decision making on dams by providing systematic and rational methods for dealing with risk and uncertainty. Risk assessment is controversial and decisions affecting risk to life are the most controversial. Tolerable criteria, based on the risks that society is prepared to accept in order to avoid excessive costs, set bounds within which risk-based decisions may be made. The components of risk associated with dam safety are addressed on an individual basis and criteria established for each component, thereby permitting flexibility in the balance between component risk and avoiding the problems of placing a monetary value on life. The guiding principle of individual risk is that dams do not impose intolerable risks on any individual. A risk to life of 1 in 10 4 per annum is generally considered the maximum tolerable risk. When considering societal risk, the safety of a dam should be proportional to the consequences of its failure. Risks of financial losses beyond the corporation's ability to finance should be so low as to be considered negligible. 17 refs., 3 figs

Short-term initiatives for enhancing cyber-safety within South African schools

Directory of Open Access Journals (Sweden)

Elmarie Kritzinger

2016-07-01

Full Text Available The rate of technological development across the globe is dramatic. The decreasing cost and increasing availability of ICT devices means that its users are no longer exclusively industry or government employees – they are now also home users. Home users integrate ICT in their daily lives for education, socialising and information gathering. However, using ICT is associated with risks and threats, such as identity theft and phishing scams. Most home users of ICT do not have the necessary information technology and Internet skills to protect themselves and their information. School learners, in particular, are not sufficiently educated on how to use technological devices safely, especially in developing countries such as South Africa. The national school curriculum in South Africa currently does not make provision for cyber-safety education, and the availability of supporting material and training for ICT teachers in South Africa is limited, resulting in a lack of knowledge and skills regarding cyber-safety. The research in hand focuses on the situation concerning cyber-safety awareness in schools and has adopted a short-term approach towards cyber-safety among teachers and school learners in South Africa until a formal long-term national approach has been implemented. This study takes a quantitative approach to investigating the current options of teachers to enhance cyber-safety among learners in their schools. The research proposes that short-term initiatives (i.e. posters can increase learners’ awareness of cyber-safety until formal cyber-safety awareness methods have been introduced.

Interferon-Beta in Pediatric Multiple Sclerosis Patients: Safety in Short-Term Prescription

Directory of Open Access Journals (Sweden)

Amir Hadi Maghzi

2012-02-01

Full Text Available Introduction: None of the approved immunomodulatory drugs in adults Multiple Sclerosis (MS patients have been officially approved for the pediatric patients and are currently used off-label in this population. Objectives: In this study, we evaluated the effectiveness and tolerability of intramuscular interferon beta1-a (Avonex® and subcutaneously injected interferon beta1-b (Betaferon® in children with definite relapsing-remitting MS (RRMS. Thirteen patients aged younger than 16, who were recently diagnosed with definite RRMS according to the McDonalds criteria, were enrolled in this study. Six patients were treated with Avonex® 30 μg, intramuscularly every week, and seven patients were treated with Betaferon® 250 μg, subcutaneously every other day. All patients were treated with adult doses; initially interferon-beta was prescribed with half dose, and it was increased to full adult dose steadily. Results: Eleven girls and two boys, mean (SD age of 14.7 (1.9 years, were studied. Following nine months of using interferon-beta, nine patients (69.2% had no relapses and the remaining four, experienced only one relapse. The mean EDSS score was decreased significantly after the study period. Conclusion: The present study provides reasonable data for the use of interferon-beta in Pediatric MS due to lack of short-term complications and safety. Studies with larger sample size and longer follow up duration are required to shed light on the long term impact of the interferon-beta therapy in children.

Long-term tolerability of tolterodine extended release in children 5-11 years of age: results from a 12-month, open-label study

DEFF Research Database (Denmark)

Nijman, Rien J M; Borgstein, Niels G; Ellsworth, Pamela

2007-01-01

OBJECTIVE: To evaluate the long-term tolerability of tolterodine extended release (ER) in children (aged 5-11 yr) with urgency urinary incontinence (UUI). METHODS: This was a multicenter, open-label extension of a 12-wk, double-blind, placebo-controlled study of tolterodine ER. Patients had UUI...... suggestive of detrusor overactivity (>/=1 diurnal incontinence episode per 24h for >/=5 of 7 d) and >/=6 voids per 24h at baseline and had completed the 12-wk double-blind study. Patients received tolterodine ER (2mg once daily) for 12 mo. The primary end points were the incidence and severity of adverse......-blind tolterodine ER, n=221; placebo, n=97). The majority of patients were white (90%), mean+/-SD age was 7.6+/-1.5 yr, and 54% were boys. Forty-nine percent of patients reported >/=1 AE during the study, similar to that observed in the preceding 12-wk study (42%). The most frequent AEs were urinary tract infection...

Treatment options for nonalcoholic steatohepatitis - a safety evaluation.

Science.gov (United States)

Issa, Danny; Wattacheril, Julia; Sanyal, Arun J

2017-08-01

There is an urgent as yet unmet need to develop highly effective and safe therapeutics for nonalcoholic fatty liver disease (NAFLD). The remarkable progress in understanding NAFLD pathogenesis allowed the identification of injury pathways which may be recruited as therapy targets. Areas covered: This article reviews the safety and tolerability data of the NAFLD therapies and explains the mechanistic basis for each of the established and investigational drugs. Treatment targets include: weight loss, anti-metabolic agents such as lipid lowering and anti-diabetic drugs, inflammation, fibrosis and others such as targeting gut microbiota, immune modulation and apoptosis. Expert opinion: Current therapies continue to remain suboptimal. Weight loss is effective but hard to achieve. Traditional and endoscopic bariatric procedures are promising although more randomized trials are needed and the long-term safety remains to be established. Clinical trials have demonstrated the efficacy of several drugs for the treatment of NASH. Of these, there remains some uncertainty about the long-term safety of vitamin E. Pioglitazone is associated with osteopenia, fluid retention and weight gain. Obeticholic acid causes pruritus in a substantial proportion of subjects and elafibranor has been associated with transient rises in creatinine. Several exciting therapies are under development and results of clinical and post-marketing trials will help elucidate their safety.

The UK system for regulating the long-term safety of radioactive waste disposal

International Nuclear Information System (INIS)

Duncan, A.

1997-01-01

The general system is described for regulation of disposal of solid, long-lived radioactive wastes. The relevant Government policy is outlined, and the framework of legislation and arrangements for implementation, the associated guidance produced by regulatory bodies and the approach to assessment by regulators of a safety case for radioactive waste disposal are reported. Also, for the purposes of discussion in the Workshop, some of the practical issues are considered which are still in development in the UK in regard to regulatory methodology. (author)

Guidance for implementing the long-term surveillance program for UMTRA Project Title I Disposal Sites

International Nuclear Information System (INIS)

1996-02-01

This guidance document has two purposes: it provides guidance for writing site-specific long-term surveillance plans (LTSP) and it describes site surveillance, monitoring, and long-term care techniques for Title I disposal sites of the Uranium Mill Tailings Radiation Control Act (UMTRCA) (42 USC Section 7901 et seq.). Long-term care includes monitoring, maintenance, and emergency measures needed to protect public health and safety and the environment after remedial action is completed. This document applies to the UMTRCA-designated Title I disposal sites. The requirements for long-term care of the Title I sites and the contents of the LTSPs are provided in U.S. Nuclear Regulatory Commission (NRC) regulations (10 CFR Section 40.27) provided in Attachment 1

Long-Term Feeding of Chitosan Ameliorates Glucose and Lipid Metabolism in a High-Fructose-Diet-Impaired Rat Model of Glucose Tolerance

Directory of Open Access Journals (Sweden)

Shing-Hwa Liu

2015-12-01

Full Text Available This study was designed to investigate the effects of long-term feeding of chitosan on plasma glucose and lipids in rats fed a high-fructose (HF diet (63.1%. Male Sprague-Dawley rats aged seven weeks were used as experimental animals. Rats were divided into three groups: (1 normal group (normal; (2 HF group; (3 chitosan + HF group (HF + C. The rats were fed the experimental diets and drinking water ad libitum for 21 weeks. The results showed that chitosan (average molecular weight was about 3.8 × 105 Dalton and degree of deacetylation was about 89.8% significantly decreased body weight, paraepididymal fat mass, and retroperitoneal fat mass weight, but elevated the lipolysis rate in retroperitoneal fats of HF diet-fed rats. Supplementation of chitosan causes a decrease in plasma insulin, tumor necrosis factor (TNF-α, Interleukin (IL-6, and leptin, and an increase in plasma adiponectin. The HF diet increased hepatic lipids. However, intake of chitosan reduced the accumulation of hepatic lipids, including total cholesterol (TC and triglyceride (TG contents. In addition, chitosan elevated the excretion of fecal lipids in HF diet-fed rats. Furthermore, chitosan significantly decreased plasma TC, low-density lipoprotein cholesterol (LDL-C, very-low-density lipoprotein cholesterol (VLDL-C, the TC/high-density lipoprotein cholesterol (HDL-C ratio, and increased the HDL-C/(LDL-C + VLDL-C ratio, but elevated the plasma TG and free fatty acids concentrations in HF diet-fed rats. Plasma angiopoietin-like 4 (ANGPTL4 protein expression was not affected by the HF diet, but it was significantly increased in chitosan-supplemented, HF-diet-fed rats. The high-fructose diet induced an increase in plasma glucose and impaired glucose tolerance, but chitosan supplementation decreased plasma glucose and improved impairment of glucose tolerance and insulin tolerance. Taken together, these results indicate that supplementation with chitosan can improve the impairment

Long-term surveillance plan for the Rifle, Colorado, Disposal site

International Nuclear Information System (INIS)

1996-09-01

This long-term surveillance plan (LTSP) describes the U.S. Department of Energy's (DOE) long-term care program for the Uranium Mill Tailings Remedial Action (UMTRA) Project Estes Gulch disposal site in Garfield County, Colorado. The U.S. Environmental Protection Agency (EPA) has developed regulations for the issuance of a general license by the U.S. Nuclear Regulatory Commission (NRC) for the custody and long-term care of UMTRA Project disposal Sites in 10 CFR Part 40. The purpose of this general license is to ensure that the UMTRA Project disposal sites, will be cared for in a manner that protects the public health and safety and the environment. For each disposal site to be licensed, the NRC requires the DOE to submit a site-specific LTSP. The DOE prepared this LTSP to meet this requirement for the Estes Gulch disposal site. The general license becomes effective when the NRC concurs with the DOE's determination of completion of remedial action for the Estes Gulch site and the NRC formally accepts this LTSP

Fondaparinux in the initial and long-term treatment of venous thromboembolism.

Science.gov (United States)

Pesavento, Raffaele; Amitrano, Maria; Trujillo-Santos, Javier; Di Micco, Pierpaolo; Mangiacapra, Sara; López-Jiménez, Luciano; Falgá, Conxita; García-Bragado, Fernando; Piovella, Chiara; Prandoni, Paolo; Monreal, Manuel

2015-02-01

Even in the absence of evidence on its long-term efficacy and safety, a number of patients with venous thromboembolism (VTE) receive long-term therapy with fondaparinux alone in everyday practice. We used the Registro Informatizado de Enfermedad Tromboembólica (RIETE) registry to compare the rate of VTE recurrences and major bleeding at 10 and 90 days in patients with and without cancer. For long-term therapy, fondaparinux was compared with vitamin K antagonists (VKA) in patients without cancer and with low-molecular-weight heparin (LMWH) in those with cancer. Of 47,378 patients recruited, 46,513 were initially treated with heparin, 865 with fondaparinux. Then, 263 patients (78 with cancer) were treated for at least 3 months with fondaparinux. After propensity-score matching, there were no differences between patients receiving initial therapy with heparin or fondaparinux. Among patients with cancer, there were no differences between fondaparinux and LMWH. Among patients without cancer, the long-term use of fondaparinux was associated with an increased risk of major bleeding (3.24 % vs. 0.95 %, p<0.05). An unexpected high rate of major bleeding was observed in non-cancer patients treated with long-term fondaparinux. Our small sample does not allow to derive relevant conclusions on the use of fondaparinux in cancer patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Andra long term memory project - 59277

International Nuclear Information System (INIS)

Charton, Patrick; Boissier, Fabrice; Martin, Guillaume

2012-01-01

Document available in abstract form only. Full text of publication follows: Long term memory of repositories is required by safety, reversibility and social expectations. Thus Andra has implemented since 2010 a long-term memory project to reinforce and diversify its current arrangements in this field, as well as to explore opportunities to extend memory keeping over thousands years. The project includes opportunity studies of dedicated facilities. The 'Ecotheque' and 'Geotheque' projects contribute to memory respectively through environmental and geological samples preservation. The options of creating (i) an archive centre for Andra's interim and permanent archives, (ii) an artist center to study the contribution of arts to memory preservation, (iii) a museum of radioactive waste disposal history and technology (radium industry..., sea disposal, current solutions...) are considered. Other studies provided by the project examine our heritage. This includes the continuity of languages and symbolic systems, the continuity of writing and engraving methods, the archaeology of landscapes (memory of the earths evolution, multi-century memory of industrial and agricultural landscapes), the archaeology practices (how might a future archaeologist be interested in our current activity?), the preservation of historical sites and industrial memory, the continuity of institutional organizations, the memory and history of science evolution as well as broad history

Near-Term Actions to Address Long-Term Climate Risk

Science.gov (United States)

Lempert, R. J.

2014-12-01

Addressing climate change requires effective long-term policy making, which occurs when reflecting on potential events decades or more in the future causes policy makers to choose near-term actions different than those they would otherwise pursue. Contrary to some expectations, policy makers do sometimes make such long-term decisions, but not as commonly and successfully as climate change may require. In recent years however, the new capabilities of analytic decision support tools, combined with improved understanding of cognitive and organizational behaviors, has significantly improved the methods available for organizations to manage longer-term climate risks. In particular, these tools allow decision makers to understand what near-term actions consistently contribute to achieving both short- and long-term societal goals, even in the face of deep uncertainty regarding the long-term future. This talk will describe applications of these approaches for infrastructure, water, and flood risk management planning, as well as studies of how near-term choices about policy architectures can affect long-term greenhouse gas emission reduction pathways.

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

Safety requirements for long term operation of NPPs

International Nuclear Information System (INIS)

Houdre, T.; Osouf, N.; Juvin, J.-C.

2012-01-01

In the future, the reactors operating at present will run alongside reactors of the EPR type or their equivalent, designed for a significantly higher level of safety. This raises the question of the acceptability of continued operation of reactors beyond 40 years when there is an available technology that is safer. Two objectives are therefore imperative. First, a re-evaluation of the safety level in the light of that required of EPR type reactors or their equivalent is necessary, with proposals to bring about significant and relevant improvements to the reactors. R and D work in France and elsewhere is already indicating orientations that could lead to answers, and improvements that would provide significant reductions in release in case of severe accident are being studied. Second, strict compliance of the reactors with the applicable regulations must be demonstrated. At the same time, ageing and obsolescence of the equipment will have to be managed. Where these two points are concerned, ASN expects far-reaching proposals from the licensee. With a view to a request for continued operation beyond 40 years, ASN has referred the matter to the Advisory Committee for nuclear reactors which will meet at the end of 2011 to establish the safety requirements for reactors at their fourth ten-yearly outage. (author)

Efficacy of golimumab in the treatment of patients with ankylosing spondylitis (according to the data of a long-term follow-up

Directory of Open Access Journals (Sweden)

A. V. Smirnov

2015-01-01

Full Text Available The paper summarizes the data of a randomized placebo-controlled phase 3 GO-RAISE trial of spondylitis (AS patients receiving two different doses (50 and 100 mg of golimumab (GLM, which evaluates its efficiency and safety and X-ray progression of changes in the axial skeleton. In AS patients, GLM therapy leads to a rapid long-lasting clinical and radiological response. The tolerability of long-term therapy with GLM generally complies with the safety profile of the entire class of tumor necrosis factor-р (TNF-р inhibitors.The data of the GO-RAISE trial has substantiated once again the established fact that the high baseline level of C-reactive protein (CRP and the presence of syndesmophytes are predictors for a rapider X-ray progression. At the same time, the results of the trial may question the recent assumptions that TNF-р suppression can exert a stimulating effect on the formation of new bone tissue with time. Further studies are to determine whether there is an association between the presence of syndesmophytes and elevated CRP levels and whether they have a combined effect on X-ray progression, and if so, whether the development of structural changes may be prevented with TNF-р inhibitors to be used at the earlier stages of the disease.

Safety and tolerability of transcranial direct current stimulation to stroke patients - A phase I current escalation study.

