WorldWideScience

Sample records for long-term safety study

  1. [Safety study of long-term video-electroencephalogram monitoring].

    Science.gov (United States)

    Ley, M; Vivanco, R; Massot, A; Jiménez, J; Roquer, J; Rocamora, R

    2014-01-01

    The increased morbidity and mortality and poorer quality of life associated with drug-resistant epilepsy justify admitting patients to epilepsy monitoring units (EMU). These units employ methods that promote the occurrence of seizures, which involves a risk of secondary adverse events. The aim of our study is to characterise and quantify these adverse events in a Spanish EMU. A descriptive, longitudinal and retrospective study of patients admitted consecutively to our EMU. Patients admitted due to status epilepticus, clusters of seizures, or as participants in a clinical trial were excluded. We included 175 patients, of whom 92.1% (161) did not suffer any adverse events. Status epilepticus was present in 3.4% (6); 1.7% (3) had traumatic injury, 1.7% (3) had interictal or postictal psychosis, and 1.1% (2) had cardiorespiratory impairment. There were no risk factors associated with these adverse events. The most frequently-identified adverse events were status epilepticus, traumatic injury, interictal or postictal psychosis, and cardiorespiratory disorders. The frequency of these adverse events was similar to that seen in international literature. The complications detected do not contraindicate VEEGM. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  2. 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.)

  3. 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.

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  5. 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.

  6. 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.

  7. French Approach for Long Term Storage Safety

    International Nuclear Information System (INIS)

    Marciano, Jacob; Carreton, Jean-Pierre; Lizot, Marie Therese; Lhomme, Veronique

    2014-01-01

    IRSN presents its statement regarding long-term storage facilities; in France, the regulatory documents do not define the long term duration. The storage facility lifetime can only be appreciated according to the needs and materials stored therein. However, the magnitude of the long-term can be estimated at a few hundred years compared to a few decades for current storage. Usually, in France, construction of storage facilities is driven from the necessity various necessities, linked to the management of radioactive material (eg spent fuel) and to the management of radioactive waste. Because of the variety of 'stored materials and objects' (fission product solutions, plutonium oxide powders, activated solids, drums containing technological waste, spent fuel...), a great number of storage facility design solutions have been developed (surface, subsurface areas, dry or wet conditions...) in the World. After describing the main functions of a storage facility, IRSN displays the safety principles and the associated design principles. The specific design principles applied to particular storage (dry or wet spent fuel storage, depleted uranium or reprocessed uranium storage, plutonium storage, waste containing tritium storage, HLW and ILLW storage...) are also presented. Finally, the concerns due to the long-term duration storage and related safety assessment are developed. After discussing these issues, IRSN displays its statement. The authorization procedures governing the facility lifetime are similar to those of any basic nuclear installation, the continuation of the facility operation remaining subject to periodic safety reviews (in France, every 10 years). The applicant safety cases have to show, that the safety requirements are always met; this requires, at minimum, to take into account at the design stage, comfortable design margins. (author)

  8. 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

  9. 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....

  10. Performance assessment studies for the long-term safety evaluation of radioactive waste disposal facility

    International Nuclear Information System (INIS)

    Bujoreanu, D.; Olteanu, M.; Bujoreanu, L.

    2008-01-01

    Especially during the last ten years, a part of Romanian research program 'Management of Radioactive Waste and Spent Fuel' was focused mainly on applicative research for the design of near-surface disposal facility, which intends to accommodate the low and intermediate radioactive waste generated from Cernavoda NPP. In this frame, our contribution was at the acquisition of technical data for the characterization of the future disposal facility. In the present, the project of the disposal facility, located on the Saligny site, near Cernavoda NPP, must be licensed. As regards to the safe disposal, the location of final disposal, the Saligny site, has been characterized through the five geological formations which contain potential routes for transport of radionuclide released from disposal facility, in the receiving zones(potential receiving zones), into liquid and gaseous phases. The technical characteristics of the disposal facility were adapted at the Romanian disposal concept using the reference data from IAEA technical report (IAEA,1999). Input parameters which characterized from physical and chemical point of view the disposal system, were partially taken from literature. The performance assessment studies, which follows the preliminary design development phases and the selection, describes how the source term is affected by the infiltration of water through the disposal facility, degradation process of engineering barriers (reflected in the distribution coefficient values) and solubility limit. The studies regard the evaluation of the source term, sensitivity and uncertainty analysis provide the information on 'how' and 'why' were evaluated, following: (i) radiological safety assessment of near-surface disposal facility on Saligny site; (ii) complexity standard assessment of the Engineering Barriers Systems (EBS); (iii) identification of the elements which must be elaborated for the increase of the disposal safety and the necessity for new technical data for

  11. 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.

  12. Long term study of mechanical

    Directory of Open Access Journals (Sweden)

    Ahmed M. Diab

    2016-06-01

    Full Text Available In this study, properties of limestone cement concrete containing different replacement levels of limestone powder were examined. It includes 0%, 5%, 10%, 15%, 20% and 25% of limestone powder as a partial replacement of cement. Silica fume was added incorporated with limestone powder in some mixes to enhance the concrete properties. Compressive strength, splitting tensile strength and modulus of elasticity were determined. Also, durability of limestone cement concrete with different C3A contents was examined. The weight loss, length change and cube compressive strength loss were measured for concrete attacked by 5% sodium sulfate using an accelerated test up to 525 days age. The corrosion resistance was measured through accelerated corrosion test using first crack time, cracking width and steel reinforcement weight loss. Consequently, for short and long term, the use of limestone up to 10% had not a significant reduction in concrete properties. It is not recommended to use blended limestone cement in case of sulfate attack. The use of limestone cement containing up to 25% limestone has insignificant effect on corrosion resistance before cracking.

  13. 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)

  14. 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

  15. Long-term safety and efficacy of Gamma Knife surgery in classical trigeminal neuralgia: a 497-patient historical cohort study.

    Science.gov (United States)

    Régis, Jean; Tuleasca, Constantin; Resseguier, Noémie; Carron, Romain; Donnet, Anne; Gaudart, Jean; Levivier, Marc

    2016-04-01

    Gamma Knife surgery (GKS) is one of the surgical alternatives for the treatment of drug-resistant trigeminal neuralgia (TN). This study aims to evaluate the safety and efficacy of GKS in a large population of patients with TN with very long-term clinical follow-up. Between July 1992 and November 2010, 737 patients presenting with TN were treated using GKS. Data were collected prospectively and were further retrospectively evaluated at Timone University Hospital. The frequency and severity of pain, as well as trigeminal nerve function, were evaluated before GKS and regularly thereafter. Radiosurgery using the Gamma Knife (model B, C, 4C, or Perfexion) was performed with the help of both MR and CT targeting. A single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.6 mm (range 4-14 mm) anterior to the emergence of the nerve (retrogasserian target). A median maximum dose of 85 Gy (range 70-90 Gy) was prescribed. The safety and efficacy are reported for 497 patients with medically refractory classical TN who were never previously treated by GKS and had a follow-up of at least 1 year. The median age in this series was 68.3 years (range 28.1-93.2 years). The median follow-up period was 43.8 months (range 12-174.4 months). Overall, 456 patients (91.75%) were initially pain free in a median time of 10 days (range 1-180 days). Their actuarial probabilities of remaining pain free without medication at 3, 5, 7, and 10 years were 71.8%, 64.9%, 59.7%, and 45.3%, respectively. One hundred fifty-seven patients (34.4%) who were initially pain free experienced at least 1 recurrence, with a median delay of onset of 24 months (range 0.6-150.1 months). However, the actuarial rate of maintaining pain relief without further surgery was 67.8% at 10 years. The hypesthesia actuarial rate at 5 years was 20.4% and at 7 years reached 21.1%, but remained stable until 14 years with a median delay of onset of 12 months (range 1-65 months

  16. Long-term corrosion studies

    International Nuclear Information System (INIS)

    Gdowski, G.

    1998-01-01

    The scope of this activity is to assess the long-term corrosion properties of metallic materials under consideration for fabricating waste package containers. Three classes of metals are to be assessed: corrosion resistant, intermediate corrosion resistant, and corrosion allowance. Corrosion properties to be evaluated are general, pitting and crevice corrosion, stress-corrosion cracking, and galvanic corrosion. The performance of these materials will be investigated under conditions that are considered relevant to the potential emplacement site. Testing in four aqueous solutions, and vapor phases above them, and at two temperatures are planned for this activity. (The environmental conditions, test metals, and matrix are described in detail in Section 3.0.) The purpose and objective of this activity is to obtain the kinetic and mechanistic information on degradation of metallic alloys currently being considered for waste package containers. This information will be used to provide assistance to (1) waste package design (metal barrier selection) (E-20-90 to E-20-92), (2) waste package performance assessment activities (SIP-PA-2), (3) model development (E-20-75 to E-20-89). and (4) repository license application

  17. 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.

  18. A security/safety survey of long term care facilities.

    Science.gov (United States)

    Acorn, Jonathan R

    2010-01-01

    What are the major security/safety problems of long term care facilities? What steps are being taken by some facilities to mitigate such problems? Answers to these questions can be found in a survey of IAHSS members involved in long term care security conducted for the IAHSS Long Term Care Security Task Force. The survey, the author points out, focuses primarily on long term care facilities operated by hospitals and health systems. However, he believes, it does accurately reflect the security problems most long term facilities face, and presents valuable information on security systems and practices which should be also considered by independent and chain operated facilities.

  19. Natural analogue studies for the long-term safety of radioactive waste disposal. Lessons learned from the nature

    International Nuclear Information System (INIS)

    Yusa, Yasuhisa

    2002-01-01

    'Natural analogues' can be defined as the processes or materials analogous to those operating in the geological disposal system of radioactive waste. Natural analogue studies provide the only means by which long-term data can be obtained under the real natural conditions, and also the most convincing support to the long-term performance assessment of the geological disposal system. The framework of our natural analogue studies concerning the stability of the engineered barrier materials for geological disposal system of high-level radioactive waste is reviewed. One of the results is that the volcanic glass included in a clay bed did not alter during the past one million years. The Tono Uranium Deposits are studied as geochemical analogues of radioactive waste disposal in Japan. We conclude that although the deposits have been subjected to a variety of geological processes and events such as faulting, erosion and uplift/subsidence, the reducing condition has been maintained and uranium has not migrated for at least the past ten million years. Application and further development of the natural analogue studies are also discussed. (author)

  20. Safety analysis SFR 1. Long-term safety

    Energy Technology Data Exchange (ETDEWEB)

    2008-12-15

    An updated assessment of the long-term safety of SKB's final repository for radioactive operational waste, SFR 1, is presented in this report. The report is included in the safety analysis report for SFR 1. The most recent account of long-term safety was submitted to the regulatory authorities in 2001. The present report has been compiled on SKB's initiative to address the regulatory authorities' viewpoints regarding the preceding account of long-term safety. Besides the new mode of working with safety functions there is another important difference between the 2001 safety assessment and the current assessment: The time horizon in the current assessment has been extended to 100,000 years in order to include the effect of future climate changes. The purpose of this renewed assessment of the long-term safety of SFR 1 is to show with improved data that the repository is capable of protecting human health and the environment against ionizing radiation in a long-term perspective. This is done by showing that calculated risks lie below the risk criteria stipulated by the regulatory authorities. SFR 1 is built to receive, and after closure serve as a passive repository for, low. and intermediate-level radioactive waste. The disposal chambers are situated in rock beneath the sea floor, covered by about 60 metres of rock. The underground part of the facility is reached via two tunnels whose entrances are near the harbour. The repository has been designed so that it can be abandoned after closure without further measures needing to be taken to maintain its function. The waste in SFR 1 is short-lived low- and intermediate-level waste. After 100 years the activity is less than half, and after 1,000 years only about 2% of the original activity remains. The report on long-term safety comprises eleven chapters. Chapter 1 Introduction. The chapter describes the purpose, background, format and contents of SAR-08, applicable regulations and injunctions, and the regulatory

  1. Safety analysis SFR 1. Long-term safety

    International Nuclear Information System (INIS)

    2008-12-01

    An updated assessment of the long-term safety of SKB's final repository for radioactive operational waste, SFR 1, is presented in this report. The report is included in the safety analysis report for SFR 1. The most recent account of long-term safety was submitted to the regulatory authorities in 2001. The present report has been compiled on SKB's initiative to address the regulatory authorities' viewpoints regarding the preceding account of long-term safety. Besides the new mode of working with safety functions there is another important difference between the 2001 safety assessment and the current assessment: The time horizon in the current assessment has been extended to 100,000 years in order to include the effect of future climate changes. The purpose of this renewed assessment of the long-term safety of SFR 1 is to show with improved data that the repository is capable of protecting human health and the environment against ionizing radiation in a long-term perspective. This is done by showing that calculated risks lie below the risk criteria stipulated by the regulatory authorities. SFR 1 is built to receive, and after closure serve as a passive repository for, low. and intermediate-level radioactive waste. The disposal chambers are situated in rock beneath the sea floor, covered by about 60 metres of rock. The underground part of the facility is reached via two tunnels whose entrances are near the harbour. The repository has been designed so that it can be abandoned after closure without further measures needing to be taken to maintain its function. The waste in SFR 1 is short-lived low- and intermediate-level waste. After 100 years the activity is less than half, and after 1,000 years only about 2% of the original activity remains. The report on long-term safety comprises eleven chapters. Chapter 1 Introduction. The chapter describes the purpose, background, format and contents of SAR-08, applicable regulations and injunctions, and the regulatory

  2. Safety analysis SFR 1. Long-term safety

    Energy Technology Data Exchange (ETDEWEB)

    2008-12-15

    An updated assessment of the long-term safety of SKB's final repository for radioactive operational waste, SFR 1, is presented in this report. The report is included in the safety analysis report for SFR 1. The most recent account of long-term safety was submitted to the regulatory authorities in 2001. The present report has been compiled on SKB's initiative to address the regulatory authorities' viewpoints regarding the preceding account of long-term safety. Besides the new mode of working with safety functions there is another important difference between the 2001 safety assessment and the current assessment: The time horizon in the current assessment has been extended to 100,000 years in order to include the effect of future climate changes. The purpose of this renewed assessment of the long-term safety of SFR 1 is to show with improved data that the repository is capable of protecting human health and the environment against ionizing radiation in a long-term perspective. This is done by showing that calculated risks lie below the risk criteria stipulated by the regulatory authorities. SFR 1 is built to receive, and after closure serve as a passive repository for, low. and intermediate-level radioactive waste. The disposal chambers are situated in rock beneath the sea floor, covered by about 60 metres of rock. The underground part of the facility is reached via two tunnels whose entrances are near the harbour. The repository has been designed so that it can be abandoned after closure without further measures needing to be taken to maintain its function. The waste in SFR 1 is short-lived low- and intermediate-level waste. After 100 years the activity is less than half, and after 1,000 years only about 2% of the original activity remains. The report on long-term safety comprises eleven chapters. Chapter 1 Introduction. The chapter describes the purpose, background, format and contents of SAR-08, applicable regulations and injunctions, and the

  3. Long-term follow-up study on the safety of deep brain stimulation for treating Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Xi WU

    2015-10-01

    Full Text Available Objective To evaluate the safety of deep brain stimulation (DBS for treating Parkinson's disease (PD under long-term follow-up and modify the surgical procedure. Methods A total of 362 PD patients underwent DBS, and almost 613 electrodes were implanted into these patients. Both surgical and hardware-related complications of DBS were retrospectively analyzed. Results Perioperative complications included postoperative confusion or delirium in 21 cases (5.80%, intracranial hemorrhage in 4 cases (1.10%; 2 asymptomatic cortical microhemorrhage and 2 basal ganglia trajectory microhemorrhage, generalized tonic-clonic seizures (GTCS in 2 cases (0.55% , urinary tract infection in 4 cases (1.10% , pulmonary infection in 7 cases (1.93%, implantable pulse generator (IPG hematoma in 11 cases (3.04%, IPG seroma in 3 cases (0.83%. All these patients were cured. They were followed-up for 12-146 months (median 34 months. Hardware-related complications included infection of incisional wound and/or skin erosion (9 cases, 2.49% , extension wire fracture caused by IPG displacement (one case, 0.28% , IPG shifting to abdomen due to fixation wire fracture (one case, 0.28%, slightly migrated electrode due to fall (one case, 0.28%, and discomfort about occipital incision (one case, 0.28%. Conclusions The overall risk of both surgical and hardware-related adverse events of DBS for treating PD is acceptably low. DOI: 10.3969/j.issn.1672-6731.2015.10.005

  4. 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

  5. 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

  6. 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.

  7. 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)

  8. NUMO's approach for long-term safety assessment - 59404

    International Nuclear Information System (INIS)

    Ebashi, Takeshi; Kaku, Kenichi; Ishiguro, Katsuhiko

    2012-01-01

    One of NUMO's policies for ensuring safety is staged and flexible project implementation and decision-making based on iterative confirmation of safety. The safety assessment takes the central role in multiple lines of reasoning and argumentation by providing a quantitative evaluation of long-term safety; a key aspect is uncertainty management. This paper presents NUMO's basic strategies for long-term safety assessment based on the above policy. NUMO's approach considering Japanese boundary conditions is demonstrated as a starting-point for evaluating the long-term safety of an actual site. In Japan, the Act on Final Disposal of Specified Radioactive Waste states that the siting process shall consist of three stages. The Nuclear Waste Management Organization of Japan (NUMO) is responsible for geological disposal of vitrified high-level waste and some types of TRU waste. NUMO has chosen to implement a volunteer approach to siting. NUMO decided to prepare the so-called 2010 technical report, which sets out three safety policies, one of which is staged project implementation and decision-making based on iterative confirmation of safety. Based on this policy, NUMO will gradually integrate relevant interdisciplinary knowledge to build a safety case when a formal volunteer application is received that would allow site investigations to be initiated. The safety assessment takes the central role in multiple lines of reasoning and argumentation by providing a quantitative evaluation of long-term safety; one of a key aspect is uncertainty management. This paper presents the basic strategies for NUMO's long-term safety assessment based on the above policy. In concrete terms, the common procedures involved in safety assessment are applied in a stepwise manner, based on integration of knowledge obtained from site investigations/evaluations and engineered measures. The results of the safety assessment are then reflected in the planning of site investigations and engineered

  9. 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

  10. 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.

  11. 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.

  12. Safety and efficacy of ipragliflozin in elderly versus non-elderly Japanese patients with type 2 diabetes mellitus: a subgroup analysis of the STELLA-LONG TERM study.

    Science.gov (United States)

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

    2018-03-01

    This subgroup analysis of STELLA-LONG TERM interim data explored the long-term safety and efficacy of ipragliflozin in non-elderly vs. elderly Japanese type 2 diabetes mellitus (T2DM) patients. STELLA-LONG TERM is an ongoing 3-year prospective surveillance study of Japanese T2DM patients receiving ipragliflozin 50 mg once daily. In this subgroup analysis, patient characteristics, laboratory variables, and adverse drug reactions (ADRs) were compared between non-elderly (<65 years) and elderly (≥65 years) patients. Non-elderly patients had significantly higher body mass index and low-density lipoprotein cholesterol than elderly patients (P < 0.001). The proportion of patients with hemoglobin A1c (HbA1c) <8.0% was significantly higher among elderly patients (P < 0.001). HbA1c, fasting plasma glucose, and body weight significantly decreased from baseline to 3 and 12 months in both groups (all P < 0.05 vs. baseline). The ADR incidence was 10.83% vs. 10.42% in non-elderly and elderly patients. The incidence of skin complications was 0.98% vs. 1.65% and that of renal disorder was 0.47% vs. 0.95% in non-elderly and elderly patients (both P = 0.003). Ipragliflozin was effective in non-elderly and elderly Japanese T2DM patients in a real-world clinical setting. The incidence of renal disorder and skin complications was significantly higher in elderly vs. non-elderly patients.

  13. Safety of Long-term Interim Storage Facilities - Workshop Proceedings

    International Nuclear Information System (INIS)

    2014-01-01

    The objective of this workshop was to discuss and review current national activities, plans and regulatory approaches for the safety of long term interim storage facilities dedicated to spent nuclear fuel (SF), high level waste (HLW) and other radioactive materials with prolonged storage regimes. It was also intended to discuss results of experiments and to identify necessary R and D to confirm safety of fuel and cask during the long-term storage. Safety authorities and their Technical Support Organisation (TSO), Fuel Cycle Facilities (FCF) operating organisations and international organisations were invited to share information on their approaches, practices and current developments. The workshop was organised in an opening session, three technical sessions, and a conclusion session. The technical sessions were focused on: - National approaches for long term interim storage facilities; - Safety requirements, regulatory framework and implementation issues; - Technical issues and operational experience, needs for R and D. Each session consisted of a number of presentations followed by a panel discussion moderated by the session Chairs. A summary of each session and subsequent discussion that ensued are provided as well as a summary of the results of the workshop with the text of the papers given and presentations made

  14. 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

    Directory of Open Access Journals (Sweden)

    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.

  15. Long-term safety and efficacy of a pasteurized nanofiltrated prothrombin complex concentrate (Beriplex P/N): a pharmacovigilance study.

    Science.gov (United States)

    Hanke, A A; Joch, C; Görlinger, K

    2013-05-01

    The rapid reversal of the effects of vitamin K antagonists is often required in cases of emergency surgery and life-threatening bleeding, or during bleeding associated with high morbidity and mortality such as intracranial haemorrhage. Increasingly, four-factor prothrombin complex concentrates (PCCs) containing high and well-balanced concentrations of vitamin K-dependent coagulation factors are recommended for emergency oral anticoagulation reversal. Both the safety and efficacy of such products are currently in focus, and their administration is now expanding into the critical care setting for the treatment of life-threatening bleeding and coagulopathy resulting either perioperatively or in cases of acute trauma. After 15 yr of clinical use, findings of a pharmacovigilance report (February 1996-March 2012) relating to the four-factor PCC Beriplex P/N (CSL Behring, Marburg, Germany) were analysed and are presented here. Furthermore, a review of the literature with regard to the efficacy and safety of four-factor PCCs was performed. Since receiving marketing authorization (February 21, 1996), ~647 250 standard applications of Beriplex P/N have taken place. During this time, 21 thromboembolic events judged to be possibly related to Beriplex P/N administration have been reported, while no incidences of viral transmission or heparin-induced thrombocytopenia were documented. The low risk of thromboembolic events reported during the observation period (one in ~31 000) is in line with the incidence observed with other four-factor PCCs. In general, four-factor PCCs have proven to be well tolerated and highly effective in the rapid reversal of vitamin K antagonists.

  16. Open-label study on the long-term efficacy, safety, and impact on quality of life of OROS hydromorphone ER in patients with chronic low back pain.

    Science.gov (United States)

    Wallace, Mark; Thipphawong, John

    2010-10-01

    To investigate the efficacy, safety, and impact on quality of life of long-term administration of OROS hydromorphone ER (8-128mg) in patients with chronic low back pain. A total of 113 adults with chronic low back pain who completed a 6-week open-label study were enrolled in this 6-month extension study. The primary end point was the daily pain relief rating obtained during monthly study visits. Secondary end points included Investigator and Patient Global Evaluations, Brief Pain Inventory scores obtained at monthly study visits, and quality-of-life measures (Medical Outcomes Study Questionnaire and 36-Item Short-Form Health Survey score) obtained at monthly intervals. Mean±SD change from baseline in pain relief with OROS hydromorphone ER for the Month 6 visit was 0.9±2.55 (P=0.0007) and for the last assessment of the extension study was 0.9±2.53 (P=0.0002). At the Month 6 visit, 81.3% of investigators and 71.0% of patients rated their satisfaction of pain relief with OROS hydromorphone ER treatment as good, very good, or excellent. Changes on the 36-item Short Form Health Survey, a quality-of-life measure, were statistically significant for the physical composite scores for all extension phase time points, including Month 6 (2.1±5.34; Psleep disturbances. Adverse events included gastrointestinal and central nervous system symptoms. The results support the long-term use of OROS hydromorphone ER in managing chronic moderate to severe low back pain. Wiley Periodicals, Inc.

  17. 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.

  18. 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)

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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

  5. Long-term efficacy and safety of tacalcitol ointment in patients with chronic plaque psoriasis.

    NARCIS (Netherlands)

    Kerkhof, P.C.M. van de; Berth-Jones, J.; Griffiths, C.E.; Harrison, P.V.; Honigsmann, H.; Marks, R.; Roelandts, R.; Schopf, E.; Trompke, C.

    2002-01-01

    BACKGROUND: As psoriasis patients often require continuous treatment optimal therapy has to provide efficacy and a good safety profile over the long term. OBJECTIVES: The aim of this multicentre study was to assess the efficacy, safety and tolerability of tacalcitol (4 microg g(-1)) ointment

  6. 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.

  7. Reduction of Parenteral Nutrition and Hydration Support and Safety With Long-Term Teduglutide Treatment in Patients With Short Bowel Syndrome-Associated Intestinal Failure: STEPS-3 Study.

    Science.gov (United States)

    Seidner, Douglas L; Fujioka, Ken; Boullata, Joseph I; Iyer, Kishore; Lee, Hak-Myung; Ziegler, Thomas R

    2018-05-15

    Patients with intestinal failure associated with short bowel syndrome (SBS-IF) require parenteral support (PS) to maintain fluid balance or nutrition. Teduglutide (TED) reduced PS requirements in patients with SBS-IF in the randomized, placebo (PBO)-controlled STEPS study (NCT00798967) and its 2-year, open-label extension, STEPS-2 (NCT00930644). STEPS-3 (NCT01560403), a 1-year, open-label extension study in patients with SBS-IF who completed STEPS-2, further monitored the safety and efficacy of TED (0.05 mg/kg/day). Baseline was the start of TED treatment, in either STEPS or STEPS-2. At the end of STEPS-3, patients treated with TED in both STEPS and STEPS-2 (TED-TED) received TED for ≤42 months, and patients treated with TED only in STEPS-2 (no TED treatment [NT]/PBO-TED) received TED for ≤36 months. Fourteen patients enrolled (TED-TED, n = 5; NT/PBO-TED, n = 9) and 13 completed STEPS-3. At the last dosing visit, mean (SD) PS was reduced from baseline by 9.8 (14.4 [50%]) and 3.9 (2.8 [48%]) L/week in TED-TED and NT/PBO-TED, respectively. Mean (SD) PS infusions decreased by 3.0 (4.6) and 2.1 (2.2) days per week from baseline in TED-TED and NT/PBO-TED, respectively. Two patients achieved PS independence; 2 additional patients who achieved independence in STEPS-2 maintained enteral autonomy throughout STEPS-3. All patients reported ≥1 treatment-emergent adverse event (TEAE); 3 patients had TEAEs that were reported as treatment related. No patient had a treatment-related treatment-emergent serious AE. Long-term TED treatment yielded a safety profile consistent with previous studies, sustained efficacy, and a further decline in PS requirements. © 2018 The Authors. Nutrition in Clinical Practice published by Wiley Periodicals, Inc. on behalf of American Society for Parenteral and Enteral Nutrition.

  8. 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

  9. Assessment of the long-term safety of repositories. Scientific basis

    International Nuclear Information System (INIS)

    Noseck, Ulrich; Becker, Dirk; Fahrenholz, Christine

    2008-12-01

    The project contributed to increase the scientific knowledge on the long-term safety assessment and the safety cases of a radioactive waste repository. International guidelines and more recent safety cases from other countries were evaluated. The feasibility study of the three safety indicators ''individual dose rate'', ''radiotoxicity concentration in the biosphere water'' and ''radiotoxicity flux from the geosphere'' showed that due to the independently derived corresponding reference values these indicators describe three different safety statements. The combination of the three values can give a stronger argument for the safety of the repository system. Another important methodological aspect of the safety cases is the definition and selection of scenarios, one of these the human intrusion scenario. Various human intrusion scenarios are considered in the different nations, which differ significantly with respect to type and time scale, the exposition type and exposition pathway. Further progress has been achieved in how to treat human intrusion scenarios in a German post-closure safety case. Another port of the project dealt with the impact of specific geochemical processes on the long-term safety of the repository. The impact of climate changes on the long-term safety of a radioactive waste repository in rock salt was investigated with respect to processes in the overburden and the biosphere where highest impact is expected. Sofa simplified models and only discrete climate estates have been considered

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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

  12. Preclinical rodent toxicity studies for long term use of ceftriaxone

    Directory of Open Access Journals (Sweden)

    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.

  13. Long-term safety and outcome of a temporary self-expanding metallic stent for achalasia: a prospective study with a 13-year single-center experience

    International Nuclear Information System (INIS)

    Zhao, Jun-Gong; Li, Yong-Dong; Li, Ming-Hua; Shang, Ke-Zhong; Cheng, Ying-Sheng; Chen, Ni-Wei; Chen, Wei-Xiong

    2009-01-01

    To prospectively evaluate the long-term clinical safety and efficacy of a newly designed self-expanding metallic stent (SEMS) in the treatment of patients with achalasia. Seventy-five patients with achalasia were treated with a temporary SEMS with a 30-mm diameter. The SEMSs were placed under fluoroscopic guidance and removed by gastroscopy 4-5 days after stent placement. Follow-up data focused on dysphagia score, technique and clinical success, clinical remissions and failures, and complications and was performed at 6 months, 1 year, and within 3 to 5 years, 5 to 8 years, 8 to 10 years, and >10 years postoperatively. Stent placement was technically successful in all patients. Complications included stent migration (n=4, 5.33%), chest pain (n=28, 38.7%), reflux (n=15, 20%), and bleeding (n=9, 12%). No perforation or 30-day mortality occurred. Clinical success was achieved in all patients 1 month after stent removal. The overall remission rates at 6 months, 1, 1-3, 3-5, 5-8, 8-10, and >10 year follow-up periods were 100%, 96%, 93.9%, 90.9%, 100%, 100%, and 83.3%, respectively. Stent treatment failed in six patients, and the overall remission rate in our series was 92%. The median and mean primary patencies were 2.8 ± 0.28 years (95% CI: 2.25-3.35) and 4.28 ± 0.40 years (95% CI: 3.51-5.05), respectively. The use of temporary SEMSs with 30-mm diameter proved to be a safe and effective approach for managing achalasia with a long-term satisfactory clinical remission rate. (orig.)

  14. Long-term safety and outcome of a temporary self-expanding metallic stent for achalasia: a prospective study with a 13-year single-center experience

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Jun-Gong; Li, Yong-Dong; Li, Ming-Hua; Shang, Ke-Zhong [Shanghai Tong Ji University, Department of Radiology, Tenth Affiliated People' s Hospital, Shanghai (China); Cheng, Ying-Sheng [Shanghai Tong Ji University, Department of Radiology, Tenth Affiliated People' s Hospital, Shanghai (China); Shanghai Jiao Tong University, Department of Radiology, Sixth Affiliated People' s Hospital, Shanghai (China); Chen, Ni-Wei; Chen, Wei-Xiong [Shanghai Jiao Tong University, Department of Gastroenterology, Sixth Affiliated People' s Hospital, Shanghai (China)

    2009-08-15

    To prospectively evaluate the long-term clinical safety and efficacy of a newly designed self-expanding metallic stent (SEMS) in the treatment of patients with achalasia. Seventy-five patients with achalasia were treated with a temporary SEMS with a 30-mm diameter. The SEMSs were placed under fluoroscopic guidance and removed by gastroscopy 4-5 days after stent placement. Follow-up data focused on dysphagia score, technique and clinical success, clinical remissions and failures, and complications and was performed at 6 months, 1 year, and within 3 to 5 years, 5 to 8 years, 8 to 10 years, and >10 years postoperatively. Stent placement was technically successful in all patients. Complications included stent migration (n=4, 5.33%), chest pain (n=28, 38.7%), reflux (n=15, 20%), and bleeding (n=9, 12%). No perforation or 30-day mortality occurred. Clinical success was achieved in all patients 1 month after stent removal. The overall remission rates at 6 months, 1, 1-3, 3-5, 5-8, 8-10, and >10 year follow-up periods were 100%, 96%, 93.9%, 90.9%, 100%, 100%, and 83.3%, respectively. Stent treatment failed in six patients, and the overall remission rate in our series was 92%. The median and mean primary patencies were 2.8 {+-} 0.28 years (95% CI: 2.25-3.35) and 4.28 {+-} 0.40 years (95% CI: 3.51-5.05), respectively. The use of temporary SEMSs with 30-mm diameter proved to be a safe and effective approach for managing achalasia with a long-term satisfactory clinical remission rate. (orig.)

  15. 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…

  16. 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)

  17. The Long-Term Safety, Public Health Impact, and Cost-Effectiveness of Routine Vaccination with a Recombinant, Live-Attenuated Dengue Vaccine (Dengvaxia): A Model Comparison Study.

    Science.gov (United States)

    Flasche, Stefan; Jit, Mark; Rodríguez-Barraquer, Isabel; Coudeville, Laurent; Recker, Mario; Koelle, Katia; Milne, George; Hladish, Thomas J; Perkins, T Alex; Cummings, Derek A T; Dorigatti, Ilaria; Laydon, Daniel J; España, Guido; Kelso, Joel; Longini, Ira; Lourenco, Jose; Pearson, Carl A B; Reiner, Robert C; Mier-Y-Terán-Romero, Luis; Vannice, Kirsten; Ferguson, Neil

    2016-11-01

    Large Phase III trials across Asia and Latin America have recently demonstrated the efficacy of a recombinant, live-attenuated dengue vaccine (Dengvaxia) over the first 25 mo following vaccination. Subsequent data collected in the longer-term follow-up phase, however, have raised concerns about a potential increase in hospitalization risk of subsequent dengue infections, in particular among young, dengue-naïve vaccinees. We here report predictions from eight independent modelling groups on the long-term safety, public health impact, and cost-effectiveness of routine vaccination with Dengvaxia in a range of transmission settings, as characterised by seroprevalence levels among 9-y-olds (SP9). These predictions were conducted for the World Health Organization to inform their recommendations on optimal use of this vaccine. The models adopted, with small variations, a parsimonious vaccine mode of action that was able to reproduce quantitative features of the observed trial data. The adopted mode of action assumed that vaccination, similarly to natural infection, induces transient, heterologous protection and, further, establishes a long-lasting immunogenic memory, which determines disease severity of subsequent infections. The default vaccination policy considered was routine vaccination of 9-y-old children in a three-dose schedule at 80% coverage. The outcomes examined were the impact of vaccination on infections, symptomatic dengue, hospitalised dengue, deaths, and cost-effectiveness over a 30-y postvaccination period. Case definitions were chosen in accordance with the Phase III trials. All models predicted that in settings with moderate to high dengue endemicity (SP9 ≥ 50%), the default vaccination policy would reduce the burden of dengue disease for the population by 6%-25% (all simulations: -3%-34%) and in high-transmission settings (SP9 ≥ 70%) by 13%-25% (all simulations: 10%- 34%). These endemicity levels are representative of the participating sites in

  18. The Long-Term Safety, Public Health Impact, and Cost-Effectiveness of Routine Vaccination with a Recombinant, Live-Attenuated Dengue Vaccine (Dengvaxia: A Model Comparison Study.