Science.gov (United States)

Chhatbar, Pratik Y; Chen, Rong; Deardorff, Rachael; Dellenbach, Blair; Kautz, Steven A; George, Mark S; Feng, Wuwei

A prior meta-analysis revealed that higher doses of transcranial direct current stimulation (tDCS) have a better post-stroke upper-extremity motor recovery. While this finding suggests that currents greater than the typically used 2 mA may be more efficacious, the safety and tolerability of higher currents have not been assessed in stroke patients. We aim to assess the safety and tolerability of single session of up to 4 mA in stroke patients. We adapted a traditional 3 + 3 study design with a current escalation schedule of 1»2»2.5»3»3.5»4 mA for this tDCS safety study. We administered one 30-min session of bihemispheric montage tDCS and simultaneous customary occupational therapy to patients with first-ever ischemic stroke. We assessed safety with pre-defined stopping rules and investigated tolerability through a questionnaire. Additionally, we monitored body resistance and skin temperature in real-time at the electrode contact site. Eighteen patients completed the study. The current was escalated to 4 mA without meeting the pre-defined stopping rules or causing any major safety concern. 50% of patients experienced transient skin redness without injury. No rise in temperature (range 26°C-35 °C) was noted and skin barrier function remained intact (i.e. body resistance >1 kΩ). Our phase I safety study supports that single session of bihemispheric tDCS with current up to 4 mA is safe and tolerable in stroke patients. A phase II study to further test the safety and preliminary efficacy with multi-session tDCS at 4 mA (as compared with lower current and sham stimulation) is a logical next step. ClinicalTrials.gov Identifier: NCT02763826. Copyright © 2017 Elsevier Inc. All rights reserved.

Long Term Financing of Infrastructure

OpenAIRE

Sinha, Sidharth

2014-01-01

Infrastructure projects, given their long life, require long term financing. The main sources of long term financings are insurance and pension funds who seek long term investments with low credit risk. However, in India household financial savings are mainly invested in bank deposits. Insurance and pension funds account for only a small percentage of household financial savings. In addition most infrastructure projects do not qualify for investment by insurance and pension funds because of t...

Study of scenarios of long term management of low-activity long-life wastes

International Nuclear Information System (INIS)

2012-01-01

This document reports the study of scenarios for the management of different low-activity long-life radioactive wastes with reference to different French legal texts. After a presentation of the legal and technical context, the report presents different existing and projected storages (description and safety principles for the Cires and Aube centres and for the Cigeo project of deep geological storage centre). It addresses the various aspects of radiferous and graphite waste management on a long term: inventory, parcel, waste peculiarities, management scenarios, assessment of storage in SCR. It also addresses the case of other wastes such as bituminous coated wastes, those presenting a reinforced natural radioactivity or residues of uranium conversion processing. The last part presents the main orientations for the project

Effect of long-term storage of LWR spent fuel on Pu-thermal fuel cycle

International Nuclear Information System (INIS)

Kurosawa, Masayoshi; Naito, Yoshitaka; Suyama, Kenya; Itahara, Kuniyuki; Suzuki, Katsuo; Hamada, Koji

1998-01-01

According to the Long-term Program for Research, Development and Utilization of Nuclear Energy (June, 1994) in Japan, the Rokkasho Reprocessing Plant will be operated shortly after the year 2000, and the planning of the construction of the second commercial plant will be decided around 2010. Also, it is described that spent fuel storage has a positive meaning as an energy resource for the future utilization of Pu. Considering the balance between the increase of spent fuels and the domestic reprocessing capacity in Japan, it can be expected that the long-term storage of UO 2 spent fuels will be required. Then, we studied the effect of long-term storage of spent fuels on Pu-thermal fuel cycle. The burnup calculation were performed on the typical Japanese PWR fuel, and the burnup and criticality calculations were carried out on the Pu-thermal cores with MOX fuel. Based on the results, we evaluate the influence of extending the spent fuel storage term on the criticality safety, shielding design of the reprocessing plant and the core life time of the MOX core, etc. As the result of this work on long-term storage of LWR spent fuels, it becomes clear that there are few demerits regarding the lifetime of a MOX reactor core, and that there are many merits regarding the safety aspects of the fuel cycle facilities. Furthermore, long-term storage is meaningful as energy storage for effective utilization of Pu to be improved by technological innovation in future, and it will allow for sufficient time for the important policymaking of nuclear fuel cycle establishment in Japan. (author)

Development of methodology for evaluation of long-term safety aspects of organic cement paste components

International Nuclear Information System (INIS)

Andersson, M.; Holgersson, S.; Ervanne, H.

2008-12-01

Long-term safety aspects of superplasticizers (SP) and other cement paste components were studied in this joint Nagra - NUMO - SKB - Posiva project with aim to develop a methodology for the evaluation of the long-term safety aspects of superplasticizers (SP) and other organic components of cement pastes. The study also evaluated the effects of SPs and other cement paste components that have already been used or that are most likely to be used in the construction of the high-level nuclear waste repositories in Sweden, Switzerland, Finland and Japan. The main long-term safety issue of concern is whether the superplasticizers and/or other organic components of cement pastes might affect the transport properties of radionuclides. A full evaluation of whether the superplasticizers can be used in a high-level nuclear waste repository cannot be answered based on the studies but a classification of the superplasticizers based on their impact on sorption of radionuclides has been done. The basic methodology for testing, leaching and analyzing of leachants and solid samples of different types was developed at CRIEPI. Two different methodologies for studying the impact of SPs on the sorption of Eu on crushed rock were tested and developed by Helsinki University (HU) and Chalmers University of Technology (CTH). Methods for analyzing organics leaching from grouts were successfully tested by CRIEPI and CTH (Chalmers University of Technology). At CRIEPI the total organic content (TOC) of the leachants was analyzed by Infrared absorption spectrometry (IR) followed by Gel Permeation Chromatography (GPC) for the identification of the organic compounds. At CTH several different analytical methods were tested (e.g. IR, UV spectroscopy, NMR, MALDI-TOF), but these methods still require improvement. In addition to SPs, organics are present in several components of cement pastes, for example in cement grinding aid (CGA) and micro silica slurry. The results suggests that the main high

NPP long term operation in Spain - First application for license renewal

International Nuclear Information System (INIS)

Francia, L.; Gorrochategui, I.; Marcos, R.

2007-01-01

Full text: In the operation of the Spanish nuclear power plants (NPP), safety is always the prime consideration. Plant Life Management Programmes have been set up with the strategic objective to operate the NPPs as long as they are considered safe and reliable. The safety of each NPP is reviewed by the Spanish nuclear regulatory authority (CSN) under a continuous process. In addition, experience is gained from operating the plants and from exchanges with operators of similar units. Current Spanish regulatory framework for renewing NPP operating licenses requires performing a Periodic Safety Review (PSR) to be performed every 10 years and submitted when applying for a new renewal of the NPP operating license. A few years ago, CSN issued a document regarding the licensing requirements that nuclear power plants should meet in order to be granted with an operating license for long term operation (i.e, operation beyond the original plant design life, typically 40 years). Besides the traditional PSR requirements, specific requirements regarding to long term operation (LTO) include: - An Aging Management and Evaluation Program, including the identification and evaluation of Time Limited Aging Analysis (TLAA). - An updated Radiological Impact Study. - A review and assessment of regulation/standard applicability. Garona NPP (GE, BWR/3 design) operated by Spanish utility Nuclenor from 1971 has a current operating license up to 2009. A decision was made to apply for a new operating license, being Garona plant the first one in Spain to face with the new long term operation requirements. The paper will provide an overview of the methodology used in Spain to address and perform the required analyses to support the LTO application for the operating license renewal. In particular, focus will be paid on the project developed in Garona (2002-2006) whose result has been the first Spanish application for License Renewal for LTO. Also it will be reported the ongoing work necessary to

Fall Protection Characteristics of Safety Belts and Human Impact Tolerance.

Science.gov (United States)

Hino, Yasumichi; Ohdo, Katsutoshi; Takahashi, Hiroki

2014-08-23

Many fatal accidents due to falls from heights have occurred at construction sites not only in Japan but also in other countries. This study aims to determine the fall prevention performance of two types of safety belts: a body belt 1) , which has been used for more than 40 yr in the Japanese construction industry as a general type of safety equipment for fall accident prevention, and a full harness 2, 3) , which has been used in many other countries. To determine human tolerance for impact trauma, this study discusses features of safety belts with reference 4-9) to relevant studies in the medical science, automobile crash safety, and aircrew safety. For this purpose, simple drop tests were carried out in a virtual workplace to measure impact load, head acceleration, and posture in the experiments, the Hybrid-III pedestrian model 10) was used as a human dummy. Hybrid-III is typically employed in official automobile crash tests (New Car Assessment Program: NCAP) and is currently recognized as a model that faithfully reproduces dynamic responses. Experimental results shows that safety performance strongly depends on both the variety of safety belts used and the shock absorbers attached onto lanyards. These findings indicate that fall prevention equipment, such as safety belts, lanyards, and shock absorbers, must be improved to reduce impact injuries to the human head and body during falls.

Investigation of the long term stability and corrosion resistance of engineering barriers

International Nuclear Information System (INIS)

Aoyama, Eri; Tachikawa, Hirokazu; Shimizu, Akihiko

2005-03-01

The Japan Nuclear Cycle Development Institute submitted 'Second Progress Report on Research and Development for the Geological Disposal of HLW in Japan' to the Japanese government. This report contains investigations of the long term behavior of alteration of bentonite, and of the corrosion life time of overpack on the basis of experimental data and past research, assuming the ranging geological environment of Japan. However some subjects, such as the behavior of the bentonite and overpack under high pH conditions and the behavior of the engineering barrier with change of near-field environmental condition with time for promoting reliability have still been left. To take into account these conditions, expert committees composed of clay science and metal corrosion science experts were established in the Nuclear Safety Research Association and past research outcomes and the theory of safety assessment were investigated from the view points of long term stability and corrosion resistance of engineering barrier. (author)

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

Long-term plutonium storage: Design concepts

International Nuclear Information System (INIS)

Wilkey, D.D.; Wood, W.T.; Guenther, C.D.

1994-01-01

An important part of the Department of Energy (DOE) Weapons Complex Reconfiguration (WCR) Program is the development of facilities for long-term storage of plutonium. The WCR design goals are to provide storage for metals, oxides, pits, and fuel-grade plutonium, including material being held as part of the Strategic Reserve and excess material. Major activities associated with plutonium storage are sorting the plutonium inventory, material handling and storage support, shipping and receiving, and surveillance of material in storage for both safety evaluations and safeguards and security. A variety of methods for plutonium storage have been used, both within the DOE weapons complex and by external organizations. This paper discusses the advantages and disadvantages of proposed storage concepts based upon functional criteria. The concepts discussed include floor wells, vertical and horizontal sleeves, warehouse storage on vertical racks, and modular storage units. Issues/factors considered in determining a preferred design include operational efficiency, maintenance and repair, environmental impact, radiation and criticality safety, safeguards and security, heat removal, waste minimization, international inspection requirements, and construction and operational costs

Workplace Violence and Safety Issues in Long-Term Medical Care Facilities: Nurses' Perspectives

Directory of Open Access Journals (Sweden)

Bankole K. Fasanya

2016-06-01

Conclusion: WPV is an epidemic problem that affects all health-care professionals. The findings of this study could help long-term medical care facilities' management identify the areas to focus on mitigating, controlling, and/or eliminating incidents of WPV.

Long-Term Neurodevelopmental Outcome after Doxapram for Apnea of Prematurity.

Science.gov (United States)

Ten Hove, Christine H; Vliegenthart, Roseanne J; Te Pas, Arjan B; Brouwer, Emma; Rijken, Monique; van Wassenaer-Leemhuis, Aleid G; van Kaam, Anton H; Onland, Wes

2016-01-01

Doxapram has been advocated as a treatment for persistent apnea of prematurity (AOP). To evaluate the effect of doxapram on long-term neurodevelopmental outcome in preterm infants as its safety still needs to be established. From a retrospective cohort of preterm infants with a gestational age (GA) large, well-designed, placebo-controlled randomized trial. © 2016 The Author(s) Published by S. Karger AG, Basel.

Long term stability of power systems

Energy Technology Data Exchange (ETDEWEB)

Kundur, P; Gao, B [Powertech Labs. Inc., Surrey, BC (Canada)

1994-12-31

Power system long term stability is still a developing subject. In this paper we provide our perspectives and experiences related to long term stability. The paper begins with the description of the nature of the long term stability problem, followed by the discussion of issues related to the modeling and solution techniques of tools for long term stability analysis. Cases studies are presented to illustrate the voltage stability aspect and plant dynamics aspect of long term stability. (author) 20 refs., 11 figs.

RBMK-1500 accident management for loss of long-term core cooling

International Nuclear Information System (INIS)

Uspuras, E.; Kaliatka, A.

2001-01-01

Results of the Level 1 probabilistic safety assessment of the Ignalina NPP has shown that in topography of the risk, transients dominate above the accidents with LOCAs and failure of the core long-term cooling are the main factors to frequency of the core damage. Previous analyses have shown, that after initial event, as a rule, the reactivity control, as well as short-term and intermediate cooling are provided. However, the acceptance criteria of the long-term cooling are not always carried out. It means that from this point of view the most dangerous accident scenarios are the scenarios related to loss of the core long-term cooling. On the other hand, the transition to the core condition due to loss of the long-term cooling specifies potential opportunities for the management of the accident consequences. Hence, accident management for the mitigation of the accident consequences should be considered and developed. The most likely initiating event, which probably leads to the loss of long term cooling accident, is station blackout. The station blackout is the loss of normal electrical power supply for local needs with an additional failure on start-up of all diesel generators. In the case of loss of electrical power supply MCPs, the circulating pumps of the service water system and MFWPs are switched-off. At the same time, TCV of both turbines are closed. Failure of diesel generators leads to the non-operability of the ECCS long-term cooling subsystem. It means the impossibility to feed MCC by water. The analysis of the station blackout for Ignalina NPP was performed using RELAP5 code. (author)

Long term integrity of spent fuel and construction materials for dry storage facilities

Energy Technology Data Exchange (ETDEWEB)

Saegusa, T [CRIEPI (Japan)

2012-07-01

In Japan, two dry storage facilities at reactor sites have already been operating since 1995 and 2002, respectively. Additionally, a large scale dry storage facility away from reactor sites is under safety examination for license near the coast and desired to start its operation in 2010. Its final storage capacity is 5,000tU. It is therefore necessary to obtain and evaluate the related data on integrity of spent fuels loaded into and construction materials of casks during long term dry storage. The objectives are: - Spent fuel rod: To evaluate hydrogen migration along axial fuel direction on irradiated claddings stored for twenty years in air; To evaluate pellet oxidation behaviour for high burn-up UO{sub 2} fuels; - Construction materials for dry storage facilities: To evaluate long term reliability of welded stainless steel canister under stress corrosion cracking (SCC) environment; To evaluate long term integrity of concrete cask under carbonation and salt attack environment; To evaluate integrity of sealability of metal gasket under long term storage and short term accidental impact force.

Long-term efficacy and safety of omalizumab in patients with persistent uncontrolled allergic asthma: a systematic review and meta-analysis

Science.gov (United States)

Lai, Tianwen; Wang, Shaobin; Xu, Zhiwei; Zhang, Chao; Zhao, Yun; Hu, Yue; Cao, Chao; Ying, Songmin; Chen, Zhihua; Li, Wen; Wu, Bin; Shen, Huahao

2015-01-01

Currently, limited information is available to clinicians regarding the long-term efficacy of omalizumab treatment for allergic asthma. In this report, we aimed to (i) systematically review the evidence regarding the long-term efficacy of omalizumab in patients with persistent uncontrolled allergic asthma, and to (ii) discuss the cost-effectiveness evidence published for omalizumab in this patient population. A comprehensive search for randomized controlled trials (RCTs; ≥52 weeks) was performed, and six studies met our final inclusion criteria (n = 2,749). Omalizumab was associated with significant improvements in quality of life and the Global Evaluation of Treatment Effectiveness. Omalizumab also allowed patients to completely withdraw from inhaled corticosteroid therapy and did not increase the overall incidence of adverse events. However, there was insufficient evidence that omalizumab reduced the incidence of exacerbations, and the cost-effectiveness of omalizumab varied across studies. Our data indicated that omalizumab use for at least 52 weeks in patients with persistent uncontrolled allergic asthma was accompanied by an acceptable safety profile, but it lacked effect on the asthma exacerbations. Use of omalizumab was associated with a higher cost than conventional therapy, but these increases may be cost-effective if the medication is used in patients with severe allergic asthma. PMID:25645133

Liabilities identification and long-term management - Review of French situation

International Nuclear Information System (INIS)

2003-01-01

In France, long term liabilities due to nuclear activities concern four main operators: Electricite de France (EDF), AREVA (an industrial group created on September 3, 2001 and covering the entire fuel cycle from ore extraction and transformation to the recycling of spent fuel), the Atomic Energy Commission (CEA, the French public research organism in the nuclear sector) and the French Agency for radioactive waste management (ANDRA, in charge with the long term operation of radioactive waste installations). Long term liabilities are due to the financing of both decommissioning of nuclear installations and radioactive waste long term management. In the current French organisational scheme, the different operators must take the responsibility of these long term liabilities. The setting of national policies and the establishment of the legislation are carried out at a national level by the French state. These include the supervision of the three operators through different Ministries and the regulatory control of safety trough the Nuclear Safety Authority (ASN). EDF, AREVA, CEA and ANDRA are responsible for all aspects of the decommissioning (from a technical and financial point of view). Within a safety regulatory frame, they have their own initiative concerning future expenses, based on estimated costs and the expected operational lifetime of the installations. They are responsible of the definition and implementation of the technical options. Through its supervision activities, the French State regularly requires updating studies of these estimated costs, which are conducted by the operators. A general review of the management of these long-term liabilities is also carried out on a four years basis by the French Court of Accounts. Operators are due to constitute provisions during the life cycle of their installations. Provisions are calculated for each installation on the basis of the decommissioning expenses and of the reasonably estimated lifetime. They are re

Long-Term Safety of In Utero Exposure to Anti-TNFα Drugs for the Treatment of Inflammatory Bowel Disease

DEFF Research Database (Denmark)

Chaparro, M; Verreth, A; Lobaton, T

2018-01-01

OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs...... in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non......-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox...

Accumulation of Cd in agricultural soil under long-term reclaimed water irrigation

International Nuclear Information System (INIS)

Chen, Weiping; Lu, Sidan; Peng, Chi; Jiao, Wentao; Wang, Meie

2013-01-01

Safety of agricultural irrigation with reclaimed water is of great concern as some potential hazardous compounds like heavy metals may be accumulated in soils over time. Impacts of long-term reclaimed water on soil Cd pollution were evaluated based on the field investigation in two main crop areas in Beijing with long irrigation history and on simulation results of STEM-profile model. Under long-term reclaimed water, Cd content in the top 20 cm soil layer was greatly elevated and was more than 2 times higher than that in the deep soil layer. There was very small differences between the field measured and model simulated Cd content in the plow layer (top 20 cm) and entire soil layer. Long-term model prediction showed that reclaimed water irrigation had a low environmental risk of soil Cd pollution, but the risk would be aggravated when there were high metal loading from other sources. The risk is also depending on the soil and plant properties. -- Highlights: •Root zone soil Cd content was elevated by one time under long-term reclaimed water irrigation. •The STEM-profile model can well track the Cd balance in the soil profile. •Reclaimed water irrigation plays a limited role on soil Cd accumulation in Beijing croplands. -- There was a low risk of soil Cd pollution under long-term reclaimed water irrigation

Long-term outcomes of Botulinum toxin in the treatment of chronic anal fissure: 5 years of follow-up.

Science.gov (United States)

Barbeiro, Sandra; Atalaia-Martins, Catarina; Marcos, Pedro; Gonçalves, Cláudia; Canhoto, Manuela; Arroja, Bruno; Silva, Filipe; Cotrim, Isabel; Eliseu, Liliana; Santos, Antonieta; Vasconcelos, Helena

2017-03-01

Chronic anal fissure is a frequent and disabling disease, often affecting young adults. Botulinum toxin and lateral internal sphincterotomy are the main therapeutic options for refractory cases. Botulinum toxin is minimally invasive and safer compared with surgery, which carries a difficult post-operative recovery and fecal incontinence risk. The long-term efficacy of Botulinum toxin is not well known. The aim of this study was to evaluate the long-term efficacy and safety of Botulinum toxin in the treatment of chronic anal fissure. This was a retrospective study at a single center, including patients treated with Botulinum toxin from 2005 to 2010, followed over at least a period of 5 years. All patients were treated with injection of 25U of Botulinum toxin in the intersphincteric groove. The response was registered as complete, partial, refractory and relapse. Botulinum toxin was administered to 126 patients, 69.8% ( n  = 88) were followed over a period of 5 years. After 3 months, 46.6% ( n  = 41) had complete response, 23.9% ( n  = 21) had partial response and 29.5% ( n  = 26) were refractory. Relapse was observed in 1.2% ( n  = 1) at 6 months, 11.4% ( n  = 10) at 1 year, 2.3% ( n  = 2) at 3 years; no relapse at 5 years. The overall success rate was 64.8% at 5 years of follow-up. Botulinum toxin was well tolerated by all patients and there were no complications. The use of Botulinum toxin to treat patients with chronic anal fissure was safe and effective in long-term follow-up.

Long-Term Efficacy, Safety, and Pharmacokinetics of Drisapersen in Duchenne Muscular Dystrophy: Results from an Open-Label Extension Study.

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Nathalie M Goemans

Full Text Available Drisapersen induces exon 51 skipping during dystrophin pre-mRNA splicing and allows synthesis of partially functional dystrophin in Duchenne muscular dystrophy (DMD patients with amenable mutations.This 188-week open-label extension of the dose-escalation study assessed the long-term efficacy, safety, and pharmacokinetics of drisapersen (PRO051/GSK2402968, 6 mg/kg subcutaneously, in 12 DMD subjects. Dosing was once weekly for 72 weeks. All subjects had a planned treatment interruption (weeks 73-80, followed by intermittent dosing (weeks 81-188.Subjects received a median (range total dose of 5.93 (5.10 to 6.02 mg/kg drisapersen. After 177 weeks (last efficacy assessment, median (mean [SD] six-minute walk distance (6MWD improved by 8 (-24.5 [161] meters for the 10 subjects able to complete the 6MWD at baseline (mean age [SD]: 9.5 [1.9] years. These statistics include 2 subjects unable to complete the test at later visits and who scored "zero". When only the 8 ambulant subjects at week 177 were taken into account, a median (mean [SD] increase of 64 (33 [121] meters in 6MWD was observed. Of 7 subjects walking ≥330 m at extension baseline, 5 walked farther at week 177. Of 3 subjects walking <330 m, 2 lost ambulation, while 1 declined overall but walked farther at some visits. Over the 188 weeks, the most common adverse events were injection-site reactions, raised urinary α1-microglobulin and proteinuria. Dystrophin expression was detected in all muscle biopsies obtained at week 68 or 72.Drisapersen was generally well tolerated over 188 weeks. Possible renal effects, thrombocytopenia and injection-site reactions warrant continued monitoring. Improvements in the 6MWD at 12 weeks were sustained after 3.4 years of dosing for most patients. For a small, uncontrolled study, the outcomes are encouraging, as natural history studies would anticipate a decline of over 100 meters over a 3-year period in a comparable cohort.ClinicalTrials.gov NCT01910649.

Environmental effects of the long term management of wastes

International Nuclear Information System (INIS)

Henry, L.C.

1980-08-01

Criteria for interim application in uranium mill tailings management, pending the outcome of a thorough investigation of the tailings problem, are outlined. For a closed-out tailings site only passive or natural barriers are to be used to control releases; surface water recharge is to be limited to that from direct natural precipitation, and no permanent water pool will be allowed; all designed systems must be evaluated in terms of their long-term durability; long-term performance and economic guarantees will be required; access must be limited to the maximum extent practical; and pathway analyses should be performed to determine the health, safety and environmental impacts of the expected level of releases. Releases to water should be no greater than those experienced during the operating phase of the facility. Radon emanation should not exceed 2-10 pCi/m 2 .s, and gamma radiation should be reduced to 10-50 μR/hr at 1 metre above the surface. Particulate emissions originating from the tailings material should be virtually non-existent

Groundwater modeling for the long-term safety assessment of uranium tailings ponds

International Nuclear Information System (INIS)

Nair, R.N.

2010-01-01

Uranium tailings ponds contain naturally occurring long lived radionuclides such as 238 U, 234 U, 230 Th and 226 Ra as sources which are the parents of a very long radionuclide decay chain. Uranium tailings ponds by the virtue of the longevity of its contents may pose as a long-term radiological hazard if not designed and monitored properly. The principal radiation risks from uranium tailings are gamma radiation: windblown radioactive dust dispersion; and radon gas and its progenies. Uranium tailings ponds are also a major source of surface and groundwater contamination due to leaching of radioactive and other toxic elements. In many countries, the tailings ponds are designed to control the radiological hazards for up to 1000 years, to the extent achievable, and in any case for at least 200 years. Stringent regulations stipulations exist worldwide for the safe design, operation and closure of uranium tailings ponds. The long- term radiological impact assessment of uranium tailings ponds, hence, is an extremely important exercise in uranium mining industry. The simulations conducted for uranium over a period of 1000 years indicate that contaminant fronts from the source with a paste permeability of 1x10 -4 m/day would migrate a probable distance of less than 50 m. The maximum computed distance for this case is less than 300 m. Indian studies show that the total annual effective dose to members of the public at 1.0 km from the centre of the tailings pond is trivial up to a period of 4000 y. The estimated dose is 0.01 mSv/y after 10,000 years and it is 10 times lower than 0.1 mSv/y, which is considered as a safe dose limit for drinking water pathway. (author)

Efficacy and safety of nimesulide long term administration in patients with osteoarthritis: results of 12-months open controlled study DINAMO (long term administration of nimesulide in osteoarthritis multifactor assessment

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L I Alexeeva

2009-01-01

Full Text Available Objective. To compare efficacy and safety of nimesulide and paracetamol in treatment of patients with osteoarthritis (OA during 12 months. Material and methods. 40 women (mean age 66,8±5,1 years with knee osteoarthritis (II-III stage according to Kellgren-Lawrence having intensive pain (>40 mm on VAS were included. Group 1 pts (n=20 received nimesulide 200-100 mg/day. Group 2 pts were treated with paracetamol till 3 g/day. WOMAC was used as efficacy measure. Safety was assessed with endoscopic examination of upper gastrointestinal tract, ECG, blood pressure and ECG Holter monitoring, clinical and biochemical blood parameters. Statistical significance of differences was assessed with Student’s t-test, χ2 and Fisher exact test Results. WOMAC index decreased during treatment from 1182,7±345,9 to 698,4±351,1 for nimesulide and from 1136,4±313,8 to 1031,6±21 for paracetamol (p<0,05. There were 6 cases of gastrointestinal complications and 4 cases of hypertension development or deterioration in each group. Coronary heart disease developed or deteriorated in 4 patients receiving nimesulide but not in control group. Liver function tests did not deteriorated during treatment with nimesulide. Conclusion. Nimesulide was more effective than paracetamol in treatment of OA. But risk of cardiovascular complications development during treatment with NSAIDs requires serious attention. Nimesulide did not induced liver damage during long term treatment.

Contemporary Reflections on the Safety of Long-Term Aspirin Treatment for the Secondary Prevention of Cardiovascular Disease

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Fanaroff, Alexander C.; Roe, Matthew T.

2018-01-01

Aspirin has been the cornerstone of therapy for the secondary prevention treatment of patients with cardiovascular disease since landmark trials were completed in the late 1970s and early 1980s that demonstrated the efficacy of aspirin for reducing the risk of ischemic events. Notwithstanding the consistent benefits demonstrated with apirin for both acute and chronic cardiovascular disease, there are a number of toxicities associated with aspirin that have been showcased by recent long-term clinical trials that have included an aspirin monotherapy arm. As an inhibitor of cyclooxygenase, aspirin impairs gastric mucosal protective mechanisms. Prior trials have shown that up to 15–20% of patients developed gastrointestinal symptoms with aspirin monotherapy and roughly 1% of patients per year had a clinically significant bleeding event, including 1 in 1000 patients who suffered an intracranial or fatal bleed. These risks have been shown to be compounded for patients with acute coronary syndromes (ACS) and those undergoing percutaneous coronary intervention (PCI), who are also treated with other anti-thrombotic agents during the acute care/procedural period, as well as for an extended time period afterwards. Given observations of substantial increases in bleeding rates from many prior long-term clinical trials that have evaluated aspirin together with other oral platelet inhibitors or oral anti-coagulants, the focus of contemporary research has pivoted towards tailored anti-thrombotic regimens that attempt to either shorten the duration of exposure to aspirin or replace aspirin with an alternative anti-thrombotic agent. While these shifts are occurring, the safety profile of aspirin when used for the secondary prevention treatment of patients with established cardiovascular disease deserves further consideration. PMID:27028617

Early aspirin desensitization in unstable patients with acute coronary syndrome: Short and long-term efficacy and safety.

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Córdoba-Soriano, Juan Gabriel; Corbí-Pascual, Miguel; López-Neyra, Isabel; Navarro-Cuartero, Javier; Hidalgo-Olivares, Víctor; Barrionuevo-Sánchez, Maria Isabel; Prieto-Mateos, Daniel; Gutiérrez-Díez, Antonio; Gallardo-López, Arsenio; Fuentes-Manso, Raquel; Gómez-Pérez, Alberto; Lafuente-Gormaz, Carlos; Jiménez-Mazuecos, Jesús

2016-11-01

Aspirin hypersensitivity is not a rare condition among patients with acute coronary syndrome. However, despite the publication of several successful desensitization protocols, the procedure is not as widespread as expected. We present a cohort of patients with acute coronary syndrome undergoing aspirin desensitization to evaluate its short- and long-term efficacy and safety and to reinforce data from previous studies. Of 1306 patients admitted to our Coronary Care Unit between February 2011 and February 2013, 24 (1.8%) had a history of aspirin hypersensitivity. All 24 patients underwent an eight-dose aspirin desensitization protocol (0.1, 0.3, 1, 3, 10, 25, 50 and 100 mg of aspirin given by mouth every 15 minutes) after premedication with antihistamines and corticosteroids or antileucotrienes. Previously prescribed β blockers and angiotensin-converting enzyme inhibitors were not discontinued. All patients were desensitized within 72 hours of admission. Those requiring urgent catheterization (five patients with ST segment elevation myocardial infarction) were desensitized within 12 hours of catheterization and the remainder before catheterization. All patients were successfully desensitized and only one presented with an urticarial reaction. The five patients with ST segment elevation myocardial infarction were treated with abciximab until desensitization was complete. All but one patient underwent catheterization and 20 underwent percutaneous coronary intervention, most (66%) with the implantation of a bare metal stent. At follow-up (a minimum of 6-24 months), only two patients had discontinued aspirin, both due to gastrointestinal bleeding, and no hypersensitivy reaction had occurred. Aspirin desensitization is effective and safe in unstable patients with acute coronary syndrome in both the short and long term.

Efficacy, safety and tolerability of rasagiline as adjunctive therapy in elderly patients with Parkinson's disease.

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Tolosa, E; Stern, M B

2012-02-01

Rasagiline, an MAO-B inhibitor, is indicated for the treatment of Parkinson's disease (PD). In this post hoc analysis, the efficacy, safety and tolerability of rasagiline as an adjunct to levodopa were compared with placebo in elderly (≥70 years) and younger (Rasagiline: Efficacy and Safety on the Treatment of 'OFF' and Lasting effect in Adjunct therapy with Rasagiline Given Once daily randomized, double-blind, placebo-controlled trials with the primary efficacy end-point being the reduction from baseline in daily OFF time. Secondary efficacy end-points included scores for Clinical Global Improvement (CGI)-Examiner during ON time, Unified Parkinson's Disease Rating Scale (UPDRS)-ADL during OFF time, UPDRS-Motor during ON time and total daily ON time with and without troublesome dyskinesia. Tolerability was evaluated from adverse events (AEs) in the two age groups. Rasagiline decreased daily OFF time versus placebo (Prasagiline but were not significant. Between-group comparisons (≥70 vs. efficacy was unaffected by age for all end-points (P>0.1), and rasagiline was well tolerated amongst both groups of patients with a comparable incidence of total and dopaminergic AEs (P>0.1). Adjunct rasagiline is efficacious and well tolerated in elderly non-demented patients (≥70 years) with moderate to advanced PD. Confirmation of the efficacy and safety of rasagiline in the elderly patient subgroup is especially relevant because of the increasing number of elderly patients with PD. © 2011 The Author(s). European Journal of Neurology © 2011 EFNS.

Long-Term Endocrine Outcomes Following Endoscopic Endonasal Transsphenoidal Surgery for Acromegaly and Associated Prognostic Factors.