    Directory of Open Access Journals (Sweden)

    Stefan Flasche

    2016-11-01

    Full Text Available Large Phase III trials across Asia and Latin America have recently demonstrated the efficacy of a recombinant, live-attenuated dengue vaccine (Dengvaxia over the first 25 mo following vaccination. Subsequent data collected in the longer-term follow-up phase, however, have raised concerns about a potential increase in hospitalization risk of subsequent dengue infections, in particular among young, dengue-naïve vaccinees. We here report predictions from eight independent modelling groups on the long-term safety, public health impact, and cost-effectiveness of routine vaccination with Dengvaxia in a range of transmission settings, as characterised by seroprevalence levels among 9-y-olds (SP9. These predictions were conducted for the World Health Organization to inform their recommendations on optimal use of this vaccine.The models adopted, with small variations, a parsimonious vaccine mode of action that was able to reproduce quantitative features of the observed trial data. The adopted mode of action assumed that vaccination, similarly to natural infection, induces transient, heterologous protection and, further, establishes a long-lasting immunogenic memory, which determines disease severity of subsequent infections. The default vaccination policy considered was routine vaccination of 9-y-old children in a three-dose schedule at 80% coverage. The outcomes examined were the impact of vaccination on infections, symptomatic dengue, hospitalised dengue, deaths, and cost-effectiveness over a 30-y postvaccination period. Case definitions were chosen in accordance with the Phase III trials. All models predicted that in settings with moderate to high dengue endemicity (SP9 ≥ 50%, the default vaccination policy would reduce the burden of dengue disease for the population by 6%-25% (all simulations: -3%-34% and in high-transmission settings (SP9 ≥ 70% by 13%-25% (all simulations: 10%- 34%. These endemicity levels are representative of the

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

    Directory of Open Access Journals (Sweden)

    Uemura N

    2018-01-01

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

  20. 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.

  1. 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.

  2. 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)

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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....

  8. Long-term Study of a Quadrivalent Human Papillomavirus Vaccine

    DEFF Research Database (Denmark)

    Ferris, Daron; Samakoses, Rudiwilai; Block, Stan L

    2014-01-01

    BACKGROUND: We present a long-term safety, immunogenicity, and effectiveness study of a quadrivalent human papillomavirus (HPV4) vaccine. METHODS: Sexually naive boys and girls aged 9 to 15 years (N = 1781) were assigned (2:1) to receive HPV4 vaccine or saline placebo at day 1 and months 2 and 6...... objective was to estimate vaccine effectiveness against HPV6/11/16/18-related persistent infection or disease. RESULTS: For each of the HPV4 vaccine types, vaccination-induced anti-HPV response persisted through month 96. Among 429 subjects who received HPV4 vaccine at a mean age of 12, none developed HPV6....../11/16/18-related disease or persistent infection of ≥12 months' duration. Acquisition of new sexual partners (among those ≥16 years) was ∼1 per year. Subjects receiving HPV4 vaccine at month 30 (mean age 15 years) had a similar baseline rate of seropositivity to ≥1 of the 4 HPV types to those vaccinated at day 1...

  9. 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.

  10. Methodology of long term behaviour study of containment materials

    International Nuclear Information System (INIS)

    Vernaz, E.; Godon, N.

    1994-01-01

    Here is the presentation of the papers shown in the colloquium on environment and ceramics; the Atomic Energy Commissariat (Cea) have been working for fifteen years on the long term behaviour of fission products glasses on very long periods, about several millions years. The method of studies is detailed. 2 refs

  11. Archiving primary data: solutions for long-term studies

    NARCIS (Netherlands)

    Mills, J.A.; Teplitsky, C.; Arroyo, B.; Charmantier, A.; H. Becker, P.; Birkhead, T.R.; Bize, P.; Blumstein, D.T.; Bonenfant, C.; Boutin, S.; Bushuev, A.; Cam, E.; Cockburn, A.; Côté, S.D.; Coulson, J.C.; Daunt, F.; Dingemanse, N.J.; Doligez, B.; Drummond, H.; Espie, R.H.M.; Festa-Bianchet, M.; Frentiu, F.; Fitzpatrick, J.W.; Furness, R.W.; Garant, D.; Gauthier, G.; Grant, P.R.; Griesser, M.; Gustafsson, L.; Hansson, B.; Harris, M.P.; Jiguet, F.; Kjellander, P.; Korpimäki, E.; Krebs, C.J.; Lens, L.; Linnell, J.D.C.; Low, M.; McAdam, A.; Margalida, A.; Merilä, J.; Møller, A.P.; Nakagawa, S.; Nilsson, J.-Å.; Nisbet, I.C.T.; van Noordwijk, A.J.; Oro, D.; Pärt, T.; Pelletier, F.; Potti, J.; Pujol, B.; Réale, D.; Rockwell, R.F.; Ropert-Coudert, Y.; Roulin, A.; Thébaud, C.; Sedinger, J.S.; Swenson, J.E.; Visser, M.E.; S.Wanless Westneat, D.F.; Wilson, A.J.; Zedrosser, A.

    2015-01-01

    The recent trend for journals to require open access to primary data included in publications has been embraced by many biologists, but has caused apprehension amongst researchers engaged in long-term ecological and evolutionary studies. A worldwide survey of 73 principal investigators (Pls) with

  12. Archiving primary data : Solutions for long-term studies

    NARCIS (Netherlands)

    Mills, James A.; Teplitsky, Celine; Arroyo, Beatriz; Charmantier, Anne; Becker, Peter. H.; Birkhead, Tim R.; Bize, Pierre; Blumstein, Daniel T.; Bonenfant, Christophe; Boutin, Stan; Bushuev, Andrey; Cam, Emmanuelle; Cockburn, Andrew; Cote, Steeve D.; Coulson, John C.; Daunt, Francis; Dingemanse, Niels J.; Doligez, Blandine; Drummond, Hugh; Espie, Richard H. M.; Festa-Bianchet, Marco; Frentiu, Francesca; Fitzpatrick, John W.; Furness, Robert W.; Garant, Dany; Gauthier, Gilles; Grant, Peter R.; Griesser, Michael; Gustafsson, Lars; Hansson, Bengt; Harris, Michael P.; Jiguet, Frederic; Kjellander, Petter; Korpimaki, Erkki; Krebs, Charles J.; Lens, Luc; Linne, John D. C.; Low, Matthew; McAdam, Andrew; Margalida, Antoni; Merila, Juha; Moller, Anders P.; Nakagawa, Shinichi; Nilsson, Jan-Ake; Nisbet, Ian C. T.; van Noordwijk, Arie J.; Oro, Daniel; Part, Tomas; Pelletier, Fanie; Potti, Jaime; Pujol, Benoit; Reale, Denis; Rockwel, Robert F.; Ropert-Coudert, Yan; Roulin, Alexandre; Sedinger, James S.; Swenson, Jon E.; Thebaud, Christophe; Visser, Marcel E.; Wanless, Sarah; Westneat, David F.; Wilson, Alastair J.; Zedrosser, Andreas

    2015-01-01

    The recent trend for journals to require open access to primary data included in publications has been embraced by many biologists, but has caused apprehension amongst researchers engaged in long-term ecological and evolutionary studies. A worldwide survey of 73 principal investigators (PIs) with

  13. Study of long-term loss of all AC power supply sources for VVER-1000/V320 in connection with application of new engineering safety features for SAMG

    International Nuclear Information System (INIS)

    Borisov, Evgeni; Grigorov, Dobrin; Mancheva, Kaliopa

    2013-01-01

    Highlights: • In this study we presented analysis for a new SAMG approach. • The approach is applicable for all PWR reactors from 2nd generation. • We investigated two scenarios with total black out. • The RELAP/MOD 3.2 computer code is used in performing the analyses. - Abstract: This paper presents the results of analysis for application of a new Severe Accident Management Guideline (SAMG) approach which is specifically applied for VVER-1000/B320 reactor installations. In general, this innovative approach is fully applicable for all the pressurized water reactors from second generation. The purposes of the analysis for the new SAMG approach application are as follows: • To represent suggestions for new engineering safety features application for SAMG strategies. • To assess the applicability of the new engineering safety features and means for SAMG strategies in case of loss of all off-site power supply sources for VVER-1000/B320 reactor installations. • To represent important operator actions and to analyse the effectiveness of these actions for accidents management in compliance with the new approach. • The RELAP5/MOD3.3 computer code has been used in performing the analyses in a VVER-1000 Nuclear Power Plant (NPP) model. The input data deck for the analysis is optimized, verified and validated

  14. 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

  15. 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

  16. Efficacy and safety of early tacrolimus conversion to sirolimus after kidney transplantation: Long-term results of a prospective randomized study

    Directory of Open Access Journals (Sweden)

    A E El-Agroudy

    2017-01-01

    Full Text Available We report a prospective, open-label, randomized study to evaluate the safety and efficacy of converting patients with a stable renal function from tacrolimus (Tac-based regimen to a sirolimus (SRL-based regimen after kidney transplantation. Fifty-eight low-risk renal allograft recipients who receiving Tac 6 months posttransplant, were randomly assigned to continue Tac (n = 29 or convert to SRL (n = 29. We evaluated the 3-year outcomes including patient and graft survival, graft function, and safety profile. Three-year patient and graft survival in SRL and Tac groups were 93.1% versus 100% (P = 0.32, and 89.7% versus 100% (P = 0.11, respectively. However, the SRL group had a significantly better renal function, from the 2nd year posttransplant until the last follow-up. Four (13.8% patients in the SRL group and 3 (10.3% in the Tac group (P = 0.5 developed biopsy-proven acute rejection. Mean urinary protein excretion increased significantly after SRL conversion. Diastolic blood pressure was significantly lower at the end of the study in patients who eliminated Tac (80.4 vs. 75.6 mmHg in Tac and SRL group, respectively (P = 0.03. Mean hemoglobin concentrations decreased after SRL conversion and remained significantly lower from 12 months to 36 months (P = 0.01. The mean serum cholesterol (540 ± 44 mg/dl and triglyceride (177 ± 27 mg/dl increased significantly in the SRL group, compared to Tac group (487 ± 62 mg/dl (P = 0.03 and (141 ± 26 mg/dl (P = 0.04. Our experience demonstrates that conversion to SRL from calcineurin inhibitors-based therapy may result in better renal function and blood pressure control in renal transplant recipients without an increased risk of acute rejection. However, these benefits have not resulted in a growing advantage in graft or patient survival.

  17. Long-term cardiac (valvulopathy) safety of cabergoline in prolactinoma

    OpenAIRE

    Khare, Shruti; Lila, Anurag R.; Patil, Rishikesh; Phadke, Milind; Kerkar, Prafulla; Bandgar, Tushar; Shah, Nalini S.

    2017-01-01

    Background: Clinical relevance of association of cabergoline use for hyperprolactinemia and cardiac valvulopathy remains unclear. Objective: The aim of the study was to determine the prevalence of valvular heart abnormalities in patients taking cabergoline for the treatment of prolactinoma and to explore any associations with the cumulative dose of drug used. Design: A cross-sectional echocardiographic study was performed in patients who were receiving cabergoline therapy for prolactinoma. Re...

  18. Long-term cardiac (valvulopathy) safety of cabergoline in prolactinoma

    Science.gov (United States)

    Khare, Shruti; Lila, Anurag R.; Patil, Rishikesh; Phadke, Milind; Kerkar, Prafulla; Bandgar, Tushar; Shah, Nalini S.

    2017-01-01

    Background: Clinical relevance of association of cabergoline use for hyperprolactinemia and cardiac valvulopathy remains unclear. Objective: The aim of the study was to determine the prevalence of valvular heart abnormalities in patients taking cabergoline for the treatment of prolactinoma and to explore any associations with the cumulative dose of drug used. Design: A cross-sectional echocardiographic study was performed in patients who were receiving cabergoline therapy for prolactinoma. Results: Hundred (61 females, 39 males) prolactinoma cases (81 macroprolactinoma and 19 microprolactinoma) were included in the study. The mean age at presentation was 33.9 ± 9.0 years (range: 16–58 years). The mean duration of treatment was 53.11 ± 43.15 months (range: 12–155 months). The mean cumulative dose was 308.6 ± 290.2 mg (range: 26–1196 mg; interquartile range: 104–416 mg). Mild mitral regurgitation was present in one patient (cumulative cabergoline dose 104 mg). Mild tricuspid regurgitation was present in another two patients (cumulative cabergoline dose 52 mg and 104 mg). Aortic and pulmonary valve functioning was normal in all the cases. There were no cases of significant valvular regurgitation (moderate to severe, Grade 3–4). None of the patients had morphological abnormalities such as thickening, calcification, and restricted mobility of any of the cardiac valves. Conclusion: Cabergoline appears to be safe in patients with prolactinoma up to the cumulative dose of ~300 mg. The screening for valvulopathy should be restricted to those with higher cumulative cabergoline exposure. PMID:28217516

  19. Long-term cardiac (valvulopathy safety of cabergoline in prolactinoma

    Directory of Open Access Journals (Sweden)

    Shruti Khare

    2017-01-01

    Full Text Available Background: Clinical relevance of association of cabergoline use for hyperprolactinemia and cardiac valvulopathy remains unclear. Objective: The aim of the study was to determine the prevalence of valvular heart abnormalities in patients taking cabergoline for the treatment of prolactinoma and to explore any associations with the cumulative dose of drug used. Design: A cross-sectional echocardiographic study was performed in patients who were receiving cabergoline therapy for prolactinoma. Results: Hundred (61 females, 39 males prolactinoma cases (81 macroprolactinoma and 19 microprolactinoma were included in the study. The mean age at presentation was 33.9 ± 9.0 years (range: 16–58 years. The mean duration of treatment was 53.11 ± 43.15 months (range: 12–155 months. The mean cumulative dose was 308.6 ± 290.2 mg (range: 26–1196 mg; interquartile range: 104–416 mg. Mild mitral regurgitation was present in one patient (cumulative cabergoline dose 104 mg. Mild tricuspid regurgitation was present in another two patients (cumulative cabergoline dose 52 mg and 104 mg. Aortic and pulmonary valve functioning was normal in all the cases. There were no cases of significant valvular regurgitation (moderate to severe, Grade 3–4. None of the patients had morphological abnormalities such as thickening, calcification, and restricted mobility of any of the cardiac valves. Conclusion: Cabergoline appears to be safe in patients with prolactinoma up to the cumulative dose of ~300 mg. The screening for valvulopathy should be restricted to those with higher cumulative cabergoline exposure.

  20. Long-term efficacy and safety of rituximab in IgG4-related disease: Data from a French nationwide study of thirty-three patients.

    Directory of Open Access Journals (Sweden)

    Mikael Ebbo

    Full Text Available To assess efficacy and safety of rituximab (RTX as induction therapy, maintenance of remission and treatment of relapses in a cohort of IgG4-related disease (IgG4-RD patients.Nationwide retrospective multicenter study of IgG4-RD patients treated with at least one course of RTX. Clinical, biological and radiological response, relapse rate and drug tolerance were analyzed. Kaplan-Meier curves were plotted and risk factors for relapse studied with a Cox regression model.Among 156 IgG4-RD patients included in the French database, 33 received rituximab. Clinical response was noted in 29/31 (93.5% symptomatic patients. Glucocorticoids withdrawal was achieved in 17 (51.5% patients. During a mean follow-up of 24.8 ±21 months, 13/31 (41.9% responder patients relapsed after a mean delay of 19 ±11 months after RTX. Active disease, as defined by an IgG4-RD Responder Index >9 before RTX, was significantly associated with relapse (HR = 3.68, 95% CI: 1.1, 12.6 (P = 0.04, whereas maintenance therapy with systematic (i.e. before occurrence of a relapse RTX retreatment was associated with longer relapse-free survival (41 versus 21 months; P = 0.02. Eight severe infections occurred in 4 patients during follow-up (severe infections rate of 12.1/100 patient-years and hypogammaglobulinemia ≤5 g/l in 3 patients.RTX is effective for both induction therapy and treatment of relapses in IgG4-RD, but relapses are frequent after B-cell reconstitution. Maintenance therapy with systematic RTX infusions is associated with longer relapse-free survival and might represent a novel treatment strategy. Yet, the high rate of infections and the temporary effect of RTX might be hindrances to such strategy.

  1. Long-term efficacy and safety of rituximab in IgG4-related disease: Data from a French nationwide study of thirty-three patients

    Science.gov (United States)

    Grados, Aurélie; Samson, Maxime; Groh, Matthieu; Loundou, Anderson; Rigolet, Aude; Terrier, Benjamin; Guillaud, Constance; Carra-Dallière, Clarisse; Renou, Frédéric; Pozdzik, Agnieszka; Labauge, Pierre; Palat, Sylvain; Berthelot, Jean-Marie; Pennaforte, Jean-Loup; Wynckel, Alain; Lebas, Céline; Le Gouellec, Noémie; Quémeneur, Thomas; Dahan, Karine; Carbonnel, Franck; Leroux, Gaëlle; Perlat, Antoinette; Mathian, Alexis; Cacoub, Patrice; Hachulla, Eric; Costedoat-Chalumeau, Nathalie; Harlé, Jean-Robert; Schleinitz, Nicolas

    2017-01-01

    Objectives To assess efficacy and safety of rituximab (RTX) as induction therapy, maintenance of remission and treatment of relapses in a cohort of IgG4-related disease (IgG4-RD) patients. Methods Nationwide retrospective multicenter study of IgG4-RD patients treated with at least one course of RTX. Clinical, biological and radiological response, relapse rate and drug tolerance were analyzed. Kaplan-Meier curves were plotted and risk factors for relapse studied with a Cox regression model. Results Among 156 IgG4-RD patients included in the French database, 33 received rituximab. Clinical response was noted in 29/31 (93.5%) symptomatic patients. Glucocorticoids withdrawal was achieved in 17 (51.5%) patients. During a mean follow-up of 24.8 ±21 months, 13/31 (41.9%) responder patients relapsed after a mean delay of 19 ±11 months after RTX. Active disease, as defined by an IgG4-RD Responder Index >9 before RTX, was significantly associated with relapse (HR = 3.68, 95% CI: 1.1, 12.6) (P = 0.04), whereas maintenance therapy with systematic (i.e. before occurrence of a relapse) RTX retreatment was associated with longer relapse-free survival (41 versus 21 months; P = 0.02). Eight severe infections occurred in 4 patients during follow-up (severe infections rate of 12.1/100 patient-years) and hypogammaglobulinemia ≤5 g/l in 3 patients. Conclusion RTX is effective for both induction therapy and treatment of relapses in IgG4-RD, but relapses are frequent after B-cell reconstitution. Maintenance therapy with systematic RTX infusions is associated with longer relapse-free survival and might represent a novel treatment strategy. Yet, the high rate of infections and the temporary effect of RTX might be hindrances to such strategy. PMID:28915275

  2. Liver safety of non-tumour necrosis factor inhibitors in rheumatic patients with past hepatitis B virus infection: an observational, controlled, long-term study.

    Science.gov (United States)

    Papalopoulos, Ioannis; Fanouriakis, Antonis; Kougkas, Nikolaos; Flouri, Irini; Sourvinos, George; Bertsias, George; Repa, Argyro; Avgoustidis, Nestor; Sidiropoulos, Prodromos

    2018-01-01

    The risk of hepatitis B virus (HBV) reactivation with non-tumour necrosis factor inhibitor (non-TNFi) biologic agents in patients with rheumatic diseases and past HBV infection has not been definively elucidated. We assessed the comparative safety of non-TNFi and TNFi biologic agents in such patients in real-life clinical settings. We carried out a retrospective cohort study from the Department of Rheumatology, University Hospital of Heraklion. Patients who received abatacept (ABA), tocilizumab (TCZ) or rituximab (RTX) during the period 2003-2016 and were HbsAg(-), anti-HBc(+), anti-HBs(±) at baseline, were monitored for HBV reactivation. Patients treated with TNFi agents during the same period were used as a control group. 101 cases of non-TNFi (39 ABA, 32 RTX and 30 TCZ) and 111 cases of TNFi treatment were identified. In non-TNFi, 76 cases (75.2%) were anti-HBc(+)/anti-HBs(+) and 25 (24.8%) were anti-HBc(+)/anti-HBs(-), as compared to 82 (73.9%) and 29 (26.1%) in TNFi-treated, respectively. After a median (IQR) observation of 24.0 (34.7) months, two cases (2.0%) of HBV reactivation were identified in the non-TNFi group; one with ABA, successfully treated with entecavir, and one fatal case with RTX and prior exposure to cyclophosphamide. No reactivation was observed in the TNFi group (p=0.226 vs. non-TNFi). Αnti-HBs titres were significantly reduced compared to baseline in the non-TNFi group [median (IQR) 203.9 (954.7) mIU/ml before treatment versus 144.9 (962.9) mIU/ml after treatment, p=0.03]. Two cases of HBV reactivation highlight the risk for this complication in patients with past HBV infection under biologic therapy.

  3. Archiving Primary Data: Solutions for Long-Term Studies.

    Science.gov (United States)

    Mills, James A; Teplitsky, Céline; Arroyo, Beatriz; Charmantier, Anne; Becker, Peter H; Birkhead, Tim R; Bize, Pierre; Blumstein, Daniel T; Bonenfant, Christophe; Boutin, Stan; Bushuev, Andrey; Cam, Emmanuelle; Cockburn, Andrew; Côté, Steeve D; Coulson, John C; Daunt, Francis; Dingemanse, Niels J; Doligez, Blandine; Drummond, Hugh; Espie, Richard H M; Festa-Bianchet, Marco; Frentiu, Francesca; Fitzpatrick, John W; Furness, Robert W; Garant, Dany; Gauthier, Gilles; Grant, Peter R; Griesser, Michael; Gustafsson, Lars; Hansson, Bengt; Harris, Michael P; Jiguet, Frédéric; Kjellander, Petter; Korpimäki, Erkki; Krebs, Charles J; Lens, Luc; Linnell, John D C; Low, Matthew; McAdam, Andrew; Margalida, Antoni; Merilä, Juha; Møller, Anders P; Nakagawa, Shinichi; Nilsson, Jan-Åke; Nisbet, Ian C T; van Noordwijk, Arie J; Oro, Daniel; Pärt, Tomas; Pelletier, Fanie; Potti, Jaime; Pujol, Benoit; Réale, Denis; Rockwell, Robert F; Ropert-Coudert, Yan; Roulin, Alexandre; Sedinger, James S; Swenson, Jon E; Thébaud, Christophe; Visser, Marcel E; Wanless, Sarah; Westneat, David F; Wilson, Alastair J; Zedrosser, Andreas

    2015-10-01

    The recent trend for journals to require open access to primary data included in publications has been embraced by many biologists, but has caused apprehension amongst researchers engaged in long-term ecological and evolutionary studies. A worldwide survey of 73 principal investigators (Pls) with long-term studies revealed positive attitudes towards sharing data with the agreement or involvement of the PI, and 93% of PIs have historically shared data. Only 8% were in favor of uncontrolled, open access to primary data while 63% expressed serious concern. We present here their viewpoint on an issue that can have non-trivial scientific consequences. We discuss potential costs of public data archiving and provide possible solutions to meet the needs of journals and researchers. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. 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.

  5. 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

  6. An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics.

    Science.gov (United States)

    Johnson, Jeremy R; Lossignol, Dominique; Burnell-Nugent, Mary; Fallon, Marie T

    2013-08-01

    Chronic pain in patients with advanced cancer poses a serious clinical challenge. The Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (U.S. Adopted Name, nabiximols; Sativex(®)) is a novel cannabinoid formulation currently undergoing investigation as an adjuvant therapy for this treatment group. This follow-up study investigated the long-term safety and tolerability of THC/CBD spray and THC spray in relieving pain in patients with advanced cancer. In total, 43 patients with cancer-related pain experiencing inadequate analgesia despite chronic opioid dosing, who had participated in a previous three-arm (THC/CBD spray, THC spray, or placebo), two-week parent randomized controlled trial, entered this open-label, multicenter, follow-up study. Patients self-titrated THC/CBD spray (n=39) or THC spray (n=4) to symptom relief or maximum dose and were regularly reviewed for safety, tolerability, and evidence of clinical benefit. The efficacy end point of change from baseline in mean Brief Pain Inventory-Short Form scores for "pain severity" and "worst pain" domains showed a decrease (i.e., improvement) at each visit in the THC/CBD spray patients. Similarly, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 scores showed a decrease (i.e., improvement) from baseline in the domains of insomnia, pain, and fatigue. No new safety concerns associated with the extended use of THC/CBD spray arose from this study. This study showed that the long-term use of THC/CBD spray was generally well tolerated, with no evidence of a loss of effect for the relief of cancer-related pain with long-term use. Furthermore, patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time, suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc

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

    Science.gov (United States)

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

    2017-12-02

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

  8. Microscopic study of rock for estimating long-term behavior

    International Nuclear Information System (INIS)

    Ichikawa, Yasuaki

    2004-02-01

    Micro-structure of rock plays an essential role for their long-term behavior. For understanding long-term characteristics of granite we here present the followings: 1) observation of microcrack initiation and propagation by Conforcal Laser Scanning Microscope (CLSM) under uniaxial compression (before loading and at each loading stage), 2) characterization of the mechanism of microcrack initiation and propagation observed by stereoscopic microscope under uniaxial/triaxial compression and relaxation tests, and 3) a study of strong discontinuity analysis included in the homogenization theory to predict the long-term behavior of micro/macro-level stress for granite. First, CLSM was used to acquire clearly focused three-dimensional images of granite specimens, and observed the change of microscale structure including the mineral configuration under applying uniaxial compression stress. Then though microcracks have ever thought to be initiated and propagated on intergranular boundaries, we understand through the CLSM observation that new microcracks are generated from the ends of pre-existing cracks which are distributed in quartz and biotite. Second, we showed the results of stress-relaxation test of granite specimens observed by an optical microscope under water-saturated triaxial compression condition. Since microcrack generation and propagation play an essential role to predict the long-term behavior of rock, we managed the experiments with careful attention of 1) keeping constant edge-displacement and constant strain in the whole specimen accurately, and 2) measuring the relaxed stress exactly. Next, in order to simulate the experimental results which indicate that initiation and propagation of microcracks control the stress-relaxation phenomenon, we introduce a homogenization analysis procedure together with the strong discontinuity analysis which has recently established the mechanical implication and mathematical foundation. The numerical results show that we can

  9. 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.

  10. 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

  11. Long-term safety of rituximab induced peripheral B-cell depletion in autoimmune neurological diseases.

    Directory of Open Access Journals (Sweden)

    Anza B Memon

    Full Text Available B-cells play a pivotal role in several autoimmune diseases, including patients with immune-mediated neurological disorders (PIMND, such as neuromyelitis optica (NMO, multiple sclerosis (MS, and myasthenia gravis (MG. Targeting B-cells has been an effective approach in ameliorating both central and peripheral autoimmune diseases. However, there is a paucity of literature on the safety of continuous B-cell depletion over a long period of time.The aim of this study was to examine the long-term safety, incidence of infections, and malignancies in subjects receiving continuous therapy with a B-cell depleting agent rituximab over at least 3 years or longer.This was a retrospective study involving PIMND who received continuous cycles of rituximab infusions every 6 to 9 months for up to 7 years. The incidence of infection related adverse events (AE, serious adverse events (SAE, and malignancies were observed.There were a total of 32 AE and 4 SAE with rituximab treatment. The 3 SAE were noted after 9 cycles (48 months and 1 SAE was observed after 11 cycles (60 months of rituximab. There were no cases of Progressive multifocal leukoencephalopathy (PML and malignancies observed throughout the treatment period. Rituximab was well tolerated without any serious infusion reactions. Also, rituximab was found to be beneficial in treating PIMND over a 7-year period.This study demonstrates that long-term depletion of peripheral B-cells appears safe and efficacious in treating PIMND. Longer and larger prospective studies with rituximab are needed to carefully ascertain risks associated with chronic B-cell depletion, including malignancies. Recognizing that this is a small, retrospective study, such data nonetheless complement the growing literature documenting the safety and tolerability of B-cell depleting agents in neurological diseases.

  12. Long-Term, Open-Label Safety and Efficacy of Atomoxetine in Adults with ADHD: Final Report of a 4-Year Study

    Science.gov (United States)

    Adler, Lenard A.; Spencer, Thomas J.; Williams, David W.; Moore, Rodney J.; Michelson, David

    2008-01-01

    Objective: Previously, data from 97 weeks of open-label atomoxetine treatment of adults with attention-deficit/hyperactivity disorder (ADHD) were reported. This final report of that study presents results from over 4 years of treatment. Method: Results were derived from the study of 384 patients (125 patients remaining in the open-label trial…

  13. Design of a long-term follow-up effectiveness, immunogenicity and safety study of women who received the 9-valent human papillomavirus vaccine

    DEFF Research Database (Denmark)

    Luxembourg, Alain; Kjaer, Susanne K; Nygard, Mari

    2017-01-01

    registries from these countries to assess incidence of cervical pre-cancers and cancers due to the 7 oncogenic types in the vaccine (HPV 16/18/31/33/45/52/58). Incidences will be compared to the estimated incidence rate in an unvaccinated cohort of similar age and risk level. This LTFU study uses a unique...

  14. 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)

  15. Development of thermal conditioning technology for alpha-contaminated wastes: a study on leaching characteristics and long-term safety assessment of simulated waste forms

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Yong Chil [Yonsei University, Seoul (Korea); Lee, Sang Hoon; Yoo, Jong Ik; Choi, Yong Cheol [Yonsei University, Seoul (Korea)

    2001-04-01

    Radioactive wastes should be stabilized for safe management during several hundred years. To assess stability of solidified waste forms, mechanical properties and chemical durability of the waste forms should be analyzed. Chemical durability is one of the most important factors in the assessment of waste forms, which could be examined by leaching tests. Various methods in leaching test are suggested by different organizations, but a formal test method in Korea is not ready yet. Therefore, the leaching test method applicable to various constituents is necessary for the safe management of radioactive wastes In this study, leaching behavior and characteristics of components such as solidification materials, heavy metals and radioactive nuclids were analyzed for cement waste form and glassy waste form. 58 refs., 25 figs., 8 tabs. (Author)

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. A study of the long-term properties of concrete

    Energy Technology Data Exchange (ETDEWEB)

    Song, Y-C; Lee, D-S; Cho, M-S [Korea Electric Power Corp. (KEPCO), Seoul (Korea, Republic of); Lee, J-H [Korea Inst. of Construction Technology (Korea, Republic of)

    1996-12-31

    Creep, drying, shrinkage, modulus of elasticity and Poisson`s ratio of concrete are influenced by a number of factors, such as mix type, member thickness, curing condition and loading cases. Particularly, creep and, shrinkage in concrete have yet to be studied due to its complicated time-dependent properties. Also they are not clearly differentiated quantitatively. In this paper, the concrete tests of creep, modulus of elasticity and Poisson`s ratio were carried out at various ages of loading -7, 28, 90, 180 and 365 days in order to investigate and quantify its long-term properties. The test procedures and analysis of the test results were also described herein. The results of this study will make it possible to calculate effective prestressing forces considering time-dependent prestressing loss and evaluate the structural integrity of the prestressing system using the representative values derived from this property test. (author). 5 refs., 4 tabs., 4 figs.

  3. A study of the long-term properties of concrete

    International Nuclear Information System (INIS)

    Song, Y-C.; Lee, D-S.; Cho, M-S.; Lee, J-H.

    1995-01-01

    Creep, drying, shrinkage, modulus of elasticity and Poisson's ratio of concrete are influenced by a number of factors, such as mix type, member thickness, curing condition and loading cases. Particularly, creep and, shrinkage in concrete have yet to be studied due to its complicated time-dependent properties. Also they are not clearly differentiated quantitatively. In this paper, the concrete tests of creep, modulus of elasticity and Poisson's ratio were carried out at various ages of loading -7, 28, 90, 180 and 365 days in order to investigate and quantify its long-term properties. The test procedures and analysis of the test results were also described herein. The results of this study will make it possible to calculate effective prestressing forces considering time-dependent prestressing loss and evaluate the structural integrity of the prestressing system using the representative values derived from this property test. (author). 5 refs., 4 tabs., 4 figs

  4. Long-term bird study records Arctic climate change

    Science.gov (United States)

    Zielinski, Sarah

    Alaska's summer of 2005 was the second warmest on record there, with a record retreat of arctic pack ice. As Alaskan temperatures gradually increase, artic birds, such as the black guillemots of Cooper Island, near Barrow, Alaska, are experiencing drastic habitat changes. Though these small black and white birds—the subjects of a long-term study of climate change—fared better this year than they have in the recent past (due to local cool conditions), they are nonetheless struggling to adapt as their artic island summer home becomes subarctic.George Divokyan ornithologist at the Institute of Arctic Biology, University of Alaska Fairbanks, discovered the Cooper Island colony of guillemots in the early 1970s and has spent every summer since 1975 there studying these birds. He presented his latest research during a 3 November talk in Washington, D.C.

  5. Study on long-term behavior of weak rock

    International Nuclear Information System (INIS)

    Okubo, Seisuke

    2003-03-01

    Using the boring core obtained in the Horonobe region, the beta in triaxial compression stress state was acquired, and the examination was carried out on the effect of the confirming pressure on long-term deformation or stability of the sample rock. At first, triaxial compression tests were carried out. In the test, loading rate (strain rate) was changed several times to obtain viscoelastic properties of the sample rock. Multi-stage creep tests were also performed in triaxial compression stress. The parameter set of a constitutive equation of variable compliance type was obtained based on the testing results. In this study, a transparent triaxial cell recently developed by this author was used. The external cylinder of this vessel was made of the transparent acrylic resin. Therefore, gradual deformation of the sample under testing was easily and clearly observed. (author)

  6. 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.

  7. Long-term Efficacy of Trabeculectomy on Chinese Patients with Pigmentary Glaucoma: A Prospective Case Series Observational Study

    Directory of Open Access Journals (Sweden)

    Guo-Ping Qing

    2016-01-01

    Conclusions: All surgical PG eyes in this study had satisfactory IOP control 8 years after the surgery with well-preserved visual function. The long-term efficacy and safety of trabeculectomy are promising in PG patients.

  8. 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

  9. 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.)