Science.gov (United States)

Babu, Harish; Ortega, Alicia; Nuno, Miriam; Dehghan, Aaron; Schweitzer, Aaron; Bonert, H Vivien; Carmichael, John D; Cooper, Odelia; Melmed, Shlomo; Mamelak, Adam N

2017-08-01

Long-term remission rates from endoscopic transsphenoidal surgery for acromegaly and their relationship to prognostic indicators of disease aggressiveness are not well documented. To investigate long-term remission rates in patients with acromegaly after endoscopic transsphenoidal surgery, and correlate this with molecular and radiographic markers of disease aggressiveness. We identified all patients undergoing endoscopic transsphenoidal surgery for acromegaly from 2005 to 2013 at Cedars-Sinai Pituitary Center. Hormonal remission was established by normal insulin-like growth factor (IGF)-1, basal serum growth hormone <2.5 ng/mL, and growth hormone suppression to <1 ng/mL following oral glucose tolerance test. Oral glucose tolerance test was performed at 3 months after surgery, and then as indicated. IGF-1 was measured at 3 months and then at least annually. We evaluated tumor granularity, nuclear expression of p21, Ki67 index, and extent of cavernous sinus invasion, and correlated these with remission status. Fifty-eight patients that underwent surgery had follow-up from 38 to 98 months (mean 64 ± 32.2 months). There were 21 microadenomas and 37 macroadenomas. Three months after surgery 40 of 58 patients (69%) were in biochemical remission. Four additional patients were in remission at 6 months after surgery, and 1 patient had recurrence within the first year after surgery. At last follow-up, 43 of 44 (74.1%) of patients remained in remission. Cavernous sinus invasion by tumor predicted failure to achieve remission. Prognostic markers of disease aggressiveness other than cavernous sinus invasion did not correlate with surgical outcome. Long-term remission after surgery alone was achieved in 74% of patients, indicating long-term efficacy of endoscopic surgery. Copyright © 2017 by the Congress of Neurological Surgeons

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

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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

Mapping the areas sensitive to long-term endotoxin tolerance in the rat brain: a c-fos mRNA study.

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Vallès, Astrid; Martí, Octavi; Armario, Antonio

2005-06-01

We have recently found that a single endotoxin administration to rats reduced the hypothalamic-pituitary-adrenal response to another endotoxin administration 4 weeks later, which may be an example of the well-known phenomenon of endotoxin tolerance. However, the time elapsed between the two doses of endotoxin was long enough to consider the above results as an example of late tolerance, whose mechanisms are poorly characterized. To know if the brain plays a role in this phenomenon and to characterize the putative areas involved, we compared the c-fos mRNA response after a final dose of endotoxin in animals given vehicle or endotoxin 4 weeks before. Endotoxin caused a widespread induction of c-fos mRNA in the brain, similar to that previously reported by other laboratories. Whereas most of the brain areas were not sensitive to the previous experience with endotoxin, a few showed a reduced response in endotoxin-pretreated rats: the parvocellular and magnocellular regions of the paraventricular hypothalamic nucleus, the central amygdala, the lateral division of the bed nucleus and the locus coeruleus. We hypothesize that late tolerance to endotoxin may involve plastic changes in the brain, likely to be located in the central amygdala. The reduced activation of the central amygdala in rats previously treated with endotoxin may, in turn, reduce the activation of other brain areas, including the hypothalamic paraventicular nucleus.

Deep repository for long-lived low- and intermediate-level waste. Preliminary safety assessment

International Nuclear Information System (INIS)

1999-11-01

A preliminary safety assessment has been performed of a deep repository for long-lived low- and intermediate-level waste, SFL 3-5. The purpose of the study is to investigate the capacity of the facility to act as a barrier to the release of radionuclides and toxic pollutants, and to shed light on the importance of the location of the repository site. A safety assessment (SR 97) of a deep repository for spent fuel has been carried out at the same time. In SR 97, three hypothetical repository sites have been selected for study. These sites exhibit fairly different conditions in terms of hydrogeology, hydrochemistry and ecosystems. To make use of information and data from the SR 97 study, we have assumed that SFL 3-5 is co-sited with the deep repository for spent fuel. A conceivable alternative is to site SFL 3-5 as a completely separate repository. The focus of the SFL 3-5 study is a quantitative analysis of the environmental impact for a reference scenario, while other scenarios are discussed and analyzed in more general terms. Migration in the repository's near- and far-field has been taken into account in the reference scenario. Environmental impact on the three sites has also been calculated. The calculations are based on an updated forecast of the waste to be disposed of in SFL 3-5. The forecast includes radionuclide content, toxic metals and other substances that have a bearing on a safety assessment. The safety assessment shows how important the site is for safety. Two factors stand out as being particularly important: the water flow at the depth in the rock where the repository is built, and the ecosystem in the areas on the ground surface where releases may take place in the future. Another conclusion is that radionuclides that are highly mobile and long-lived, such as 36 Cl and 93 Mo , are important to take into consideration. Their being long-lived means that barriers and the ecosystems must be regarded with a very long time horizon

Microcrack growing and long-term mechanical stability in a HLW deep-borehole repository in granite

International Nuclear Information System (INIS)

Biurrun, E.; Hahne, K.

1989-01-01

The long-term host rock integrity assessment of a deep borehole emplacement for HLW in granite has been addressed with a detailed new constitutive model considering temperature and pressure effects on microscale phenomena (as microcracking) under repository conditions. The results of these finite element calculations have been compared with results obtained using conventional, state-of-the-art constitutive modelling. While the results of conventional modelling did suggest the existence of an important safety margin before failure, the improved calculations with the new model predict a thin but very long region of degradated host rock along the waste canister column. The results obtained up to now may well be considered as safety relevant, because they suggest that the actual long-term granite strength lies well below the conventionally determined failure limits, thus challenging the barrier properties of this host rock if the actual strength is not properly considered in the repository design

Preliminary safety analysis of the PWR with accident-tolerant fuels during severe accident conditions

International Nuclear Information System (INIS)

Wu, Xiaoli; Li, Wei; Wang, Yang; Zhang, Yapei; Tian, Wenxi; Su, Guanghui; Qiu, Suizheng; Liu, Tong; Deng, Yongjun; Huang, Heng

2015-01-01

Highlights: • Analysis of severe accident scenarios for a PWR fueled with ATF system is performed. • A large-break LOCA without ECCS is analyzed for the PWR fueled with ATF system. • Extended SBO cases are discussed for the PWR fueled with ATF system. • The accident-tolerance of ATF system for application in PWR is illustrated. - Abstract: Experience gained in decades of nuclear safety research and previous nuclear accidents direct to the investigation of passive safety system design and accident-tolerant fuel (ATF) system which is now becoming a hot research point in the nuclear energy field. The ATF system is aimed at upgrading safety characteristics of the nuclear fuel and cladding in a reactor core where active cooling has been lost, and is preferable or comparable to the current UO 2 –Zr system when the reactor is in normal operation. By virtue of advanced materials with improved properties, the ATF system will obviously slow down the progression of accidents, allowing wider margin of time for the mitigation measures to work. Specifically, the simulation and analysis of a large break loss of coolant accident (LBLOCA) without ECCS and extended station blackout (SBO) severe accident are performed for a pressurized water reactor (PWR) loaded with ATF candidates, to reflect the accident-tolerance of ATF

Safety objectives and basic design for surface centres for long-term storage of solid radioactive waste with short or medium half-life and low or medium specific activity

International Nuclear Information System (INIS)

1984-06-01

RFS or Regles Fondamentales de Surete (Basic Safety Rules) applicable to certain types of nuclear facilities lay down requirements with which compliance, for the type of facilities and within the scope of application covered by the RFS, is considered to be equivalent to compliance with technical French regulatory practice. The object of the RFS is to take advantage of standardization in the field of safety, while allowing for technical progress in that field. They are designed to enable the operating utility and contractors to know the rules pertaining to various subjects which are considered to be acceptable by the Service Central de Surete des Installations Nucleaires, or the SCSIN (Central Department for the Safety of Nuclear Facilities). These RFS should make safety analysis easier and lead to better understanding between experts and individuals concerned with the problems of nuclear safety. The SCSIN reserves the right to modify, when considered necessary, any RFS and specify, if need be, the terms under which a modification is deemed retroactive. The role of this RFS is to define the safety objectives and the basic design philosophy for surface centres for long-term storage of packages of radioactive waste with short or medium half-life and with low or medium specific activity

Long-term results of golimumab therapy for rheumatoid arthritis. Therapy compliance issues

Directory of Open Access Journals (Sweden)

N. V. Chichasova

2016-01-01

Full Text Available The goal of therapy for rheumatoid arthritis (RA is to suppress inflammation, to prevent or delay destructive changes in the joints, and to normalize functions during the longest monitoring of the course of RA. The data of randomized controlled trials and national registries are of great importance to a clinician. The paper reviews the literature data characterizing the long-term results of RA therapy with the tumor necrosis factor-α inhibitor golimumab (GLM and patient compliance with the therapy. Treatment with GLM at the registered subcutaneous dose of 50 mg once every 4 weeks gives rise to an effect in the vast majority of patients regardless of the type of previous ineffective therapy, the dose of concurrently administered methotrexate, the number of previous ineffective disease-modifying antirheumatic drugs, and the use and nonuse of glucocorticoids. GLM is characterized by a long-term (as long as 5 years effect with suppressed progression of destruction, functional recovery, and satisfactory tolerability with no additional risk for adverse events as the therapy is continued.

Assessment of the short-term safety and tolerability of a quantified 80 % ethanol extract from the stem bark of Nauclea pobeguinii (PR 259 CT1) in healthy volunteers: a clinical phase I study.

Science.gov (United States)

Mesia, Kahunu; Cimanga, Kanyanga; Tona, Lutete; Mampunza, Ma Miezi; Ntamabyaliro, Nsengi; Muanda, Tsobo; Muyembe, Tamfum; Totté, Jozef; Mets, Tony; Pieters, Luc; Vlietinck, Arnold

2011-01-01

The aim of this study was to evaluate the short-term safety and tolerability of an antimalarial herbal medicinal product (PR 259 CT1) consisting of a quantified 80 % ethanol extract from the stem bark of Nauclea pobeguinii when given orally to healthy adult male volunteers. The amount of the major alkaloid strictosamide in the extract was determined by a validated HPLC method and was shown to be 5.6 %. The herbal preparation was formulated in a gelatine capsule form containing 500 mg of PCR 259 CT1. A sample of 15 healthy male volunteers, selected using the Lot Quality Assurance of Sampling (LQAS) method, was eligible for inclusion after fulfillment of the inclusion criteria and clinical examination by a physician. The volunteers were treated in an outpatient clinic with a drug regimen of two 500 mg capsules three times daily (each eight hours) for seven days, during meals. Safety and tolerability were monitored clinically, haematologically, biochemically and by electrocardiographic (ECG) examination at days 0, 1, 3, 7 and 14. Adverse effects were recorded by self-reporting of the participants or by detection of abnormalities in clinical examinations by a physician. The oral administration of PR 259 CT1 at high doses of 2 × 500 mg/capsule/day for 7 days was found to induce no significant changes in the concentration levels of all investigated haematological, biochemical, electrocardiogram and vital sign parameters and physical characteristics after 14 days of treatment compared to those seen in the baseline data. The concentration levels of all evaluated parameters were within the normal limits as reported in the literature. All adverse events noted were mild and self-resolving including increase of appetite (33 %), headache (20 %) and nausea (20 %). Other minor side effects were insomnia, somnolence and asthenia (7 %). Thus, PR 259 CT1 presented a significant safety and tolerability in healthy volunteers to allow its further development by starting a phase II

Radioembolization for Neuroendocrine Liver Metastases: Safety, Imaging, and Long-Term Outcomes

Energy Technology Data Exchange (ETDEWEB)

Memon, Khairuddin; Lewandowski, Robert J. [Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Mulcahy, Mary F. [Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Riaz, Ahsun; Ryu, Robert K.; Sato, Kent T.; Gupta, Ramona; Nikolaidis, Paul; Miller, Frank H.; Yaghmai, Vahid; Gates, Vanessa L.; Atassi, Bassel [Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Newman, Steven [Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Omary, Reed A. [Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Benson, Al B. [Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Salem, Riad, E-mail: r-salem@northwestern.edu [Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States)

2012-07-01

Purpose: To present long-term outcomes on the safety and efficacy of Yttrium-90 radioembolization in the treatment of unresectable hepatic neuroendocrine metastases refractory to standard-of-care therapy. Methods and Materials: This study was approved by our institutional review board and was compliant with the Health Insurance Portability and Accountability Act. Forty patients with hepatic neuroendocrine metastases were treated with {sup 90}Y radioembolization at a single center. Toxicity was assessed using National Cancer Institute Common Terminology Criteria v3.0. Response to therapy was assessed by World Health Organization (WHO) guidelines for size and European Association for the Study of the Liver disease (EASL) guidelines for necrosis. Time to response and overall survival were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed. Results: The median dose was 113 Gy (29-299 Gy). Clinical toxicities included fatigue (63%), nausea/vomiting (40%), abdominal pain (18%), fever (8%), diarrhea and weight loss (5%); Grade 3 and 4 bilirubin toxicities were experienced by 2 patients and 1 patient, respectively. Different responses were noted by WHO (complete response, 1.2%; partial response, 62.7%) and EASL (complete response, 20.5%; partial response, 43.4%). Median time to response was 4 and 4.9 months by lesion and patient, respectively. The 1-, 2-, and 3-year overall survival rates were 72.5%, 62.5%, and 45%, respectively. Eastern Cooperative Oncology Group (ECOG) performance score 0 (p < 0.0001), tumor burden {<=}25% (p = 0.0019), albumin {>=}3.5 g/dL (p = 0.017), and bilirubin {<=}1.2 mg/dL (p = 0.002) prognosticated survival on univariate analysis; only ECOG performance score 0 and bilirubin {<=}1.2 mg/dL prognosticated better survival outcome on multivariate analysis (p = 0.0001 and p = 0.02). Conclusion: Yttrium-90 therapy for hepatic neuroendocrine metastases leads to satisfactory tumor response and patient survival

Neuromyelitis optica spectrum disorders: long-term safety and efficacy of rituximab in Caucasian patients.

Science.gov (United States)

Radaelli, M; Moiola, L; Sangalli, F; Esposito, F; Barcella, V; Ferrè, L; Rodegher, M; Colombo, B; Fazio, R; Martinelli, V; Comi, G

2016-04-01

To assess the long-term benefit-risk profile of repeated courses of rituximab in Caucasian patients affected by neuromyelitis optica (NMO) and related disorders, in everyday clinical practice. This is a prospective observational study performed at San Raffaele Hospital, Milan, Italy. From February 2006, we recruited 21 patients affected by NMO and NMO spectrum of disorders (NMOSD) whom underwent at least one cycle of intravenous (i.v.) rituximab and then were followed for at least 2 years. At a mean follow-up time of 48 months, we observed a significant reduction of the annualized relapse rate (ARR), from 2.0 to 0.16 (p < 0.01); and of the median Expanded Disability Status Scale (EDSS), from 5.5 to 4.0 (p < 0.013). There were 12 patients (57%) who remained disease free during the follow-up period. Five patients (24%) reported mild hematological adverse events. Serious infectious adverse events were reported by another four patients: These were all wheelchair bound at the beginning of their rituximab treatment. A fixed treatment scheme of rituximab, with re-treatment every 6 months, was efficacious for NMO and NMOSD, with a good safety profile; however, to obtain an even better benefit-risk ratio, close monitoring of CD19(+) B cells should be performed before the re-treatment of patients with high-level disability, concomitant leukopenia and hypogammaglobulinemia. © The Author(s), 2015.

Nurse-physician communication in the long-term care setting: perceived barriers and impact on patient safety.

Science.gov (United States)

Tjia, Jennifer; Mazor, Kathleen M; Field, Terry; Meterko, Vanessa; Spenard, Ann; Gurwitz, Jerry H

2009-09-01

Clear and complete communication between health care providers is a prerequisite for safe patient management and is a major priority of the Joint Commission's 2008 National Patient Safety Goals. The goal of this study was to describe nurses' perceptions of nurse-physician communication in the long-term care (LTC) setting. Mixed-method study including a self-administered questionnaire and qualitative semistructured telephone interviews of licensed nurses from 26 LTC facilities in Connecticut. The questionnaire measured perceived openness to communication, mutual understanding, language comprehension, frustration, professional respect, nurse preparedness, time burden, and logistical barriers. Qualitative interviews focused on identifying barriers to effective nurse-physician communication that may not have previously been considered and eliciting nurses' recommendations for overcoming those barriers. Three hundred seventy-five nurses completed the questionnaire, and 21 nurses completed qualitative interviews. Nurses identified several barriers to effective nurse-physician communication: lack of physician openness to communication, logistic challenges, lack of professionalism, and language barriers. Feeling hurried by the physician was the most frequent barrier (28%), followed by finding a quiet place to call (25%), and difficulty reaching the physician (21%). In qualitative interviews, there was consensus that nurses needed to be brief and prepared with relevant clinical information when communicating with physicians and that physicians needed to be more open to listening. A combination of nurse and physician behaviors contributes to ineffective communication in the LTC setting. These findings have important implications for patient safety and support the development of structured communication interventions to improve quality of nurse-physician communication.