  10. Deferasirox: appraisal of safety and efficacy in long-term therapy

    Directory of Open Access Journals (Sweden)

    Chaudhary P

    2013-08-01

    Full Text Available Preeti Chaudhary, Vinod PullarkatJane Ann Nohl Division of Hematology, University of Southern California Keck School of Medicine, Los Angeles, CA, USAAbstract: Deferasirox is a once-daily, oral iron chelator that is widely used in the management of patients with transfusional hemosiderosis. Several Phase II trials along with their respective extension studies as well as a Phase III trial have established the efficacy and safety of this novel agent in transfusion-dependent patients with β-thalassemia, sickle-cell disease and bone marrow-failure syndromes, including myelodysplastic syndrome and aplastic anemia. Data from various clinical trials show that a deferasirox dose of 20 mg/kg/day stabilizes serum ferritin levels and liver iron concentration, while a dose of 30–40 mg/kg/day reduces these parameters and achieves negative iron balance in red cell transfusion-dependent patients with iron overload. Across various pivotal clinical trials, deferasirox was well tolerated, with the most common adverse events being gastrointestinal disturbances, skin rash, nonprogressive increases in serum creatinine, and elevations in liver enzyme levels. Longer-term extension studies have also confirmed the efficacy and safety of deferasirox. However, it is essential that patients on deferasirox therapy are monitored regularly to ensure timely management for any adverse events that may occur with long-term therapy.Keywords: deferasirox, iron overload, thalassemia, sickle-cell disease, myelodysplastic syndrome

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. Microscopic study of rock for estimating long-term behavior

    International Nuclear Information System (INIS)

    Ichikawa, Yasuaki

    1997-03-01

    One must consider micro-structures of rock and rock mass in order to predict the long-term behavior for more than ten thousand years. First we observe the micro-crack distribution of granite which is commonly distributed in Japan, and is widely used for several structures. The creep under constant load and the relaxation under constant displacement are typical time dependent phenomena, and we performed a series of relaxation tests under microscope observation in laboratory. The specimen that is preserved in water is granite as mentioned above. The aim of this experiment is to observe the sequential propagation of micro-cracks and its affect to the macroscopic response of the rock material under relaxation state. Next, a viscoelastic homogenization method is applied for analyzing the behavior of granite that is composed of several kinds of minerals (i.e., a polycrystalline material). The homogenization method developed for analyzing mechanics of composite materials is a mathematical theory that can describe the macroscopic behavior accounting for the microscopic characteristics with periodic microstructures. In this study, it is applied to a polycrystalline rock which involves a few minerals and micro-cracks. Furthermore, it is required to apply the homogenization analysis for rock materials which show a nonlinear time dependent behavior, so we develop a new elasto-visco-plastic homogenization theory, and its validity is checked for some ground structures made by clay. (author)

  16. Pilot study of long-term anaesthesia in broiler chickens.

    Science.gov (United States)

    O'Kane, Peter M; Connerton, Ian F; White, Kate L

    2016-01-01

    To provide stable anaesthesia of long duration in broiler chickens in order to perform a terminal caecal ligated loop procedure. Prospective experimental study. Seven clinically healthy broiler chickens (Gallus domesticus) aged 27-36 days, weighing 884-2000 g. Anaesthesia was induced and maintained with isoflurane in oxygen. All birds underwent intermittent positive pressure ventilation for the duration. End-tidal carbon dioxide, peripheral haemoglobin oxygen saturation, heart rate and oesophageal temperature were monitored continuously. All birds received intraosseous fluids. Butorphanol (2 mg kg(-1)) was administered intramuscularly at two hourly intervals. Euthanasia by parenteral pentobarbitone was performed at the end of procedure. Stable anaesthesia was maintained in four chickens for durations ranging from 435 to 510 minutes. One bird died and one was euthanized after 130 and 330 minutes, respectively, owing to surgical complications and another died from anaesthetic complication after 285 minutes. Long-term, stable anaesthesia is possible in clinically healthy chickens, provided complications such as hypothermia and hypoventilation are addressed and vital signs are carefully monitored. There are no known previous reports describing monitored, controlled anaesthesia of this duration in chickens. © 2015 The Authors Veterinary Anaesthesia and Analgesia published by John Wiley & Sons Ltd on behalf of Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  17. 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)

  18. 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

  19. 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...

  20. 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)

  1. Microscopic study of rock for estimating long-term behavior

    International Nuclear Information System (INIS)

    Ichikawa, Yasuaki

    2002-03-01

    Micro-structure of rock plays a essential role for their long-term behavior. For elucidating long-term characteristics of granite we here present the followings: 1) Conforcal Laser Scanning Microscope (LSM) observation of joint surfaces of granite and Fourier analysis, 2) characterization of the mechanism of microcrack initiation and propagation observed by stereoscopic microscope under uniaxial/triaxial compression and relaxation tests, 3) observation of microcrack initiation and propagation by LSM under uniaxial compression, and 4) a viscoelastic homogenization theory to predict the long-term behavior of micro/macro-level stress for granite. Rock image processing and analysis become a fundamental procedure to determine rock surface discontinuities. But the complexity of rock surface discontinuities seems beyond the manual image processing method. In Chapter 2 a Conforcal Laser Scanning Microscope that can acquire three-dimensional images is introduced to observe the rock roughness of a discontinuity. Then, scanning three-dimensional images are changed its data form in order to adapt various image analysis programs, and granitic rock roughness of discontinuities are displayed by graphic images. For example, these datas are analyzed by Discrete Fourier Transformation (DFT) program and Inverse Discrete Fourier Transformation (IDFT) program. Microcrack generation and propagation play an essential role to predict the long-term behavior of rock. In Chapter 3 a progressive development of cracking in granite is revealed by using stereoscopic microscope under triaxial compression condition and by using LSM under uniaxial compression condition. With a viscoelastic theory applied in homogenization method, we can calculate macro behavior of medium influenced by its micro structure by analyse the long-term time-dependent behavior of granite under the same condition to the relaxation experiment. (author)

  2. 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.

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

    Science.gov (United States)

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

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

  4. 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.)

  5. 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.

  6. 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

  7. A modelling study of long term green roof retention performance.

    Science.gov (United States)

    Stovin, Virginia; Poë, Simon; Berretta, Christian

    2013-12-15

    This paper outlines the development of a conceptual hydrological flux model for the long term continuous simulation of runoff and drought risk for green roof systems. A green roof's retention capacity depends upon its physical configuration, but it is also strongly influenced by local climatic controls, including the rainfall characteristics and the restoration of retention capacity associated with evapotranspiration during dry weather periods. The model includes a function that links evapotranspiration rates to substrate moisture content, and is validated against observed runoff data. The model's application to typical extensive green roof configurations is demonstrated with reference to four UK locations characterised by contrasting climatic regimes, using 30-year rainfall time-series inputs at hourly simulation time steps. It is shown that retention performance is dependent upon local climatic conditions. Volumetric retention ranges from 0.19 (cool, wet climate) to 0.59 (warm, dry climate). Per event retention is also considered, and it is demonstrated that retention performance decreases significantly when high return period events are considered in isolation. For example, in Sheffield the median per-event retention is 1.00 (many small events), but the median retention for events exceeding a 1 in 1 yr return period threshold is only 0.10. The simulation tool also provides useful information about the likelihood of drought periods, for which irrigation may be required. A sensitivity study suggests that green roofs with reduced moisture-holding capacity and/or low evapotranspiration rates will tend to offer reduced levels of retention, whilst high moisture-holding capacity and low evapotranspiration rates offer the strongest drought resistance. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. 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.

  9. 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.

  10. Long-Term Efficacy and Safety of Cyclosporine in a Cohort of Steroid-Refractory Acute Severe Ulcerative Colitis Patients from the ENEIDA Registry (1989-2013): A Nationwide Multicenter Study.

    Science.gov (United States)

    Ordás, I; Domènech, E; Mañosa, M; García-Sánchez, V; Iglesias-Flores, E; Peñalva, M; Cañas-Ventura, A; Merino, O; Fernández-Bañares, F; Gomollón, F; Vera, M; Gutiérrez, A; Garcia-Planella, E; Chaparro, M; Aguas, M; Gento, E; Muñoz, F; Aguirresarobe, M; Muñoz, C; Fernández, L; Calvet, X; Jiménez, C E; Montoro, M A; Mir, A; De Castro, M L; García-Sepulcre, M F; Bermejo, F; Panés, J; Esteve, M

    2017-11-01

    To determine the efficacy and safety of cyclosporine (CyA) in a large national registry-based population of patients with steroid-refractory (SR) acute severe ulcerative colitis (ASUC) and to establish predictors of efficacy and adverse events. Multicenter study of SR-ASUC treated with CyA, based on data from the ENEIDA registry. SR-ASUC patients treated with infliximab (IFX) or sequential rescue therapy (CyA-IFX or IFX-CyA) were used as comparators. Of 740 SR-ASUC patients, 377 received CyA, 131 IFX and 63 sequential rescue therapy. The cumulative colectomy rate was higher in the CyA (24.1%) and sequential therapy (32.7%) than in the IFX group (14.5%; P=0.01) at 3 months and 5 years. There were no differences in early and late colectomy between CyA and IFX in patients treated after 2005. 62% of patients receiving CyA remained colectomy-free in the long term (median 71 months). There were no differences in mortality between CyA (2.4%), IFX (1.5%) and sequential therapy (0%; P=0.771). The proportion of patients with serious adverse events (SAEs) was lower in CyA (15.4%) than in IFX treated patients (26.5%) or sequential therapy (33.4%; P<0.001). This difference in favor of CyA was maintained when only patients treated after 2005 were analyzed. Treatment with CyA showed a lower rate of SAE and a similar efficacy to that of IFX thereby supporting the use of either CyA or IFX in SR-ASUC. In addition, the risk-benefit of sequential CyA-IFX for CyA non-responders is acceptable.

  11. 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)

  12. Long-term safety and effectiveness of once-daily, single-entity, extended-release hydrocodone over 76 weeks of an open-label study in patients with chronic noncancer and nonneuropathic pain.

    Science.gov (United States)

    Taber, Louise; Lynch, Shau Yu; He, Ellie; Ripa, Steven R

    2016-01-01

    To evaluate long-term use of Hysingla(®) ER (HYD), a single-entity, extended-release, once-daily hydrocodone bitartrate tablet with abuse-deterrent properties in patients with moderate-to-severe chronic noncancer and nonneuropathic pain. This open-label study consisted of a dose-titration period (up to 45 days), a 52-week maintenance period and a 24-week extension period. Opioid-naïve or opioid-experienced patients with controlled or uncontrolled chronic pain conditions were treated with HYD 20-120 mg daily. Supplemental nonopioid and short-acting opioid analgesics were permitted. This paper presents the results of 106 patients who continued HYD treatment for up to 76 weeks. Primary safety measures included the incidence of adverse events, as well as audiologic, clinical laboratory and electrocardiogram measurements. Effectiveness was measured by the change between baseline and the overall 76-week treatment period in "average pain over the last 24 h" (0 = no pain, 10 = pain as bad as you can imagine), Brief Pain Inventory-Short Form survey, Medical Outcomes Study 36-Item Short Form Health Survey, Medical Outcomes Study Sleep Scale-Revised and concomitant nonstudy opioid analgesic use. Among 410 patients who completed the maintenance period, 106 continued into the extension. Of these, 83 (78%) completed the entire 76-week treatment period. Treatment-emergent adverse events were typical of those observed with μ-opioid agonists. No study drug abuse or diversion was reported. Clinically important analgesia and functional improvement were achieved during the dose-titration period and were maintained in most patients throughout 76 weeks without the need for continued HYD dose increases or changes in concomitant nonstudy opioid analgesics. The mean pain score was 6.1 at baseline, 3.8 at the end of the dose titration period and 3.8 through 76 weeks. HYD was generally well tolerated. No unexpected safety concerns emerged. Pain control was sustained throughout 76 weeks of

  13. 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

  14. 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

  15. 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

  16. Long-term Studies of Marine Halogen Release

    Science.gov (United States)

    Tschritter, J.; Holla, R.; Frieß, U.; Platt, U.

    2009-04-01

    Institute of Enviromental Physics, Heidelberg, Germany. Long term measurements of atmospheric trace gases using multi-axis DOAS instruments are pursued at the new SOLAS observatory on the island of Sao Vicente, (Cape Verde). This research is part of the SOPRAN (Surface Ocean Processes in the ANthropocene) project (Fördernummer:03F0462F). Reactive halogen species (RHS) such as bromine- and iodine- containing species play major roles in the chemistry of ozone in both the troposphere and lower stratosphere and thus possibly influence the ozone budget on a global scale. In addition iodine-species emitted from the ocean surface have been shown to be responsible for the production of new atmospheric particles in the marine boundary layer. This may have an effect on cloud formation and radiation transfer on local and global scales. Long term measurements of RHS abundances will help to identify their key regions and processes for formation. A new long term Multi-MAX-DOAS instrument has been installed at the SOLAS observatory on the island of Sao Vicente, (Cape Verde). The main focus of these unique measurements is the investigation of reactive halogen chemistry in the subtropical marine boundary layer based on measurements of BrO, IO, and possibly OIO. Because of its wide spectral range also the use for O4-retrievals to gain aerosol profiles is possible. IO has been detected with mixing ratios up to 1.3 ppt. For BrO an upper limit of 2 ppt could be determined.

  17. 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

  18. 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)

  19. 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.

  20. 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)

  1. 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.

  2. Hydrotherapy for the long-term ventilated patient: A case study and implications for practice.

    Science.gov (United States)

    Wegner, Sally; Thomas, Peter; James, Christine

    2017-11-01

    Hydrotherapy of mechanically ventilated patients has been shown to be safe and feasible in both the acute stages of critical illness and in those requiring long term mechanical ventilation. This case study describes the hydrotherapy sessions of a 36 year old female, who after suffering complications of pneumococcal meningitis, became an incomplete quadriplegic and required long term mechanical ventilation. When implementing hydrotherapy with patients on mechanical ventilation a number of factors should be considered. These include staff resources and training, airway and ventilation management, patient preparation and safety procedures. Hydrotherapy can be safely utilised with mechanically ventilated patients, and may facilitate a patient's ability to participate in active exercise and rehabilitation. Copyright © 2017 Australian College of Critical Care Nurses Ltd. All rights reserved.

  3. 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)

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

    OpenAIRE

    Bankole K. Fasanya; Emmanuel A. Dada

    2016-01-01

    Background: 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. Methods: A structure questionnaire was used to collect data for the study. Three facilities were...

  5. Long-term Efficacy and Safety of Enzalutamide Monotherapy in Hormone-naïve Prostate Cancer

    DEFF Research Database (Denmark)

    Tombal, Bertrand; Borre, Michael; Rathenborg, Per

    2015-01-01

    BACKGROUND: Enzalutamide is an androgen receptor inhibitor with a demonstrated overall survival benefit in metastatic castration-resistant prostate cancer. A phase 2 study of enzalutamide monotherapy in patients with hormone-naïve prostate cancer (HNPC) showed a high response rate...... cancer, enzalutamide maintained long-term reductions in prostate-specific antigen, with a minimal impact on total-body bone mineral density. TRIAL REGISTRATION: NCT01302041....... for the prespecified primary endpoint (ie, prostate-specific antigen [PSA] response at week 25), regardless of metastases at baseline, and favorable tolerability. OBJECTIVE: To determine the long-term efficacy and safety of enzalutamide monotherapy at 1 and 2 yr. DESIGN, SETTING, AND PARTICIPANTS: Open-label, single...

  6. Efficacy and Safety of a Traditional Herbal Medicine, Hochu-ekki-to in the Long-Term Management of Kikyo (Delicate Constitution Patients with Atopic Dermatitis: A 6-Month, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study

    Directory of Open Access Journals (Sweden)

    Hiromi Kobayashi

    2010-01-01

    Full Text Available Hochu-ekki-to is a traditional herbal (Kampo medicine that has been shown to be effective for patients with Kikyo (delicate, easily fatigable, or hypersensitive constitution. Previous case reports have suggested that this herbal drug was effective for a certain subgroup of patients with atopic dermatitis (AD. We aimed to evaluate the efficacy and safety of Hochu-ekki-to in the long-term management of Kikyo patients with AD. In this multicenter, double blind, randomized, placebo-controlled study, 91 Kikyo patients with AD were enrolled. Kikyo condition was evaluated by a questionnaire scoring system. All patients continued their ordinary treatments (topical steroids, topical tacrolimus, emollients or oral antihistamines before and after their protocol entry. Hochu-ekki-to or placebo was orally administered twice daily for 24 weeks. The skin severity scores, total equivalent amount (TEA of topical agents used for AD treatment, prominent efficacy (cases with skin severity score = 0 at the end of the study rate and aggravated rate (more than 50% increase of TEA of topical agents from the beginning of the study were monitored and evaluated. Seventy-seven out of 91 enrolled patients completed the 24-week treatment course (Hochu-ekki-to: n = 37, placebo: n = 40. The TEA of topical agents (steroids and/or tacrolimus was significantly (P < 0.05 lower in the Hochu-ekki-to group than in the placebo group, although the overall skin severity scores were not statistically different. The prominent efficacy rate was 19% (7 of 37 in the Hochu-ekki-to group and 5% (2 of 40 in the placebo group (P = 0.06. The aggravated rate was significantly (P < 0.05 lower in the Hochu-ekki-to group (3%; 1 of 37 than in the placebo group (18%; 7 of 39. Only mild adverse events such as nausea and diarrhea were noted in both groups without statistical difference. This placebo-controlled study demonstrates that Hochu-ekki-to is a useful adjunct to conventional treatments for AD

  7. 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...

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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.

  13. Long-term study on workers occupationally exposed to ethylbenzene.

    Science.gov (United States)

    Bardodĕj, Z; Círek, A

    1988-01-01

    Ethylbenzene is synthesized from benzene; subject to catalytic dehydrogenation it yields styrene, a raw material for the production of synthetic rubber and plastics. Long-term biomonitoring of occupational ethylbenzene exposures, carried out in the past 20 years in some 200 ethylbenzene-production workers, revealed this substance to pose little hazard to human health. As it turned out, mandelic acid concentrations in these workers' urine never exceeded 3.25 mmol.l-1 and none of the exposed showed damage to hematopoiesis and/or liver tissue. Over the last 10 years no case of malignancy has been recorded in this industrial facility belonging to a larger chemical complex where the overall incidence of cancer is about 3 times the national average. Today's low-level ethylbenzene exposures would make it fully justifiable if the present-day MAC limits, both whole-shift (200 mg.m-3) and peak (1,000 mg.m-3), were to be halved, i.e. to be lowered to 100 mg.m3 and 500 mg.m3 respectively. These newly recommended limit values are no more exceeded nowadays.

  14. 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

  15. 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)

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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.)

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

    Directory of Open Access Journals (Sweden)

    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

  5. 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)

  6. Science and society: the role of long-term studies in environmental stewardship

    Science.gov (United States)

    Charles T. Driscoll; Kathleen F. Lambert; F. Stuart Chapin; David J. Nowak; Thomas A. Spies; Frederick J. Swanson; David B. Kittredge; Clarisse M. Hart

    2012-01-01

    Long-term research should play a crucial role in addressing grand challenges in environmental stewardship. We examine the efforts of five Long Term Ecological Research Network sites to enhance policy, management, and conservation decisions for forest ecosystems. In these case studies, we explore the approaches used to inform policy on atmospheric deposition, public...

  7. Long-term studies of the natural history of asthma in childhood

    DEFF Research Database (Denmark)

    Bisgaard, Hans; Bønnelykke, Klaus

    2010-01-01

    secondary prevention through the use of inhaled corticosteroids can effectively halt the long-term disease progression in childhood. In conclusion, the natural history of asthma and the associated airway changes is still poorly understood, and we have not managed to translate findings from long-term studies...

  8. Live kidney donation: are concerns about long-term safety justified?—A methodological review

    International Nuclear Information System (INIS)

    Janki, Shiromani; Steyerberg, Ewout W.; Hofman, Albert; IJzermans, Jan N. M.

    2017-01-01

    Live kidney donors are exhaustively screened pre-donation, creating a cohort inherently healthier at baseline than the general population. In recent years, three renowned research groups reported unfavourable outcomes for live kidney donors post-donation that contradicted their previous studies. Here, we compared the study design and analysis of the most recent and previous studies to determine whether the different outcomes were due to methodological design or reflect a real potential disadvantage for living kidney donors. All six studies on long-term risk after live kidney donation were thoroughly screened for the selection of study population, controls, data quality, and statistical analysis. Our detailed review of the methodology revealed key differences with respect to selection of donors and compared non-donors, data quality, follow-up duration, and statistical analysis. In all studies, the comparison group of non-donors was healthier than the donors due to more extensive exclusion criteria for non-donors. Five of the studies used both restriction and matching to address potential confounding. Different matching strategies and statistical analyses were used in the more recent studies compared to previous studies and follow-up was longer. Recently published papers still face bias. Strong points compared to initial analyses are the extended follow-up time, large sample sizes and better analysis, hence increasing the reliability to estimate potential risks for living kidney donors on the long-term. Future studies should focus on equal selection criteria for donors and non-donors, and in the analysis, follow-up duration, matched sets, and low absolute risks among donors should be accounted for when choosing the statistical technique.

  9. 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.

  10. Safety indicators adopted in the Finnish regulations for long-term safety of spent fuel disposal

    International Nuclear Information System (INIS)

    Ruokola, E.

    2002-01-01

    A regulatory guide for the safety of spent fuel disposal has recently been issued to guide the implementer's programme in the preconstruction phase. The guide is based on dose criteria in the time frame, which is reasonably predictable with respect to assessment of human exposure. For the time frame that involves major climate changes such as permafrost and glaciation, the guide defines constraints for the activity releases to the environment. This paper discusses the rationale for the selected approach and the derivation of the activity release constraints. (author)

  11. Waste Disposal: Long-term Performance Studies for Radioactive Waste Disposal and Hydrogeological Modelling

    Energy Technology Data Exchange (ETDEWEB)

    Marivoet, J

    2000-07-01

    The main objectives of SCK-CEN's R and D programme on long-term performance studies are: (1) to develop a methodology and associated tools for assessing the long-term safety of geological disposal of all types of radioactive waste in clay formations and of the shallow-land burial of low-level waste; (2) to assess the performance and to identify the most influential elements of integrated repository systems for the disposal of radioactive waste; (3) to collect geological, piezometric and hydraulic data required for studying the hydrogeological system in north-eastern Belgium; (4) to develop a regional aquifer model for north-easter Belgium and to apply it in the performance assessments for the Mol site; (5) to test, verify and improve computer codes used in the performance assessment calculations of waste disposal concepts and contaminated sites (the computer codes simulate water flow and transport of radionuclides in engineered barriers, aquifers and contaminated sites). The scientific programme and achievements in 1999 are described.

  12. Long-term decontamination engineering study. Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    Geuther, W.J.

    1995-04-03

    This report was prepared by Westinghouse Hanford Company (WHC) with technical and cost estimating support from Pacific Northwest Laboratories (PNL) and Parsons Environmental Services, Inc. (Parsons). This engineering study evaluates the requirements and alternatives for decontamination/treatment of contaminated equipment at the Hanford Site. The purpose of this study is to determine the decontamination/treatment strategy that best supports the Hanford Site environmental restoration mission. It describes the potential waste streams requiring treatment or decontamination, develops the alternatives under consideration establishes the criteria for comparison, evaluates the alternatives, and draws conclusions (i.e., the optimum strategy for decontamination). Although two primary alternatives are discussed, this study does identify other alternatives that may warrant additional study. hanford Site solid waste management program activities include storage, special processing, decontamination/treatment, and disposal facilities. This study focuses on the decontamination/treatment processes (e.g., waste decontamination, size reduction, immobilization, and packaging) that support the environmental restoration mission at the Hanford Site.

  13. Long-term decontamination engineering study. Volume 1

    International Nuclear Information System (INIS)

    Geuther, W.J.

    1995-01-01

    This report was prepared by Westinghouse Hanford Company (WHC) with technical and cost estimating support from Pacific Northwest Laboratories (PNL) and Parsons Environmental Services, Inc. (Parsons). This engineering study evaluates the requirements and alternatives for decontamination/treatment of contaminated equipment at the Hanford Site. The purpose of this study is to determine the decontamination/treatment strategy that best supports the Hanford Site environmental restoration mission. It describes the potential waste streams requiring treatment or decontamination, develops the alternatives under consideration establishes the criteria for comparison, evaluates the alternatives, and draws conclusions (i.e., the optimum strategy for decontamination). Although two primary alternatives are discussed, this study does identify other alternatives that may warrant additional study. hanford Site solid waste management program activities include storage, special processing, decontamination/treatment, and disposal facilities. This study focuses on the decontamination/treatment processes (e.g., waste decontamination, size reduction, immobilization, and packaging) that support the environmental restoration mission at the Hanford Site

  14. 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)

  15. Comparing Safety and Efficacy of "Third-Generation" Antiepileptic Drugs: Long-Term Extension and Post-marketing Treatment.

    Science.gov (United States)

    Kwok, Charlotte S; Johnson, Emily L; Krauss, Gregory L

    2017-11-01

    Four "third-generation" antiepileptic drugs (AEDs) were approved for adjunctive treatment of refractory focal onset seizures during the past 10 years. Long-term efficacy and safety of the drugs were demonstrated in large extension studies and in reports of subgroups of patients not studied in pivotal trials. Reviewing extension study and post-marketing outcome series for the four newer AEDs-lacosamide, perampanel, eslicarbazepine acetate and brivaracetam-can guide clinicians in treating and monitoring patients. AED extension studies evaluate treatment retention, drug tolerability, and drug safety during individualized treatment with flexible dosing and thus provide information not available in rigid pivotal trials. Patient retention in the studies ranged from 75 to 80% at 1 year and from 36 to 68% at 2-year treatment intervals. Safety findings were generally similar to those of pivotal trials, with no major safety risks identified and with several specific adverse drug effects, such as hyponatremia, reported. The third-generation AEDs, some through new mechanisms and others with improved tolerability compared to related AEDs, provide new options in efficacy and tolerability.

  16. Collagenase chemonucleolysis: a long term radiographic study in normal dogs

    International Nuclear Information System (INIS)

    Atilola, M.A.O.; Cockshutt, J.R.; Mclaughlin, R.; Cochrane, S.M.; Pennock, P.W.

    1993-01-01

    Five clinically normal five year old dogs were used in this study. From a randomized table intervertebral discs were each injected with either collagenase or calcium chloride diluent. The surgically exposed cervical discs were injected with 50 units whereas thoracic and lumbar discs were injected under fluoroscopic guidance with 100 units of the enzyme. Postinjection radiographs revealed significant (p ltoreq .05) disc space narrowing in enzyme injected discs. The cervical discs had the highest frequency of radiographic narrowing (87%) followed by the thoracic (70%) and lumbar (53%) discs. Spondylosis deformans developed at the sites of cervical enzyme injections. None of the dogs had neurologic abnormalities one year postinjection

  17. Long term telemedicine study of compliance in paranoid schizophrenia.

    Science.gov (United States)

    Krzystanek, Marek; Krzeszowski, Dariusz; Jagoda, Karolina; Krysta, Krzysztof

    2015-09-01

    Low compliance is one of the crucial problems of contemporary psychiatry. Relapses, deterioration of cognitive functioning, negative symptoms, neuroleptic resistance are the examples of many consequences of noncompliance in schizophrenia The study was designed to assess the compliance in the 200 patients diagnosed with paranoid schizophrenia, all in the state of symptomatic remission and on the stable neuroleptic treatment. The compliance was assessed using a telepsychiatric system, sending reminders: 1 hour before the planned dose to remind them that drug intake is approaching, and at the moment of intake to check if they took the drug. The confirmed drug intakes were counted by the telepsychiatric system. 158 patients completed the study period. The compliance in the first month of the treatment was 44.6% and decreased over the rest of the period to the level of 33.4%. 50% of the schizophrenic patients were compliant at a level lower than 37%. This group was considered the low compliance group, and in this group the compliance increased after 6 months from 9.3% to 10.3% (p<0.0001). The compliance in the group of schizophrenic patients in remission is very low. The telemedicine system improves the compliance in the patients with the worst compliance.

  18. Studi Pemanfaatan Digital Dividend Untuk Layanan Long Term Evolution (LTE

    Directory of Open Access Journals (Sweden)

    Sri Ariyanti

    2013-09-01

    Full Text Available Sesuai dengan Permen kominfo No. 22/PER/M/KOMINFO/11/2011 tentang Penyelenggaraan Penyiaran Televisi Digital Terestrial Penerimaan Tetap Tidak Berbayar (Free To Air, pada tahun 2018 semua TV analog migrasi secara penuh ke TV digital. Dengan demikian ada alokasi tersisa sebesar 2 x 45 Mhz FDD yang disebut sebagai digital dividend. Frekuensi tersebut rencananya akan digunakan untuk teknologi LTE. Namun sebelum digelar teknologi LTE pada frekuensi digital dividend tersebut maka perlu dikaji bagaimana penggunaan digital dividend untuk layanan LTE. Penelitian ini bertujuan untuk mengetahui hasil perhitungan link budget frekuensi 700 MHz untuk LTE, mengetahui perbandingan kapasitas user pada daerah tipe dense-urban, urban, sub-urban dan rural, mengetahui estimasi jumlah pelanggan LTE, mengetahui jumlah operator LTE optimum dan pembagian bandwidthnya.  Metode penelitian dengan menggunakan studi literatur. Kajian ini menggunakan teknik analisis kuantitatif deskriptif.  Hasil penelitian menunjukkan bahwa jangkauan paling besar yaitu daerah rural kemudian disusul berturut-turut daerah sub urban, dense urban dan urban. Kapasitas user per site dalam 1 Km2 dari urutan terbesar ke kecil berturut-turut yaitu daerah rural, sub urban, urban dan dense urban. Estimasi jumlah pelanggan LTE di Indonesia paling besar yaitu di daerah dense-urban yaitu mencapai 500 user/Km2 pada tahun ke 8. Jumlah operator LTE-700 MHz paling optimum sebanyak 3 operator dengan pembagian bandwidth masing-masing 15 MHz.

  19. 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

  20. Electroacupuncture for tapering off long-term benzodiazepine use: study protocol of randomized controlled trial.

    Science.gov (United States)

    Yeung, Wing-Fai; Chung, Ka-Fai; Zhang, Zhang-Jin; Chan, Wai-Chi; Zhang, Shi-Ping; Ng, Roger Man-Kin; Chan, Connie Lai-Wah; Ho, Lai-Ming; Yu, Yee-Man; Lao, Li-Xing

    2017-03-31

    Conventional approaches for benzodiazepine tapering have their limitations. Anecdotal studies have shown that acupuncture is a potential treatment for facilitating successful benzodiazepine tapering. As of today, there was no randomized controlled trial examining its efficacy and safety. The purpose of the study is to evaluate the efficacy of using electroacupuncture as an adjunct treatment to gradual tapering of benzodiazepine doses in complete benzodiazepine cessation in long-term benzodiazepine users. The study protocol of a randomized, assessor- and subject-blinded, controlled trial is presented. One hundred and forty-four patients with histories of using benzodiazepines in ≥50% of days for more than 3 months will be randomly assigned in a 1:1 ratio to receive either electroacupuncture or placebo electroacupuncture combined with gradual benzodiazepine tapering schedule. Both experimental and placebo treatments will be delivered twice per week for 4 weeks. Major assessments will be conducted at baseline, week 6 and week 16 post-randomization. Primary outcome is the cessation rate of benzodiazepine use. Secondary outcomes include the percentage change in the doses of benzodiazepine usage and the severity of withdrawal symptoms experienced based on the Benzodiazepine Withdrawal Symptom Questionnaire, insomnia as measured by the Insomnia Severity Index, and anxiety and depressive symptoms as evaluated by the Hospital Anxiety and Depression Scale. Adverse events will also be measured at each study visit. Results of this study will provide high quality evidence of the efficacy and safety of electroacupuncture as an adjunct treatment for benzodiazepine tapering in long-term users. ClinicalTrials.gov NCT02475538 .

  1. The NordiNet® International Outcome Study and NovoNet® ANSWER Program®: rationale, design, and methodology of two international pharmacoepidemiological registry-based studies monitoring long-term clinical and safety outcomes of growth hormone therapy (Norditropin®).

    Science.gov (United States)

    Höybye, Charlotte; Sävendahl, Lars; Christesen, Henrik Thybo; Lee, Peter; Pedersen, Birgitte Tønnes; Schlumpf, Michael; Germak, John; Ross, Judith

    2013-01-01

    Randomized controlled trials have shown that growth hormone (GH) therapy has effects on growth, metabolism, and body composition. GH therapy is prescribed for children with growth failure and adults with GH deficiency. Carefully conducted observational study of GH treatment affords the opportunity to assess long-term treatment outcomes and the clinical factors and variables affecting those outcomes, in patients receiving GH therapy in routine clinical practice. The NordiNet® International Outcome Study (IOS) and the American Norditropin® Web Enabled Research (ANSWER Program®) are two complementary, non-interventional, observational studies that adhere to current guidelines for pharmacoepidemiological data. The studies include pediatric and adult patients receiving Norditropin®, as prescribed by their physicians. The studies gather long-term data on the safety and effectiveness of reallife treatment with the recombinant human GH, Norditropin®. We describe the origins, aims, objectives, and design methodology of the studies, as well as their governance and validity, strengths, and limitations. The NordiNet® IOS and ANSWER Program® studies will provide valid insights into the effectiveness and safety of GH treatment across a diverse and large patient population treated in accordance with real-world clinical practice and following the Good Pharmacoepidemiological Practice and STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines.

  2. 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.

  3. 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

  4. 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)

  5. A Cohort Study on Long-Term Adverse Effects of Parental Drinking: Background and Study Design

    Directory of Open Access Journals (Sweden)

    Ingunn Olea Lund

    2015-01-01

    Full Text Available Although many studies have addressed adverse outcomes in children of parents with alcohol abuse/dependence, less is known about the possible long-term effects of more normative patterns of parental alcohol consumption, including drinking at lower risk levels and heavy episodic or binge drinking. The extent of harm from parental drinking may therefore be underestimated. With this research proposal, we describe a project that aims to assess possible long-term adverse effects of parental drinking by combining survey and nationwide registry data. Advantages of a longitudinal general population cohort design include that it allows for detailed information on parental drinking through survey data and identification of possible negative long-term health and social outcomes from exposure to parental drinking 1–19 years after exposure through continuously updated nationwide registers. The rich information available from combining survey and registry data allows us to take into account important confounders, mediators, and moderators.

  6. Long-Term Studies of Prescribed Burning in Loblolly Pine Forests of the Southeastern Coastal Plain

    Science.gov (United States)

    Thomas A. Waldrop; David H. van Lear; F. Thomas Lloyd; William R. Harms

    1987-01-01

    Prescribed fire provides many benefits in southern pine A study begun in 1946 provides a unique opportunity stands. to observe long-term changes in understory vegetation, soil properties, and overstory tree growth caused by repeated burning.

  7. 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...

  8. A study on shear behavior of R/C beams subjected to long-term heating

    International Nuclear Information System (INIS)

    Maruta, M.; Yamazaki, M.