Long-term urethral catheterisation.

Science.gov (United States)

Turner, Bruce; Dickens, Nicola

This article discusses long-term urethral catheterisation, focusing on the relevant anatomy and physiology, indications for the procedure, catheter selection and catheter care. It is important that nurses have a good working knowledge of long-term catheterisation as the need for this intervention will increase with the rise in chronic health conditions and the ageing population.

Guidance for implementing the UMTRA Project long-term surveillance program

International Nuclear Information System (INIS)

1992-09-01

The US Nuclear Regulatory Commission (NRC) has issued a general license for the custody and long-term care of US Department of Energy (DOE) Uranium Mill Tailings Remedial Action (UMTRA) Project permanent disposal sites. The purpose of this general license is to ensure that the UMTRA disposal sites will be cared for in such a manner as to protect the public health and safety and the environment upon completion of remedial actions. The general license will be in effect for a disposal site when NRC accepts the disposal site long-term surveillance plan (LTSP) that meets the requirements of 10 CFR 40.27. The site LTSP describes in detail the long-term surveillance program, including any monitoring, maintenance, and emergency measures necessary to fulfill the conditions of the general license. This guidance document provides (1) instructions for preparing the disposal site LTSPs and (2) instructions for carrying out the UMTRA Project long-term surveillance program, including any monitoring that may be required. The information provided in this document also is in accordance with the regulatory requirements set forth in 40 CFR 192. On January 5, 1985, the US Tenth Circuit Court of Appeals remanded the groundwater standards, 40 CFR 192.02. Proposed groundwater standards were issued for comment on September 24, 1987 (52 FR 3600). When the groundwater standards become final, this document will be revised, as appropriate. This document also will be updated in response to any changes to 10 CFR 40, or in response to changes in the manner in which the long-term care of the licensed disposal sites is carried out

Endovascular occlusion of intracranial wide-necked aneurysms with stenting (Neuroform) and coiling: mid-term and long-term results

Energy Technology Data Exchange (ETDEWEB)

Sedat, Jacques; Chau, Yves; Mondot, Lydiane [CHU Nice, Unite de Neurointerventionnelle, Hopital St. Roch, Nice (France); Vargas, Julian; Szapiro, Jacek; Lonjon, Michel [CH Bastia, Service de Neurochirurgie, Bastia (France)

2009-06-15

Coiling associated with placement of self-expandable intracranial stents has amplified the treatment of intracranial wide-necked aneurysms, but the durability of this treatment and the existence of delayed recurrence are not yet well known. The purpose of this report is to present our experience with the Neuroform Stent associated with coiling and to evaluate complications, effectiveness, and long-term results of this technique. A retrospective study of 42 patients with wide-necked cerebral aneurysms treated with the Neuroform Stent was performed. Mean aneurysm size was 11.3 mm. Mean neck size was 5.33 mm. All patients were treated with coiling and stenting. Clinical and angiographic follow-up was available in 38 patients (90.5%). The overall follow-up time ranged from 6 months to 5 years (mean, 42 months), but most of the patients (92%) had a follow-up period superior to 1 year. Successful deployment of 41 stents (97%) was obtained. Permanent procedural morbidity was observed in only one patient (2.4%). Long-term complete aneurysmal occlusion was obtained in 27 patients (71%). Aneurysmal regrowth was observed in four patients (9.5%) on the first control angiogram. After the first control angiogram, no delayed recanalization or regrowth was observed. During the follow-up period, there were no hemorrhagic events, no delayed thrombosis, and no stent displacement. Our results demonstrate the effectiveness of the technique, a small rate of procedural complications, and long-term tolerance of the Neuroform Stent. Despite some evidence of early aneurysmal recurrence, long-term durability of stent-assisted aneurysm occlusion is stable after the first year. (orig.)

The long term storage of advanced gas-cooled reactor (AGR) fuel

International Nuclear Information System (INIS)

Standring, P.N.

1999-01-01

The approach being taken by BNFL in managing the AGR lifetime spent fuel arisings from British Energy reactors is given. Interim storage for up to 80 years is envisaged for fuel delivered beyond the life of the Thorp reprocessing plant. Adopting a policy of using existing facilities, to comply with the principles of waste minimisation, has defined the development requirements to demonstrate that this approach can be undertaken safely and business issues can be addressed. The major safety issues are the long term integrity of both the fuel being stored and structure it is being stored in. Business related issues reflect long term interactions with the rest of the Sellafield site and storage optimisation. Examples of the development programme in each of these areas is given. (author)

Nagra technical report 14-02, geological basics - Dossier III - Long-term geological developments

International Nuclear Information System (INIS)

Schnellmann, M.; Madritsch, H.

2014-01-01

This dossier is the third of a series of eight reports concerning the safety and technical aspects of locations for the disposal of radioactive wastes in Switzerland. Dossier III takes a look at long-term geological developments. Developments in the topography and river networks of northern Switzerland over the past five million years are looked at. Data and information derived from high-resolution models and compilations of gravel deposition, glacier developments and moraines are reviewed. Tectonic developments, seismological aspects and erosion are discussed. Their consequences for the long-term geological developments in the proposed depository areas are looked at

Long-term surveillance plan for the South Clive Disposal Site, Clive, Utah

International Nuclear Information System (INIS)

1996-03-01

This long-term surveillance plan (LTSP) describes the US Department of Energy's (DOE) long-term care program for the Uranium Mill Tailings Remedial Action (UMTRA) Project South Clive disposal site in Clive, Utah. The US Nuclear Regulatory Commission (NRC) has developed regulations for the issuance of a general license for the custody and long-term care of UMTRA Project disposal sites in 10 CRF Part 40. The purpose of this general license is to ensure that the UMTRA Project disposal sites will be cared for in a manner that protects the public health and safety and the environment. For each disposal site to be licensed, the NRC requires the DOE to submit a site-specific LTSP. The DOE prepared this LTSP to meet this requirement for the South Clive disposal site. The general license becomes effective when the NRC concurs with the DOE's determination of completion of remedial action for the South Clive site and the NRC formally accepts this LTSP. This LTSP describes the long-term surveillance program the DOE will implement to ensure that the South Clive disposal site performs as designed. The program's primary activity is site inspections to identify threats to disposal cell integrity

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....

Research on geosphere stability for long-term isolation of radioactive waste. Scientific programme for fiscal years 2015-2021

International Nuclear Information System (INIS)

Umeda, Koji; Yasue, Ken-ichi; Saito-Kokubu, Yoko; Niwa, Masakazu; Asamori, Koichi; Fujita, Natsuko; Shimizu, Mayuko; Shimada, Akiomi; Matsubara, Akihiro; Tamura, Hajimu; Yokoyama, Tatsunori; Watanabe, Takahiro; Tokuyasu, Kayoko; Hama, Yuki

2015-08-01

The study on long-term geological stability has three objectives, namely, (1) development of technologies for determining the past and present conditions of the geological environment, (2) development of technologies for long-term prediction and evaluation of impacts and (3) development of dating techniques using advanced equipment on isotope geology and geochronology, in order to make contribution to site investigation and safety assessment for the geological disposal of high-level radioactive waste (HLW). This report is to outline 7 years plan (fiscal years 2015-2021) of research and development (R and D) for geosphere stability for long-term isolation of the HLW in Japan Atomic Energy Agency. Background of this research is clarified with the necessity and the significance for site investigation and safety assessment, and the past progress in this report. The objectives, outline, contents and schedule during the next 7 years are described in detail. In addition, the plan framework is structured into the following categories: (1) Development and Systematization of investigation techniques, (2) Development of models for long-term estimation and effective assessment, (3) Development of dating techniques. (author)

Long-term safety of left renal vein division and ligation to expedite complex abdominal aortic surgery.

Science.gov (United States)

Samson, Russell H; Lepore, Michael R; Showalter, David P; Nair, Deepak G; Lanoue, Julien B

2009-09-01

Left renal vein division and ligation (LRVDAL) is performed to facilitate complex abdominal aortic surgery. Surgeons restore continuity of the vein due to concern that ligation could cause renal compromise or hematuria. However, we report the short and long-term safety of left renal vein division and ligation. Between 1992 and 2007, we divided the left renal vein in 56 patients (40 males, 16 females) ages 57 to 84 (average 74-years-old) who were treated for aortic occlusive disease (9) or abdominal aortic aneurysm (47). Patients requiring concomitant renal artery reconstruction were excluded from this review. Suprarenal cross-clamp was used in 51 patients with temporary vessel-loop control of the renal arteries. Creatinine (Cr) and glomerular filtration rates (eGFR) were measured pre-, post-, and long-term after surgery. Outpatient records of all patients that had survived more than 12 months were also reviewed in order to evaluate the late effects on renal function or symptoms possibly related to LRVDAL. Median procedure duration was 157 (61-375) minutes. Median cross-clamp time was 16 (10-45) minutes. Median intensive care unit (ICU) and hospital length of stays were 2 (1-11) days and 7 (4-58) days, respectively. There were no deaths. There were no complications directly related to renal vein ligation. Hematuria, seen in 2 patients, was a result of traumatic insertion of a Foley catheter. Median pre-op and discharge Cr levels were 1.1 mg/dL (0.7-2.4 mg/dL) and 1.1 mg/dL (0.6-2.1 mg/dL), respectively (P 2.0 mg/dL remained unchanged post-op. Only 2 patients with a Cr of 2.0 mg/dL and both returned to normal by day 3 post-op. Thirty-six patients have been followed for more than a year (median 34.5 months, maximum 144 months) and Cr has remained stable in all but 2 patients. These 2 patients, both with a pre-op Cr of 1.5 mg/dL, subsequently developed Cr levels of 2.1 mg/dL and 2.4 mg/dL but maintained baseline Cr levels for 25 and 34 months, respectively, before

Perceptions of safety and exposure to violence in public places among working age adults with disabilities or long-term health conditions in the UK: cross sectional study.

Science.gov (United States)

Emerson, E; Krnjacki, L; Llewellyn, G; Vaughan, C; Kavanagh, A

2016-06-01

To examine perceptions of safety and exposure to violence in public places among working age adults with and without disabilities in the UK and to assess the extent to which any between-group differences may be moderated by gender and socio-economic situation. Cross-sectional study. Secondary analysis of data collected in Wave 3 (2011-13) of Understanding Society. Data were extracted on a subsample of 5069 respondents aged 16 to 64 years (28% of whom had a disability/long-term health condition) who were administered a questionnaire module addressing experiences of harassment. Between-group comparisons were made on four self-reported indicators of safety. Respondents with disabilities/long-term health conditions were significantly more likely to have been attacked (adjusted OR 2.30, 95%CI 1.17-4.50, P condition are at significantly increased risk of exposure to interpersonal violence, particularly if they are living in poverty or are women. As such, there is a clear need to develop interventions that are targeted to the particular circumstances and needs of these high risk groups. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Long-term monitoring as aging management component in the NPP Grohnde

International Nuclear Information System (INIS)

Reese, Sven H.; Seichter, Johannes

2009-01-01

In the frame of aging management of safety relevant mechanical systems, structures and components (SSC) a classification is performed with respect to the safety relevance. For SSC of group M1 integrity has to be assured, i.e. components must not fail. The other safety relevant components are classified as group M2, i.e. failure is admissible as isolated case. SSC of group M1 in the NPP Grohnde are included into the long-term monitoring system, the annual status report ''fatigue'' has to identify the actual usage value and predict the end-of-life usage. The authors describe the used methodology concerning loading evaluation based on temperature cycling data, the thermal hydraulic modeling using finite element methods for fatigue relevant components.

Safety and feasibility of long-term intravenous sodium nitrite infusion in healthy volunteers.

Directory of Open Access Journals (Sweden)

Ryszard M Pluta

Full Text Available BACKGROUND: Infusion of sodium nitrite could provide sustained therapeutic concentrations of nitric oxide (NO for the treatment of a variety of vascular disorders. The study was developed to determine the safety and feasibility of prolonged sodium nitrite infusion. METHODOLOGY: Healthy volunteers, aged 21 to 60 years old, were candidates for the study performed at the National Institutes of Health (NIH; protocol 05-N-0075 between July 2007 and August 2008. All subjects provided written consent to participate. Twelve subjects (5 males, 7 females; mean age, 38.8±9.2 years (range, 21-56 years were intravenously infused with increasing doses of sodium nitrite for 48 hours (starting dose at 4.2 µg/kg/hr; maximal dose of 533.8 µg/kg/hr. Clinical, physiologic and laboratory data before, during and after infusion were analyzed. FINDINGS: The maximal tolerated dose for intravenous infusion of sodium nitrite was 267 µg/kg/hr. Dose limiting toxicity occurred at 446 µg/kg/hr. Toxicity included a transient asymptomatic decrease of mean arterial blood pressure (more than 15 mmHg and/or an asymptomatic increase of methemoglobin level above 5%. Nitrite, nitrate, S-nitrosothiols concentrations in plasma and whole blood increased in all subjects and returned to preinfusion baseline values within 12 hours after cessation of the infusion. The mean half-life of nitrite estimated at maximal tolerated dose was 45.3 minutes for plasma and 51.4 minutes for whole blood. CONCLUSION: Sodium nitrite can be safely infused intravenously at defined concentrations for prolonged intervals. These results should be valuable for developing studies to investigate new NO treatment paradigms for a variety of clinical disorders, including cerebral vasospasm after subarachnoid hemorrhage, and ischemia of the heart, liver, kidney and brain, as well as organ transplants, blood-brain barrier modulation and pulmonary hypertension. CLINICAL TRIAL REGISTRATION INFORMATION: http

Long-term, interventional, open-label extension study evaluating the safety of tocilizumab treatment in patients with polyarticular-course juvenile idiopathic arthritis from Poland and Russia who completed the global, international CHERISH trial.

Science.gov (United States)

Opoka-Winiarska, Violetta; Żuber, Zbigniew; Alexeeva, Ekaterina; Chasnyk, Vyacheslav; Nikishina, Irina; Dębowska, Grażyna; Smolewska, Elżbieta

2018-04-13

Efficacy and safety of tocilizumab (TCZ), an interleukin-6 receptor inhibitor, were demonstrated in juvenile idiopathic arthritis (JIA) with polyarticular course (pJIA) in the CHERISH trial. This observational, III phase study evaluated long-term treatment of TCZ in pJIA patients was conducted by members of the Pediatric Rheumatology International Trials Organization (PRINTO) from Poland and Russia. Forty-one patients, who had completed the CHERISH core study (104 weeks), were extensionally treated with TCZ (8 mg/kg, intravenous infusion every 4 weeks). Total treatment time was from 131 to 193 weeks. The long-term safety (the primary endpoint) and efficacy were evaluated. All patients achieved ACR70 response in the core study and continued to achieve at least ACR50 response up to week 24 of this study. The safety population comprised 46.41 patient-years (PY). Rates per 100 PY of adverse (AEs) and serious events (SAEs) were 181.0 and 6.46, respectively. Pharyngitis and respiratory tract infections were the most common AEs. Except one AE (severe neutropenia), all others were classified as mild (24.4%) or moderate (29.3%). The incidence of SAEs was low (7.3%). No new safety findings were observed. The safety profile of over 2.5-year treatment with TCZ is consistent with the pre-marketing CHERISH clinical trial. Presented data and continued efficacy response support the use of TCZ in pJIA. EUDRACT No: 2011-001607-12. https://clinicaltrials.gov/ct2/show/study/NCT01575769?term=ML27783.

Experimental Setup for Reflood Quench of Accident Tolerant Fuel Claddings

Energy Technology Data Exchange (ETDEWEB)

Lee, Chan; Lee, Kwan Geun; In, Wang Kee [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2016-10-15

The concept of accident tolerant fuel (ATF) is a solution to suppress the hydrogen generation in loss of coolant accident (LOCA) situation without safety injection, which was the critical incident in the severe accident in the Fukushima. The changes in fuel and cladding materials may cause a significant difference in reactor performance in long term operation. Properties in terms of material science and engineering have been tested and showed promising results. However, numerous tests are still required to ensure the design performance and safety. Thermal hydraulic tests including boiling and quenching are partly confirmed, but not yet complete. We have been establishing the experimental setup to confirm the properties in the terms of thermal hydraulics. Design considerations and preliminary tests are introduced in this paper. An experimental setup to test thermal hydraulic characteristics of new ATF claddings are established and tested. The W heater set inside the cladding is working properly, exceeding 690 W/m linear power with thermocouples and insulating ceramic sheaths inside. The coolant injection control was also working in good conditions. The setup is about to complete and going to simulate quenching behavior of the ATF in the LOCA situation.