    1993-01-01

    In nuclear power plants, many structural members are subjected to long term heating. There are few experimental data available on the behavior especially in shear of reinforced concrete (R/C) members subjected to long term heating. This paper describes a study aimed at experimentally determining the shear behavior of R/C members in nuclear power plant facilities following sustained heating at high temperatures

  9. 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.

  10. Acute and long-term survival in chronically critically ill surgical patients: a retrospective observational study.

    Science.gov (United States)

    Hartl, Wolfgang H; Wolf, Hilde; Schneider, Christian P; Küchenhoff, Helmut; Jauch, Karl-Walter

    2007-01-01

    Various cohort studies have shown that acute (short-term) mortality rates in unselected critically ill patients may have improved during the past 15 years. Whether these benefits also affect acute and long-term prognosis in chronically critically ill patients is unclear, as are determinants relevant to prognosis. We conducted a retrospective analysis of data collected from March 1993 to February 2005. A cohort of 390 consecutive surgical patients requiring intensive care therapy for more than 28 days was analyzed. The intensive care unit (ICU) survival rate was 53.6%. Survival rates at one, three and five years were 61.8%, 44.7% and 37.0% among ICU survivors. After adjustment for relevant covariates, acute and long-term survival rates did not differ significantly between 1993 to 1999 and 1999 to 2005 intervals. Acute prognosis was determined by disease severity during ICU stay and by primary diagnosis. However, only the latter was independently associated with long-term prognosis. Advanced age was an independent prognostic determinant of poor short-term and long-term survival. Acute and long-term prognosis in chronically critically ill surgical patients has remained unchanged throughout the past 12 years. After successful surgical intervention and intensive care, long-term outcome is reasonably good and is mainly determined by age and underlying disease.

  11. 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)

  12. Long-term efficacy and safety of prophylaxis with recombinant factor VIII in Chinese pediatric patients with hemophilia A: a multi-center, retrospective, non-interventional, phase IV (ReCARE) study.

    Science.gov (United States)

    Li, Changgang; Zhang, Xinsheng; Zhao, Yongqiang; Wu, Runhui; Hu, Qun; Xu, Weiqun; Sun, Jing; Yang, Renchi; Li, Xiaojing; Zhou, Rongfu; Lian, Shinmei; Gu, Jian; Wu, Junde; Hou, Qingsong

    2017-07-01

    The first recombinant factor VIII (rFVIII) product was launched in China in 2007. However, until now, no study has been conducted to describe the efficacy and safety of prophylaxis with rFVIII in Chinese pediatric patients with hemophilia A (HA). To summarize the efficacy and safety data on prophylaxis with rFVIII in Chinese pediatric patients with HA. ReCARE (Retrospective study in Chinese pediatric hemophilia A patients with rFVIII contained regular prophylaxis) was a retrospective study conducted in 12 hemophilia treatment centers (HTCs) across China. The primary endpoints included reduction in annualized bleeding rate (ABR); the secondary endpoints included evaluation of joint function (number and sites of target joints) using Gilbert score and Hemophilia Joint Health Score (HJHS), quality of life (QoL) and factors affecting treatment choices. Safety assessment of rFVIII was also conducted. We analyzed a total of 183 male pediatric patients (mean age, 7.1 ± 4.23 years) who received prophylaxis between 1 November 2007 and 31 May 2013. Compared with baseline, prophylaxis with rFVIII significantly reduced overall annualized joint bleed rate (AJBR) (p < .001) and ABR (p < .001). Inhibitor formation was reported in 5 (2.7%) patients and hemarthrosis was reported in 1 patient. The mean number of target joints was positively related to age (p < .001) and weight (p = .003) at baseline. Responses from survey questionnaires reported that effective bleeding control, joint protection, improvement in quality of life, favorable medical insurance policies, and economic capability were reasons for choosing prophylaxis. Prophylaxis with rFVIII reduced bleeding and number of target joints, even with a low-dose regimen, in Chinese pediatric patients with HA. Other than the efficacy and safety, factors such as poor disease control, improved economic stability and stable financial support made prophylaxis as an attractive treatment option. ClinicalTrials.gov ID

  13. Long-term Safety of Pregnancy Following Breast Cancer According to Estrogen Receptor Status

    DEFF Research Database (Denmark)

    Lambertini, Matteo; Kroman, Niels; Ameye, Lieveke

    2018-01-01

    Safety of pregnancy in women with history of estrogen receptor (ER)-positive breast cancer remains controversial. In this multicenter case-control study, 333 patients with pregnancy after breast cancer were matched (1:3) to 874 nonpregnant patients of similar characteristics, adjusting for guaran......Safety of pregnancy in women with history of estrogen receptor (ER)-positive breast cancer remains controversial. In this multicenter case-control study, 333 patients with pregnancy after breast cancer were matched (1:3) to 874 nonpregnant patients of similar characteristics, adjusting...

  14. Long-term safety and efficacy of fractionated stereotactic body radiation therapy for spinal metastases

    Energy Technology Data Exchange (ETDEWEB)

    Mantel, Frederick; Glatz, Stefan; Toussaint, Andre; Flentje, Michael; Guckenberger, Matthias [University Hospital Wuerzburg, Department of Radiation Oncology, Wuerzburg (Germany)

    2014-12-15

    Patients with long life expectancy despite metastatic status might benefit from long-term local control of spinal metastases. Dose-intensified radiotherapy (RT) is believed to control tumor growth better and thus offers longer pain relief. This single-institution study reports on fractionated stereotactic body radiation therapy (SBRT) for spinal metastases in patients with good life expectancy based on performance status, extent of metastases, histology, and time to metastasis. Between 2004 and 2010, 36 treatment sites in 32 patients (median age 55 years; male 61 %; median Karnofsky performance score 85) were treated with fractionated SBRT. The median treatment dose was 60 Gy (range, 48.5-65 Gy) given in a median of 20 fractions (range, 17-33); the median maximum dose to the planning risk volume for the spinal cord (PRV-SC) was 46.6 Gy. All patients suffering from pain prior to RT reported pain relief after treatment; after a median follow-up of 20.3 months, 61 % of treatment sites were pain-free, another 25 % associated with mild pain. In 86 % of treatments, patients were free from neurological symptoms at the time of the last clinical follow-up. Acute grade 1 toxicities (CTCAE 3.0) were observed in 11 patients. Myelopathy did not occur in any patient. Radiologically controlled freedom from local progression was 92 and 84 % after 12 and 24 months, respectively. Median overall survival (OS) was 19.6 months. Patient selection resulted in long OS despite metastatic disease, and dose-intensified fractionated SBRT for spinal metastases was safe and achieved long-term local tumor control and palliation of pain. (orig.) [German] Patienten mit guter Lebenserwartung trotz metastasierter Erkrankung koennten von einer lang andauernden lokalen Kontrolle von Wirbelsaeulenmetastasen profitieren. Eine dosisintensivierte Radiotherapie (RT) kann vermutlich eine bessere Tumorkontrolle und daher eine laengere Schmerzpalliation erreichen. Ausgewertet wurden die monozentrischen

  15. Pitavastatin demonstrates long-term efficacy, safety and tolerability in elderly patients with primary hypercholesterolaemia or combined (mixed) dyslipidaemia

    DEFF Research Database (Denmark)

    Stender, Steen; Budinski, Dragos; Hounslow, Neil

    2013-01-01

    Aims: To assess the long-term efficacy, safety and tolerability of pitavastatin (2 and 4 mg) in elderly patients (≥65 years of age) with primary hypercholesterolaemia or combined (mixed) dyslipidaemia.Design: Patients (n = 545) who had completed a 12-week double-blind comparative study (core study...... Cholesterol Education Program Adult Treatment Plan III (NCEP ATP III) targets for low-density lipoprotein cholesterol (LDL-C) was determined.Results: Of the patients enrolled, 539 received at least one dose of pitavastatin (safety population: men, 45.5%; Caucasian, 99.1%; mean age, 70.3 years; range, 65......-89 years). Only 17% of patients required up-titration to pitavastatin 4 mg. After 60 weeks, NCEP ATP III and EAS targets were attained by 93.8% and 89.0% of patients, respectively. Plasma LDL-C declined by 43.4% and high-density lipoprotein cholesterol increased by 9.6% versus core-study baseline values...

  16. 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)

  17. Long-term sickness absence from work due to physical inactivity: A registry-based study.

    Science.gov (United States)

    Høgsbro, Cecilie; Davidsen, Michael; Sørensen, Jan

    2018-01-01

    The aim of this study was to explore the relationship between leisure-time physical inactivity and long-term sickness absence in a representative sample of individuals aged 16-54 years, within the labour market and in good health. It was hypothesised that physically inactive individuals have a higher risk of long-term sickness absence and longer duration of sickness absence. The study population was identified from the National Health and Morbidity Survey, 2010. Weekly data on long-term sickness absence were obtained from the National Register on Social Transfer Payments (the DREAM registry). The association of incidence and duration of long-term sickness absence with physical inactivity was explored using logistic and Poisson regression. Data were fitted to models with levels of physical activity, demographic, social and lifestyle characteristics as independent variables. A combined hurdle model was used to estimate the difference in mean number of absence weeks. Logistic regression showed that physically inactive individuals had a 27% higher incidence of long-term sickness absence compared with physically active individuals. The Poisson regression showed that long-term sickness absence was only slightly shorter (1 week less) for moderately active individuals compared with inactive individuals. The hurdle model estimated longer absence periods for inactive individuals (additional 2.5 weeks) in comparison with moderately and highly active individuals. The study showed that physically inactive individuals have a higher incidence of long-term absence and that physically inactive individuals have longer periods with sickness absence than moderately and highly active individuals. When adjustments for social and health behaviour were included, the estimated associations became statistically insignificant.

  18. 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)

  19. Geosphere Stability for long-term isolation of radioactive waste. Case study for hydrological change with earthquakes and faulting

    International Nuclear Information System (INIS)

    Niwa, Masakazu

    2016-01-01

    Appropriate estimation and safety assessment for long-term changes in geological environment are essential to an improvement of reliability for geological disposal. Specifically, study on faults is important for understanding regional groundwater flow as well as an assessment as a trigger of future earthquakes. Here, possibility of changes in permeability of faulted materials induced by earthquakes was examined based on monitoring data of groundwater pressure before and after the 2011 off the Pacific coast of Tohoku Earthquake. (author)

  20. 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

  1. A study of the long-term effect of malar fat repositioning in face lift surgery: short-term success but long-term failure.

    Science.gov (United States)

    Hamra, Sam T

    2002-09-01

    In 1990, the author reported on a series of 403 cases of deep plane face lifts, the first published technique describing the repositioning of the cheek fat, known as malar fat, in face lift surgery. This study examines the long-term results of 20 of the original series in an attempt to determine what areas of the rejuvenated face (specifically, the malar fat) showed long-term improvement. The results were judged by comparing the preoperative and long-term postoperative views in a half-and-half same-side hemiface photograph. The anatomy of the jawline (superficial musculoaponeurotic system [SMAS]), the nasolabial fold (malar fat), and the periorbital diameter were evaluated. The results confirmed that repositioning of the SMAS remained for longer than improvement in the nasolabial fold and that the vertical diameter of the periorbit did not change at all. The early results of malar fat repositioning shown at 1 to 2 years were successful, but the long-term results showed failure of the early improvement, manifested by recurrence of the nasolabial folds. There was, however, continuation of the improved results of the forehead lift and SMAS maneuvers of the original procedure. The conclusion is that only a direct excision will produce a permanent correction of the aging nasolabial fold.

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

    Science.gov (United States)

    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.

  3. Preservation of RK and M for Long Term Storage Facilities: The Results of a French Study

    International Nuclear Information System (INIS)

    Schneider, Thierry

    2012-01-01

    Due to the specific long lasting radioactivity of high level waste types, new issues may arise for radiation protection. In this perspective, technical, societal and organizational aspects have to be considered. For the two latter aspects, it is interesting to analyse the efficiency of protection systems available in other fields than nuclear waste management, in order either to protect society from specific risk or to preserve world heritage. Few years ago, CEPN together with MUTADIS have performed a specific study, commissioned by CEA (Commissariat a l'Energie Atomique). The presentation briefly presented the case studies performed on long term protection, as well as the key lessons related to the continuity and sustainability of the surveillance and control of radioactive waste facilities, and the effectiveness of financing schemes for the long term management of radioactive waste. This study has identified a set of performance criteria to deal with long term protection. These results were notably discussed within the framework of the European project COWAM 2 in a working group involving experts, authorities, waste managers, locally elected representatives and NGOs. One part of the study was to analyse the characteristics of protection systems used to manage risks associated with the presence of past underground cavities and mines. A case study presented was the following: After the closing of last mines, maintenance also ended, which, years later, caused ground collapses which led to discussions on responsibility. The connection between the safety problems and the loss of economic activities was underlined. In this context, the IGC (Inspection Generale des Carrieres) was set up. An important part of its functioning is the interaction with the building owners of Paris. The arrangement is that the current owners pay for assuring safety, even though the cause of the safety issue goes back long before owners bought the premises. It was pointed out that market value

  4. Long-Term Engagement in Formal Volunteering and Well-Being: An Exploratory Indian Study.

    Science.gov (United States)

    Elias, Jereesh K; Sudhir, Paulomi; Mehrotra, Seema

    2016-09-27

    Sustained engagement in volunteering and its correlates have been examined in many studies across the globe. However, there is a dearth of research that explores the perspectives of long-term formal volunteers on the nature of changes perceived in oneself as a result of volunteering. Moreover, the linkages between psychological well-being and volunteering have been insufficiently explored. The present study was aimed at addressing these gaps. A heterogeneous sample of 20 long-term formal volunteer engaged in volunteering across different voluntary organisations in a southern metropolitan Indian city formed the primary sample for the study. In addition, a group of 21 short-term volunteers, matched on age, income and gender, was utilised for comparison with long-term volunteers on well-being indices. A semi structured interview schedule was used to explore self-perceived changes attributable to volunteering experience. In addition, a few standardised measures were used to comprehensively assess subjective well-being and psychological well-being. The interview data provided rich descriptions of perceived positive changes in self across cognitive, behavioral and emotional domains. Mirroring these patterns, the quantitative analyses indicated that long-term volunteers experienced higher levels of psychological well-being (sense of mastery and competence, self-acceptance and sense of engagement and growth) than short-term volunteers. The potential mechanisms involved in beneficial outcomes of long-term volunteering and implications for further research are highlighted.

  5. Gauging the Purported Costs of Public Data Archiving for Long-Term Population Studies.

    Science.gov (United States)

    Evans, Simon Robin

    2016-04-01

    It was recently proposed that long-term population studies be exempted from the expectation that authors publicly archive the primary data underlying published articles. Such studies are valuable to many areas of ecological and evolutionary biological research, and multiple risks to their viability were anticipated as a result of public data archiving (PDA), ultimately all stemming from independent reuse of archived data. However, empirical assessment was missing, making it difficult to determine whether such fears are realistic. I addressed this by surveying data packages from long-term population studies archived in the Dryad Digital Repository. I found no evidence that PDA results in reuse of data by independent parties, suggesting the purported costs of PDA for long-term population studies have been overstated.

  6. 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.

  7. Comparable long-term efficacy, as assessed by patient-reported outcomes, safety and pharmacokinetics, of CT-P13 and reference infliximab in patients with ankylosing spondylitis: 54-week results from the randomized, parallel-group PLANETAS study.

    Science.gov (United States)

    Park, Won; Yoo, Dae Hyun; Jaworski, Janusz; Brzezicki, Jan; Gnylorybov, Andriy; Kadinov, Vladimir; Sariego, Irmgadt Goecke; Abud-Mendoza, Carlos; Escalante, William Jose Otero; Kang, Seong Wook; Andersone, Daina; Blanco, Francisco; Hong, Seung Suh; Lee, Sun Hee; Braun, Jürgen

    2016-01-20

    CT-P13 (Remsima®, Inflectra®) is a biosimilar of the infliximab reference product (RP; Remicade®) and is approved in Europe and elsewhere, mostly for the same indications as RP. The aim of this study was to compare the 54-week efficacy, immunogenicity, pharmacokinetics (PK) and safety of CT-P13 with RP in patients with ankylosing spondylitis (AS), with a focus on patient-reported outcomes (PROs). This was a multinational, double-blind, parallel-group study in patients with active AS. Participants were randomized (1:1) to receive CT-P13 (5 mg/kg) or RP (5 mg/kg) at weeks 0, 2, 6 and then every 8 weeks up to week 54. To assess responses, standardized assessment tools were used with an intention-to-treat analysis of observed data. Anti-drug antibodies (ADAs), PK parameters, and safety outcomes were also assessed. Of 250 randomized patients (n = 125 per group), 210 (84.0 %) completed 54 weeks of treatment, with similar completion rates between groups. At week 54, Assessment of Spondylo Arthritis international Society (ASAS)20 response, ASAS40 response and ASAS partial remission were comparable between treatment groups. Changes from baseline in PROs such as mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; CT-P13 -3.1 versus RP -2.8), Bath Ankylosing Spondylitis Functional Index (BASFI; -2.9 versus -2.7), and Short Form Health Survey (SF-36) scores (9.26 versus 10.13 for physical component summary; 7.30 versus 6.54 for mental component summary) were similar between treatment groups. At 54 weeks, 19.5 % and 23.0 % of patients receiving CT-P13 and RP, respectively, had ADAs. All observed PK parameters of CT-P13 and RP, including maximum and minimum serum concentrations, were similar through 54 weeks. The influence of ADAs on PK was similar in the two treatment groups. Most adverse events were mild or moderate in severity. There was no notable difference between treatment groups in the incidence of adverse events, serious adverse events

  8. Long-term increased risk of unemployment after young stroke: A long-term follow-up study

    NARCIS (Netherlands)

    Maaijwee, N.A.M.M.; Rutten-Jacobs, L.C.A.; Arntz, R.M.; Schaapsmeerders, P.; Schoonderwaldt, H.C.; Dijk, E.J. van; Leeuw, F.E. de

    2014-01-01

    OBJECTIVE: To investigate the prevalence, excess risk, and risk factors of unemployment in patients after a TIA, ischemic stroke, or intracerebral hemorrhage at ages 18 through 50 years, compared with nationwide controls. METHODS: We performed a hospital-based cohort study among 694 patients, aged

  9. 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

  10. Long-term particulate matter exposure and mortality: a review of European epidemiological studies

    Directory of Open Access Journals (Sweden)

    Boffetta Paolo

    2009-12-01

    Full Text Available Abstract Background Several studies considered the relation between long-term exposure to particulate matter (PM and total mortality, as well as mortality from cardiovascular and respiratory diseases. Our aim was to provide a comprehensive review of European epidemiological studies on the issue. Methods We searched the Medline database for epidemiological studies on air pollution and health outcomes published between January 2002 and December 2007. We also examined the reference lists of individual papers and reviews. Two independent reviewers classified the studies according to type of air pollutant, duration of exposure and health outcome considered. Among European investigations that examined long-term PM exposure we found 4 cohort studies (considering total and cardiopulmonary mortality, 1 case-control study (considering mortality from myocardial infarction, and 4 ecologic studies (2 studies considering total and cardiopulmonary mortality and 2 studies focused on cardiovascular mortality. Results Measurement indicators of PM exposure used in European studies, including PM10, PM2.5, total suspended particulate and black smoke, were heterogeneous. This notwithstanding, in all analytic studies total mortality was directly associated with long-term exposure to PM. The excesses in mortality were mainly due to cardiovascular and respiratory causes. Three out of 4 ecologic studies found significant direct associations between PM indexes and mortality. Conclusion European studies on long-term exposure to PM indicate a direct association with mortality, particularly from cardiovascular and respiratory diseases.

  11. The long-term use of cyproterone acetate in pedophilia: a case study.

    Science.gov (United States)

    Cooper, A J; Cernovsky, Z; Magnus, R V

    1992-01-01

    This investigation reports the long-term use of the antiandrogen cyproterone acetate (CPA) in a pedophile, who was studied continuously over 38 months. Measures of sexual arousal, serum testosterone, and gonadotropin levels were significantly reduced by the drug as compared with placebo and no treatment; prolactin levels were significantly elevated. Some workers have observed that long-term administration of CPA (more than one year, which was then discontinued) produced enduring (in some cases apparently permanent) anti-libidinal effects; however, in the case described, within three weeks of stopping the drug, all measures had returned to pretrial levels. The importance of continuous long-term monitoring in sex offenders receiving an antiandrogen is discussed.

  12. Validation of traffic-related air pollution exposure estimates for long-term studies

    NARCIS (Netherlands)

    Van Roosbroeck, S.

    2007-01-01

    This thesis describes a series of studies that investigate the validity of using outdoor concentrations and/or traffic-related indicator exposure variables as a measure for exposure assessment in epidemiological studies on the long-term effect of traffic-related air pollution. A pilot study was

  13. An Instrument for Every Child: A Study on Long-Term Effects of Extended Music Education in German Primary Schools

    Science.gov (United States)

    Krupp-Schleußner, Valerie; Lehmann-Wermser, Andreas

    2018-01-01

    Does extended music education during primary school foster long-term musical participation? What other factors contribute to long-term musical participation? In our study on "Impacts and Long-Term Effects of Musical Participation," we investigate how the German programme "An Instrument for Every Child (JeKi)," which fosters the…

  14. Stroke and Long-Term Exposure to Outdoor Air Pollution From Nitrogen Dioxide A Cohort Study

    DEFF Research Database (Denmark)

    Andersen, Zorana Jovanovic; Kristiansen, Luise Cederkvist; Andersen, Klaus K.

    2012-01-01

    Background and Purpose-Years of exposure to tobacco smoke substantially increase the risk for stroke. Whether long-term exposure to outdoor air pollution can lead to stroke is not yet established. We examined the association between long-term exposure to traffic-related air pollution and incident...... and fatal stroke in a prospective cohort study.Methods-We followed 57 053 participants of the Danish Diet, Cancer and Health cohort in the Hospital Discharge Register for the first-ever hospital admission for stroke (incident stroke) between baseline (1993-1997) and 2006 and defined fatal strokes as death...

  15. Climate change and population dynamics at the tree line: the importance of long-term studies

    Directory of Open Access Journals (Sweden)

    Anfodillo T

    2007-01-01

    Full Text Available Temperature-limited ecosystems are believed to be extremely sensitive to global warming and the upward treeline migration is one of the most relevant phenomenon. Long term monitoring of demographic trends appears essential in order to understand possible effects of higher temperatures on cold ecosystems. Long-term monitoring of natality and mortality of a Pinus sylvestris population in the Swedish Scandes from 1973 to 2005 (Kullman 2007 showed that number of trees increased in the study plots due to higher natality rate, especially in the last decade. This reverses a natural trend of treeline decline and recession occurred in the past.

  16. Model-based studies into ground water movement, with water density depending on salt content. Case studies and model validation with respect to the long-term safety of radwaste repositories. Final report

    International Nuclear Information System (INIS)

    Schelkes, K.

    1995-12-01

    Near-to-reality studies into ground water movement in the environment of planned radwaste repositories have to take into account that the flow conditions are influenced by the water density which in turn depends on the salt content. Based on results from earlier studies, computer programs were established that allow computation and modelling of ground water movement in salt water/fresh water systems, and the programs were tested and improved according to progress of the studies performed under the INTRAVAL international project. The computed models of ground water movement in the region of the Gorlebener Rinne showed for strongly simplified model profiles that the developing salinity distribution varies very sensitively in response to the applied model geometry, initial input data for salinity distribution, time frame of the model, and size of the transversal dispersion length. The WIPP 2 INTRAVAL experiment likewise studied a large-area ground water movement system influenced by salt water. Based on the concept of a hydraulically closed, regional ground water system (basin model), a sectional profile was worked out covering all relevant layers of the cap rock above the salt formation planned to serve as a repository. The model data derived to describe the salt water/fresh water movements in this profile resulted in essential enlargements and modifications of the ROCKFLOW computer program applied, (relating to input data for dispersion modelling, particle-tracker, computer graphics interface), and yielded important information for the modelling of such systems (relating to initial pressure data at the upper margin, network enhancement for important concentration boundary conditions, or treatment of permeability contrasts). (orig.) [de

  17. 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.

  18. State-dependent life-history strategies : A long-term study on oystercatchers

    NARCIS (Netherlands)

    van de Pol, Martijn

    2006-01-01

    The research described in this thesis is part of a long-term field study on free-living Oystercatchers (Haematopus ostralegus), on the Dutch Wadden Sea island of Schiermonnikoog.The study was started in 1983 by Jan Hulscher, and since then a lineage of PhDstudents has investigated life-history

  19. A Long-Term Outcome Study of Selective Mutism in Childhood

    Science.gov (United States)

    Steinhausen, Hans-Christoph; Wachter, Miriam; Laimbock, Karin; Metzke, Christa Winkler

    2006-01-01

    Objective: Controlled study of the long-term outcome of selective mutism (SM) in childhood. Method: A sample of 33 young adults with SM in childhood and two age- and gender-matched comparison groups were studied. The latter comprised 26 young adults with anxiety disorders in childhood (ANX) and 30 young adults with no psychiatric disorders during…

  20. 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)

  1. 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)

  2. Locomotor training using an overground robotic exoskeleton in long-term manual wheelchair users with a chronic spinal cord injury living in the community: Lessons learned from a feasibility study in terms of recruitment, attendance, learnability, performance and safety.

    Science.gov (United States)

    Gagnon, Dany H; Escalona, Manuel J; Vermette, Martin; Carvalho, Lívia P; Karelis, Antony D; Duclos, Cyril; Aubertin-Leheudre, Mylène

    2018-03-01

    For individuals who sustain a complete motor spinal cord injury (SCI) and rely on a wheelchair as their primary mode of locomotion, overground robotic exoskeletons represent a promising solution to stand and walk again. Although overground robotic exoskeletons have gained tremendous attention over the past decade and are now being transferred from laboratories to clinical settings, their effects remain unclear given the paucity of scientific evidence and the absence of large-scale clinical trials. This study aims to examine the feasibility of a locomotor training program with an overground robotic exoskeleton in terms of recruitment, attendance, and drop-out rates as well as walking performance, learnability, and safety. Individuals with a SCI were invited to participate in a 6 to 8-week locomotor training program with a robotic exoskeleton encompassing 18 sessions. Selected participants underwent a comprehensive screening process and completed two familiarization sessions with the robotic exoskeleton. The outcome measures were the rate of recruitment of potential participants, the rate of attendance at training sessions, the rate of drop-outs, the ability to walk with the exoskeleton, and its progression over the program as well as the adverse events. Out of 49 individuals who expressed their interest in participating in the study, only 14 initiated the program (recruitment rate = 28.6%). Of these, 13 individuals completed the program (drop-out rate = 7.1%) and attended 17.6 ± 1.1 sessions (attendance rate = 97.9%). Their greatest standing time, walking time, and number of steps taken during a session were 64.5 ± 10.2 min, 47.2 ± 11.3 min, and 1843 ± 577 steps, respectively. During the training program, these last three parameters increased by 45.3%, 102.1%, and 248.7%, respectively. At the end of the program, when walking with the exoskeleton, most participants required one therapist (85.7%), needed stand-by or contact

  3. Long-term functional sequelae of sacrococcygeal teratoma : a national study in the Netherlands

    NARCIS (Netherlands)

    Derikx, Joep P. M.; De Backer, Antoine; van de Schoot, Leon; Aronson, Daniel C.; de Langen, Zacharias J.; van den Hoonaard, Thelma L.; Bax, Nicolaas M. A.; van der Staak, Frans; van Heurn, L. W. Ernest

    Background: Long-term functional sequelac after resection of sacrococcygeal teratoma (SCT) are relatively common. This study determines the incidence of these sequelae associated clinical variables and its impact on quality of life (QoL). Patients and methods: Patients with SCT treated from 1980 to

  4. Studying screen interactions long-term : the library as a case

    NARCIS (Netherlands)

    Kanis, Marije; Groen, Maarten; Meys, W.T.; Veenstra, Mettina

    2012-01-01

    This paper presents the design and long-term study of BiebBeep, a large interactive touchscreen that has been developed with the aim to augment the information and social function of a library. BiebBeep displays user-generated and context-relevant content, such as information about local events and

  5. Comparative study of different stochastic weather generators for long-term climate data simulation

    Science.gov (United States)

    Climate is one of the single most important factors affecting watershed ecosystems and water resources. The effect of climate variability and change has been studied extensively in some places; in many places, however, assessments are hampered by limited availability of long term continuous climate ...

  6. LONG TERM STABILITY STUDY AT FNAL AND SLAC USING BINP DEVELOPED HYDROSTATIC LEVEL SYSTEM

    Energy Technology Data Exchange (ETDEWEB)

    Seryi, Andrei

    2003-05-28

    Long term ground stability is essential for achieving the performance goals of the Next Linear Collider. To characterize ground motion on relevant time scales, measurements have been performed at three geologically different locations using a hydrostatic level system developed specifically for these studies. Comparative results from the different sites are presented in this paper.

  7. Orbital irradiation for Graves' ophthalmopathy - Is it safe? A long-term follow-up study

    NARCIS (Netherlands)

    Wakelkamp, Iris M. M. J.; Tan, Hendra; Saeed, Peerooz; Schlingemann, Reinier O.; Verbraak, Frank D.; Blank, Leo E. C. M.; Prummel, Mark F.; Wiersinga, Wilmar M.

    2004-01-01

    Purpose: We evaluated the frequency of long-term complications of orbital irradiation (radiation-induced tumors, cataract, and retinopathy) in comparison with glucocorticoids. Design: We conducted a follow-up study in a cohort of 245 Graves' ophthalmopathy patients who had been treated with

  8. Toward the Long-Term Scientific Study of Encounter Group Phenomena: I. Methodological Considerations.

    Science.gov (United States)

    Diamond, Michael Jay; Shapiro, Jerrold Lee

    This paper proposes a model for the long-term scientific study of encounter, T-, and sensitivity groups. The authors see the need for overcoming major methodological and design inadequacies of such research. They discuss major methodological flaws in group outcome research as including: (1) lack of adequate base rate or pretraining measures; (2)…

  9. Long-term postoperative cognitive dysfunction in the elderly: ISPOCD1 study

    NARCIS (Netherlands)

    Moller, J.T.; Cluitmans, P.J.M.; Rasmussen, L.S.; Houx, P.J.; Rasmussen, H.; Canet, J.; Rabbitt, P.; Jolles, J.; Larsen, K.; Hanning, C.D.; Langeron, O.; Johnson, T.; Lauven, P.M.; Kristensen, P.A.; Biedler, A.; Beem, van H.; Fraidakis, O.; Silverstein, J.H.; Beneken, J.E.W.; Gravenstein, J.S.

    1998-01-01

    Summary Background Long-term postoperative cognitive dysfunction may occur in the elderly. Age may be a risk factor and hypoxaemia and arterial hypotension causative factors. We investigated these hypotheses in an international multicentre study. Methods 1218 patients aged at least 60 years

  10. Long-term follow-up for efficacy and safety of treatment of retinitis pigmentosa with valproic acid.

    Science.gov (United States)

    Bhalla, Sheena; Joshi, Deval; Bhullar, Shaminder; Kasuga, Daniel; Park, Yeonhee; Kay, Christine N

    2013-07-01

    The purpose of this study was to determine the long-term efficacy and safety of valproic acid (VPA) treatment in patients with pigmentary retinal dystrophies. A retrospective chart review was conducted on 31 patients with a diagnosis of pigmentary retinal dystrophy prescribed VPA at a single centre. Visual field (VF), visual acuity (VA), length of treatment, liver enzymes and side effects were analysed. VF areas were defined using Goldmann VF (GVF) tracings recorded before, during and after VPA treatment using the V4e isopter for each eye. Using custom software, planimetric areas of VF were calculated. Five of the patients (10 eyes) had two Goldmann VF tracings, allowing comparison between baseline and follow-up VF. After 9.8 months of VPA, VF decreased by 0.145 cm(2) (26.478%) (p=0.432). For 22 of the patients (41 eyes), VA data was available, and logarithm of the minimum angle of resolution (logMAR) score changed by 0.056 log units (representing a decline in VA) after 14.9 months on VPA (p=0.002). Twelve patients (38.7%) reported negative side effects related to VPA use. VPA plays a complex role in patients with pigmentary retinal dystrophies and may be associated with VA and field decline as well as adverse side effects. Physicians should use caution with using VPA for pigmentary retinal dystrophies.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. Confidence in the long-term safety of deep geological repositories. Its development and communication

    International Nuclear Information System (INIS)

    1999-01-01

    The technical aspects of confidence have been the subject of considerable debate, especially the concept of model validation. The safety case that is provided at a particular stage in the planning, construction, operation or closure of a deep geological repository is a part of a broader decision basis that guides the repository-development process. The basic steps for deriving the safety case at various stages of repository development involve: a safety assessment; and the documentation of the safety assessment, a statement of confidence in the safety indicated by the assessment, and the confirmation of the appropriateness of the safety strategy. The approaches to establish confidence in the evaluation of safety should aim to ensure that the decisions taken within the incremental process of repository development are well-founded. Various aspects of confidence in the evaluation of safety, and their integration within a safety case, are presented in detail in the present report. When communicating confidence in the findings of a safety assessment, clarity in the communication of concepts is always required. Consistent with this requirement, key concepts are specifically defined in the main text of the report. (R.P.)

  16. Relating long-term studies to conservation practice: the case of the Serengeti Cheetah Project.

    Science.gov (United States)

    Durant, Sarah M; Bashir, Sultana; Maddox, Thomas; Laurenson, M Karen

    2007-06-01

    Although detailed, long-term scientific studies provide potentially crucial information for conservation, they are rare. Moreover, there is often a disjunction between scientists and managers that can affect whether scientific results are applied to help solve conservation problems. Long-term studies can promote increased communication between scientists and managers and hence offer an opportunity for constructive engagement between the two groups. We examined direct and indirect impacts of a 30-year study, the Serengeti Cheetah Project (SCP). Much of what is currently known about wild cheetahs comes from the SCP. In particular, the SCP has demonstrated that cheetahs have a combination of semisociality and ranging patterns that is unique among mammals. This system arises because cheetahs need to be mobile to avoid predators and competitors, yet maintain access to prey; this results in densities much lower than for other large carnivores and a requirement for large areas of heterogenous and connected habitat. The SCP started as a research project, but expanded into a national program, developing capacity for carnivore conservation within Tanzania. Long-term studies such as the SCP are uniquely placed to establish effective working relationships between scientists and managers, engage local and national institutions, and strengthen national capacity for biodiversity conservation. This process is best realized through the establishment of frameworks for conservation that seek to align scientific research with management needs. Long-term studies also play an important role in identifying international priorities for conservation. Nonetheless, the integration of science and management in conservation is a two-way process that requires concerted efforts by both sides to improve and maintain dialogue. Ultimately, conservation depends on people, and maintaining a commitment to a particular area over many years-such as through implementation of a long-term research project

  17. 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.