Long-term oxytocin administration improves social behaviors in a girl with autistic disorder.

Science.gov (United States)

Kosaka, Hirotaka; Munesue, Toshio; Ishitobi, Makoto; Asano, Mizuki; Omori, Masao; Sato, Makoto; Tomoda, Akemi; Wada, Yuji

2012-08-13

Patients with autism spectrum disorders (ASDs) exhibit core autistic symptoms including social impairments from early childhood and mostly show secondary disabilities such as irritability and aggressive behavior based on core symptoms. However, there are still no radical treatments of social impairments in these patients. Oxytocin has been reported to play important roles in multiple social behaviors dependent on social recognition, and has been expected as one of the effective treatments of social impairments of patients with ASDs. We present a case of a 16-year-old girl with autistic disorder who treated by long-term administration of oxytocin nasal spray. Her autistic symptoms were successfully treated by two month administration; the girl's social interactions and social communication began to improve without adverse effects. Her irritability and aggressive behavior also improved dramatically with marked decreases in aberrant behavior checklist scores from 69 to 7. This case is the first to illustrate long-term administration of oxytocin nasal spray in the targeted treatment of social impairments in a female with autistic disorder. This case suggests that long-term nasal oxytocin spray is promising and well-tolerated for treatment of social impairments of patients with ASDs.

Long-term safety of growth hormone replacement therapy after childhood medulloblastoma and PNET: it is time to set aside old concerns.

Science.gov (United States)

Indini, Alice; Schiavello, Elisabetta; Biassoni, Veronica; Bergamaschi, Luca; Magni, Maria Chiara; Puma, Nadia; Chiaravalli, Stefano; Pallotti, Federica; Seregni, Ettore; Diletto, Barbara; Pecori, Emilia; Gandola, Lorenza; Poggi, Geraldina; Massimino, Maura

2017-01-01

To assess the long-term safety of administering growth hormone (GH) in patients with GH deficiency due to treatment for childhood medulloblastoma and primitive neuroectodermal tumor (PNET). Data were retrospectively retrieved on children receiving GH supplementation, assessing their disease-free and overall survival outcomes and risk of secondary malignancies using Kaplan-Meier and Cox models. Overall 65 children were consecutively collected from May 1981 to April 2013. All patients had undergone craniospinal irradiation (total dose 18-39 Gy), and subsequently received GH for a median (interquartile range, IQR) of 81 (50.6-114.9) months. At a median (IQR) of 122.4 months (74.4-149.5) after the end of their adjuvant cancer treatment, two patients (3 %) experienced recurrent disease and 8 (12.3 %) developed secondary malignancies, all but one of them (an osteosarcoma) related to radiation exposure and occurring within the radiation fields. There was no apparent correlation between the administration of GH replacement therapy (or its duration) and primary tumor relapse or the onset of secondary malignancies [HR: 1.01 (95 % CI: 0.98, 1.03) for every additional 12 months of GH supplementation; p = 0.36). At univariate analysis, the large cell or anaplastic medulloblastoma subtype, metastases and myeloablative chemotherapy correlated with a higher risk of secondary malignancies (p < 0.1), but multivariate analysis failed to identify any factors independently associated with this risk. Our data supports once more the safety of long-term GH replacement therapy in children treated for medulloblastoma/PNET, previously reported in larger data sets. The neurooncology community now need to warrant large-scale meta-analyses or international prospective trials in order to consolidate our knowledge of factors other than GH, such as genetic predisposition, high-grade/metastatic disease, high-dose chemotherapy and era of treatment, in promoting the occurrence of

Remaining uncertainties in predicting long-term performance of nuclear waste glass from experiments

International Nuclear Information System (INIS)

Grambow, B.

1994-01-01

The current knowledge on the glass dissolution mechanism and the representation of glass dissolution concepts within overall repository performance assessment models are briefly summarized and uncertainties related to mechanism, radionuclide chemistry and parameters are discussed. Understanding of the major glass dissolution processes has been significantly increased in recent years. Long-term glass stability is related to the long-term maintenance of silica saturated conditions. The behavior of individual radionuclides in the presence of a dissolving glass has not been sufficiently and results do no yet allow meaningful predictions. Conserving long-term predictions of glass matrix dissolution as upper limit for radionuclide release can be made with sufficient confidence, however these estimations generally result in a situation where the barrier function of the glass is masked by the efficiency of the geologic barrier. Realistic long-term predictions may show that the borosilicate waste glass contributes to overall repository safety to a much larger extent than indicated by overconservatism. Today realistic predictions remain highly uncertain and much more research work is necessary. In particular, the long-term rate under silica saturated conditions needs to be understood and the behavior of individual radionuclides in the presence of a dissolving glass deserves more systematic investigations

Properties and long-term behaviour of bitumen and radioactive waste-bitumen mixtures

International Nuclear Information System (INIS)

Eschrich, H.

1980-10-01

Part I represents a survey of the properties and the long-term behaviour of pure bitumens and mixtures of bitumens with radioactive reactor and reprocessing wastes. This survey includes information on the origin, amounts, and composition of the various wastes considered for bituminization and the different waste bituminization techniques used. The influence of various factors on the quality of waste-bitumen products and on the radiological safety during transport, short- and long-term storage of the final products is described. Special consideration is given to the most important safety relevant factors associated to the use of bitumen as matrix material for radioactive wastes, such as leach-resistance, radiolysis, chemical and mechanical stability, combustibility, and microbial attack. Part II consists of a comprehensive bibliography on the bituminization of radioactive wastes, giving about 300 references to literature published from the beginning of the use of bitumen in radioactive waste management in 1960 until the beginning of 1979. Methods for the quality control of bituminous materials and some useful data are given in an annex. (author)

Long-term associative learning predicts verbal short-term memory performance.

Science.gov (United States)

Jones, Gary; Macken, Bill

2018-02-01

Studies using tests such as digit span and nonword repetition have implicated short-term memory across a range of developmental domains. Such tests ostensibly assess specialized processes for the short-term manipulation and maintenance of information that are often argued to enable long-term learning. However, there is considerable evidence for an influence of long-term linguistic learning on performance in short-term memory tasks that brings into question the role of a specialized short-term memory system separate from long-term knowledge. Using natural language corpora, we show experimentally and computationally that performance on three widely used measures of short-term memory (digit span, nonword repetition, and sentence recall) can be predicted from simple associative learning operating on the linguistic environment to which a typical child may have been exposed. The findings support the broad view that short-term verbal memory performance reflects the application of long-term language knowledge to the experimental setting.

Long-term efficacy and safety of ExPress implantation for treatment of open angle glaucoma

Directory of Open Access Journals (Sweden)

Geun Young Lee

2017-09-01

Full Text Available AIM: To compare the long-term efficacy and safety of ExPress implantation and standard trabeculectomy in patients with primary open angle glaucoma (POAG. METHODS: In this retrospective study, we compared 17 eyes treated by ExPress implantation with 23 eyes treated by trabeculectomy. Efficacy was assessed according to the relevant intraocular pressure (IOP values and success rates during the first year of follow-up. Postoperative corneal endothelial cell loss was also compared. RESULTS: The number of antiglaucoma medications and the IOP reduction were similar between the 2 groups during the follow-up period. Although the mean IOP was similar, the IOP-fluctuation rate during the early postoperative period was significantly lower in the ExPress group than in the trabeculectomy group (P=0.038. A Kaplan-Meier survival curve analysis showed no significant success-rate difference between the groups (P=0.810. The corneal endothelial cell loss rate, moreover, was significantly lower in the ExPress group (P=0.05. CONCLUSION: ExPress implantation compared with trabeculectomy showed similar IOP-reduction and success rates along with lower IOP fluctuation and endothelial cell loss rates. For this reason, it can be considered to be the treatment of choice for patients with advanced glaucoma or low corneal endothelial cell density.

Long-term efficacy and safety of ExPress implantation for treatment of open angle glaucoma.

Science.gov (United States)

Lee, Geun Young; Lee, Chong Eun; Lee, Kyoo Won; Seo, Sam

2017-01-01

To compare the long-term efficacy and safety of ExPress implantation and standard trabeculectomy in patients with primary open angle glaucoma (POAG). In this retrospective study, we compared 17 eyes treated by ExPress implantation with 23 eyes treated by trabeculectomy. Efficacy was assessed according to the relevant intraocular pressure (IOP) values and success rates during the first year of follow-up. Postoperative corneal endothelial cell loss was also compared. The number of antiglaucoma medications and the IOP reduction were similar between the 2 groups during the follow-up period. Although the mean IOP was similar, the IOP-fluctuation rate during the early postoperative period was significantly lower in the ExPress group than in the trabeculectomy group ( P =0.038). A Kaplan-Meier survival curve analysis showed no significant success-rate difference between the groups ( P =0.810). The corneal endothelial cell loss rate, moreover, was significantly lower in the ExPress group ( P =0.05). ExPress implantation compared with trabeculectomy showed similar IOP-reduction and success rates along with lower IOP fluctuation and endothelial cell loss rates. For this reason, it can be considered to be the treatment of choice for patients with advanced glaucoma or low corneal endothelial cell density.

Long-term efficacy and safety of ExPress implantation for treatment of open angle glaucoma

Science.gov (United States)

Lee, Geun Young; Lee, Chong Eun; Lee, Kyoo Won; Seo, Sam

2017-01-01

AIM To compare the long-term efficacy and safety of ExPress implantation and standard trabeculectomy in patients with primary open angle glaucoma (POAG). METHODS In this retrospective study, we compared 17 eyes treated by ExPress implantation with 23 eyes treated by trabeculectomy. Efficacy was assessed according to the relevant intraocular pressure (IOP) values and success rates during the first year of follow-up. Postoperative corneal endothelial cell loss was also compared. RESULTS The number of antiglaucoma medications and the IOP reduction were similar between the 2 groups during the follow-up period. Although the mean IOP was similar, the IOP-fluctuation rate during the early postoperative period was significantly lower in the ExPress group than in the trabeculectomy group (P=0.038). A Kaplan-Meier survival curve analysis showed no significant success-rate difference between the groups (P=0.810). The corneal endothelial cell loss rate, moreover, was significantly lower in the ExPress group (P=0.05). CONCLUSION ExPress implantation compared with trabeculectomy showed similar IOP-reduction and success rates along with lower IOP fluctuation and endothelial cell loss rates. For this reason, it can be considered to be the treatment of choice for patients with advanced glaucoma or low corneal endothelial cell density. PMID:28944196

Long-term radiation effects on commercial cable-insulating materials irradiated at CERN

International Nuclear Information System (INIS)

Maier, P.; Stolarz, A.

1983-01-01

Long-term irradiation damage tests have been carried out on a variety of flexible cable-insulating materials offered to CERN by different European cable manufacturers. Tensile test specimens were exposed for a maximum of three years in high-level radiation areas of the Super Proton Synchrotron (SPS) and for comparison at high dose rates in a nuclear reactor. The degradation of mechanical properties after irradiation in air depends not only on the total absorbed dose, but also on the dose rate for most of these polymer compounds. These dose-rate effects vary between material types and for different compounds. The results presented here illustrate the difference in radiation damage between short-term and long-term irradiation conditions in a typical service application for the various materials tested. They also allow safety factors to be estimated for the extrapolation of the limiting exposure in service from accelerated material tests in the range of dose rates covered. A discussion of the available models of the dose-rate effects results in a conservative estimate for extrapolation to low dose rates from measured values at intermediate dose rates of the order of 0.1 Gy/s. Based on short-term irradiation tests only, the safety factors to be applied depend on the end-point criterion used, and may vary between 1 and 10 for the range of dose rates and materials considered here. (orig.)

Long-term management of high-level radioactive waste. The meaning of a demonstration

International Nuclear Information System (INIS)

1983-01-01

The ''demonstration'' of the safe management of high level radioactive waste is a prerequisite for the further development of nuclear energy. It is therefore essential to be clear about both the meaning of the term ''demonstration'' and the practical means to satisfy this request. In the complex sequence of operations necessary to the safe management of high level waste, short term activities can be directly demonstrated. For longer term activities, such as the long term isolation of radioactive waste in deep undergroung structures, demonstration must be indirect. The ''demonstration'' of deep underground disposal for high level radioactive waste involves two steps: one direct, to prove that the system could be built, operated and closed safely and at acceptable costs, and one indirect, to make a convincing evaluation of the system's performance and long term safety on the basis of predictive analyses confirmed by a body of varied technical and scienfic data, much of it deriving from experimental work. The assessment of the evidence collected from current operations, existing experience in related fields and specific research and development activities, calls for specialized scientific expertise. Uncertainties in far future situations and probabilistic events can be taken into account in a scientific assessment. Competent national authorithies will have to satisfy themselves that the proposed waste management solutions can meet long term safety objectives. An element of judgement will always be needed in determining the acceptability of a waste disposal concept. However, the level of confidence in our ability to predict the performance of waste management systems will increase as supporting evidence is collected from current research and development activities and as our predictive techniques improve

Safety and tolerability of combination antimalarial therapies for uncomplicated falciparum malaria in Ugandan children

Science.gov (United States)

Maiteki-Sebuguzi, Catherine; Jagannathan, Prasanna; Yau, Vincent M; Clark, Tamara D; Njama-Meya, Denise; Nzarubara, Bridget; Talisuna, Ambrose O; Kamya, Moses R; Rosenthal, Philip J; Dorsey, Grant; Staedke, Sarah G

2008-01-01

Background Combination antimalarial therapy is recommended for the treatment of uncomplicated falciparum malaria in Africa; however, some concerns about the safety and tolerability of new regimens remain. This study compared the safety and tolerability of three combination antimalarial regimens in a cohort of Ugandan children. Methods A longitudinal, single-blind, randomized clinical trial of children was conducted between November 2004 and May 2007 in Kampala, Uganda. Upon diagnosis of the first episode of uncomplicated malaria, participants were randomized to treatment with amodiaquine + sulphadoxine-pyrimethamine (AQ+SP), artesunate + amodiaquine (AS+AQ), or artemether-lumefantrine (AL). Once randomized, participants received the same regimen for all subsequent episodes of uncomplicated malaria. Participants were actively monitored for adverse events for the first 14 days after each treatment, and then passively followed until their next study medication treatment, or withdrawal from study. Outcome measures included the risk of adverse events at 14 and 42 days after treatment. Results Of 601 enrolled children, 382 were diagnosed with at least one episode of uncomplicated malaria and were treated with study medications. The median age at treatment was 6.3 years (range 1.1 – 12.3 years). At 14 days of follow-up, AQ+SP treatment was associated with a higher risk of anorexia, weakness, and subjective fever than treatment with AL, and a higher risk of weakness, and subjective fever than treatment with AS+AQ. Treatment with AL was associated with a higher risk of elevated temperature. Repeated episodes of neutropaenia associated with AS+AQ were detected in one participant. Considering only children less than five years, those who received AQ+SP were at higher risk of developing moderate or severe anorexia and weakness than those treated with AL (anorexia: RR 3.82, 95% CI 1.59 – 9.17; weakness: RR 5.40, 95% CI 1.86 – 15.7), or AS+AQ (anorexia: RR 2.10, 95% CI 1

Safety and tolerability of combination antimalarial therapies for uncomplicated falciparum malaria in Ugandan children

Directory of Open Access Journals (Sweden)

Kamya Moses R

2008-06-01

Full Text Available Abstract Background Combination antimalarial therapy is recommended for the treatment of uncomplicated falciparum malaria in Africa; however, some concerns about the safety and tolerability of new regimens remain. This study compared the safety and tolerability of three combination antimalarial regimens in a cohort of Ugandan children. Methods A longitudinal, single-blind, randomized clinical trial of children was conducted between November 2004 and May 2007 in Kampala, Uganda. Upon diagnosis of the first episode of uncomplicated malaria, participants were randomized to treatment with amodiaquine + sulphadoxine-pyrimethamine (AQ+SP, artesunate + amodiaquine (AS+AQ, or artemether-lumefantrine (AL. Once randomized, participants received the same regimen for all subsequent episodes of uncomplicated malaria. Participants were actively monitored for adverse events for the first 14 days after each treatment, and then passively followed until their next study medication treatment, or withdrawal from study. Outcome measures included the risk of adverse events at 14 and 42 days after treatment. Results Of 601 enrolled children, 382 were diagnosed with at least one episode of uncomplicated malaria and were treated with study medications. The median age at treatment was 6.3 years (range 1.1 – 12.3 years. At 14 days of follow-up, AQ+SP treatment was associated with a higher risk of anorexia, weakness, and subjective fever than treatment with AL, and a higher risk of weakness, and subjective fever than treatment with AS+AQ. Treatment with AL was associated with a higher risk of elevated temperature. Repeated episodes of neutropaenia associated with AS+AQ were detected in one participant. Considering only children less than five years, those who received AQ+SP were at higher risk of developing moderate or severe anorexia and weakness than those treated with AL (anorexia: RR 3.82, 95% CI 1.59 – 9.17; weakness: RR 5.40, 95% CI 1.86 – 15.7, or AS

A METHOD FOR THE EXTRACTION OF LONG-TERM DEFORMATION CHARACTERISTICS OF LONG-SPAN HIGH-SPEED RAILWAY BRIDGES USING HIGH-RESOLUTION SAR IMAGES

OpenAIRE

Jia, H. G.; Liu, L. Y.