  18. Long term safety and tolerability of Tafluprost 0.0015% vs Timolol 0.1% preservative-free in ocular hypertensive and in primary open-angle glaucoma patients: a cross sectional study.

    Science.gov (United States)

    Rolle, Teresa; Spinetta, Roberta; Nuzzi, Raffaele

    2017-08-03

    The effects of preservatives of antiglaucoma medications on corneal surface and tear function have been widely shown in literature; it's not the same as regards the active compounds themselves. The purpose of our study was to compare Ocular Surface Disease (OSD) signs and symptoms of Tafluprost 0.0015% versus preservative free (PF) Timolol 0.1% eyedrops in ocular hypertensive (OH) and in primary open-angle glaucoma (POAG) patients. A cross-sectional study included patients in monotherapy for at least 36 months with Tafluprost 0.0015% (27) or PF Timolol 0.1% (24) and 20 healthy age and sex-matched volunteers. All subjects underwent clinical tests (Schirmer I and break-up time), in vivo confocal microscopy (IVCM) and were surveyed using Ocular Surface Disease Index (OSDI) and Glaucoma Symptoms Scale (GSS) questionnaires. The groups were compared with ANOVA, Kruskal-Wallis test, t-test, Mann-Whitney test and Bonferroni's adjustment of p-values. No significant differences were found in questionnaires scores, clinical tests, IVCM variables between therapy groups. Tafluprost 0.0015% group showed significantly higher OSDI score, basal epithelial cells density, stromal reflectivity, sub-basal nerves tortuosity (p = 0.0000, 0.037, 0.006, 0.0000) and less GSS score, number of sub-basal nerves (p = 0.0000, 0.037) than controls but similar clinical tests results (p > 0.05). PF Timolol group had significantly higher OSDI score, basal epithelial cells density, stromal reflectivity and sub-basal nerve tortuosity (p = 0.000, 0.014, 0.008, 0.002), less GSS score, BUT and number of sub-basal nerves (p = 0.0000, 0.026, 0.003) than controls. Compared to PF Timolol 0.1%, Tafluprost 0.0015% showed similar safety with regards to tear function and corneal status and a similar tolerability profile. Both therapy groups show some alterations in corneal microstructure but no side effects on tear function except for an increased tear instability in PF Timolol 0.1% group

  19. An idealised study for the long term evolution of crescentic bars

    Science.gov (United States)

    Chen, W. L.; Dodd, N.; Tiessen, M. C. H.; Calvete, D.

    2018-01-01

    An idealised study that identifies the mechanisms in the long term evolution of crescentic bar systems in nature is presented. Growth to finite amplitude (i.e., equilibration, sometimes referred to as saturation) and higher harmonic interaction are hypothesised to be the leading nonlinear effects in long-term evolution of these systems. These nonlinear effects are added to a linear stability model and used to predict crescentic bar development along a beach in Duck, North Carolina (USA) over a 2-month period. The equilibration prolongs the development of bed patterns, thus allowing the long term evolution. Higher harmonic interaction enables the amplitude to be transferred from longer to shorter lengthscales, which leads to the dominance of shorter lengthscales in latter post-storm stages, as observed at Duck. The comparison with observations indicates the importance of higher harmonic interaction in the development of nearshore crescentic bar systems in nature. Additionally, it is concluded that these nonlinear effects should be included in models simulating the development of different bed patterns, and that this points a way forward for long-term morphodynamical modelling in general.

  20. Comparative study of short- and long-term indoor radon measurements

    Energy Technology Data Exchange (ETDEWEB)

    Al-Jarallah, M.I. [Department of Physics, King Fahd University of Petroleum and Minerals, Dhahran 31261 (Saudi Arabia)], E-mail: mibrahim@kfupm.edu.sa; Fazal-ur-Rehman,; Abdalla, Khalid [Department of Physics, King Fahd University of Petroleum and Minerals, Dhahran 31261 (Saudi Arabia)

    2008-08-15

    Short-term indoor radon measurements are used widely. Therefore, it is interesting to find out a correlation between these measurements and long-term measurements which reflect a better average radon concentration of individual measurement. To find the correlation between the two measurements of indoor radon concentrations at low radon levels, a study was carried out at 34 locations of King Fahd University of Petroleum and Minerals (KFUPM), Dhahran, Saudi Arabia using active and passive methods. In the short-term active method, a radon gas analyzer (AlphaGUARD) was used for a duration of 24 h in each measurement. In the long-term passive method, CR-39 based radon dosimeters were utilized for a period of 6 months, from January 2006 to June 2006. The short-term active measurements showed that the average, minimum and maximum radon concentrations were 19, 8 and 58Bqm{sup -3}, respectively, with a standard deviation of 8.6Bqm{sup -3}. The long-term passive measurements showed that the average, minimum and maximum radon concentrations were 25, 10 and 67Bqm{sup -3}, respectively, with a standard deviation of 12Bqm{sup -3}. The two measurements showed a poor correlation (R{sup 2}=0.38). The long-term measurements showed on the average higher concentrations by a factor of 1.3.

  1. Stability of rapid maxillary expansion and facemask therapy: a long-term controlled study.

    Science.gov (United States)

    Masucci, Caterina; Franchi, Lorenzo; Defraia, Efisio; Mucedero, Manuela; Cozza, Paola; Baccetti, Tiziano

    2011-10-01

    The aim of this prospective controlled study was to evaluate the long-term effects of rapid maxillary expansion and facemask therapy in Class III subjects. Twenty-two subjects (9 boys, 13 girls; mean age, 9.2 years ± 1.6) with Class III disharmony were treated consecutively with rapid maxillary expansion and facemask therapy followed by fixed appliances. The patients were reevaluated at the end of the 2-phase treatment (mean age, 14.5 years ± 1.9) and then recalled about 8.5 years after the end of rapid maxillary expansion and facemask treatment (mean age, 18.7 years ± 2.1). Two groups of controls with untreated Class III malocclusion were used for statistical comparisons of the short-term and long-term intervals. Statistical comparisons were performed with the Mann-Whitney U test. In the long term, no significant differences in maxillary changes were recorded, whereas the treatment group showed significantly smaller increases in mandibular protrusion. The sagittal maxillomandibular skeletal variables maintained significant improvements in the treatment group vs the control groups. In the long term, rapid maxillary expansion and facemask therapy led to successful outcomes in about 73% of the Class III patients. Favorable skeletal changes were mainly due to significant improvements in the sagittal position of the mandible. Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  2. Long-term safety and efficacy of etanercept in the treatment of ankylosing spondylitis

    Directory of Open Access Journals (Sweden)

    Senabre-Gallego JM

    2013-09-01

    Full Text Available José Miguel Senabre-Gallego,1 Carlos Santos-Ramirez,2 Gregorio Santos-Soler,1 Esteban Salas-Heredia,1 Mabel Sánchez-Barrioluengo,3 Xavier Barber,4 José Rosas1 On behalf of the AIRE-MB group 1Rheumatology, Hospital Marina Baixa, Villajoyosa, 2Rheumatology, Hospital Marina Salud, Denia, 3INGENIO (Instituto de Gestión de la Inovación y del Conocimiento (CSIC [Consejo Superior de Investigaciones Científicas]-UPV [Universidad Politécnica de Valencia], Universitat Politècnica de València, Valencia, 4CIO (Centro de Investigación Operativa-UMH (Universidad Miguel Hernández, Universidad Miguel Henández, Elche, Spain Abstract: To date, anti-tumor necrosis factor alfa (anti-TNF-α therapy is the only alternative to nonsteroidal anti-inflammatory drugs for the treatment of ankylosing spondylitis. Etanercept is a soluble TNF receptor, with a mode of action and pharmacokinetics different to those of antibodies and distinctive efficacy and safety. Etanercept has demonstrated efficacy in the treatment of ankylosing spondylitis, with or without radiographic sacroiliitis, and other manifestations of the disease, including peripheral arthritis, enthesitis, and psoriasis. Etanercept is not efficacious in inflammatory bowel disease, and its efficacy in the treatment of uveitis appears to be lower than that of other anti-TNF drugs. Studies of etanercept confirmed regression of bone edema on magnetic resonance imaging of the spine and sacroiliac joint, but failed to reduce radiographic progression, as do the other anti-TNF drugs. It seems that a proportion of patients remain in disease remission when the etanercept dose is reduced or administration intervals are extended. Etanercept is generally well tolerated with an acceptable safety profile in the treatment of ankylosing spondylitis. The most common adverse effect of etanercept treatment is injection site reactions, which are generally self-limiting. Reactivation of tuberculosis, reactivation of

  3. Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results.

    Science.gov (United States)

    Wang, Michael L; Blum, Kristie A; Martin, Peter; Goy, Andre; Auer, Rebecca; Kahl, Brad S; Jurczak, Wojciech; Advani, Ranjana H; Romaguera, Jorge E; Williams, Michael E; Barrientos, Jacqueline C; Chmielowska, Ewa; Radford, John; Stilgenbauer, Stephan; Dreyling, Martin; Jedrzejczak, Wieslaw Wiktor; Johnson, Peter; Spurgeon, Stephen E; Zhang, Liang; Baher, Linda; Cheng, Mei; Lee, Dana; Beaupre, Darrin M; Rule, Simon

    2015-08-06

    Ibrutinib, an oral inhibitor of Bruton tyrosine kinase, is approved for patients with mantle cell lymphoma (MCL) who have received one prior therapy. We report the updated safety and efficacy results from the multicenter, open-label phase 2 registration trial of ibrutinib (median 26.7-month follow-up). Patients (N = 111) received oral ibrutinib 560 mg once daily, and those with stable disease or better could enter a long-term extension study. The primary end point was overall response rate (ORR). The median patient age was 68 years (range, 40-84), with a median of 3 prior therapies (range, 1-5). The median treatment duration was 8.3 months; 46% of patients were treated for >12 months, and 22% were treated for ≥2 years. The ORR was 67% (23% complete response), with a median duration of response of 17.5 months. The 24-month progression-free survival and overall survival rates were 31% (95% confidence interval [CI], 22.3-40.4) and 47% (95% CI, 37.1-56.9), respectively. The most common adverse events (AEs) in >30% of patients included diarrhea (54%), fatigue (50%), nausea (33%), and dyspnea (32%). The most frequent grade ≥3 infections included pneumonia (8%), urinary tract infection (4%), and cellulitis (3%). Grade ≥3 bleeding events in ≥2% of patients were hematuria (2%) and subdural hematoma (2%). Common all-grade hematologic AEs were thrombocytopenia (22%), neutropenia (19%), and anemia (18%). The prevalence of infection, diarrhea, and bleeding was highest for the first 6 months of therapy and less thereafter. With longer follow-up, ibrutinib continues to demonstrate durable responses and favorable safety in relapsed/refractory MCL. The trial is registered to www.ClinicalTrials.gov as #NCT01236391. © 2015 by The American Society of Hematology.

  4. 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

  5. LOng-term follow-up after liVE kidney donation (LOVE) study: A longitudinal comparison study protocol

    NARCIS (Netherlands)

    S. Janki (Shiromani); K.W.J. Klop (Karel); H.J.A.N. Kimenai (Hendrikus); J. van de Wetering (Jacqueline); W. Weimar (Willem); E.K. Massey (Emma); A. Dehghan (Abbas); D. Rizopoulos (Dimitris); H. Völzke (Henry); A. Hofman (Albert); J.N.M. IJzermans (Jan)

    2016-01-01

    textabstractBackground: The benefits of live donor kidney transplantation must be balanced against the potential harm to the donor. Well-designed prospective studies are needed to study the long-term consequences of kidney donation. Methods: The "LOng-term follow-up after liVE kidney donation"

  6. 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.

  7. 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

  8. Evaluation of uncertainty associated with parameters for long-term safety assessments of geological disposal

    International Nuclear Information System (INIS)

    Yamaguchi, Tetsuji; Minase, Naofumi; Iida, Yoshihisa; Tanaka, Tadao; Nakayama, Shinichi

    2005-01-01

    This paper describes the current status of our data acquisition on quantifying uncertainties associated with parameters for safety assessment on groundwater scenarios for geological disposal of radioactive wastes. First, sources of uncertainties and the resulting priority in data acquisition were briefed. Then, the current status of data acquisition for quantifying the uncertainties in assessing solubility, diffusivity in bentonite buffer and distribution coefficient on rocks is introduced. The uncertainty with the solubility estimation is quantified from that associated with thermodynamic data and that in estimating groundwater chemistry. The uncertainty associated with the diffusivity in bentonite buffer is composed of variations of relevant factors such as porosity of the bentonite buffer, montmorillonite content, chemical composition of pore water and temperature. The uncertainty of factors such as the specific surface area of the rock, pH, ionic strength, carbonate concentration in groundwater compose uncertainty of the distribution coefficient of radionuclides on rocks. Based on these investigations, problems to be solved in future studies are summarized. (author)

  9. Long-term safety and efficacy of ramelteon in Japanese patients with chronic insomnia.

    Science.gov (United States)

    Uchiyama, Makoto; Hamamura, Misako; Kuwano, Tomoaki; Nagata, Hiroshi; Hashimoto, Takamasa; Ogawa, Atsushi; Uchimura, Naohisa

    2011-02-01

    To evaluate the safety of ramelteon, a highly selective MT₁/MT₂ melatonin receptor agonist, during 24 weeks' treatment of Japanese patients with chronic insomnia. In a single-blind, flexible-titration, multicenter study incorporating placebo run-in and run-out periods, 190 adults with chronic insomnia received ramelteon 4 or 8 mg, titrated up to 16 mg if necessary, for 24 weeks. Primary endpoints included adverse events, residual effects, rebound insomnia, withdrawal symptoms, and dependence. Secondary endpoints included subjective sleep latency and total sleep time. Drug-related adverse events occurred in 11.6% of patients. No clinically important changes occurred in biochemical, hematological or endocrine parameters. There were no signs of next-day residual effect, rebound insomnia, withdrawal symptoms or dependence. Mean subjective sleep latency decreased significantly, and total sleep time increased significantly; both reached a plateau by week 20 and were sustained thereafter (Pinsomnia and did not cause deterioration of efficacy, residual effects, rebound insomnia, withdrawal symptoms, or dependence after 24 weeks' treatment. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. 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

  11. 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

  12. Some aspects of nuclear power development in Russian and studies on its optimal long term structure

    International Nuclear Information System (INIS)

    Ermakov, N.I.; Poplavsky, V.M.; Troyanov, M.F.; Oussanov, V.I.; Chebeskov, A.N.; Malenkov, A.V.; Gordeev, B.K.

    1997-01-01

    The paper presents the authors' outlook for nuclear power development in Russia. The analysis is based on the documents published and other materials as well as on the experience of the authors who participated in working out the state fuel-power program Power Strategy of Russia. The crucial point of the Strategy is that moratorium on the nuclear power development in Russia is inadmissible and a part of electricity production in the country will be covered by NPPs with increased safety. The studies which have been carried out by the organizations of MINATOM and ROSENERGOATOM and by some authors have shown that a potential of the Russia nuclear power complex meets the requirements of the nuclear power development up to year 2010. From the standpoint of the authors of the paper the investment climate in the country is the most important and uncertain factor influencing the program realization. But nuclear power preserves competitive ability in any option of new electric capacities introduced in Russia. Application of the market-oriented IAEA's planning tools have confirmed the competitive ability of nuclear power in the central region of Russia. This study is to be continued for other Russian regions. The estimates of the long-term prospects of nuclear power development in Russia made by the authors are based on the assumptions of natural uranium resources conservation, plutonium stockpile minimization and reduction of the radiotoxical waste to the lowest possible level. These requirements may be answered in the plutonium balanced system of thermal and fast reactors with a very economical consumption of natural uranium and a very small quantity of radioactive waste (mainly consisting of fission products and losses in reprocessing operations). (author)

  13. Controlling for unmeasured confounding and spatial misalignment in long?term air pollution and health studies

    OpenAIRE

    Lee, Duncan; Sarran, Christophe

    2015-01-01

    The health impact of long?term exposure to air pollution is now routinely estimated using spatial ecological studies, owing to the recent widespread availability of spatial referenced pollution and disease data. However, this areal unit study design presents a number of statistical challenges, which if ignored have the potential to bias the estimated pollution?health relationship. One such challenge is how to control for the spatial autocorrelation present in the data after accounting for the...

  14. Field study of the long-term release of block copolymers from fouling-release coatings

    DEFF Research Database (Denmark)

    Noguer, Albert Camós; Olsen, A.; Hvilsted, Søren

    2017-01-01

    The addition of block copolymers (i.e. oils) is a common technique to enhance the biofouling-resistance properties of poly(dimethylsiloxane) (PDMS)-based fouling-release coatings. These copolymers diffuse from the bulk to the surface of the coating, thus modifying the properties of the surface an...... fouling-release coatings. Finally, the potential of long-term field-studies is discussed, as compared to short-term laboratory experiments usually performed within fouling-release coatings studies....

  15. The value of animations in biology teaching: a study of long-term memory retention.

    Science.gov (United States)

    O'Day, Danton H

    2007-01-01

    Previous work has established that a narrated animation is more effective at communicating a complex biological process (signal transduction) than the equivalent graphic with figure legend. To my knowledge, no study has been done in any subject area on the effectiveness of animations versus graphics in the long-term retention of information, a primary and critical issue in studies of teaching and learning. In this study, involving 393 student responses, three different animations and two graphics-one with and one lacking a legend-were used to determine the long-term retention of information. The results show that students retain more information 21 d after viewing an animation without narration compared with an equivalent graphic whether or not that graphic had a legend. Students' comments provide additional insight into the value of animations in the pedagogical process, and suggestions for future work are proposed.

  16. Long-term safety and efficacy of AAV gene therapy in the canine model of glycogen storage disease type Ia.

    Science.gov (United States)

    Lee, Young Mok; Conlon, Thomas J; Specht, Andrew; Coleman, Kirsten E; Brown, Laurie M; Estrella, Ana M; Dambska, Monika; Dahlberg, Kathryn R; Weinstein, David A

    2018-05-25

    Viral mediated gene therapy has progressed after overcoming early failures, and gene therapy has now been approved for several conditions in Europe and the USA. Glycogen storage disease (GSD) type Ia, caused by a deficiency of glucose-6-phosphatase-α, has been viewed as an outstanding candidate for gene therapy. This follow-up report describes the long-term outcome for the naturally occurring GSD-Ia dogs treated with rAAV-GPE-hG6PC-mediated gene therapy. A total of seven dogs were treated with rAAV-GPE-hG6PC-mediated gene therapy. The first four dogs were treated at birth, and three dogs were treated between 2 and 6 months of age to assess the efficacy and safety in animals with mature livers. Blood and urine samples, radiographic studies, histological evaluation, and biodistribution were assessed. Gene therapy improved survival in the GSD-Ia dogs. With treatment, the biochemical studies normalized for the duration of the study (up to 7 years). None of the rAAV-GPE-hG6PC-treated dogs had focal hepatic lesions or renal abnormalities. Dogs treated at birth required a second dose of rAAV after 2-4 months; gene therapy after hepatic maturation resulted in improved efficacy after a single dose. rAAV-GPE-hG6PC treatment in GSD-Ia dogs was found to be safe and efficacious. GSD-Ia is an attractive target for human gene therapy since it is a monogenic disorder with limited tissue involvement. Blood glucose and lactate monitoring can be used to assess effectiveness and as a biomarker of success. GSD-Ia can also serve as a model for other hepatic monogenic disorders.

  17. Climate Considerations in Long-Term Safety Assessments for Nuclear Waste Repositories

    Energy Technology Data Exchange (ETDEWEB)

    Naeslund, Jens-Ove; Brandefelt, Jenny; Claesson Liljedahl, Lillemor [Svensk Kaernbraenslehantering AB, Stockholm (Sweden)], E-mail: jens-ove.naslund@skb.se

    2013-05-15

    For a deep geological repository for spent nuclear fuel planned in Sweden, the safety assessment covers up to 1 million years. Climate scenarios range from high-end global warming for the coming 100 000 years, through deep permafrost, to large ice sheets during glacial conditions. In contrast, in an existing repository for short-lived waste the activity decays to low levels within a few tens of thousands of years. The shorter assessment period, 100 000 years, requires more focus on climate development over the coming tens of thousands of years, including the earliest possibility for permafrost growth and freezing of the engineered system. The handling of climate and climate change in safety assessments must be tailor-made for each repository concept and waste type. However, due to the uncertain future climate development on these vast time scales, all safety assessments for nuclear waste repositories require a range of possible climate scenarios.

  18. Climate considerations in long-term safety assessments for nuclear waste repositories.

    Science.gov (United States)

    Näslund, Jens-Ove; Brandefelt, Jenny; Liljedahl, Lillemor Claesson

    2013-05-01

    For a deep geological repository for spent nuclear fuel planned in Sweden, the safety assessment covers up to 1 million years. Climate scenarios range from high-end global warming for the coming 100 000 years, through deep permafrost, to large ice sheets during glacial conditions. In contrast, in an existing repository for short-lived waste the activity decays to low levels within a few tens of thousands of years. The shorter assessment period, 100 000 years, requires more focus on climate development over the coming tens of thousands of years, including the earliest possibility for permafrost growth and freezing of the engineered system. The handling of climate and climate change in safety assessments must be tailor-made for each repository concept and waste type. However, due to the uncertain future climate development on these vast time scales, all safety assessments for nuclear waste repositories require a range of possible climate scenarios.

  19. The associations between workplace bullying, salivary cortisol, and long-term sickness absence: a longitudinal study

    Directory of Open Access Journals (Sweden)

    Matias Brødsgaard Grynderup

    2017-09-01

    Full Text Available Abstract Background Workplace stressors, such as bullying, are strongly related to subsequent long-term sickness absence, but little is known of the possible physiological mechanisms linking workplace stressors and sickness absence. The primary aim of this study was to investigate to what extent cortisol levels were associated with subsequent sickness absence and if cortisol mediated the association between workplace bullying and sickness absence. We additionally investigated possible bidirectional associations between bullying, cortisol, and long-term sickness absence. Methods Participants came from two Danish cohort studies, the “Psychosocial RIsk factors for Stress and MEntal disease” (PRISME cohort and the “Workplace Bullying and Harassment” (WBH cohort (n = 5418. Information about exposure to workplace bullying and morning and evening salivary cortisol was collected at three time points with approximately two years in between. After each data collection, all participants were followed for two years in registers, and cases with long-term sickness absence lasting 30 or more consecutive days were identified. The association between cortisol levels and subsequent sickness absence was assessed by logistic regression, while the extent to which the association between bullying and sickness absence was mediated by cortisol was quantified through natural direct and indirect effects. Results High evening cortisol was associated with a decreased risk of sickness absence (OR = 0.82, 95% CI = 0.68–0.99, but we did not find that high morning cortisol levels (OR = 0.98, 95% CI = 0.81–1.18 or high morning-to-evening slope (OR = 0.99, 95% CI = 0.82–1.18 were associated with subsequent sickness absence. We also tested for reverse causation and found that long-term sickness absence, but not salivary cortisol, was a strong risk factor for subsequent workplace bullying. There was no indication that cortisol mediated the association

  20. The associations between workplace bullying, salivary cortisol, and long-term sickness absence: a longitudinal study.

    Science.gov (United States)

    Grynderup, Matias Brødsgaard; Nabe-Nielsen, Kirsten; Lange, Theis; Conway, Paul Maurice; Bonde, Jens Peter; Garde, Anne Helene; Gullander, Maria; Kaerlev, Linda; Persson, Roger; Rugulies, Reiner; Vammen, Marianne Agergaard; Høgh, Annie; Hansen, Åse Marie

    2017-09-16

    Workplace stressors, such as bullying, are strongly related to subsequent long-term sickness absence, but little is known of the possible physiological mechanisms linking workplace stressors and sickness absence. The primary aim of this study was to investigate to what extent cortisol levels were associated with subsequent sickness absence and if cortisol mediated the association between workplace bullying and sickness absence. We additionally investigated possible bidirectional associations between bullying, cortisol, and long-term sickness absence. Participants came from two Danish cohort studies, the "Psychosocial RIsk factors for Stress and MEntal disease" (PRISME) cohort and the "Workplace Bullying and Harassment" (WBH) cohort (n = 5418). Information about exposure to workplace bullying and morning and evening salivary cortisol was collected at three time points with approximately two years in between. After each data collection, all participants were followed for two years in registers, and cases with long-term sickness absence lasting 30 or more consecutive days were identified. The association between cortisol levels and subsequent sickness absence was assessed by logistic regression, while the extent to which the association between bullying and sickness absence was mediated by cortisol was quantified through natural direct and indirect effects. High evening cortisol was associated with a decreased risk of sickness absence (OR = 0.82, 95% CI = 0.68-0.99), but we did not find that high morning cortisol levels (OR = 0.98, 95% CI = 0.81-1.18) or high morning-to-evening slope (OR = 0.99, 95% CI = 0.82-1.18) were associated with subsequent sickness absence. We also tested for reverse causation and found that long-term sickness absence, but not salivary cortisol, was a strong risk factor for subsequent workplace bullying. There was no indication that cortisol mediated the association between workplace bullying and sickness absence. We found no

  1. 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

  2. The long-term career outcome study: lessons learned and implications for educational practice.

    Science.gov (United States)

    Durning, Steven J; Dong, Ting; LaRochelle, Jeffrey L; Artino, Anthony R; Gilliland, William R; DeZee, Kent J; Saguil, Aaron; Cruess, David F; Picho, Katherine; McManigle, John E

    2015-04-01

    The work of the Long-Term Career Outcome Study has been a program of scholarship spanning 10 years. Borrowing from established quality assurance literature, the Long-Term Career Outcome Study team has organized its scholarship into three phases; before medical school, during medical school, and after medical school. The purpose of this commentary is to address two fundamental questions: (1) what has been learned? and (2) how does this knowledge translate to educational practice and policy now and into the future? We believe that answers to these questions are relevant not only to our institution but also to other educational institutions seeking to provide high-quality health professions education. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

  3. Pacemaker replacement in nonagenarians: Procedural safety and long-term follow-up.

    Science.gov (United States)

    Loirat, Aurélie; Fénéon, Damien; Behaghel, Albin; Behar, Nathalie; Le Helloco, Alain; Mabo, Philippe; Daubert, Jean-Claude; Leclercq, Christophe; Martins, Raphaël P

    2015-01-01

    The rate of pacemaker implantation is rising. Given that the life expectancy of the population is projected to increase, a large number of elderly patients are likely to be implanted in the future. As pacemaker batteries can last for 8-10years, an increasing number of pacemaker recipients will require replacement of their devices when they become nonagenarians. To analyse the short- and long-term outcomes after device replacement in nonagenarians. Patients aged≥90years referred to a tertiary centre for pacemaker replacement from January 2004 to July 2014 were included retrospectively. Clinical follow-up data were obtained from clinical visits or telephone interviews with patients or their families. The primary clinical endpoint was total mortality. Secondary endpoints included early and delayed procedure-related complications and predictive risk factors for total mortality. Sixty-two patients were included (mean age 93.3±2.9years at time of pacemaker replacement). Mean procedure duration was 35.7±17.2minutes. Mean hospital stay was 2.2±1.1days. One patient died from a perioperative complication. Thirty-seven patients (59.7%) died during a median follow-up of 22.1months (interquartile range, 11.8-39.8months). Survival rates were 84.2% (95% confidence interval [CI] 71.8-91.5%) at 1year, 66.9% (95% CI 51.8-78.2%) at 2years and 22.7% (95% CI 10.6-37.7%) at 5years. Atrial fibrillation (hazard ratio 2.47, 95% CI 1.1-5.6) and non-physiological pacing (i.e. VVI pacing in patients in sinus rhythm) (hazard ratio 2.20, 95% CI 1.0-4.9) were predictors of mortality. Pacemaker replacement in nonagenarians is a safe and straightforward procedure. These data suggest that procedures can be performed securely in this old and frail population, with patients living for a median of 30months afterwards. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  4. Long-term e-cigarette use and smoking cessation: a longitudinal study with US population.

    Science.gov (United States)

    Zhuang, Yue-Lin; Cummins, Sharon E; Sun, Jessica Y; Zhu, Shu-Hong

    2016-10-01

    E-cigarettes have grown popular. The most common pattern is dual use with conventional cigarettes. Dual use has raised concerns that it might delay quitting of cigarette smoking. This study examined the relationship between long-term use of e-cigarettes and smoking cessation in a 2-year period. A nationally representative sample of 2028 US smokers were surveyed in 2012 and 2014. Long-term e-cigarette use was defined as using e-cigarettes at baseline and follow-up. Use of e-cigarettes only at baseline or at follow-up was defined as short-term use. Non-users did not use e-cigarettes at either survey. Quit attempt rates and cessation rates (abstinent for 3 months or longer) were compared across the three groups. At 2-year follow-up, 43.7% of baseline dual users were still using e-cigarettes. Long-term e-cigarette users had a higher quit attempt rate than short-term or non-users (72.6% vs 53.8% and 45.5%, respectively), and a higher cessation rate (42.4% vs 14.2% and 15.6%, respectively). The difference in cessation rate between long-term users and non-users remained significant after adjusting for baseline variables, OR=4.1 (95% CI 1.5 to 11.4) as did the difference between long-term users and short-term users, OR=4.8 (95% CI 1.6 to 13.9). The difference in cessation rate between short-term users and non-users was not significant, OR=0.9 (95% CI 0.5 to 1.4). Among those making a quit attempt, use of e-cigarettes as a cessation aid surpassed that of FDA-approved pharmacotherapy. Short-term e-cigarette use was not associated with a lower rate of smoking cessation. Long-term use of e-cigarettes was associated with a higher rate of quitting smoking. 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/.

  5. Short- versus long-term radon detectors: a comparative study in Galicia, NW Spain

    International Nuclear Information System (INIS)

    Ruano-Ravina, A.; Castro-Bernardez, M.; Sande-Meijide, M.; Vargas, A.; Barros-Dios, J.M.

    2008-01-01

    As reported in previous studies, Galicia (NW Spain) is an area of high radon concentrations. This study was sought to analyze the correlation between short-term (activated carbon) and long-term (alpha particle track) detectors in this geographic area, and ascertain whether there were differences in their readings that might be influenced by other variables. A comparison study, as part of a case-control study was designed in which two detectors, one of each type, were placed in the selected homes. A total of 391 homes yielded readings with both detectors. The results indicated that there was a relatively good correlation between both types of monitors (correlation coefficient 0.608; p < 0.001). The highest correlations between both detectors were observed for unventilated homes, coastal sites, and the oldest buildings. Short-term and long-term detectors do not show a similar performance in all settings or situations. It is advisable to use long-term detectors whenever possible

  6. Short- versus long-term radon detectors: a comparative study in Galicia, NW Spain

    Energy Technology Data Exchange (ETDEWEB)

    Ruano-Ravina, A. [Department of Preventive Medicine and Public Health, School of Medicine, University of Santiago de Compostela, C/San Francisco s/n, 15782 Santiago de Compostela (Spain); Galician Agency for Health Technology Assessment, Galician Health Service, Santiago de Compostela (Spain); CIBER de Epidemiologia y Salud Publica, CIBERESP (Spain)], E-mail: mralbert@usc.es; Castro-Bernardez, M. [Epidemiology Department, Directorate-General for Public Health, Galician Regional Authority (Spain); Sande-Meijide, M. [Preventive Medicine Unit, Ourense Hospital Complex, Galician Health Service (Spain); Vargas, A. [Energy Techniques Institute, Polytechnic University of Catalonia, Barcelona (Spain); Barros-Dios, J.M. [Department of Preventive Medicine and Public Health, School of Medicine, University of Santiago de Compostela, C/San Francisco s/n, 15782 Santiago de Compostela (Spain); CIBER de Epidemiologia y Salud Publica, CIBERESP (Spain); Preventive Medicine Unit, Santiago de Compostela University Hospital, Galician Health Service (Spain)

    2008-07-15

    As reported in previous studies, Galicia (NW Spain) is an area of high radon concentrations. This study was sought to analyze the correlation between short-term (activated carbon) and long-term (alpha particle track) detectors in this geographic area, and ascertain whether there were differences in their readings that might be influenced by other variables. A comparison study, as part of a case-control study was designed in which two detectors, one of each type, were placed in the selected homes. A total of 391 homes yielded readings with both detectors. The results indicated that there was a relatively good correlation between both types of monitors (correlation coefficient 0.608; p < 0.001). The highest correlations between both detectors were observed for unventilated homes, coastal sites, and the oldest buildings. Short-term and long-term detectors do not show a similar performance in all settings or situations. It is advisable to use long-term detectors whenever possible.

  7. Long Term Performance Study of a Direct Methanol Fuel Cell Fed with Alcohol Blends

    OpenAIRE

    Teresa J. Leo; Miguel A. Raso; Emilio Navarro; Eleuterio Mora

    2013-01-01

    The use of alcohol blends in direct alcohol fuel cells may be a more environmentally friendly and less toxic alternative to the use of methanol alone in direct methanol fuel cells. This paper assesses the behaviour of a direct methanol fuel cell fed with aqueous methanol, aqueous ethanol and aqueous methanol/ethanol blends in a long term experimental study followed by modelling of polarization curves. Fuel cell performance is seen to decrease as the ethanol content rises, and subsequent opera...

  8. Dementia Rating Scale psychometric study and its applicability in long term care institutions in Brazil

    OpenAIRE

    Alessandro Ferrari Jacinto; Ana Cristina Procópio de Oliveira Aguiar; Fabio Gazelato de Melo Franco; Miriam Ikeda Ribeiro; Vanessa de Albuquerque Citero

    2012-01-01

    Objective: To evaluate the diagnostic sensitivity, specificity, andagreement of the Dementia Rating Scale with clinical diagnosis ofcognitive impairment and to compare its psychometric measureswith those from Mini Mental State Examination. Methods: Eighty-sixelders from a long-term care institution were invited to participatein a study, and fifty-eight agreed to participate. The global healthassessment protocol applied to these elders contained Mini MentalState Examination and Dementia Rating...

  9. 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)

  10. 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)

  11. Long-term studies of the natural history of asthma in childhood

    DEFF Research Database (Denmark)

    Bisgaard, Hans; Bønnelykke, Klaus

    2010-01-01

    Segmentation of children with asthma and other wheezy disorders remains the main research challenge today, as it was when described 2 centuries ago. Early childhood wheezy disorders follow different temporal trajectories, probably representing different underlying mechanisms (endophenotypes...... secondary prevention through the use of inhaled corticosteroids can effectively halt the long-term disease progression in childhood. In conclusion, the natural history of asthma and the associated airway changes is still poorly understood, and we have not managed to translate findings from long-term studies......). Prospective identification of endophenotypes allowing accurate prediction of the clinical course is currently not possible. The variability of the clinical course remains an enigma and difficult to predict. Three of 4 school-aged children with asthma have outgrown disease by midadulthood. The risk...

  12. Long-term effects of parental divorce timing on depression: A population-based longitudinal study.

    Science.gov (United States)

    Chun, Sung-Youn; Jang, Suk-Yong; Choi, Jae-Woo; Shin, Jaeyong; Park, Eun-Cheol

    2016-09-08

    We examined the long-term effects of parental divorce timing on depression using longitudinal data from the Korean Welfare Panel Study. Depression symptoms were measured using the 11 items of Center for Epidemiologic Scale for Depression (CES-D-11), and we categorized parental divorce timing into 'early childhood', 'adolescent' and 'none'. Although participants who experienced parental divorce during adolescence exhibited a significantly higher CES-D-11 score (p = .0468), 'early childhood' participants displayed the most increased CES-D-11 score compared to the control group (p = .0007). Conversely, among participants who were unsatisfied with their marriage, those who experienced parental divorce in early childhood showed lower CES-D-11 scores, while 'adolescent period' participants exhibited significantly higher CES-D-11 scores (p = .0131). We concluded that timing of parental divorce exerts substantial yet varied effects on long-term depression symptoms and future marriage satisfaction. © The Author(s) 2016.

  13. Microclimatic effects on outdoor radon and its progeny in a long-term study

    International Nuclear Information System (INIS)

    Schuetz, M.; Keller, G.; Kappel, R.J.A.

    1994-01-01

    The dose due to the long term radon exposure is estimated from the radon concentration and from an equilibrium factor that in the literature is reported with a wide uncertainty. Therefore the radon equilibrium factor outdoors and its dependence on climatic effects should be investigated in a long-term study. Both the outdoor concentrations of radon and of its progeny near Ellweiler/Hunsrueck were measured continuously during 12 months and the resulting equilibrium factors were determined. Simultaneously to the every 2 hour's radon data many meterological parameters as temperature and relative to humidity of the air, barometric pressure and duration and amount of rainfall were recorded. At a height of 6 meters above ground and in 10 minute intervals the local wind direction and velocity were registered. By that a set of more than 3000 single measurements of the equilibrium factor and of the corresponding weather conditions was collected

  14. Study plan for research on long-term stability of geological environments in FY2009

    International Nuclear Information System (INIS)

    Yasue, Ken-ichi; Hanamuro, Takahiro; Kokubu, Yoko; Ishimaru, Tsuneari; Umeda, Koji

    2009-09-01

    The Japanese islands lie in a region of the Circum-Pacific orogenic belt characterized by active tectonics such as volcanism and earthquakes. The concept of geological disposal of HLW in Japan is based on a multi-barrier system which consists of the engineered barrier in the stable geological environments and the natural barrier. The natural phenomena which potentially affect the geological environments in tectonically active Japan are volcanism, faulting, uplift, denudation, climatic change, and sea-level change. Investigation technologies to evaluate their long-term stability of the geological environments have been developed. In fiscal year 2009, we continue researches to develop technologies for detecting latent geotectonic events in preliminary investigation. With regard to modelling technology, we plan to develop prediction models for evaluating the changes of geological environment (e.g., thermal, hydraulic, mechanical, and geochemical conditions) for long term. In addition to these, the development of dating techniques prerequisite for these studies is also carried out. (author)

  15. A study about long-term deformation of soft rock. 2

    International Nuclear Information System (INIS)

    Inoue, Hiroyuki; Yoshino, Naoto; Miyanomae, Shunichi; Mizutani, Kazuhiko; Noda, Kenji

    2004-02-01

    In this study, the laboratory mechanical tests of sedimentary soft rock sampled at Horonobe area in Hokkaido prefecture were conducted in order to build the confidence of Okubo model for long term deformation of sedimentary rock. And the stability of rock around tunnel in building under the condition assumed the underground of Horonobe area was examined by numerical simulation using information of boring data obtained before 2002 year. As a result, authors could obtain many values of parameter in Okubo model under various conditions. These conditions have the difference of temperature and water saturation. In addition, the life time in creep predicted by Okubo model could be compared with the real one. And numerical simulations, assuming various conditions such as stiffness of buffer material and yielding of support, had been carried out to evaluate the long-term stability of rock surrounding buffer material. Results show the decreasing tendency of time dependency of rock. (author)

  16. Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab.

    Science.gov (United States)

    McDermott, David F; Drake, Charles G; Sznol, Mario; Choueiri, Toni K; Powderly, John D; Smith, David C; Brahmer, Julie R; Carvajal, Richard D; Hammers, Hans J; Puzanov, Igor; Hodi, F Stephen; Kluger, Harriet M; Topalian, Suzanne L; Pardoll, Drew M; Wigginton, Jon M; Kollia, Georgia D; Gupta, Ashok; McDonald, Dan; Sankar, Vindira; Sosman, Jeffrey A; Atkins, Michael B

    2015-06-20

    Blockade of the programmed death-1 inhibitory cell-surface molecule on immune cells using the fully human immunoglobulin G4 antibody nivolumab mediates tumor regression in a portion of patients with advanced treatment-refractory solid tumors. We report clinical activity, survival, and long-term safety in patients with advanced renal cell carcinoma (RCC) treated with nivolumab in a phase I study with expansion cohorts. A total of 34 patients with previously treated advanced RCC, enrolled between 2008 and 2012, received intravenous nivolumab (1 or 10 mg/kg) in an outpatient setting once every two weeks for up to 96 weeks and were observed for survival and duration of response after treatment discontinuation. Ten patients (29%) achieved objective responses (according to RECIST [version 1.0]), with median response duration of 12.9 months; nine additional patients (27%) demonstrated stable disease lasting > 24 weeks. Three of five patients who stopped treatment while in response continued to respond for ≥ 45 weeks. Median overall survival in all patients (71% with two to five prior systemic therapies) was 22.4 months; 1-, 2-, and 3-year survival rates were 71%, 48%, and 44%, respectively. Grade 3 to 4 treatment-related adverse events occurred in 18% of patients; all were reversible. Patients with advanced treatment-refractory RCC treated with nivolumab demonstrated durable responses that in some responders persisted after drug discontinuation. Overall survival is encouraging, and toxicities were generally manageable. Ongoing randomized clinical trials will further assess the impact of nivolumab on overall survival in patients with advanced RCC. © 2015 by American Society of Clinical Oncology.

  17. 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.

  18. Evaluating the Long-Term Safety of a Repository at Yucca Mountain

    International Nuclear Information System (INIS)

    Luik, Abe Van

    2002-01-01

    Regulations require that the repository be evaluated for its health and safety effects for 10,000 years for the Site Recommendation process. Regulations also require potential impacts to be evaluated for up to a million years in an Environmental Impact Statement. The Yucca Mountain Project is in the midst of the Site Recommendation process. The Total System Performance Assessment (TSPA) that supports the Site Recommendation evaluated safety for these required periods of time. Results showed it likely that a repository at this site could meet the licensing requirements promulgated by the Nuclear Regulatory Commission. The TSPA is the tool that integrates the results of many years of scientific investigations with design information to allow evaluations of potential far-future impacts of building a Yucca Mountain repository. Knowledge created in several branches of physics is part of the scientific basis of the TSPA that supports the Site Recommendation process.

  19. Microscopic study of rock for estimating long-term behavior. Research document

    International Nuclear Information System (INIS)

    Ichikawa, Yasuaki

    2003-02-01

    Micro-structure of rock plays an essential role for their long-term behavior. For elucidating long-term characteristics of granite we here present the followings: 1) Conformal Lase Scanning Microscope (LSM) observation of configuration of a joint in granite, its Fourier analysis and the change under uniaxial stress condition, 2) characterization of the mechanism of microcrack initiation and propagation observed by stereoscopic microscope under uniaxial/triaxial compression and relaxation tests, 3) observation of microcrack initiation and propagation by LSM under uniaxial compression, and 4) a study of strong discontinuity analysis included in the homogenization theory to predict the long-term behavior of micro/macro-level stress for granite. Rock image processing and analysis become a fundamental procedure to determine rock surface discontinuities. In Chapter 2 LSM that can acquire three-dimensional images is introduced to observe the roughness of discontinuity in a rock specimen. Then, discontinuities appeared on circular sections are identified by LSM and characterized by a Discrete Fourier Transform (DFT) analysis. The change of discontinuities is observed under applying stress. Microcrack generation and propagation play an essential role to predict the long-term behavior of rock. In Chapter 3 a progressive development of cracking in granite is revealed by using stereoscopic microscope under water-saturated triaxial compression condition. Next by using LSM observe the procedure of micro-cracking under uniaxial compression condition. Obviously the micro-crack initiation and propagation controls the time-dependent behavior of granite. We have analysed the behavior by a viscoelastic theory applied in homogenization method. However since it is difficult to determine the inter-granular properties of constituent crystals and to represent the stress-dependent nonlinear characteristics by this method, we study a strong discontinuity analysis included in the

  20. Study on crystalline rock for evaluating method of long-term behavior. FY2012 (Contract research)

    International Nuclear Information System (INIS)

    Fukui, Katsunori; Hashiba, Kimihiro; Tanno, Takeo; Hikima, Ryoichi; Sanada, Hiroyuki; Sato, Toshinori

    2013-12-01

    Rock shows time-dependent behavior such as creep/relaxation. With respect to high-level radioactive waste disposal, knowledge of the long-term mechanical stability of shafts and galleries excavated in rock are required, over a period of thousands of years after closure as well as during construction and operation. Therefore, it is very important to understand the time-dependent behavior of rock for evaluating long-term mechanical stability. The purpose of this study is to determine the mechanisms of time-dependent behavior of rock by the precise test (e.g. laboratory creep test), observation and measurement and to develop methods for evaluating long-term mechanical stability. In previous works, testing techniques were established and basic evaluation methods were developed. Recently, some parameters, which required for simulation of time-dependent behavior, were determined for the modeling of biotite granite (Toki granite) distributed around the Mizunami underground research laboratory. However, we were not able to obtain enough data to assess the reliability of the method to evaluate these parameters. This report describes the results of the research activities carried out in fiscal year 2012. In Chapter 1, we provide background and an overview of this study. In Chapter 2, the results of a long-term creep test on Tage tuff, started in fiscal year 1997, are described. In Chapter 3, the experimental results concerning the loading-rate dependency of rock strength were examined to understand the time-dependent behavior of rock. In Chapter 4, the stability of tunnels, under conditions which rock stress is larger than that around a circular tunnel, were examined to obtain useful information on the future plan for in-situ tests in the underground research laboratory. (author)

  1. A study about the long-term stability of sedimentary rock

    International Nuclear Information System (INIS)

    Yoshino, Naoto; Miyanomae, Shun-ichi; Inoue, Hiroyuki; Nashimoto, Yutaka

    2005-02-01

    In this paper, following two issues were examined and estimated, (1) the influence of near field condition factor to the dynamical behavior of sedimentary soft rock, (2) the long term estimation of the dynamical behavior considering the condition of Horonobe area. As the study about the influence of near field condition factor to the dynamical behavior of sedimentary soft rock, the thermal factor was focused on and the laboratory tests using test pieces which were sampled in Horonobe area were carried out under the water temperature were 20 degrees and 80 degrees. As a result, the time dependence parameter in variable-compliance-type constitutive-equation could be obtained. And comparison between creep property under 20 degrees and 80 degrees was conducted. In addition, the general properties of sedimentary soft rock under several conditions were identified by the survey of the literature. And the way how to confirm the dynamical properties of sedimentary soft rock with in-situ test were presented. For the study on the short-term and long-term stability of rock surrounding buffer materials, numerical simulations were carried out assuming several conditions. The direction of disposal tunnels and the ratio of rock strength by initial stress were estimated to be the main factor affecting the short-term stability of rock. Time dependency of rock and the stiffness of buffer material were estimated to be the main factor affecting the long-term stability of rock. (author)

  2. Xerostomia and medication: a cross-sectional study in long-term geriatric wards.

    Science.gov (United States)

    Desoutter, A; Soudain-Pineau, M; Munsch, F; Mauprivez, C; Dufour, T; Coeuriot, J-L

    2012-01-01

    The purpose of this study was to determine the prevalence of xerostomia in old people living in long-term geriatric wards, and to measure the relationship between xerostomia and etiologic factors such as age and medication (total number of medications, xerogenic medications, anticholinergic medications and medications that induce hypersialorrhea). An observational retrospective, comparative, multicentre epidemiological study. Long-term geriatric wards, in Reims, France. 769 old people living in long-term geriatric wards. Prevalence of xerostomia assessed from age, total number of medications, xerogenic medications, anticholinergic medications and those that induce hypersialorrhea. Multivariable logistic regression was used to calculate Odds Ratios (OR) and their 95% Confidence Intervals (95% CI). Among 769 old people (average age 84.6±8.4 years old), 287 residents suffered from xerostomia (37.3%). Significant predictors of xerostomia were: resident's age OR=1.56, 95% CI (1.30-1.88), pxerostomia identified was medications that induce hypersialorrhea OR=0.81, 95% CI (0.67-0.98), p=0.03. The total number of medications and xerogenic medications did not play a significant role in xerostomia. Increasing Age and anticholinergic medications induce a dry mouth. Conversely, the total number of medications and xerogenic medications do not influence xerostomia. Medications that induce hypersialorrhea protect against the occurrence of dry mouth.

  3. Data collection and storage in long-term ecological and evolutionary studies: The Mongoose 2000 system.

    Science.gov (United States)

    Marshall, Harry H; Griffiths, David J; Mwanguhya, Francis; Businge, Robert; Griffiths, Amber G F; Kyabulima, Solomon; Mwesige, Kenneth; Sanderson, Jennifer L; Thompson, Faye J; Vitikainen, Emma I K; Cant, Michael A

    2018-01-01

    Studying ecological and evolutionary processes in the natural world often requires research projects to follow multiple individuals in the wild over many years. These projects have provided significant advances but may also be hampered by needing to accurately and efficiently collect and store multiple streams of the data from multiple individuals concurrently. The increase in the availability and sophistication of portable computers (smartphones and tablets) and the applications that run on them has the potential to address many of these data collection and storage issues. In this paper we describe the challenges faced by one such long-term, individual-based research project: the Banded Mongoose Research Project in Uganda. We describe a system we have developed called Mongoose 2000 that utilises the potential of apps and portable computers to meet these challenges. We discuss the benefits and limitations of employing such a system in a long-term research project. The app and source code for the Mongoose 2000 system are freely available and we detail how it might be used to aid data collection and storage in other long-term individual-based projects.

  4. A study of long-term complications associated with enteral ostomy and their contributory factors.

    Science.gov (United States)

    Jayarajah, Umesh; Samarasekara, Asuramuni M P; Samarasekera, Dharmabandhu N

    2016-12-05

    Complications of ostomy significantly affect the quality of life of ostomates. There is little evidence on the rate of long-term complications in ostomates, especially from the developing countries which include Sri Lanka. This study was aimed to describe the long-term complications of enteral ostomies and their contributory factors. A retrospective analysis was carried out on 192 patients who underwent ostomy creation over a period of 5 years. Data on type of complications, age, sex, type of ostomy, type of surgery and perioperative care by enteric stoma therapist were gathered. Associations were established using Chi square test and multiple logistic regression. Out of 192 patients, only 146 patients presented regularly for follow up. The mean follow up duration was 28 months (range: 3-183). Around 34.2% developed surgical long-term complications related to the ostomy. Common complications were prolapse (n = 24, 16.4%), skin excoriation (n = 22, 15.1%) and parastomal hernia (n = 14, 9.6%). Overall complication rate was significantly less in loop ostomies (p ostomies (p ostomies (p < 0.05). Perioperative care by enteric stoma therapist reduced the overall and specific complications (p < 0.001). The overall complication rate in our cohort of patients was 34.2%. The perioperative care of a stoma therapist may be very effective in preventing complications particularly in a setting with limited resources.

  5. A clinical case study of long-term injury of the thoracic and lumbar spine

    Directory of Open Access Journals (Sweden)

    Vladimir V Zaretskov

    2016-06-01

    Full Text Available Overestimation of the efficacy of conservative treatment of spine injuries children often leads to unsatisfactory long-term results. The effective correction of post-traumatic spinal column deformities occurs in patients who undergo the operation in the early post-traumatic period. While choosing treatment strategies for children, higher reparative opportunities, which provide early fracture consolidation, including those in faulty positions, should be considered. This study presents a case of surgical treatment for uncomplicated injury of the thoracic and lumbar spine, with long-term compression fragmental fracture of the L1 vertebra body in a 12-year-old child. Due to the long-standing character of the injury right thoraco-frenotomy was conducted with partial L1 vertebral body and resection of the adjacent discs, deformity correction of the thoracic and lumbar spine with a transpedicular system, and ventral spondylodesis with an autograft. This extensive intervention was justified by the peculiarities in the vertebral body damage and the post-traumatic segmental kyphotic deformity that resulted from delayed medical treatment. An anterior approach was chosen to achieve immobilization at the site of the damage before correction using the transpedicular system. Surgical correction of long-term spinal injuries in children, with the use of a combined approach, is usually laborious and traumatic. The prevention of rigid post-traumatic spine deformities with the help of timely diagnostics and appropriate treatment, including surgery, should be a priority to prevent such cases.

  6. Long-Term Efficacy and Safety of Biodegradable-Polymer Biolimus-Eluting Stents

    DEFF Research Database (Denmark)

    Kaiser, Christoph; Galatius, Søren; Jeger, Raban

    2015-01-01

    -DES, or thin-strut silicon-carbide-coated BMS in 8 European centers. All patients were treated with aspirin and risk-adjusted doses of prasugrel. The primary end point was combined cardiac death, myocardial infarction, and clinically indicated target-vessel revascularization within 2 years. The combined...... secondary safety end point was a composite of VLST, myocardial infarction, and cardiac death. The cumulative incidence of the primary end point was 7.6% with BP-DES, 6.8% with DP-DES, and 12.7% with BMS. By intention-to-treat BP-DES were noninferior (predefined margin, 3.80%) compared with DP-DES (absolute...

  7. 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)

  8. Phenomenological study on crystalline rock for evaluating of long-term behavior (Contract research)

    International Nuclear Information System (INIS)

    Okubo, Seisuke; Fukui, Katsunori; Hashiba, Kimihiro; Hikima, Ryoichi; Tanno, Takeo; Sanada, Hiroyuki; Matsui, Hiroya; Sato, Toshinori

    2012-02-01

    Rock, under in situ conditions, shows time-dependent behavior such as creep/relaxation. With respect to high-level radioactive waste disposal, knowledge of the long-term mechanical stability of shafts and galleries excavated in rock is required, not only during construction and operation but also over a period of thousands of years after closure. Therefore, it is very important to understand the time-dependent behavior of rock for evaluating long-term mechanical stability. The purpose of this study is determining the mechanisms of time-dependent behavior of rock by precise testing, observation and measurement in order to develop methods for evaluating long-term mechanical stability of a rock mass. In the previous work, testing techniques have been established and basic evaluation methods were developed. Recently, some parameters needed for simulation of time-dependent behavior were determined at the Mizunami underground research facilities. However, sufficient data to check the reliability of the evaluation method for these parameters were not available. This report describes the results of the activities in fiscal year 2010. In Chapter 1, we provide an overview and the background to this study. In Chapter 2, the results of a long-term creep test on Tage tuff, started in fiscal year 1997 are described. In Chapter 3, the relation of loading-rate dependency of strength and stress dependency of creep life, the relation of time dependency, probability distribution and size effects are discussed to indicate more clearly the meaning of the value of 'n' to express the degree of time dependency of the rock. Furthermore, past studies concerning the value of 'n' are reviewed and the tests that could be carried out in future studies of mechanical properties and time dependency of Toki granite are considered in this Chapter. In Chapter 4, failure criterions of a rock mass considering time dependency are discussed. In Chapter 5, the FEM analysis implemented with a generalized

  9. 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

  10. Long-term efficacy, safety and tolerability of Remoxy for the management of chronic pain.

    Science.gov (United States)

    Pergolizzi, Joseph V; Zampogna, Gianpietro; Taylor, Robert; Raffa, Robert B

    2015-03-01

    Historically, chronic pain generally went under-treated for a variety of objective and subjective reasons, including difficulty to objectively diagnose and manage over a long period of time, potential serious adverse effects of commonly available medications, and patient, healthcare and societal concerns over opioid medications. More recently, in an effort to redress the under-treatment of pain, the number of prescriptions of opioid analgesics has risen dramatically. However, paralleling the increased legitimate use has been a concomitant increase in opioid abuse, misuse and diversion. Pharmaceutical companies have responded by developing a variety of opioid formulations designed to deter abuse by making the products more difficult to tamper with. One such product is Remoxy(®), an extended-release formulation of the strong opioid oxycodone. We review the efficacy, safety and tolerability of this formulation based on the available published literature.

  11. 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.

  12. [Transparency and replicability of nursing intervention studies in long-term care: A selective literature review].

    Science.gov (United States)

    Gspörer, Irene; Schrems, Berta M

    2018-05-01

    The development and evaluation of interventions in long-term care is time-consuming and expensive due to their complexity. To ensure reproducibility and successful implementation, these interventions must be described and published in a comprehensible and qualitative manner. The aim of this study is to analyze intervention studies from the inpatient long-term care setting with regard to their completeness, reporting quality, transparency and thus reproducibility. The completeness and the reporting quality of the interventions described in the publications were examined in the context of a selective literature review by means of intervention studies from the long-term care setting (n=22). To this end, the Template for Intervention Description and Replication (TIDieR) checklist and the Criteria for Reporting the Development and Evaluation of Complex Interventions in Healthcare 2 (CReDECI2-DE) list were used. Transparency criteria included study registration and access to study protocols. The TIDieR checklist examination revealed that only three studies contained all the information necessary; the CReDECI2 test provided a complete description for only one study. Frequent shortcomings were observed concerning the information on modifications and titrations for the study participants and the location. Protocols were available for eight studies, 14 studies were registered. In terms of science, this means that the reproducibility of scientific findings is limited, which is why they cannot provide secure knowledge. As a result, the practical benefit to be derived from published studies that are accessible to decision-makers is limited as well. As far as publishers are concerned they should pay more attention to the completeness, registration and availability of materials. Copyright © 2018. Published by Elsevier GmbH.

  13. Nuclear Materials Diversion Safety and the Long-term Future of Nuclear Energy

    International Nuclear Information System (INIS)

    Knapp, V.

    2002-01-01

    Primarily due to irresponsible cold war politics of nuclear weapon countries nuclear proliferation situation is little short of getting out of control. In addition to five nominal nuclear weapon countries there are at present at least three more nuclear weapon countries and several countries with nuclear weapon potential. Non-proliferation treaty (NPT), signed in 1970, has been recognized by most non-nuclear weapon countries as unjust and ineffective. After the initial, deliberate, nuclear weapon developments of five nominal nuclear weapon countries, subsequent paths to nuclear weapons have been preceded by nominal peaceful use of nuclear energy. Uranium enrichment installations as well as reprocessing installations in non-nuclear weapon countries are the weakest spots of fuel cycle for diversion of nuclear materials either by governments or by illicit groups. An energy scenario, which would, by the end of century, replace the large part of fossil fuels use through extension of present nuclear practices, would mean very large increase in a number of such installations, with corresponding increase of the probability of diversion of nuclear materials. Such future is not acceptable from the point of view of proliferation safety. Recent events make it clear, that it cannot be accepted from the requirements of nuclear terrorism safety either. Nuclear community should put it clearly to their respective governments that the time has come to put general interest before the supposed national interest, by placing all enrichment and reprocessing installations under full international control. Such internationalization has a chance to be accepted by non-nuclear weapon countries, only in case should it apply to nuclear weapon countries as well, without exception. Recent terrorist acts, however horrible they were, are child,s play compared with possible acts of nuclear terrorism. Nuclear energy can be made proliferation safe and diversion of nuclear materials safe, and provide

  14. 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

  15. Mortality and life expectancy in relation to long-term cigarette, cigar and pipe smoking: The Zutphen Study

    NARCIS (Netherlands)

    Streppel, M.T.; Boshuizen, H.C.; Ocké, M.C.; Kok, F.J.; Kromhout, D.

    2007-01-01

    Study objective: To study the effect of long-term smoking on all-cause and cause-specific mortality, and to estimate the effects of cigarette and cigar or pipe smoking on life expectancy. Design: A long-term prospective cohort study. Setting: Zutphen, The Netherlands. Participants: 1373 men from the

  16. Safety of long-term subcutaneous free flap skin banking after skin-sparing mastectomy.

    Science.gov (United States)

    Verstappen, Ralph; Djedovic, Gabriel; Morandi, Evi Maria; Heiser, Dietmar; Rieger, Ulrich Michael; Bauer, Thomas

    2018-03-01

    A persistent problem in autologous breast reconstruction in skin-sparing mastectomies is skin restoration after skin necrosis or secondary oncological resection. As a solution to facilitate reconstruction, skin banking of free-flap skin has been proposed in cases where the overlying skin envelope must be resected, as this technique spares the patient an additional donor site. Herein, we present the largest series to date in which this method was used. We investigated its safety and the possibility of skin banking for prolonged periods of time. All skin-sparing mastectomies and immediate autologous breast reconstructions from December 2009 until June 2013 at our institution were analysed. We identified 31 patients who underwent 33 free flap reconstructions in which skin banking was performed. Our median skin banking period was 7 days, with a maximum duration of 171 days. In 22.5% of cases, the banked skin was used to reconstruct overlying skin defects, and in 9.6% of cases to reconstruct the nipple-areolar complex. Microbiological and histological investigations of the banked skin revealed neither clinical infections nor malignancies. In situ skin banking, even for prolonged periods of time, is a safe and cost-effective method to ensure that skin defects due to necrosis or secondary oncological resection can be easily reconstructed.

  17. Safety of long-term subcutaneous free flap skin banking after skin-sparing mastectomy

    Directory of Open Access Journals (Sweden)

    Ralph Verstappen

    2018-03-01

    Full Text Available Background A persistent problem in autologous breast reconstruction in skin-sparing mastectomies is skin restoration after skin necrosis or secondary oncological resection. As a solution to facilitate reconstruction, skin banking of free-flap skin has been proposed in cases where the overlying skin envelope must be resected, as this technique spares the patient an additional donor site. Herein, we present the largest series to date in which this method was used. We investigated its safety and the possibility of skin banking for prolonged periods of time. Methods All skin-sparing mastectomies and immediate autologous breast reconstructions from December 2009 until June 2013 at our institution were analysed. Results We identified 31 patients who underwent 33 free flap reconstructions in which skin banking was performed. Our median skin banking period was 7 days, with a maximum duration of 171 days. In 22.5% of cases, the banked skin was used to reconstruct overlying skin defects, and in 9.6% of cases to reconstruct the nipple-areolar complex. Microbiological and histological investigations of the banked skin revealed neither clinical infections nor malignancies. Conclusions In situ skin banking, even for prolonged periods of time, is a safe and cost-effective method to ensure that skin defects due to necrosis or secondary oncological resection can be easily reconstructed.

  18. The long term storage of radioactive waste: Safety and sustainability. A position paper of international experts

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2003-06-01

    The purpose of the report is to reflect the currently prevailing views among experts in the field of radioactive waste storage and disposal. It is intended for use as a central and authoritative reference point for national discussions and policy papers. It is therefore potentially useful to national committees and bodies concerned with the management of radioactive waste. It may also be of value to concerned members of the public since it is written in language that should be comprehensible to the informed lay person. It was produced as a result of several meetings of experts in the first part of 2002. Since then, it has been reviewed by the international Waste Safety Standards Committee (WASSC), by the WASSC Subgroup on Principles and Criteria for the Disposal of Radioactive Waste at its meeting in October 2000 and by a technical committee convened specifically to review the paper at a meeting held in November 2002. Finally, the essential conclusions of the paper were presented to and discussed with participants to the International Conference on Issues and Trends in Radioactive Waste Management, held in Vienna in December 2002.

  19. The long term storage of radioactive waste: Safety and sustainability. A position paper of international experts

    International Nuclear Information System (INIS)

    2003-06-01

    The purpose of the report is to reflect the currently prevailing views among experts in the field of radioactive waste storage and disposal. It is intended for use as a central and authoritative reference point for national discussions and policy papers. It is therefore potentially useful to national committees and bodies concerned with the management of radioactive waste. It may also be of value to concerned members of the public since it is written in language that should be comprehensible to the informed lay person. It was produced as a result of several meetings of experts in the first part of 2002. Since then, it has been reviewed by the international Waste Safety Standards Committee (WASSC), by the WASSC Subgroup on Principles and Criteria for the Disposal of Radioactive Waste at its meeting in October 2000 and by a technical committee convened specifically to review the paper at a meeting held in November 2002. Finally, the essential conclusions of the paper were presented to and discussed with participants to the International Conference on Issues and Trends in Radioactive Waste Management, held in Vienna in December 2002

  20. Long-term conditioning of deep-seated rockslides in deglaciated valleys: the Spriana case study

    Science.gov (United States)

    Agliardi, Federico; Crosta, Giovanni B.

    2015-04-01

    Deep-seated rockslides in alpine valleys evolve over long time under the action of multiple triggers. Early Warning based on monitoring is often the only effective approach to cope with these landslides, but it requires an improved understanding of mechanisms interplaying over long time. Deep-seated rockslides are often characterized by long-term 'creep' and seasonal displacement components, contributing to measured displacement patterns which are often modelled as rockslide responses to hydrologic perturbations. Although this hydro-mechanical modelling approach fits the behaviour of disrupted rockslide masses with well-developed shear zones, it is often insufficient to explain the initial onset and the long-term components of creep movements of deep-seated rockslides. This outlines the need to link long-term evolution of rock slopes and their sensitivity to triggers. We discuss the Spriana rockslide, affecting the steep left-hand flank of Val Malenco (italian Central Alps). Documented instabilities date back to 1912, whereas the rockslide underwent major acceleration stages in 1960 and 1977-78 and later minor reactivations. We reviewed a large amount of data collected since 1978 by extensive geotechnical site investigation (borehole drilling, exploratory adits, and seismic refraction) and monitoring activities (ground surface and deep displacements, pore pressures) motivated by potential catastrophic collapse threatening the city of Sondrio area. We performed rock mass characterization based on laboratory studies on intact rock samples, field surveys and drillcore logging. These data allowed re-evaluating the geological model of the Spriana rockslide, which is a compound slide of up to 50 Mm3 of slope debris and fractured gneiss, with multiple shear failure zones up to 90 m deep. Two main scarps developed in different stages, suggesting progressive failure processes. The rockslide creeps at slow rates of 0.4-3 cm/a, and undergoes acceleration stages (weeks to

  1. Long-term Conventionally Dosed Vancomycin Therapy In Patients With Orthopaedic Implant-related Infections Seems As Effective And Safe As Long-term Penicillin Or Clindamycin Therapy. A Retrospective Cohort Study Of 103 Patients.

    Science.gov (United States)

    Aleman, Jacomien; Moojen, Dirk Jan F; van Ogtrop, Marc L; Poolman, Rudolf W; Franssen, Eric J F

    2018-01-01

    Objectives : Antimicrobial therapy is one of the cornerstones of orthopaedic implant-related infections (OIRI) treatment. Infections with Gram-positive bacteria are often treated with vancomycin, penicillin or clindamycin. A recent IDSA guideline suggests increasing the dose of vancomycin to increase the trough vancomycin target serum concentrations. This is deemed necessary because of an observed decrease in vancomycin susceptibility among Gram-positive bacteria. However, elevated vancomycin concentrations are correlated with the risk of nephrotoxicity, especially with prolonged therapy. Compared to most countries, rates of resistance against antibiotics among bacteria in the Netherlands are lower for currently available antibiotics, therefore lower target concentrations of vancomycin are probably efficacious for the treatment of infections. In this study we evaluated the efficacy and safety of long-term conventionally dosed vancomycin therapy, as an initial therapy for OIRI, and compared this with long-term penicillin and clindamycin therapy, as initial therapy, in patients with Gram-positive orthopaedic implant-related infections. Methods : A retrospective, observational study was conducted in 103 adult patients treated for OIRI, with vancomycin, penicillin or clindamycin for at least 10 days. The target trough serum concentration of vancomycin was 10-15 mg/l. Results : 74% of our patients were treated successfully with vancomycin, as initial therapy, (no reinfection within 1 year) versus 55% of our patients treated with either an antibiotic of the penicillin class (mostly flucloxacillin) or clindamycin (p=0.08), as initial therapy. For patients treated with vancomycin we observed a serum creatinine increase of 6 μmol/l, for patients treated with either an antibiotic of the penicillin class or clindamycin the serum creatinine increase was 4 μmol/l (p=0.395). Conclusions : In our population of patients with OIRI long-term treatment with conventionally dosed

  2. 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.

  3. 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

  4. Long-term effects of traffic-related air pollution on mortality in a Dutch cohort (NLCS-AIR study)

    NARCIS (Netherlands)

    Beelen, R.; Hoek, G.; Brandt, P.A. van den; Goldbohm, R.A.; Fischer, P.; Schouten, L.J.; Jerrett, M.; Hughes, E.; Armstrong, B.; Brunekreef, B.

    2008-01-01

    Background: Several studies have found an effect on mortality of between-city contrasts in long-term exposure to air pollution. The effect of within-city contrasts is still poorly understood. Objectives: We studied the association between long-term exposure to traffic-related air pollution and

  5. Mathematical models as tools for probing long-term safety of CO2 storage

    Energy Technology Data Exchange (ETDEWEB)

    Pruess, Karsten; Birkholzer, Jens; Zhou, Quanlin

    2009-02-01

    Subsurface reservoirs being considered for storing CO{sub 2} include saline aquifers, oil and gas reservoirs, and unmineable coal seams (Baines and Worden, 2004; IPCC, 2005). By far the greatest storage capacity is in saline aquifers (Dooley et al., 2004), and our discussion will focus primarily on CO{sub 2} storage in saline formations. Most issues for safety and security of CO{sub 2} storage arise from the fact that, at typical temperature and pressure conditions encountered in terrestrial crust, CO{sub 2} is less dense than aqueous fluids. Accordingly, CO{sub 2} will experience an upward buoyancy force in most subsurface environments, and will tend to migrate upwards whenever (sub-)vertical permeable pathways are available, such as fracture zones, faults, or improperly abandoned wells (Bachu, 2008; Pruess, 2008a, b; Tsang et al., 2008). CO{sub 2} injection will increase fluid pressures in the target formation, thereby altering effective stress distributions, and potentially triggering movement along fractures and faults that could increase their permeability and reduce the effectiveness of a caprock in containing CO{sub 2} (Rutqvist et al., 2008; Chiaramonte et al., 2008). Induced seismicity as a consequence of fluid injection is also a concern (Healy et al., 1968; Raleigh et al., 1976; Majer et al., 2007). Dissolution of CO{sub 2} in the aqueous phase generates carbonic acid, which may induce chemical corrosion (dissolution) of minerals with associated increase in formation porosity and permeability, and may also mediate sequestration of CO{sub 2} as solid carbonate (Gaus et al., 2008). Chemical dissolution of caprock minerals could promote leakage of CO{sub 2} from a storage reservoir (Gherardi et al., 2007). Chemical dissolution and geomechanical effects could reinforce one another in compromising CO{sub 2} containment. Additional issues arise from the potential of CO{sub 2} to mobilize hazardous chemical species (Kharaka et al., 2006), and from migration of

  6. Psychiatric disorders in long-term sickness absence -- a population-based cross-sectional study

    DEFF Research Database (Denmark)

    Søgaard, Hans Jørgen; Bech, Per

    2009-01-01

    AIMS: The study estimates the incidence of psychiatric disorders in long-term sickness absence (LSA; more than eight weeks of continuous sickness absence) over one year. The study is the first accounting for everybody on LSA by linking a psychiatric assessment for all persons on LSA to public...... registers. METHODS: In a Danish population of 120,000 inhabitants all 2,414 incident persons on LSA within one year were posted a questionnaire, of whom 1,121 (46.4%) responded. In a two phase design the 1,121 sick-listed persons were screened for psychiatric disorders. Phase 2 consisted of 844 people...