2016-01-01

Natural causes and high-speed train load will result in the structural deformation of long-span bridges, which greatly influence the safety operation of high-speed railway. Hence it is necessary to conduct the deformation monitoring and regular status assessment for long-span bridges. However for some traditional surveying technique, e.g. control-point-based surveying techniques, a lot of human and material resources are needed to perform the long-term monitoring for the whole bridge. In this...

Long-term observation of the geological environment: needs and techniques

International Nuclear Information System (INIS)

1993-01-01

For site characterization programmes aimed at determining the suitability of sites for the disposal of radioactive waste, attention must be given to collecting data over long periods of time for adequate understanding of certain processes in the geological environment (hydrologic conditions, seismicity etc.). It is important for all national projects to carefully plan and implement programmes to observe the long-term behaviour of the geological environment in order to secure high-quality, reliable data for use in safety assessments. These proceedings present the results of a workshop organized to discuss the needs and techniques related to the planning and implementation of such programmes. 13 papers have been presented

Long-Term Safety Issues of iPSC-Based Cell Therapy in a Spinal Cord Injury Model: Oncogenic Transformation with Epithelial-Mesenchymal Transition

Directory of Open Access Journals (Sweden)

Satoshi Nori

2015-03-01

Full Text Available Previously, we described the safety and therapeutic potential of neurospheres (NSs derived from a human induced pluripotent stem cell (iPSC clone, 201B7, in a spinal cord injury (SCI mouse model. However, several safety issues concerning iPSC-based cell therapy remain unresolved. Here, we investigated another iPSC clone, 253G1, that we established by transducing OCT4, SOX2, and KLF4 into adult human dermal fibroblasts collected from the same donor who provided the 201B7 clone. The grafted 253G1-NSs survived, differentiated into three neural lineages, and promoted functional recovery accompanied by stimulated synapse formation 47 days after transplantation. However, long-term observation (for up to 103 days revealed deteriorated motor function accompanied by tumor formation. The tumors consisted of Nestin+ undifferentiated neural cells and exhibited activation of the OCT4 transgene. Transcriptome analysis revealed that a heightened mesenchymal transition may have contributed to the progression of tumors derived from grafted cells.

Long-term complications of splenectomy in adult immune thrombocytopenia.

Science.gov (United States)

Thai, Lan-Huong; Mahévas, Matthieu; Roudot-Thoraval, Françoise; Limal, Nicolas; Languille, Laetitia; Dumas, Guillaume; Khellaf, Mehdi; Bierling, Philippe; Michel, Marc; Godeau, Bertrand

2016-11-01

The recent large decrease in splenectomy use for chronic immune thrombocytopenia (ITP) is partly due to still-unsolved questions about long-term safety. We performed the first single-center exposed/unexposed cohort study evaluating the long-term incidence of splenectomy complications in patients with primary ITP. Overall, 83 patients who underwent splenectomy more than 10 years ago (exposed) were matched with 83 nonsplenectomized patients (unexposed) on the date of ITP diagnosis ±5 years, age and gender. After a median follow-up of 192 months (range 0.5-528), 43 patients (52%) achieved overall response after splenectomy. Splenectomized patients experienced more venous thromboembolism (VTE) than controls (n = 13 vs n = 2, P = 0.005). On multivariate analysis, splenectomy was an independent risk factor of VTE (hazard ratio = 4.006, P = 0.032 [95% confidence interval: 1.13-14.21]). Splenectomized patients presented more severe infections on long-term follow-up: all required hospitalization, and 5/26 (19%) infections led to severe sepsis or septic shock and to death for 3 cases (none in controls). However, the incidence of malignancy was similar in both groups, as was cardiovascular risk, which appeared to be related more to ITP than splenectomy. Finally, splenectomy did not significantly decrease overall survival. Despite the risk of thrombosis and severe sepsis, splenectomy remains an effective and curative treatment for ITP.

Conditioning radium needles for long term storage : Sri Lankan experience

International Nuclear Information System (INIS)

Ranjith, H.L.A.; Shantha, T.H.S.; Gunaratne, M.G.J.; De Silva, U.W.K.H.; Perera, H.P.H.

2000-01-01

Radium the first radioisotope invented by Madame Curie was used for cancer therapy for the intracavitory treatment of cervical cancers and as oral implants etc. Radium needles and other geometries were made in standard strengths and Radium therapy enjoyed a heyday during the 1st half of the 20th century. Radium-226 is a long-lived radioactive material with a half-life of 1600 years. The use of radium was abandoned in the world in 1980s with the invention of short lived radioactive materials offering remote after loading systems which minimise radiation protection and waste disposal problems associated with long lived radioactive materials. This paper reports the conditioning procedure of the spent radium sources for long term storage (less than 20 years) and transport to national/ international stores if needed. The dose received by those involved in this exercise is also discussed in terms of radiation protection. The Ra was contained for long term storage according to international radiation safety regulations with a surface dose of less than 2 mSv per hour in a conditioned package having 17.5 GBq activity and can be transported to national/international stores if needed. The highest dose received during the exercise is well within the recommended dose limits for occupational exposures (20 and 500 mSv per year) for whole body and extremities respectively

Laser-assisted endoscopic third ventriculostomy: long-term results in a series of 202 patients

NARCIS (Netherlands)

van Beijnum, Janneke; Hanlo, Patrick W.; Fischer, Kathelijn; Majidpour, Mohsen M.; Kortekaas, Marlous F.; Verdaasdonk, Rudolf M.; Vandertop, W. Peter

2008-01-01

OBJECTIVE: Endoscopic third ventriculostomy is a well-known surgical option in the treatment of noncommunicating hydrocephalus. We studied complications and long-term success in 202 patients to demonstrate the safety and efficacy of laser-assisted endoscopic third ventriculostomy (LA-ETV) using a

Plant life management for long term operation of nuclear power plants

International Nuclear Information System (INIS)

2005-01-01

The world's fleet of Nuclear Power Plants (NPPs) is approximately 20 years old on average, and most plants are believed to be able to operate for 60 years or more. The design life of a NPP is typically 30 to 40 years. This may be extended by 10 to 20 years, or more, provided that the plant can demonstrate by analysis, trending, equipment and system upgrades, increased vigilance, testing, ageing management, and other means that license renewal presents no threat to public health and safety. The basic goal of Plant Life Management (PLiM) is to satisfy requirements for safe long-term supplies of electricity in an economically competitive way. The basic goal of the operating company and the owners to operate as long as economically reasonable and possible from safety point of view. PLiM is a management tool for doing that. PLiM is a system of programmes and procedures to satisfy safety requirements for safe operation and for power production in a competitive way and for time which is rational from technical and economical point of view. PLiM is not only a technical system, it is also an attitude of the operational company to keep the plant in operation as long as possible from safety and business point of view. The common objectives of PLiM assessment is to help and review the pre-conditions for PLiM and long-term operation approaches. PLiM should not be associated with extension of operational life-time of the NPP only. It is an owner's attitude and rational approach of the operating company to run the business economically and safely. The effectiveness of PLiM Programme can be assessed by three complementary kinds of assessment: self-assessment, peer review and comprehensive programme review by the plant owner/ operator. IAEA will provide the assessment service for peer review of PLiM. Preparation for a PLiM Assessment service will be initiated only after the IAEA has been formally approached by a MS and funding (e.g. an existing Technical cooperation project) has

Stability analysis of roadway embankments supported by stone columns with the presence of water table under short-term and long-term conditions

Directory of Open Access Journals (Sweden)

Kadhim Shaymaa Tareq

2018-01-01

Full Text Available Use of stone column technique to improve soft foundation soils under roadway embankments has proven to increase the bearing capacity and reduce the potential settlement. The potential contribution of stone columns to the stability of roadway embankments against general (i.e. deep-seated failure needs to be thoroughly investigated. Therefore, a two-dimensional finite difference model implemented by FLAC/SLOPE 7.0 software, was employed in this study to assess the stability of a roadway embankment fill built on a soft soil deposit improved by stone column technique. The stability factor of safety was obtained numerically under both short-term and long-term conditions with the presence of water table. Two methods were adopted to convert the three-dimensional model into plane strain condition: column wall and equivalent improved ground methods. The effect of various parameters was studied to evaluate their influence on the factor of safety against embankment instability. For instance, the column diameter, columns’ spacing, soft soil properties for short-term and long-term conditions, and the height and friction angle of the embankment fill. The results of this study are developed in several design charts.

a Method for the Extraction of Long-Term Deformation Characteristics of Long-Span High-Speed Railway Bridges Using High-Resolution SAR Images

Science.gov (United States)

Jia, H. G.; Liu, L. Y.

2016-06-01

Natural causes and high-speed train load will result in the structural deformation of long-span bridges, which greatly influence the safety operation of high-speed railway. Hence it is necessary to conduct the deformation monitoring and regular status assessment for long-span bridges. However for some traditional surveying technique, e.g. control-point-based surveying techniques, a lot of human and material resources are needed to perform the long-term monitoring for the whole bridge. In this study we detected the long-term bridge deformation time-series by persistent scatterer interferometric synthetic aperture radar (PSInSAR) technique using the high-resolution SAR images and external digital elevation model. A test area in Nanjing city in China is chosen and TerraSAR-X images and Tandem-X for this area have been used. There is the Dashengguan bridge in high speed railway in this area as study object to evaluate this method. Experiment results indicate that the proposed method can effectively extract the long-term deformation of long-span high-speed railway bridge with higher accuracy.

A METHOD FOR THE EXTRACTION OF LONG-TERM DEFORMATION CHARACTERISTICS OF LONG-SPAN HIGH-SPEED RAILWAY BRIDGES USING HIGH-RESOLUTION SAR IMAGES

Directory of Open Access Journals (Sweden)

H. G. Jia

2016-06-01

Full Text Available Natural causes and high-speed train load will result in the structural deformation of long-span bridges, which greatly influence the safety operation of high-speed railway. Hence it is necessary to conduct the deformation monitoring and regular status assessment for long-span bridges. However for some traditional surveying technique, e.g. control-point-based surveying techniques, a lot of human and material resources are needed to perform the long-term monitoring for the whole bridge. In this study we detected the long-term bridge deformation time-series by persistent scatterer interferometric synthetic aperture radar (PSInSAR technique using the high-resolution SAR images and external digital elevation model. A test area in Nanjing city in China is chosen and TerraSAR-X images and Tandem-X for this area have been used. There is the Dashengguan bridge in high speed railway in this area as study object to evaluate this method. Experiment results indicate that the proposed method can effectively extract the long-term deformation of long-span high-speed railway bridge with higher accuracy.

HLW Long-term Management Technology Development

International Nuclear Information System (INIS)

Choi, Jong Won; Kang, C. H.; Ko, Y. K.

2010-02-01

Permanent disposal of spent nuclear fuels from the power generation is considered to be the unique method for the conservation of human being and nature in the present and future. In spite of spent nuclear fuels produced from power generation, based on the recent trends on the gap between supply and demand of energy, the advance on energy price and reduction of carbon dioxide, nuclear energy is expected to play a role continuously in Korea. It means that a new concept of nuclear fuel cycle is needed to solve problems on spent nuclear fuels. The concept of the advanced nuclear fuel cycle including PYRO processing and SFR was presented at the 255th meeting of the Atomic Energy Commission. According to the concept of the advanced nuclear fuel cycle, actinides and long-term fissile nuclides may go out of existence in SFR. And then it is possible to dispose of short term decay wastes without a great risk bearing. Many efforts had been made to develop the KRS for the direct disposal of spent nuclear fuels in the representative geology of Korea. But in the case of the adoption of Advanced nuclear fuel cycle, the disposal of PYRO wastes should be considered. For this, we carried out the Safety Analysis on HLW Disposal Project with 5 sub-projects such as Development of HLW Disposal System, Radwaste Disposal Safety Analysis, Feasibility study on the deep repository condition, A study on the Nuclide Migration and Retardation Using Natural Barrier, and In-situ Study on the Performance of Engineered Barriers

Factors related to the high fall rate in long-term care residents with dementia

NARCIS (Netherlands)

Kosse, Nienke M.; de Groot, Maartje H.; Vuillerme, Nicolas; Hortobagyi, Tibor; Lamoth, Claudine J. C.

Background: Falls in long-term care residents with dementia represent a costly but unresolved safety issue. The aim of the present study was to (1) determine the incidence of falls, fall-related injuries and fall circumstances, and (2) identify the relationship between patient characteristics and

The Barrier code for predicting long-term concrete performance

International Nuclear Information System (INIS)

Shuman, R.; Rogers, V.C.; Shaw, R.A.

1989-01-01

There are numerous features incorporated into a LLW disposal facility that deal directly with critical safety objectives required by the NRC in 10 CFR 61. Engineered barriers or structures incorporating concrete are commonly being considered for waste disposal facilities. The Barrier computer code calculates the long-term degradation of concrete structures in LLW disposal facilities. It couples this degradation with water infiltration into the facility, nuclide leaching from the waste, contaminated water release from the facility, and associated doses to members of the critical population group. The concrete degradation methodology of Barrier is described

ENSI's view on technical safety for the long term operation of reactors 1 and 2 in the Beznau nuclear power plant

International Nuclear Information System (INIS)

2010-11-01

The reactors 1 and 2 of the Beznau nuclear power plant (KKB) are operated since about 40 years. For an operation beyond the design period of 40 years the Swiss Federal Nuclear Safety Inspectorate (ENSI) demands the evidence to be brought that the design limits of the safety relevant components will not be reached during the extended operation period. In 2008 the license holder of KKB delivered the requested documentation on material ageing on the basis of deterministic as well as probabilistic safety analyses and concluded that both reactors can be safely operated beyond 40 years. Thanks to continuous additional outfits, both reactors are in good condition from the point of view of technical safety. With a view to the extension of operation beyond 40 years, KKB already applied the necessary measures regarding technics, finances and personnel in order to keep the present technical level. Since 1991 KKB has analysed and checked components that are difficult to replace. From the evidence presented, ENSI concluded that both reactors are able to be operated up to 60 years long, however with two restrictions for reactor 1 because there the material used for the reactor pressure vessel (RPV) suffered more neutron brittleness than in reactor 2. In addition, reactor 1 is much more affected by ageing phenomena than reactor 2, but, according to neutron fluence calculations, the limiting criteria will not be reached even after 60 years of operation. Some corrosion damages were noted at the lower part of the RPV due to water containing boron acid; they are more pronounced in reactor 1 than in reactor 2. Even though the calculations done by KKB are very conservative, they show that also in the long term the operation limiting criteria about the mechanical resistance of the RPV are never reached. ENSI concludes that the safety design of both KKB reactors ensures safe control of the design basis accidents. Both reactors were continuously fitted with new equipment. With the planed

Long-term nickel exposure altered the bacterial community composition but not diversity in two contrasting agricultural soils.

Science.gov (United States)

Li, Jing; Hu, Hang-Wei; Ma, Yi-Bing; Wang, Jun-Tao; Liu, Yu-Rong; He, Ji-Zheng

2015-07-01

Nickel pollution imposes deleterious effects on soil ecosystem. The responses of soil microorganisms to long-term nickel pollution under field conditions remain largely unknown. Here, we used high-throughput sequencing to elucidate the impacts of long-term nickel pollution on soil bacterial communities in two contrasting agricultural soils. Our results found that the soil microbial biomass carbon consistently decreased along the nickel gradients in both soils. Nickel pollution selectively favored or impeded the prevalence of several dominant bacterial guilds, in particular, Actinobacteria showed tolerance, while Acidobacteria and Planctomycetes displayed sensitivity. Despite the apparent shifts in the bacterial community composition, no clear tendency in the bacterial diversity and abundance was identified along the nickel gradients in either soil. Collectively, we provide evidence that long-term nickel pollution shifted the soil bacterial communities, resulting in the decrease of microbial biomass although the bacterial diversity was not significantly changed.