  7. Senescence in the wild: Insights from a long-term study on Seychelles warblers.

    Science.gov (United States)

    Hammers, Martijn; Kingma, Sjouke A; Bebbington, Kat; van de Crommenacker, Janske; Spurgin, Lewis G; Richardson, David S; Burke, Terry; Dugdale, Hannah L; Komdeur, Jan

    2015-11-01

    Senescence--the progressive age-dependent decline in performance--occurs in most organisms. There is considerable variation in the onset and rate of senescence between and within species. Yet the causes of this variation are still poorly understood, despite being central to understanding the evolution of senescence. Long-term longitudinal studies on wild animals are extremely well-suited to studying the impact of environmental and individual characteristics (and the interaction between the two) on senescence, and can help us to understand the mechanisms that shape the evolution of senescence. In this review, we summarize and discuss the insights gained from our comprehensive long-term individual-based study of the Seychelles warbler (Acrocephalus sechellensis). This species provides an excellent model system in which to investigate the evolution of senescence in the wild. We found that Seychelles warblers show senescent declines in survival and reproduction, and discuss how individual characteristics (body condition, body size) and environmental effects (low- versus high-quality environments) may affect the onset and rate of senescence. Further, we highlight the evidence for trade-offs between early-life investment and senescence. We describe how key cellular and physiological processes (oxidative stress and telomere shortening) underpinning senescence are affected by individual and environmental characteristics in the Seychelles warbler (e.g. food availability, reproductive investment, disease) and we discuss how such physiological variation may mediate the relationship between environmental characteristics and senescence. Based on our work using Seychelles warblers as a model system, we show how insights from long-term studies of wild animals may help unravel the causes of the remarkable variation in senescence observed in natural systems, and highlight areas for promising future research.

  8. EFFECTS OF LONG-TERM PHYSICAL ACTIVITY ON CARDIAC STRUCTURE AND FUNCTION: A TWIN STUDY

    Directory of Open Access Journals (Sweden)

    Urho M.Kujala

    2009-12-01

    Full Text Available Previous studies have shown that athletic training or other physical activity causes structural and functional adaptations in the heart, but less is known how long-term physical activity affects heart when genetic liability and childhood environment are taken into account. The aim of this study was to investigate the effects of long-term physical activity vs. inactivity on cardiac structure and function in twin pairs discordant for physical activity for 32 years. Twelve same-sex twin pairs (five monozygotic and seven dizygotic, 50-67 years were studied as a part of the TWINACTIVE study. Discordance in physical activity was initially determined in 1975 and it remained significant throughout the follow-up. At the end of the follow-up in 2007, resting echocardiographic and electrocardiographic measurements were performed. During the follow-up period, the active co-twins were on average 8.2 (SD 4.0 MET hours/day more active than their inactive co-twins (p < 0.001. At the end of the follow-up, resting heart rate was lower in the active than inactive co-twins [59 (SD 5 vs. 68 (SD 10 bpm, p=0.03]. The heart rate-corrected QT interval was similar between the co-twins. Also, there was a tendency for left ventricular mass per body weight to be greater and T wave amplitude in lead II to be higher in the active co-twins (18% and 15%, respectively, p=0.08 for both. Similar trends were found for both monozygotic and dizygotic twin pairs. In conclusion, the main adaptation to long- term physical activity is lowered resting heart rate, even after partially or fully controlling for genetic liability and childhood environment

  9. 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...

  10. Insomnia in long-term care facilities: a comparison of seven European countries and Israel: the Services and Health for Elderly in Long TERm care study.

    Science.gov (United States)

    Gindin, Jacob; Shochat, Tamar; Chetrit, Angela; Epstein, Shulamit; Ben Israel, Yehoshua; Levi, Sarah; Onder, Graziano; Carpenter, Ian; Finne-Soveri, Harriet; van Hout, Hein; Henrard, Jean-Claude; Nikolaus, Thorsten; Topinkova, Eva; Fialová, Daniela; Bernabei, Roberto

    2014-11-01

    To assess insomnia and its correlates as part of the Services and Health for Elderly in Long TERm care (SHELTER) study, funded by the 7th Framework Programme of the European Union. Cross-cultural investigation. Long-term care facilities (LTCFs) in eight European countries (Czech Republic, France, Finland, Germany, England, the Netherlands, Italy) and one non-European country (Israel). Elderly residents (N = 4,156) of 57 LTCFs. Information on insomnia, age, sex, activities of daily living (ADLs), cognitive status, depression, major stressful life events, physical activity, fatigue, pain, and sleep medication use was extracted from the International Resident Assessment Instrument (interRAI)LTCF instrument. Rates of insomnia and its correlates were analyzed. Multivariate logistic regression was used to assess factors associated with insomnia, controlling for demographic variables. The prevalence of insomnia was 24% (range 13-30%), with significant differences between countries (P < .001). More insomnia complaints were reported in older than younger residents (P < .001). Higher rates of insomnia were associated with hypnosedatives and depression in all countries (P < .001) and with stressful life events, fatigue, and pain in most countries (P < .001). No associations were found between insomnia and ADLs, physical activity, or cognitive status. Age, depression, stressful life events, fatigue, pain and hypnosedatives were independent significant predictors of insomnia, controlling for all other variables and for country. Hypnosedatives and depression were strong predictors of insomnia beyond cultural differences. Overall, psychosocial variables were more strongly related to insomnia than functional and mental capacities. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

  11. [Prevalence of hypertension in elderly long-term care residents in Spain. The Geriatric HTA study].

    Science.gov (United States)

    Martín-Baranera, Montserrat; Sánchez Ferrín, Pau; Armario, Pedro

    2006-11-11

    This study aimed to estimate the prevalence of hypertension in elderly long-term care residents in Spain and to describe such population in terms of comorbidity and hypertension treatment and control. A countrywide cross-sectional study was conducted in May 2003 among long-term care residents aged 65 or more. Patients in palliative care units were excluded. Hypertension was defined in patients who fulfilled at least one of the following criteria: diagnosis of hypertension on the medical record, antihypertensive medication and/or highest blood pressure values during the previous year > or = 140/90 mmHg. Overall, 13,272 subjects - mean age (standard deviation) 82.9 (7.5) years (range: 65-106 years) - were included from 223 centres; 70.6% were women. Almost 2 thirds of patients met at least one hypertension criterion (8,242 patients, 62.1%; 95% confidence interval, 61.3-62.9%). In those patients, other frequent cardiovascular risk factors were obesity (26.3%), diabetes (25.7%) and dislipemia (23.8%). A concomitant diagnosis of dementia, peripheral vascular disease, stroke or congestive heart failure was present in 37.1%, 28.3%, 26.0% and 25.1%, respectively. The proportion of hypertensive patients receiving at least one antihypertensive drug was 69.7%. Diuretics were the most commonly used agents (46.3%), followed by angiotensine converting enzyme inhibitors (34.6%). The latest blood pressure measurement was < 140/90 mmHg in 60.4% of the hypertensive patients. Elderly long-term care residents in Spain showed a high prevalence of hypertension and other cardiovascular risk factors, and a substantial degree of associated clinical conditions. The proportion of antihypertensive drug therapy was comparable to those reported in similar studies.

  12. Studies of long-term noopept and afobazol treatment in rats with learned helplessness neurosis.

    Science.gov (United States)

    Uyanaev, A A; Fisenko, V P

    2006-08-01

    Long-lasting effects of new Russian psychotropic drugs Noopept and Afobazol on active avoidance conditioning and formation of learned helplessness neurosis were studied on an original experimental model in rats. Noopept eliminated the manifestations of learned helplessness after long-term (21-day) treatment by increasing the percent of trained animals. Afobazol was low effective in preventing manifestations of learned helplessness, but if used for a long time, it reduced the incidence of learned helplessness development by increasing the percent of untrained animals.

  13. Study of the effect of aggressive media on the long-term stability of reinforced plates

    International Nuclear Information System (INIS)

    Zelentsov, D.G.; Pochtman, Yu.M.

    1995-01-01

    Many important load-bearing structural elements that operate in agressive media are subjected to simultaneous mechanical and chemical attack. The current status of the problem of designing such members is adequately reflected. It follows from that only a few studies have been devoted to the long-term stability of reinforced plates in aggressive media, and most of them were based on structurally orthotropic theory. Such an approach makes it impossible to construct an adequate model of the deformation process. In particular, it precludes allowance for the effect of the discreteness of the reinforcement on plate stability and determination of changes in the character of deformation of the plate during service

  14. Study of long term chemo-hydro-mechanic behaviour of hydraulic barrier reinforced by polymer

    International Nuclear Information System (INIS)

    Razakamanantsoa, Andry Rico

    2009-01-01

    Passive barrier for landfill liners are designed with bentonite material as Geo-synthetic Clay Liners (GCL's) or Sand Bentonite Mixtures (SBM). This thesis is focused on the experimental study of the long term Chemo-Hydro-Mechanic behaviour of polymer treated geo-materials. Tests are performed with two powder polyelectrolyte polymers (P1, P2). Soil and one selected type of bentonite from a set of six are used. The corresponding testing fluid is composed with: synthesized leachate, CaCl_2 and NaCl. This first step of the study is to select the suitable bentonite (B) and the corresponding polymer concentration (2%) that gives the best swelling ability to the bentonite. Compatibility test of the bentonite polymer mixture with synthesized leachable is done. Tests are performed by fabricating GL's, with filter press and oedo-permeameter. Results show that hydraulic performance grows with the bentonite concentration. And the LS aggressiveness occurs immediately in a case of bentonite. The effects of polymer treatment are different: P1 increases the swelling ability of bentonite by flocculation, P2 increases the hydraulic performance of the bentonite by dispersion. The long term hydraulic performance tests with SBM are carried out with a rigid wall permeameter. Tests results show that pre-hydration delays only the fluid aggressiveness in spite of reducing the corresponding effects. The long term effect of polymer treatment reveals benefits to geo-material behaviour by increasing water retention and reducing the undesired effects of pollutant. The chemical index is proposed to forecast the geo-material degradation. (author)

  15. Long-term contraception in a small implant: A review of Suprelorin (deslorelin) studies in cats.

    Science.gov (United States)

    Fontaine, Christelle

    2015-09-01

    Deslorelin (Suprelorin®; Virbac) is a gonadotropin-releasing hormone (GnRH) agonist licensed in select countries for the long-term suppression of fertility in adult male dogs and male ferrets. This article summarizes studies investigating the use of deslorelin implants for the long-term suppression of fertility in male and female domestic cats. Slow-release deslorelin implants have been shown to generate effective, safe and reversible long-term contraception in male and female cats. In pubertal cats, a 4.7 mg deslorelin implant suppressed steroid sex hormones for an average of approximately 20 months (range 15-25 months) in males and an average of approximately 24 months (range 16-37 months) in females. Reversibility has been demonstrated by fertile matings approximately 2 years post-treatment in both male and female adult cats. In prepubertal female cats of approximately 4 months of age, puberty was postponed to an average of approximately 10 months of age (range 6-15 months) by a 4.7 mg deslorelin implant. The large variability in the duration of suppression of gonadal activity makes the definition of the optimal time for reimplantation quite challenging. In addition, the temporary stimulation phase occurring in the weeks following deslorelin implantation can induce in adult female cats a fertile estrus that needs to be managed to avoid unwanted pregnancy. Longer duration and larger scale controlled field studies implementing blinding, a negative control group and a carefully controlled randomization to each group are needed. Furthermore, the effects of repeated treatment need to be investigated. Finally, the effect of treatment on growth and bone quality of prepubertal cats needs to be assessed. However, the ease of use, long-lasting effects and reversibility of deslorelin implants are strong positive points supporting their use for controlling feline reproduction. © The Author(s) 2015.

  16. A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones

    NARCIS (Netherlands)

    Asscheman, H.; Giltay, E.J.; Megens, J.A.J.; de Ronde, W.; van Trotsenburg, M.A.A.; Gooren, L.J.G.

    2011-01-01

    Objective: Adverse effects of long-term cross-sex hormone administration to transsexuals are not well documented. We assessed mortality rates in transsexual subjects receiving long-term cross-sex hormones. Design: A cohort study with a median follow-up of 18.5 years at a university gender clinic.

  17. Effects of long-term exposure to particulate matter and metal components on mortality in the Rome longitudinal study

    NARCIS (Netherlands)

    Badaloni, Chiara; Cesaroni, Giulia; Cerza, Francesco; Davoli, Marina; Brunekreef, Bert; Forastiere, Francesco

    2017-01-01

    BACKGROUND: The effect of long-term exposure to metal components in particulate matter on mortality are still controversial. OBJECTIVES: To study the association between long-term exposure to PM10, PM2.5, PM2.5 absorbance, particulate matter components (copper, iron, zinc, sulfur, silicon,

  18. Factors influencing antibiotic prescribing in long-term care facilities: a qualitative in-depth study.

    Science.gov (United States)

    van Buul, Laura W; van der Steen, Jenny T; Doncker, Sarah M M M; Achterberg, Wilco P; Schellevis, François G; Veenhuizen, Ruth B; Hertogh, Cees M P M

    2014-12-16

    Insight into factors that influence antibiotic prescribing is crucial when developing interventions aimed at a more rational use of antibiotics. We examined factors that influence antibiotic prescribing in long-term care facilities, and present a conceptual model that integrates these factors. Semi-structured qualitative interviews were conducted with physicians (n = 13) and nursing staff (n = 13) in five nursing homes and two residential care homes in the central-west region of the Netherlands. An iterative analysis was applied to interviews with physicians to identify and categorize factors that influence antibiotic prescribing, and to integrate these into a conceptual model. This conceptual model was triangulated with the perspectives of nursing staff. The analysis resulted in the identification of six categories of factors that can influence the antibiotic prescribing decision: the clinical situation, advance care plans, utilization of diagnostic resources, physicians' perceived risks, influence of others, and influence of the environment. Each category comprises several factors that may influence the decision to prescribe or not prescribe antibiotics directly (e.g. pressure of patients' family leading to antibiotic prescribing) or indirectly via influence on other factors (e.g. unfamiliarity with patients resulting in a higher physician perceived risk of non-treatment, in turn resulting in a higher tendency to prescribe antibiotics). Our interview study shows that several non-rational factors may affect antibiotic prescribing decision making in long-term care facilities, suggesting opportunities to reduce inappropriate antibiotic use. We developed a conceptual model that integrates the identified categories of influencing factors and shows the relationships between those categories. This model may be used as a practical tool in long-term care facilities to identify local factors potentially leading to inappropriate prescribing, and to subsequently

  19. [Study on mechanism of SOM stabilization of paddy soils under long-term fertilizations].

    Science.gov (United States)

    Luo, Lu; Zhou, Ping; Tong, Cheng-Li; Shi, Hui; Wu, Jin-Shui; Huang, Tie-Ping

    2013-02-01

    Fourier transform infrared spectroscopy (FTIR) was applied to study the structure of soil organic matter (SOM) of paddy soils under long-term different fertilization treatments. The aim was to clarify the different distribution of SOM between different fertilization methods and between topsoil and subsoil, and to explore the stability mechanism of SOM under different fertilization treatments. The results showed that the content of topsoil organic carbon (SOC) was the highest under organic-inorganic fertilizations, with the increment of SOC by 18.5%, 12.9% and 18.4% under high organic manure (HOM), low organic manure (LOM) and straw returning (STW) respectively compared with no fertilization treatment (CK). The long-term fertilizations also changed the chemical structure of SOM. As compared with CK, different fertilization treatments increased the functional group absorbing intensity of chemical resistance compounds (aliphatic, aromaticity), carbohydrate and organo-silicon compounds, which was the most distinctive under treatments of HOM, LOM and STW. For example, the absorbing intensity of alkyl was 0.30, 0.25 and 0.29 under HOM, LOM and STW, respectively. These values were increased by 87% , 56% and 81% as compared with that under CK treatment. The functional group absorbing intensity of SOM in the topsoil was stronger than that in the subsoil, with the most distinctive difference under HOM, LOM and STW treatments. The present research indicated that the enhanced chemical resistance of functional group of SOM may contribute to the high contents of SOC in the paddy soils under long-term organic-inorganic fertilizations, which also suggested a chemical stabilization mechanism of SOM in the paddy soils.

  20. [Preoperational study for the improvement of hygiene conditions in long-term care facilities].

    Science.gov (United States)

    Adler, A C; Spegel, H; Kolb, S; Hierl, W; Müller, C; Höller, C; Liebl, B; Rudolph, P; Herr, C

    2014-12-01

    Hygiene is becoming more and more important in long-term care facilities. Long-term care facilities are subject to monitoring by the Public Health Service (PHS) and other authorities. For the PHS in Bavaria the Bavarian Health and Food Safety Authority (Landesamt für Gesundheit und Lebensmittelsicherheit, LGL) published a hygiene monitoring concept and there exists an inspection guide developed by a specialist department for nursing homes and institutions for the handicapped (Fachstelle für Pflege und Behinderteneinrichtungen, FQA). Because inspections are performed in multiprofessional teams, it makes sense to use a coordinated inspection catalog. The aim was to integrate hygienic requirements specified in the Bavarian guidelines for hygiene by the LGL into the inspection guide published by the FQA to obtain a quality assured surveillance. The involved parties were questioned about the inspection guide and their hygiene management and then the hygiene criteria of the LGL were implemented into the inspection guide. Questions dealing with hygiene requirements concerning intensive care, management of multidrug resistant bacteria and interviews with the person responsible for infection control in the facility itself were developed for the first time and were integrated into the inspection guide. The revised inspection guide was tested for its applicability. With the revised inspection guide there now exists a tool which allows not only comprehensive inspections of the facilities including hygiene issues but also a good cooperation of the various parties involved. There are many actions which have to be conveyed into the future, especially programs to train staff to apply the inspection guide and to enhance the ability of all participants to act in cooperation. The guide will also allow the facilities to cooperate more easily and more closely, as the guide takes the respective problems and challenges of the different facilities into consideration. Additionally the

  1. Barrier analogs: Long-term performance issues, preliminary studies, and recommendations

    Energy Technology Data Exchange (ETDEWEB)

    Waugh, W.J. [Rust Geotech, Inc., Grand Junction, CO (United States). Environmental Sciences Lab.; Chatters, J.C.; Last, G.V.; Bjornstad, B.N.; Link, S.O. [Pacific Northwest Lab., Richland, WA (United States); Hunter, C.R. [Cascade Earth Sciences, La Grande, OR (United States)

    1994-02-01

    The US Department of Energy`s Hanford Protective Barrier Development Program is funding studies of natural analogs of the long-term performance of waste site covers. Natural-analog studies examine past environments as evidence for projecting the future performance of engineered structures. The information generated by analog studies is needed to (1) evaluate the designs and results of short term experiments and demonstrations, (2) formulate performance-modeling problems that bound expected changes in waste site environments, and (3) understand emergent system attributes that cannot be evaluated with short-term experiments or computer models. Waste site covers will be part of dynamic environmental systems with attributes that transcend the traits of engineered components. This report discusses results of the previously unreported preliminary studies conducted in 1983 and 1984. These results indicate that analogs could play an important role in predicting the long-term behavior of engineered waste covers. Layered exposures of glacial-flood-deposited gravels mantled with silt or sand that resemble contemporary barrier designs were examined. Bergmounds, another anomaly left by cataclysmic glacial floods, were also examined as analogs of surface gravel.

  2. Controlling for unmeasured confounding and spatial misalignment in long-term air pollution and health studies.

    Science.gov (United States)

    Lee, Duncan; Sarran, Christophe

    2015-11-01

    The health impact of long-term exposure to air pollution is now routinely estimated using spatial ecological studies, owing to the recent widespread availability of spatial referenced pollution and disease data. However, this areal unit study design presents a number of statistical challenges, which if ignored have the potential to bias the estimated pollution-health relationship. One such challenge is how to control for the spatial autocorrelation present in the data after accounting for the known covariates, which is caused by unmeasured confounding. A second challenge is how to adjust the functional form of the model to account for the spatial misalignment between the pollution and disease data, which causes within-area variation in the pollution data. These challenges have largely been ignored in existing long-term spatial air pollution and health studies, so here we propose a novel Bayesian hierarchical model that addresses both challenges and provide software to allow others to apply our model to their own data. The effectiveness of the proposed model is compared by simulation against a number of state-of-the-art alternatives proposed in the literature and is then used to estimate the impact of nitrogen dioxide and particulate matter concentrations on respiratory hospital admissions in a new epidemiological study in England in 2010 at the local authority level. © 2015 The Authors. Environmetrics published by John Wiley & Sons Ltd.

  3. Measuring forgetting: a critical review of accelerated long-term forgetting studies.

    Science.gov (United States)

    Elliott, Gemma; Isaac, Claire L; Muhlert, Nils

    2014-05-01

    Accelerated long-term forgetting (ALF) refers to abnormal forgetting over hours to weeks despite normal acquisition or initial consolidation. Since standardised assessments of memory typically only test at delays of up to 40-minutes, ALF may go undetected in clinical practice. The memory difficulties associated with ALF can however cause considerable distress to patients. It is important therefore that clinicians are aware that ALF may represent a distinct phenomenon that will require additional and careful assessment to aid patients' understanding of the condition and assist in developing strategies to address its effects. At the same time, ALF may also provide insight into long-term memory processes. Studies of ALF in patients with epilepsy have so far demonstrated mixed results, which may reflect differences in methodology. This review explores the methodological issues that can affect forgetting, such as the effects of age, general cognitive function, test sensitivity and initial learning. It then evaluates the extent to which existing studies have considered these key issues. We outline the points to consider when designing ALF studies that can be used to help improve their validity. These issues can also help to explain some of the mixed findings in studies of ALF and inform the design of standardised tests for assessing ALF in clinical practice. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Risperidone long-acting injection: a review of its long term safety and efficacy

    Directory of Open Access Journals (Sweden)

    Michael K Rainer

    2008-08-01

    Full Text Available Michael K RainerMemory-Clinic and Psychiatric Department, Donauspital, Vienna, AustriaAbstract: A long-acting form of the second-generation antipsychotic drug risperidone is now broadly available for the treatment of schizophrenia and closely related psychiatric conditions. It combines the advantage of previously available depot formulations for first-generation drugs with the favorable characteristics of the modern “atypical” antipsychotics, namely higher efficacy in the treatment of the negative symptoms of schizophrenia and reduced motor disturbances. Published clinical studies show an objective clinical efficacy (as per psychiatric symptom scores and relapse data that exceeds that of oral atypical antipsychotics when patients are switched to the long-acting injectable form, a low incidence of treatment-emergent extrapyramidal side effects, and very good acceptance by patients. Available data for maintenance treatment of bipolar disorder show equivalence with the oral form instead of superiority, but are still limited. As it seems likely that efficacy benefits are mostly due to the fact that the injectable form reduces the demand for patient compliance to one physician visit every 2 weeks instead of self-administration on a daily or twice-daily basis, additional potential could exist in other psychiatric disorders where atypical antipsychotic drugs are of benefit but where patient adherence to treatment schedules is typically low.Keywords: risperidone, schizophrenia, psychotic disorders, patient compliance; delayed-action preparations, injections, intramuscular

  5. Creating Long Term Income Streams for the 100 Year Starship Study Initiative

    Science.gov (United States)

    Sylvester, A. J.

    Development and execution of long term research projects are very dependent on a consistent application of funding to maximize the potential for success. The business structure for the 100 Year Starship Study project should allow for multiple income streams to cover the expenses of the research objectives. The following examples illustrate the range of potential avenues: 1) affiliation with a charitable foundation for creating a donation program to fund a long term endowment for research, 2) application for grants to fund initial research projects and establish the core expertise of the research entity, 3) development of intellectual property which can then be licensed for additional revenue, 4) creation of spinout companies with equity positions retained by the lab for funding the endowment, and 5) funded research which is dual use for the technology goals of the interstellar flight research objectives. With the establishment of a diversified stream of funding options, then the endowment can be funded at a level to permit dedicated research on the interstellar flight topics. This paper will focus on the strategy of creating spinout companies to create income streams which would fund the endowment of the 100 Year Starship Study effort. This technique is widely used by universities seeking to commercially develop and market technologies developed by university researchers. An approach will be outlined for applying this technique to potentially marketable technologies generated as a part of the 100 Year Starship Study effort.

  6. Treatment of anorexia nervosa with long-term risperidone in an outpatient setting: case study.

    Science.gov (United States)

    Kracke, Elsa J; Tosh, Aneesh K

    2014-01-01

    There are currently few studies focusing on the efficacy of long-term atypical antipsychotics to treat anorexia nervosa in the pediatric population. This case report follows the treatment of a 17 year-old female with anorexia nervosa over her four-year undergraduate career. After two years of multidisciplinary treatment, low-dose risperidone was initiated due to persistence of her disease. She expressed decreased rigidity around meal times, her weight improved and she had resumption of menses. She was compliant with treatment through graduation and maintained her weight gain. Atypical antipsychotics are a treatment option in the management of anorexia nervosa. Risperidone has not been studied as frequently as olanzapine for eating disorders. Risperidone was chosen for its more favorable side effect profile and decreased cost to the patient. Previous studies on anorexia nervosa treatment have occurred during inpatient treatment and have limited follow-up due to patients' refusal to initiate or maintain medication compliance. This case presents 17 months of outpatient data. The efficacy of risperidone therapy was evaluated with frequent weight checks, subjective decrease in rigidity, serial complete metabolic panels, and restoration of menses. In this case report, an adolescent female treated with low-dose risperidone had decreased rigid thinking, weight gain and resolution of secondary amenorrhea without medication side effects. Therefore, the atypical antipsychotic risperidone may be an effective long-term outpatient treatment option for patients with anorexia nervosa.

  7. 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

  8. 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/

  9. 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

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

    Science.gov (United States)

    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

  11. 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)

  12. 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)

  13. Henoch-Schönlein purpura: a long-term prospective study in Greek children.

    Science.gov (United States)

    Fretzayas, Andrew; Sionti, Irini; Moustaki, Maria; Papadimitriou, Anastasios; Nicolaidou, Polyxeni

    2008-12-01

    Henoch-Schönlein purpura is a common vasculitis of childhood. The present study, comprising 74 children enrolled during a 9-year period, aimed to delineate the clinical spectrum and the long term follow-up of the disease. Patients were diagnosed strictly on the criteria established by the American College of Rheumatology. The diagnosis was further strengthened by a skin biopsy performed in more than half of cases (42/74), which revealed leukocytoclastic vasculitis in all patients, whereas IgA deposits were found in 37/42 children. There was a predominance of boys (41 males), and the mean age of study population was 5.2 +/- 2.54 years. Palpable purpura was identified in 73/74 children, whereas transient arthritis manifested in 68/74 children. Gastrointestinal blood loss was elicited in 30 children, 11 of whom had also renal involvement. The latter was seen in 19/74 (25.7%) children, and in the long term follow-up (extended to 2004, from 4-12 years, mean duration 7.3 years), 2 children remained with persistent occult hematuria. Relapses occurred in 49 children (66%), and half of them experienced more than 1 recurrence. Arthritis was less common in the relapsed episodes, and this difference was statistically significant (P period. Recurrences often differ to some extent from the initial episode with arthritis being less common with relapses.

  14. Homeopathic medical practice: Long-term results of a cohort study with 3981 patients

    Directory of Open Access Journals (Sweden)

    Baur Roland

    2005-11-01

    Full Text Available Abstract Background On the range of diagnoses, course of treatment, and long-term outcome in patients who chose to receive homeopathic medical treatment very little is known. We investigated homeopathic practice in an industrialized country under everyday conditions. Methods In a prospective, multicentre cohort study with 103 primary care practices with additional specialisation in homeopathy in Germany and Switzerland, data from all patients (age >1 year consulting the physician for the first time were observed. The main outcome measures were: Patient and physician assessments (numeric rating scales from 0 to 10 and quality of life at baseline, and after 3, 12, and 24 months. Results A total of 3,981 patients were studied including 2,851 adults (29% men, mean age 42.5 ± 13.1 years; 71% women, 39.9 ± 12.4 years and 1,130 children (52% boys, 6.5 ± 3.9 years; 48% girls, 7.0 ± 4.3 years. Ninety-seven percent of all diagnoses were chronic with an average duration of 8.8 ± 8 years. The most frequent diagnoses were allergic rhinitis in men, headache in women, and atopic dermatitis in children. Disease severity decreased significantly (p Conclusion Disease severity and quality of life demonstrated marked and sustained improvements following homeopathic treatment period. Our findings indicate that homeopathic medical therapy may play a beneficial role in the long-term care of patients with chronic diseases.

  15. Renal function and long-term decline in cognitive function: the Baltimore Longitudinal Study of Aging.

    Science.gov (United States)

    Seliger, Stephen L; Wendell, Carrington R; Waldstein, Shari R; Ferrucci, Luigi; Zonderman, Alan B

    2015-01-01

    Renal disease has been associated with greater risk of dementia and greater cognitive impairment. However, the relationship of lower renal function with long-term decline in specific domains of cognitive function remains unclear among community-dwelling, non-demented individuals. Stroke- and dementia-free participants (n = 2,116) were enrolled in the Baltimore Longitudinal Study of Aging, a community-based, prospective, longitudinal study. Renal function was estimated by the inverse of serum creatinine adjusted for age, sex and race and (in sensitivity analyses) estimated glomerular filtration rate (eGFR) using the MDRD formula. Outcome measures were changes in scores on 6 cognitive tests encompassing a range of cognitive functions, measured at 2-year intervals. Mixed-effects regression models examined the longitudinal relations of renal function with cognitive functions after adjusting for demographics, comorbidity and other potential confounders. Mean age at initial testing was 53.9 years (SD 17.1), and 94 participants (4.4%) had an eGFR age, longitudinal increases in creatinine concentrations were associated with more rapid decline in performance on several cognitive measures, including the learning slope of the California Verbal Learning Test, a test of verbal learning (p renal function independently associated with greater long-term declines in visual memory and verbal memory and learning. © 2015 National Institutes of Health (NIH). Published by S. Karger AG, Basel.

  16. A time-course study of long term over-expression of ARR19 in mice

    Science.gov (United States)

    Qamar, Imteyaz; Ahmad, Mohammad Faiz; Narayanasamy, Arul

    2015-01-01

    A leucine-rich protein, ARR19 (androgen receptor corepressor-19 kDa), is highly expressed in male reproductive organs and moderately in others. Previously, we have reported that ARR19 is differentially expressed in adult Leydig cells during the testis development and inhibits steroidogenesis by reducing the expression of steroidogenic enzymes. Whereas in prostate, ARR19 represses the transcriptional activity of AR (androgen receptor), it is important for male sexual differentiation and maturation in prostate and epididymis, through the recruitment of HDAC4. In this study we show that long term adenovirus mediated overexpression of ARR19 in mice testis has the potential of inhibiting the differentiation of testicular and prostatic cells by reducing the size of testis and prostate but has no effect on the growth of seminal vesicles. Further, it reduces the level of progesterone and testosterone by reducing the steroidogenic enzymes such as 3HSD, P450c17 and StAR. This is the first study reporting a time-course analysis of the implications of long term overexpression of ARR19 in mice testis and its effect on other organs such as prostate and seminal vesicles. Taken together, these results suggest that ARR19 may play an important role in the differentiation of male reproductive organs such as testis and prostate. PMID:26260329

  17. Efficacy and safety of pimecrolimus cream in the long-term management of atopic dermatitis in children.

    Science.gov (United States)

    Wahn, Ulrich; Bos, Jan D; Goodfield, Mark; Caputo, Ruggero; Papp, Kim; Manjra, Ahmed; Dobozy, Attila; Paul, Carle; Molloy, Stephen; Hultsch, Thomas; Graeber, Michael; Cherill, Robert; de Prost, Yves

    2002-07-01

    Pimecrolimus cream (SDZ ASM 981), a nonsteroid inhibitor of inflammatory cytokines, is effective in atopic dermatitis (AD). We assessed whether early treatment of AD signs/symptoms with pimecrolimus could influence long-term outcome by preventing disease flares. Early intervention with pimecrolimus was compared with a conventional AD treatment strategy (ie, emollients and topical corticosteroids). In this 1-year, controlled, double-blind study, 713 AD patients (2-17 years) were randomized 2:1 to a pimecrolimus-based or conventional regimen. Both groups used emollients for dry skin. Early AD signs/symptoms were treated with pimecrolimus cream or, in the conventional treatment group, vehicle to prevent progression to flares. If flares occurred, moderately potent topical corticosteroids were mandated. The primary efficacy endpoint was ranked flares at 6 months. Safety was monitored clinically, and a skin recall-antigen test was performed at study completion. BASELINE CHARACTERISTICS OF THE PATIENTS: The mean age for both groups was approximately 8 years, and the majority of patients had moderate disease at baseline. PATIENT FOLLOW-UP AND EXPOSURE TO STUDY MEDICATION: The mean duration of follow-up (+/-standard error) was 303.7 (+/-5.30) days in the pimecrolimus group and 235.2 (+/-9.40) days in the control group. The discontinuation rate was significantly higher in the control group than in the pimecrolimus group (51.5% vs 31.6% at 12 months), and proportionately more patients with severe or very severe disease discontinued in the control group. The main reason for the higher discontinuation rate in the control group was unsatisfactory therapeutic effect (30.4% vs 12.4%). This resulted in a substantially higher mean number of study medication treatment days in the pimecrolimus group compared with the control group: 211.9 (69.8% of study days) versus 156.0 (66.3% of study days). Of those patients who completed 12 months on study, 14.2% and 7.0% of patients in the

  18. Anaemia and long term mortality in heart failure patients: a retrospective study

    DEFF Research Database (Denmark)

    Charlot, Mette; Torp-Pedersen, Christian; Valeur, Nana

    2010-01-01

    Anaemia has been demonstrated as a risk factor in patients with heart failure over periods of a few years, but long term data are not available. We examined the long-term risk of anaemia in heart failure patients during 15 years of follow-up.......Anaemia has been demonstrated as a risk factor in patients with heart failure over periods of a few years, but long term data are not available. We examined the long-term risk of anaemia in heart failure patients during 15 years of follow-up....