Deep repository for long-lived low- and intermediate-level waste. Preliminary safety assessment

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-11-01

A preliminary safety assessment has been performed of a deep repository for long-lived low- and intermediate-level waste, SFL 3-5. The purpose of the study is to investigate the capacity of the facility to act as a barrier to the release of radionuclides and toxic pollutants, and to shed light on the importance of the location of the repository site. A safety assessment (SR 97) of a deep repository for spent fuel has been carried out at the same time. In SR 97, three hypothetical repository sites have been selected for study. These sites exhibit fairly different conditions in terms of hydrogeology, hydrochemistry and ecosystems. To make use of information and data from the SR 97 study, we have assumed that SFL 3-5 is co-sited with the deep repository for spent fuel. A conceivable alternative is to site SFL 3-5 as a completely separate repository. The focus of the SFL 3-5 study is a quantitative analysis of the environmental impact for a reference scenario, while other scenarios are discussed and analyzed in more general terms. Migration in the repository's near- and far-field has been taken into account in the reference scenario. Environmental impact on the three sites has also been calculated. The calculations are based on an updated forecast of the waste to be disposed of in SFL 3-5. The forecast includes radionuclide content, toxic metals and other substances that have a bearing on a safety assessment. The safety assessment shows how important the site is for safety. Two factors stand out as being particularly important: the water flow at the depth in the rock where the repository is built, and the ecosystem in the areas on the ground surface where releases may take place in the future. Another conclusion is that radionuclides that are highly mobile and long-lived, such as {sup 36}Cl and {sup 93}Mo , are important to take into consideration. Their being long-lived means that barriers and the ecosystems must be regarded with a very long time horizon.

Vaccination for the expatriate and long-term traveler.

Science.gov (United States)

Shepherd, Suzanne M; Shoff, William H

2014-06-01

Duration of travel is an important factor in addressing travel health safety due to cumulative risk of exposure to illness and injury. The diverse group of expatriate and long-term business and leisure travelers present a different spectrum of issues for the travel medicine practitioner to address during consultation than does the short-term traveler, due to changes in travel patterns and activities, lifestyle alterations, and increased interaction with local populations. Immunization provides one safe and reliable method of preventing infectious illness in this group. We review travel patterns and available data on illnesses that they may be exposed to, including the increased risk of certain vaccine-preventable illnesses. We review the pre-travel management of these travelers, particularly the increased risk of certain vaccine-preventable illnesses as it applies to routine vaccines, recommended travel vaccines and required travel vaccines.

Understanding the safety and tolerability of facial filling therapeutics.

Science.gov (United States)

Kulichova, Daniela; Borovaya, Alyona; Ruzicka, Thomas; Thomas, Peter; Gauglitz, Gerd G

2014-09-01

Aesthetic medicine represents an emerging field for many specialties. Nowadays, a plethora of approaches are available to rejuvenate the human body and face, the latter being a frequent target for the placement of filling substances to correct wrinkles and volume loss. Nevertheless, based on the many products on the market, treating clinicians must pay specific attention to the properties of the respective materials, their associated side effects and any specific handling requirements to prevent potential short- and long-term adverse events. Types of filling materials, including biodegradable and non-biodegradable products, related complications, their conservative and invasive treatment options, as well as prevention strategies are described in this review. A profound knowledge of the facial anatomy as well as extensive experience with the various filling techniques and suitable materials for the respective areas remains crucial to prevent adverse events associated with filling procedures to the human face. Since side effects such as malar edema and foreign body granuloma do affect patients physically and psychologically to a significant extent and their successful treatment still remains challenging, further in depth studies on the tolerability of many filling materials utilized are required.

Clinical characteristics and course of dying in patients with amyotrophic lateral sclerosis withdrawing from long-term ventilation.

Science.gov (United States)

Kettemann, Dagmar; Funke, Andreas; Maier, André; Rosseau, Simone; Meyer, Robert; Spittel, Susanne; Münch, Christoph; Meyer, Thomas

2017-02-01

Non-invasive ventilation (NIV) or tracheotomy with invasive ventilation (TIV) are treatment options in ALS. However, a proportion of patients receiving long-term ventilation decide to have it withdrawn. The objective of this study was to analyse the clinical characteristics and palliative approaches in ALS patients withdrawing from long-term ventilation (WLTV). In a cohort study, two different palliative concepts in WLTV were studied: (1) augmented symptom control (ASC; sedation not intended) in patients with ventilator-free tolerance; (2) continuous deep sedation (CDS; sedation intended) in patients without ventilator-free tolerance. Results showed that WLTV was realised in 49 ALS patients (NIV = 13; TIV = 36). Mean daily ventilation was 23.4 h. The ALS Functional Rating Scale (ALSFRS-R) was low (5.6 of 48). Forty-one per cent of patients (n = 20) presented with ophthalmoplegia. ASC was performed in 20 patients, CDS in 29 patients. The mean time to death following disconnection was 32 (0.3-164) h during ASC and 0.3 (0.2-0.6) h in CDS. In conclusion, a low ALSFRS-R, high incidence of ophthalmoplegia and extended ventilator dependency were found before WLTV. The presence or absence of ventilator-free tolerance determined the approach to the management of symptoms, the setting for immediate end-of-life care and the course of dying in WLTV.

NAGRA - Long-term safety - The main task of deep repositories for radioactive wastes

International Nuclear Information System (INIS)

2015-10-01

This comprehensive brochure published by the Swiss National Cooperative for the Disposal of Radioactive Waste (NAGRA) examines the necessity for the safe disposal of radioactive wastes in Switzerland and discusses the requirements placed on such long-term waste depositories The effects of ionizing radiation on people and the protection provided by the deep repositories are examined. The construction of such deep repositories is looked at, as are the developments expected in the depositories over thousands of years. A comparison with natural occurrences is made and lessons to be learned from nature are discussed. Ideas for the marking of the depository sites are presented. A glossary of relevant terms completes the report

Parental Effect of Long Acclimatization on Thermal Tolerance of Juvenile Sea Cucumber Apostichopus japonicus.

Directory of Open Access Journals (Sweden)

Qing-Lin Wang

Full Text Available To evaluate the thermal resistance of marine invertebrates to elevated temperatures under scenarios of future climate change, it is crucial to understand parental effect of long acclimatization on thermal tolerance of offspring. To test whether there is parental effect of long acclimatization, adult sea cucumbers (Apostichopus japonicus from the same broodstock were transplanted southward and acclimatized at high temperature in field mesocosms. Four groups of juvenile sea cucumbers whose parents experienced different durations of high temperature acclimatization were established. Upper thermal limits, oxygen consumption and levels of heat shock protein mRNA of juveniles was determined to compare thermal tolerance of individuals from different groups. Juvenile sea cucumbers whose parents experienced high temperature could acquire high thermal resistance. With the increase of parental exposure duration to high temperature, offspring became less sensitive to high temperature, as indicated by higher upper thermal limits (LT50, less seasonal variations of oxygen consumption, and stable oxygen consumption rates between chronic and acute thermal stress. The relatively high levels of constitutive expression of heat-shock proteins should contribute to the high thermal tolerance. Together, these results indicated that the existence of a parental effect of long acclimatization would increase thermal tolerance of juveniles and change the thermal sensitivity of sea cucumber to future climate change.

Long-term surveillance plan for the Cheney disposal site near Grand Junction, Colorado

International Nuclear Information System (INIS)

1997-04-01

This long-term surveillance plan (LTSP) describes the U.S. Department of Energy's (DOE) long-term care program for the Uranium Mill Tailings Remedial Action (UMTRA) Project Cheney disposal site. The site is in Mesa County near Grand Junction, Colorado. The U.S. Nuclear Regulatory Commission (NRC) has developed regulations for the issuance of a general license for the custody and long-term care of UMTRA Project disposal sites in 10 CFR Part 40. The purpose of this general license is to ensure that the UMTRA Project disposal sites are cared for in a manner that protects public health and safety and the environment. Before each disposal site may be licensed, the NRC requires the DOE to submit a site-specific LTSP. The DOE prepared this LTSP to meet this requirement for the Cheney disposal site. The general license becomes effective when the NRC concurs with the DOE's determination that remedial action is complete and the NRC formally accepts this plan. This document describes the long-term surveillance program the DOE will implement to ensure that the Cheney disposal site performs as designed. The program is based on site inspections to identify potential threats to disposal cell integrity. The LTSP is based on the UMTRA Project long-term surveillance program guidance and meets the requirements of 10 CFR section 40.27(b) and 40 CFR section 192.03

Long-term pharmacotherapy for obesity in elderly patients: a retrospective evaluation of medical records from a specialized obesity outpatient clinic.

Science.gov (United States)

Horie, Nídia Celeste; Cercato, Cintia; Mancini, Marcio C; Halpern, Alfredo

2010-06-01

Obesity is a serious chronic disease and the prevalence of this condition is increasing among the elderly. Although the benefits of weight loss to improve control of associated diseases are well known in young adults, they are not in older patients. The use of anti-obesity drugs to promote weight loss is widespread in Brazil and other countries, and obesity specialists frequently prescribe medicines in doses and for durations previously unreported in the literature. Sibutramine, orlistat and amfepramone (diethylpropion) have been evaluated in clinical trials of more than 2 years' duration in adults, demonstrating safety and efficacy, but long-term studies in obesity treatment are absent for other drugs. The efficacy and safety of obesity pharmacotherapy among the elderly is unknown. To describe the experience of obesity pharmacotherapy in the elderly in a specialized obesity care setting in Brazil, with a focus on efficacy and safety. A retrospective evaluation was conducted on medical charts from an outpatient clinic of a specialized tertiary centre for the treatment of obesity. We included patients who had had at least one consultation between January and December 2007, were aged > or =60 years at the beginning of the treatment, had had at least 6 months of follow-up and had received a prescription of at least one potential weight-loss drug. Diagnoses reported on medical records were documented. Age, weight, height and body mass index (BMI) were recorded at admission, after 6, 12, 18 and 24 months, and at the last available visit. The medicines prescribed, together with the dose, duration of use, adverse effects and reasons for discontinuation, were documented. The group consisted of 44 women (86%) and 7 men (14%), with a mean +/- SD age of 65.2 +/- 4.5 years, weight of 95.3 +/- 12.5 kg and BMI of 38.5 +/- 4.3 kg/m2. The mean +/- SD time of follow-up was 39.3 +/- 26.4 months, and the mean weight loss was 6.65 kg (p or =5% was achieved by 64.71%, 63.64%, 62

Long-term characteristics of geological conditions in Japan. Pt. 1. Fundamental concept for future's prediction of geological conditions and the subjects

International Nuclear Information System (INIS)

Tanaka, Kazuhiro; Chigira, Masahiro.

1997-01-01

It is very important to evaluate the long-term stability of geological conditions such as volcanic activity, uplift-subsidence, earthquakes, faulting and sea level change when the long-term safety performance of HLW geological disposal is investigated. We proposed the extrapolation method using the geological date obtained in the geologic time of the last 500 ka to predict the future's tectonic movements in Japan. Furthermore, we extract geological conditions that would affect the long-term safety of HLW geological disposal with regard to direct and indirect radionuclide release scenarios. As a result, it was concluded that volcanic activity and tectonic movements including faulting and uplift-subsidence, should be considered and their surveying system and evaluating method should be developed. (author)

Study on behaviour in long term of vitrified materials

International Nuclear Information System (INIS)

Vernaz, E.

1993-01-01

In collaboration with EDF (Electricite de France), after testing fusion of Refiom (Residus d'Epuration des Fumees d'Incineration d'Ordures Menageres), residues from purification of incineration smokes of household rubbish, realised at Porcheville and at the Laboratory of Renardieres with experimental processing of vitrification by plasma, CEA (Centre d'Etudes Atomiques), atomic center of research, began study on resistance in long term of vitrified products. From about thirty five years, CEA carries out research to confine radioactive waste of high activity in stable materials. Glass was the first best one which allowed to incorporate about thirty different chemical elements found in fission products solutions into a stable die with a good chemical durability; three vitrification shops raised, one at Marcoule ('AVM', 1978) in the south of France, the two other ones at La Hague ('R7', 1989 and 'T7', 1992) in Normandy. To determine a possible impact of a deep radioactive waste disposal on human and environment, several studies began. In particular, studies on aqueous corrosion of glasses to determine behaviour in long term of glass package (first barrier of confinement) and to estimate kinetics of releasing confined toxical elements on periods of several thousands years. Principal results are exposed in this conference. Experience shows that safety analysis cannot be based on long term extrapolation of a simple lixiviation result. This analysis must include: a sufficient knowledge in basic mechanisms of alteration to predict the kinetic evolution in a long term. To take in account environment conditions with a normal or accidental scheme (acidity, clay, organic compounds,...). This knowledge broadly developed by CEA for nuclear glasses seems to be easily transposable to different wastes (industrial ones or from hospitals) and takes place in a contract of research CEA/EDF to valorize vitrified products. 9 figs. 4 refs

Islet Transplantation in Type 1 Diabetes: Ongoing Challenges, Refined Procedures, and Long-Term Outcome

Science.gov (United States)

Shapiro, A.M. James

2012-01-01

Remarkable progress has been made in islet transplantation over a span of 40 years. Once just an experimental curiosity in mice, this therapy has moved forward, and can now provide robust therapy for highly selected patients with type 1 diabetes (T1D), refractory to stabilization by other means. This progress could not have occurred without extensive dynamic international collaboration. Currently, 1,085 patients have undergone islet transplantation at 40 international sites since the Edmonton Protocol was reported in 2000 (752 allografts, 333 autografts), according to the Collaborative Islet Transplant Registry. The long-term results of islet transplantation in selected centers now match registry data of pancreas-alone transplantation, with 6 sites reporting five-year insulin independence rates ≥50%. Islet transplantation has been criticized for the use of multiple donor pancreas organs, but progress has also occurred in single-donor success, with 10 sites reporting increased single-donor engraftment. The next wave of innovative clinical trial interventions will address instant blood-mediated inflammatory reaction (IBMIR), apoptosis, and inflammation, and will translate into further marked improvements in single-donor success. Effective control of auto- and alloimmunity is the key to long-term islet function, and high-resolution cellular and antibody-based assays will add considerable precision to this process. Advances in immunosuppression, with new antibody-based targeting of costimulatory blockade and other T-B cellular signaling, will have further profound impact on the safety record of immunotherapy. Clinical trials will move forward shortly to test out new human stem cell derived islets, and in parallel trials will move forward, testing pig islets for compatibility in patients. Induction of immunological tolerance to self-islet antigens and to allografts is a difficult challenge, but potentially within our grasp. PMID:23804275

Reforming Long-Term Care Funding in Alberta.

Science.gov (United States)

Crump, R Trafford; Repin, Nadya; Sutherland, Jason M

2015-01-01

Like many provinces across Canada, Alberta is facing growing demand for long-term care. Issues with the mixed funding model used to pay long-term care providers had Alberta Health Services concerned that it was not efficiently meeting the demand for long-term care. Consequently, in 2010, Alberta Health Services introduced the patient/care-based funding (PCBF) model. PCBF is similar to activity-based funding in that it directly ties the complexity and care needs of long-term care residents to the payment received by long-term care providers. This review describes PCBF and discusses some of its strengths and weaknesses. In doing so, this review is intended to inform other provinces faced with similar long-term care challenges and contemplating their own funding reforms.

Long-Term Stability Evaluation and Pillar Design Criterion for Room-and-Pillar Mines

Directory of Open Access Journals (Sweden)

Yang Yu

2017-10-01

Full Text Available The collapse of abandoned room-and-pillar mines is often violent and unpredictable. Safety concerns often resulted in mine closures with no post-mining stability evaluations. As a result, large amounts of land resources over room-and-pillar mines are wasted. This paper attempts to establish an understanding of the long-term stability issues of goafs (abandoned mines. Considering progressive pillar failures and the effect of single pillar failure on surrounding pillars, this paper proposes a pillar peeling model to evaluate the long-term stability of coal mines and the associated criteria for evaluating the long-term stability of room-and-pillar mines. The validity of the peeling model was verified by numerical simulation, and field data from 500 pillar cases from China, South Africa, and India. It is found that the damage level of pillar peeling is affected by the peel angle and pillar height and is controlled by the pillar width–height ratio.