  19. Evaluation of the long-term efficacy and safety of an imidacloprid 10%/flumethrin 4.5% polymer matrix collar (Seresto® in dogs and cats naturally infested with fleas and/or ticks in multicentre clinical field studies in Europe

    Directory of Open Access Journals (Sweden)

    Stanneck Dorothee

    2012-03-01

    Full Text Available Abstract Background The objective of these two GCP multicentre European clinical field studies was to evaluate the long-term efficacy and safety of a new imidacloprid/flumethrin collar (Seresto®, Bayer AnimalHealth, Investigational Veterinary Product(IVP in dogs and cats naturally infested with fleas and/or ticks in comparison to a dimpylat collar ("Ungezieferband fuer Hunde/fuer Katzen", Beaphar, Control Product (CP. Methods 232 (IVP and 81 (CP cats and 271(IVP and 129 (CP dogs were treated with either product according to label claims and formed the safety population. Flea and tick counts were conducted in monthly intervals for up to 8 months in the efficacy subpopulation consisting of 118 (IVP + 47 (CP cats and 197 (IVP + 94 (CP dogs. Efficacy was calculated as reduction of infestation rate within the same treatment group and statistically compared between the two treatment groups. Results Preventive efficacy against fleas in cats/dogs varied in the IVP group between 97.4%/94.1% and 100%/100% (overall mean: 98.3%/96.7% throughout the 8 month period and in the CP group between 57.1%/28.2% and 96.1%/67.8% (overall mean: 79.3%/57.9%. Preventive efficacy against ticks in cats/dogs varied in the IVP group between 94.0%/91.2% and 100%/100% (overall mean: 98.4%/94.7% throughout the 8 month period and in the CP group between 90.7%/79.9% and 100%/88.0% (overall mean: 96.9%/85.6%. The IVP group was statistically non-inferior to the CP group, and on various assessment days, statistical superiority was proven for flea and tick count reduction in dogs and cats. Both treatments proved to be safe in dogs and cats with mainly minor local observations at the application site. There was moreover, no incidence of any mechanical problem with the collar in dogs and cats during the entire study period. Conclusions The imidacloprid/flumethrin collar proved to reduce tick counts by at least 90% and flea counts by at least 95% for a period of at least 7-8 months in

  20. Evaluation of the long-term efficacy and safety of an imidacloprid 10%/flumethrin 4.5% polymer matrix collar (Seresto®) in dogs and cats naturally infested with fleas and/or ticks in multicentre clinical field studies in Europe

    Science.gov (United States)

    2012-01-01

    Background The objective of these two GCP multicentre European clinical field studies was to evaluate the long-term efficacy and safety of a new imidacloprid/flumethrin collar (Seresto®, Bayer AnimalHealth, Investigational Veterinary Product(IVP)) in dogs and cats naturally infested with fleas and/or ticks in comparison to a dimpylat collar ("Ungezieferband fuer Hunde/fuer Katzen", Beaphar, Control Product (CP)). Methods 232 (IVP) and 81 (CP) cats and 271(IVP) and 129 (CP) dogs were treated with either product according to label claims and formed the safety population. Flea and tick counts were conducted in monthly intervals for up to 8 months in the efficacy subpopulation consisting of 118 (IVP) + 47 (CP) cats and 197 (IVP) + 94 (CP) dogs. Efficacy was calculated as reduction of infestation rate within the same treatment group and statistically compared between the two treatment groups. Results Preventive efficacy against fleas in cats/dogs varied in the IVP group between 97.4%/94.1% and 100%/100% (overall mean: 98.3%/96.7%) throughout the 8 month period and in the CP group between 57.1%/28.2% and 96.1%/67.8% (overall mean: 79.3%/57.9%). Preventive efficacy against ticks in cats/dogs varied in the IVP group between 94.0%/91.2% and 100%/100% (overall mean: 98.4%/94.7%) throughout the 8 month period and in the CP group between 90.7%/79.9% and 100%/88.0% (overall mean: 96.9%/85.6%). The IVP group was statistically non-inferior to the CP group, and on various assessment days, statistical superiority was proven for flea and tick count reduction in dogs and cats. Both treatments proved to be safe in dogs and cats with mainly minor local observations at the application site. There was moreover, no incidence of any mechanical problem with the collar in dogs and cats during the entire study period. Conclusions The imidacloprid/flumethrin collar proved to reduce tick counts by at least 90% and flea counts by at least 95% for a period of at least 7-8 months in cats and dogs

  1. Long term mortality study of chromate pigment workers who suffered lead poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Davies, J.M.

    1984-05-01

    Long term mortality was studied in a group of 57 chromate pigment workers who suffered clinical lead poisoning, mostly between 1930 and 1945. One death was attributed to lead poisoning and there were significant excesses of deaths from nephritis (observed/expected 3/0.24) and cerebrovascular disease (9/2.20), as well as non-significant excesses for respiratory diseases (7/3.59) and accidents and violence (3/1.13). The deaths from nephritis followed long spells of service exceeding 10 years. Poisoning appeared to have more adverse long term effects on older workers: 15 men aged 40 or over at the time of acute poisoning experienced generally high mortality, and 30 years later or by the end of 1981 only two survived instead of the seven expected. The risk of cerebrovascular disease appeared to be unrelated to duration of exposure and affected even men employed for under one year. Excluding the 57 lead poisoned men, other contemporary workers at the factories showed no excess mortality from cerebrovascular disease.

  2. ALTERATIONS IN BRAIN CREATINE CONCENTRATIONS UNDER LONG-TERM SOCIAL ISOLATION (EXPERIMENTAL STUDY).

    Science.gov (United States)

    Koshoridze, N; Kuchukashvili, Z; Menabde, K; Lekiashvili, Sh; Koshoridze, M

    2016-02-01

    Stress represents one of the main problems of modern humanity. This study was done for understanding more clearly alterations in creatine content of the brain under psycho-emotional stress induced by long-term social isolation. It was shown that under 30 days social isolation creatine amount in the brain was arisen, while decreasing concentrations of synthesizing enzymes (AGAT, GAMT) and creatine transporter protein (CrT). Another important point was that such changes were accompanied by down-regulation of creatine kinase (CK), therefore the enzyme's concentration was lowered. In addition, it was observed that content of phosphocreatine (PCr) and ATP were also reduced, thus indicating down-regulation of energy metabolism of brain that is really a crucial point for its normal functioning. To sum up the results it can be underlined that long-term social isolation has negative influence on energy metabolism of brain; and as a result reduce ATP content, while increase of free creatine concentration, supposedly maintaining maximal balance for ATP amount, but here must be also noted that up-regulated oxidative pathways might have impact on blood brain barrier, resulting on its permeability.

  3. Long-term psychological consequences of symptomatic pulmonary embolism: a qualitative study.

    Science.gov (United States)

    Noble, Simon; Lewis, Rhian; Whithers, Jodie; Lewis, Sarah; Bennett, Paul

    2014-04-02

    To explore the psychological consequences of experiencing symptomatic pulmonary embolism (PE). Qualitative interview-based study using interpretative phenomenological analysis. Outpatients who attended an anticoagulation clinic in a district general hospital. Patients attending an anticoagulation clinic following hospital admission for symptomatic PE were approached to participate. A total of 9 (4 women, 5 men) of 11 patients approached agreed to be interviewed. Participants were aged between 26 and 72 years and had previously experienced a PE between 9 and 60 months (median=26 months, mean=24 months). Audiotaped semistructured qualitative interviews were undertaken to explore participants experiences of having a PE and how it had affected their lives since. Data were transcribed and analysed using interpretative phenomenological analysis to identify emergent themes. Three major themes with associated subthemes were identified. Participants described having a PE as a life-changing experience comprising initial shock, followed by feeling of loss of self, life-changing decisions and behaviour modification. Features of post-traumatic stress disorder (PTSD) were described with flashbacks, hypervigilance and intrusive thoughts being most prevalent. Participants identified several areas of support needed for such patients including easier access to support through information giving and emotional support. Long-term consequences of venous thromboembolism go beyond the physical alone. Patients describe experiencing symptomatic PE to be a life-changing distressing event leading to behaviour modification and in some PTSD. It is likely that earlier psychological intervention may reduce such long-term sequelae.

  4. The Long-Term Consumption of Oats in Celiac Disease Patients Is Safe: A Large Cross-Sectional Study

    Science.gov (United States)

    Aaltonen, Katri; Laurikka, Pilvi; Huhtala, Heini; Mäki, Markku; Kaukinen, Katri; Kurppa, Kalle

    2017-01-01

    A strict gluten-free diet (GFD) can be diversified by non-contaminated oats, but there is a shortage of long-term studies concerning its safety. We compared long-term treatment outcomes and factors associated with the introduction of oats between celiac patients on a GFD with or without oats. Eight hundred sixty-nine previously diagnosed celiac patients were interviewed. The validated Gastrointestinal Symptom Rating Scale (GSRS), Psychological General Well-Being (PGWB), and Short-Form 36 Health Survey (SF-36) questionnaires were used to assess symptoms and quality of life, serological tests were performed, and results of histology were confirmed from patient records. We found the median duration of GFD to be 10 years and 82% using oats. Factors predicting the consumption of oats were diagnosis after the year 2000, advice from a dietitian, detection by screening, and mild clinical presentation. Oat consumers and non-consumers did not differ in dietary adherence (96.5% vs. 97.4%, p = 0.746), the prevalence of symptoms (22.9% vs. 22.5%, p = 0.931), positivity for endomysial antibodies (8.8% vs. 6.0%, p = 0.237), histological recovery after one year (63.1% vs. 60.0%, p = 0.773), malignancy (4.8% vs. 3.3%, p = 0.420), osteoporosis/osteopenia (9.2% vs. 11.0%, p = 0.489), or fractures (26.9% vs. 27.9%, p = 0.791). The oat consumers had better SF-36 physical role limitations and general health scores. Based on our results, the long-term consumption of oats in celiac disease patients is safe and may improve quality of life. PMID:28617328

  5. 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

  6. 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.)

  7. The Cottonwood Lake study area, a long-term wetland ecosystem monitoring site

    Science.gov (United States)

    Mushet, David M.; Euliss, Ned H.

    2012-01-01

    The Cottonwood Lake study area is one of only three long-term wetland ecosystem monitoring sites in the prairie pothole region of North America; the other two are Orchid Meadows in South Dakota and St. Denis in Saskatchewan. Of the three, Cottonwood Lake has, by far, the longest continuous data-collection record. Research was initiated at the study area in 1966, and intensive investigations of the hydrology, chemistry, and biology of prairie pothole wetlands continue at the site today. This fact sheet describes the study area, provides an overview of wetland ecology research that has been conducted at the site in the past, and provides an introduction to current work being conducted at the study area by USGS scientists.

  8. Long-term studies of Markarian 421 from 2007 to 2009

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, Sonja; Overkemping, Ann-Kristin [TU Dortmund, Dortmund (Germany); Manganaro, Marina [IAC La Laguna, Teneriffa (Spain); Tescaro, Diego [INFN, Padova (Italy); Collaboration: MAGIC-Collaboration

    2016-07-01

    The MAGIC experiment consists of two Imaging Air shower Cherenkov Telescopes to detect and study gamma-rays from galactic and extragalactic sources. Blazars are a special type of extragalactic sources hosting an Active Galactic Nucleus (AGN) with a jet directed towards earth. The AGN Mrk 421 is one of the strongest and brightest known blazars suitable for very high-energy (VHE) observations. This talk gives an overview over long-term variability and correlation studies of the blazar Mrk 421. For this study a VHE dataset collected by MAGIC-I covering the extensive timespan from February 2007 to June 2009 was examined together with data of different wavelengths from other telescopes. These kind of studies could allow for an increase of knowledge about the possible emission processes inside Mrk 421.

  9. Long-term risk of carotid restenosis in patients randomly assigned to endovascular treatment or endarterectomy in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): long-term follow-up of a randomised trial.

    LENUS (Irish Health Repository)

    Bonati, Leo H

    2009-10-01

    In the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), early recurrent carotid stenosis was more common in patients assigned to endovascular treatment than it was in patients assigned to endarterectomy (CEA), raising concerns about the long-term effectiveness of endovascular treatment. We aimed to investigate the long-term risks of restenosis in patients included in CAVATAS.

  10. 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.

  11. Long-term risk of recurrent vascular events after young stroke: The FUTURE study

    NARCIS (Netherlands)

    Rutten-Jacobs, L.C.A.; Maaijwee, N.A.M.M.; Arntz, R.M.; Schoonderwaldt, H.C.; Dorresteijn, L.D.A.; Vlugt, M.J. van der; Dijk, E.J. van; Leeuw, F.E. de

    2013-01-01

    OBJECTIVE: Long-term data on recurrent vascular events after young stroke are limited. Our objective was to examine the long-term risk of recurrent vascular events after young stroke. METHODS: We prospectively included 724 consecutive patients with a first-ever transient ischemic attack (TIA),

  12. Climate Change Impacts on pricing Long-Term Flood Insurance: A Comprehensive Study for the Netherlands

    NARCIS (Netherlands)

    Aerts, J.C.J.H.; Botzen, W.J.W.

    2011-01-01

    Recently long-term flood insurance contracts with a duration of 5, 10 or 15 years have been proposed as a solution for covering flood risk and mitigating increasing flood losses. Establishing a long-term relation between the policyholder and the insurer can provide better incentives to reduce risk

  13. Short- and long-term prognosis for very old stroke patients. The Copenhagen Stroke Study

    DEFF Research Database (Denmark)

    Kammersgaard, Lars Peter; Jørgensen, H S; Reith, J

    2004-01-01

    BACKGROUND AND PURPOSE: The very old are expected to become a growing part of the stroke population in the industrialised part of the world. The aims of this study were to evaluate clinical characteristics of patients aged 85 years or more at stroke onset and to investigate very old age as an ind...... and rehabilitation after stroke.......BACKGROUND AND PURPOSE: The very old are expected to become a growing part of the stroke population in the industrialised part of the world. The aims of this study were to evaluate clinical characteristics of patients aged 85 years or more at stroke onset and to investigate very old age...... as an independent predictor of short- and long-term outcome. METHODS: In the community-based Copenhagen Stroke Study we recorded admission clinical characteristics in 1197 consecutive stroke patients. Patients were stratified according to age groups on admission. Follow-up was performed at a mean of 7 years after...

  14. The Need for Total Hip Arthroplasty in Perthes Disease: A Long-term Study

    DEFF Research Database (Denmark)

    Froberg, Lonnie; Christensen, Finn; Pedersen, Niels Wisbech

    2010-01-01

    BACKGROUND: Legg-Calvé-Perthes disease (LCPD) was described a century ago. In previous long-term reports of patients with LCPD, nonoperative treatment varied considerably. The likelihood of hip osteoarthritis (OA) developing in patients with LCPD and possible need for THA are not well defined...... with hips with Classes I/II femoral heads. PATIENTS AND METHODS: The study population consisted of 167 patients with LCPD treated with a Thomas splint. The control population consisted of gender- and age-matched control subjects who were participants in the Copenhagen City Heart Study: the Osteoarthritis...... OF EVIDENCE: Level III, prognostic study. See Guidelines for Authors for a complete description of levels of evidence....

  15. Surgical Treatment of Nonlesional Neocortical Epilepsy: Long-term Longitudinal Study.

    Science.gov (United States)

    Kim, Dong Wook; Lee, Sang Kun; Moon, Hye-Jin; Jung, Ki-Young; Chu, Kon; Chung, Chun-Ki

    2017-03-01

    The proportion of surgery for nonlesional neocortical epilepsy has recently increased, with a decrease in surgery for mesial temporal lobe epilepsy. However, there are only a few studies regarding the long-term surgical outcome and the potential prognostic factors for patients with nonlesional neocortical epilepsy. To evaluate the long-term surgical outcome and to identify possible prognostic factors in patients with nonlesional neocortical epilepsy. In a surgical cohort from September 1995 to December 2005 at the Seoul National University Hospital, we included 109 consecutive patients without lesions identifiable by magnetic resonance imaging who underwent focal surgical resection for drug-resistant neocortical epilepsy. Follow-up information for at least 10 years was available for all but 1 patient. Univariate and standard multiple logistic regression analyses were performed to identify the predictors of surgical outcomes, and a generalized estimation equation model was used for the longitudinal multiple logistic regression analysis of up to 21 years of follow-up. The patients consisted of 64 men and 45 women with ages at surgery ranging from 7 to 56 years (mean [SD], 27.1 [7.8] years). At 1 year after surgery, 59 of 109 patients (54.1%) achieved seizure freedom, and 64 of 108 patients (59.3%) achieved seizure freedom at the last follow-up. Only 11 of 108 patients (10.2%) experienced definite changes in postoperative seizure status. Localizing patterns in functional neuroimaging (strongest odds ratio [OR], 0.30 [95% CI, 0.14-0.66] for fluorodeoxyglucose-positron emission tomography; 0.37 [95% CI, 0.15-0.87] for ictal single-photon emission computed tomography), concordant results in presurgical diagnostic evaluations (OR, 3.15 [95% CI, 1.42-7.02]), the presence of aura (OR, 3.49 [95% CI, 1.54-7.92]), and complete resection of areas of ictal onset with frequent interictal spikes during the intracranial electroencephalographic study (OR, 0.37 [95% CI, 0

  16. Long-term airborne contamination studied by attic dust in an industrial area: Ajka, Hungary

    Science.gov (United States)

    Völgyesi, P.; Jordan, G.; Szabo, Cs.

    2012-04-01

    Heavy industrial activities such as mining, metal industry, coal fired power plants have produced large amount of by-products and wide-spread pollution, particularly in the period of centrally dictated economy after WWII, in Hungary. Several studies suggest that significant amount of these pollutants have been deposited in the urban environment. Nowadays, more than half of the world's population is living in urban areas and people spend almost 80% of their lives indoors in developed countries increasing human health risk due to contamination present in urban dwellings. Attic dust sampling was applied to determine the long-term airborne contamination load in the industrial town of Ajka (Hungary). There has been a high industrial activity in Ajka since the end of the 19th century. In addition to aluminum and alumina industry, coal mining, coal fired power plant and glass industry sites, generated numerous waste heaps which act as multi-contamination sources in the area. In October 2010 the Ajka red mud tailings pond failed and caused an accidental regional contamination of international significance. The major objective of this research was to study and map the spatial distribution of heavy metal contamination in airborne attic dust samples. At 27 sampling sites 30 attic dust samples were collected. Sampling strategy followed a grid-based stratified random sampling design. In each cell a house for attic dust sample collection was selected that was located the closest to a randomly generated point in the grid cell. The project area covers a 8x8 grid of 1x1 km cells with a total area of 64 km2. In order to represent long-term industrial pollution, houses with attics kept intact for at least 30-40 years were selected for sampling. Sampling included the collection of background samples remotely placed from the industrialized urban area. The concentration of the major and toxic elements (Al, Ca, Fe, K, Mg, Mn, Na, P, S, and As, Ba, Cd, Co, Cr, Cu, Li, Mo, Ni, Pb, Se, Sn

  17. Microsphere-based gradient implants for osteochondral regeneration: a long-term study in sheep

    Science.gov (United States)

    Mohan, Neethu; Gupta, Vineet; Sridharan, Banu Priya; Mellott, Adam J; Easley, Jeremiah T; Palmer, Ross H; Galbraith, Richard A; Key, Vincent H; Berkland, Cory J; Detamore, Michael S

    2015-01-01

    Background: The microfracture technique for cartilage repair has limited ability to regenerate hyaline cartilage. Aim: The current study made a direct comparison between microfracture and an osteochondral approach with microsphere-based gradient plugs. Materials & methods: The PLGA-based scaffolds had opposing gradients of chondroitin sulfate and β-tricalcium phosphate. A 1-year repair study in sheep was conducted. Results: The repair tissues in the microfracture were mostly fibrous and had scattered fissures with degenerative changes. Cartilage regenerated with the gradient plugs had equal or superior mechanical properties; had lacunated cells and stable matrix as in hyaline cartilage. Conclusion: This first report of gradient scaffolds in a long-term, large animal, osteochondral defect demonstrated potential for equal or better cartilage repair than microfracture. PMID:26418471

  18. Air Traffic Controllers’ Long-Term Speech-in-Noise Training Effects: A Control Group Study

    Science.gov (United States)

    Zaballos, María T.P.; Plasencia, Daniel P.; González, María L.Z.; de Miguel, Angel R.; Macías, Ángel R.

    2016-01-01

    Introduction: Speech perception in noise relies on the capacity of the auditory system to process complex sounds using sensory and cognitive skills. The possibility that these can be trained during adulthood is of special interest in auditory disorders, where speech in noise perception becomes compromised. Air traffic controllers (ATC) are constantly exposed to radio communication, a situation that seems to produce auditory learning. The objective of this study has been to quantify this effect. Subjects and Methods: 19 ATC and 19 normal hearing individuals underwent a speech in noise test with three signal to noise ratios: 5, 0 and −5 dB. Noise and speech were presented through two different loudspeakers in azimuth position. Speech tokes were presented at 65 dB SPL, while white noise files were at 60, 65 and 70 dB respectively. Results: Air traffic controllers outperform the control group in all conditions [P<0.05 in ANOVA and Mann-Whitney U tests]. Group differences were largest in the most difficult condition, SNR=−5 dB. However, no correlation between experience and performance were found for any of the conditions tested. The reason might be that ceiling performance is achieved much faster than the minimum experience time recorded, 5 years, although intrinsic cognitive abilities cannot be disregarded. Discussion: ATC demonstrated enhanced ability to hear speech in challenging listening environments. This study provides evidence that long-term auditory training is indeed useful in achieving better speech-in-noise understanding even in adverse conditions, although good cognitive qualities are likely to be a basic requirement for this training to be effective. Conclusion: Our results show that ATC outperform the control group in all conditions. Thus, this study provides evidence that long-term auditory training is indeed useful in achieving better speech-in-noise understanding even in adverse conditions. PMID:27991470

  19. Long-term mortality in patients with tuberculous meningitis: a Danish nationwide cohort study.

    Directory of Open Access Journals (Sweden)

    Anne-Sophie Halkjær Christensen

    Full Text Available BACKGROUND: With high short-term mortality and substantial excess morbidity among survivors, tuberculous meningitis (TBM is the most severe manifestation of extra-pulmonary tuberculosis (TB. The objective of this study was to assess the long-term mortality and causes of death in a TBM patient population compared to the background population. METHODS: A nationwide cohort study was conducted enrolling patients notified with TBM in Denmark from 1972-2008 and alive one year after TBM diagnosis. Data was extracted from national registries. From the background population we identified a control cohort of individuals matched on gender and date of birth. Kaplan-Meier survival curves and Cox regression analysis were used to estimate mortality rate ratios (MRR and analyse causes of death. FINDINGS: A total of 55 TBM patients and 550 individuals from the background population were included in the study. Eighteen patients (32.7% and 107 population controls (19.5% died during the observation period. The overall MRR was 1.79 (95%CI: 1.09-2.95 for TBM patients compared to the population control cohort. TBM patients in the age group 31-60 years at time of diagnosis had the highest relative risk of death (MRR 2.68; 95%CI 1.34-5.34. The TBM patients had a higher risk of death due to infectious disease, but not from other causes of death. CONCLUSION: Adult TBM patients have an almost two-fold increased long-term mortality and the excess mortality stems from infectious disease related causes of death.

  20. [Frailty and long term mortality, disability and hospitalisation in Spanish older adults. The FRADEA Study].

    Science.gov (United States)

    Martínez-Reig, Marta; Flores Ruano, Teresa; Fernández Sánchez, Miguel; Noguerón García, Alicia; Romero Rizos, Luis; Abizanda Soler, Pedro

    2016-01-01

    The objective of this study was to analyse whether frailty is related to long-term mortality, incident disability in basic activities of daily living (BADL), and hospitalisation. A concurrent cohort study conducted on 993 participants over age 70 from the FRADEA Study. Frailty was determined with Fried frailty phenotype. Data was collected on mortality, hospitalisation and incident disability in BADL (bathing, grooming, dressing, toileting, eating or transferring) during the follow-up period. The risk of adverse events was determined by logistic regression, Kaplan-Meier analysis, and Cox proportional hazard analysis adjusted for age, sex, Barthel index, comorbidity and institutionalization. Mean follow-up was 952 days (SD 408), during which 182 participants (18.4%) died. Frail participants had an increased adjusted risk of death (HR 4.5, 95%CI: 1.8-11.1), incident disability in BADL (OR 2.7, 95%CI: 1.3-5.9) and the combined event mortality or incident disability (OR 3.0, 95%CI: 1.5-6.1). Pre-frail subjects had an increased adjusted risk of death (HR 2.9, 95%CI: 1.2-6.5), incident disability in BADL (OR 2.1, 95%CI: 1.2-3.6), and the combined event mortality or incident disability (OR 2.2, 95%CI: 1.3-3.6). There was a positive association between frailty and hospitalisation, which almost reached statistical significance (OR 1.7, 95%CI: 1.0-3.0). Frailty is long-term associated with mortality and incident disability in BADL in a Spanish cohort of older adults. Copyright © 2016 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Air traffic controllers' long-term speech-in-noise training effects: A control group study.

    Science.gov (United States)

    Zaballos, Maria T P; Plasencia, Daniel P; González, María L Z; de Miguel, Angel R; Macías, Ángel R

    2016-01-01

    Speech perception in noise relies on the capacity of the auditory system to process complex sounds using sensory and cognitive skills. The possibility that these can be trained during adulthood is of special interest in auditory disorders, where speech in noise perception becomes compromised. Air traffic controllers (ATC) are constantly exposed to radio communication, a situation that seems to produce auditory learning. The objective of this study has been to quantify this effect. 19 ATC and 19 normal hearing individuals underwent a speech in noise test with three signal to noise ratios: 5, 0 and -5 dB. Noise and speech were presented through two different loudspeakers in azimuth position. Speech tokes were presented at 65 dB SPL, while white noise files were at 60, 65 and 70 dB respectively. Air traffic controllers outperform the control group in all conditions [P<0.05 in ANOVA and Mann-Whitney U tests]. Group differences were largest in the most difficult condition, SNR=-5 dB. However, no correlation between experience and performance were found for any of the conditions tested. The reason might be that ceiling performance is achieved much faster than the minimum experience time recorded, 5 years, although intrinsic cognitive abilities cannot be disregarded. ATC demonstrated enhanced ability to hear speech in challenging listening environments. This study provides evidence that long-term auditory training is indeed useful in achieving better speech-in-noise understanding even in adverse conditions, although good cognitive qualities are likely to be a basic requirement for this training to be effective. Our results show that ATC outperform the control group in all conditions. Thus, this study provides evidence that long-term auditory training is indeed useful in achieving better speech-in-noise understanding even in adverse conditions.

  2. Long-term leisure time physical activity and properties of bone: a twin study.

    Science.gov (United States)

    Ma, Hongqiang; Leskinen, Tuija; Alen, Markku; Cheng, Sulin; Sipilä, Sarianna; Heinonen, Ari; Kaprio, Jaakko; Suominen, Harri; Kujala, Urho M

    2009-08-01

    Effects of physical activity on bone properties, when controlled for genetic effects, are not fully understood. We aimed to study the association between long-term leisure time physical activity (LTPA) and bone properties using twin pairs known to be discordant for leisure time physical activity for at least 30 yr. Volumetric BMD and geometric properties were measured at the tibia shaft and distal end using pQCT in 16 middle-aged (50-74 yr) same-sex twin pairs (seven monozygotic [MZ] and nine dizygotic [DZ] pairs) selected from a population-based cohort. Paired differences between active and inactive co-twins were studied. Active members of MZ twin pairs had larger cortical bone cross-sectional area (intrapair difference: 8%, p = 0.006), thicker cortex (12%, p = 0.003), and greater moment of inertia (I(max), 20%, p = 0.024) at the tibia shaft than their inactive co-twins. At the distal tibia, trabecular BMD (12%, p = 0.050) and compressive strength index (18%, p = 0.038) were also higher in physically active MZ pair members than their inactive co-twins. The trends were similar, but less consistently so, in DZ pairs as in MZ pairs. Our genetically controlled study design shows that LTPA during adulthood strengthens bones in a site-specific manner, that is, the long bone shaft has a thicker cortex, and thus higher bending strength, whereas the distal bone has higher trabecular density and compressive strength. These results suggest that LTPA has a potential causal role in decreasing the long-term risk of osteoporosis and thus preventing osteoporotic fractures.

  3. Long term follow up study of survival associated with cleft lip and palate at birth

    DEFF Research Database (Denmark)

    Christensen, Kaare; Juel, K.; Herskind, Anne Maria

    2004-01-01

    OBJECTIVE: To assess the overall and cause specific mortality of people from birth to 55 years with cleft lip and palate. DESIGN: Long term follow up study. SETTING: Danish register of deaths. PARTICIPANTS: People born with cleft lip and palate between 1943 and 1987, followed to 1998. MAIN OUTCOME...... MEASURES: Observed and expected numbers of deaths, summarised as overall and cause specific standardised mortality ratios. RESULTS: 5331 people with cleft lip and palate were followed for 170 421 person years. The expected number of deaths was 259, but 402 occurred, corresponding to a standardised...... of death. CONCLUSIONS: People with cleft lip and palate have increased mortality up to age 55. Children born with cleft lip and palate and possibly other congenital malformations may benefit from specific preventive health measures into and throughout adulthood....

  4. Coping, Cognitive Emotion Regulation, and Burnout in Long-Term Care Nursing Staff: A Preliminary Study.

    Science.gov (United States)

    Bamonti, Patricia; Conti, Elizabeth; Cavanagh, Casey; Gerolimatos, Lindsay; Gregg, Jeffrey; Goulet, Carol; Pifer, Marisa; Edelstein, Barry

    2017-06-01

    Direct care workers (e.g., certified nursing assistants [CNAs]) employed in long-term care (LTC) are particularly vulnerable to the experience of burnout, yet they have received relatively less research attention compared to Licensed Practical Nurses and Registered Nurses. Within the burnout literature, evidence suggests that the deployment of certain coping strategies influences levels of burnout. The current study examined the extent to which coping (e.g., problem-focused, emotion-focused, and dysfunctional coping) and cognitive emotion regulation strategies (e.g., positive reappraisal) predicted burnout after controlling for covariates (age, sleep duration). Fifty-six CNAs were surveyed at four skilled nursing facilities in the United States. Dysfunctional coping was significantly associated with emotional exhaustion and depersonalization. Among cognitive emotion regulation strategies, positive reappraisal was significantly associated with depersonalization. Shorter sleep duration was associated with significantly greater depersonalization. Findings suggest the need to develop interventions for CNAs aimed at reducing dysfunctional coping strategies and increasing sleep duration.

  5. Long-term optical stimulation of channelrhodopsin-expressing neurons to study network plasticity

    Science.gov (United States)

    Lignani, Gabriele; Ferrea, Enrico; Difato, Francesco; Amarù, Jessica; Ferroni, Eleonora; Lugarà, Eleonora; Espinoza, Stefano; Gainetdinov, Raul R.; Baldelli, Pietro; Benfenati, Fabio

    2013-01-01

    Neuronal plasticity produces changes in excitability, synaptic transmission, and network architecture in response to external stimuli. Network adaptation to environmental conditions takes place in time scales ranging from few seconds to days, and modulates the entire network dynamics. To study the network response to defined long-term experimental protocols, we setup a system that combines optical and electrophysiological tools embedded in a cell incubator. Primary hippocampal neurons transduced with lentiviruses expressing channelrhodopsin-2/H134R were subjected to various photostimulation protocols in a time window in the order of days. To monitor the effects of light-induced gating of network activity, stimulated transduced neurons were simultaneously recorded using multi-electrode arrays (MEAs). The developed experimental model allows discerning short-term, long-lasting, and adaptive plasticity responses of the same neuronal network to distinct stimulation frequencies applied over different temporal windows. PMID:23970852

  6. Resident challenges with daily life in Chinese long-term care facilities: A qualitative pilot study.

    Science.gov (United States)

    Song, Yuting; Scales, Kezia; Anderson, Ruth A; Wu, Bei; Corazzini, Kirsten N

    As traditional family-based care in China declines, the demand for residential care increases. Knowledge of residents' experiences with long-term care (LTC) facilities is essential to improving quality of care. This pilot study aimed to describe residents' experiences in LTC facilities, particularly as it related to physical function. Semi-structured open-ended interviews were conducted in two facilities with residents stratified by three functional levels (n = 5). Directed content analysis was guided by the Adaptive Leadership Framework. A two-cycle coding approach was used with a first-cycle descriptive coding and second-cycle dramaturgical coding. Interviews provided examples of challenges faced by residents in meeting their daily care needs. Five themes emerged: staff care, care from family members, physical environment, other residents in the facility, and personal strategies. Findings demonstrate the significance of organizational context for care quality and reveal foci for future research. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Birth Outcomes after the Fukushima Daiichi Nuclear Power Plant Disaster: A Long-Term Retrospective Study.

    Science.gov (United States)

    Leppold, Claire; Nomura, Shuhei; Sawano, Toyoaki; Ozaki, Akihiko; Tsubokura, Masaharu; Hill, Sarah; Kanazawa, Yukio; Anbe, Hiroshi

    2017-05-19

    Changes in population birth outcomes, including increases in low birthweight or preterm births, have been documented after natural and manmade disasters. However, information is limited following the 2011 Fukushima Daiichi Nuclear Power Plant Disaster. In this study, we assessed whether there were long-term changes in birth outcomes post-disaster, compared to pre-disaster data, and whether residential area and food purchasing patterns, as proxy measurements of evacuation and radiation-related anxiety, were associated with post-disaster birth outcomes. Maternal and perinatal data were retrospectively collected for all live singleton births at a public hospital, located 23 km from the power plant, from 2008 to 2015. Proportions of low birthweight (effects on maternal and perinatal health.

  8. Development of a mechanical testing and loading system for trabecular bone studies for long term culture

    Directory of Open Access Journals (Sweden)

    DB Jones

    2003-03-01

    Full Text Available A highly accurate (�3% mechanical loading and measurement system combined with a trabecular bone diffusion culture-loading chamber has been developed, which provides the ability to study trabecular bone (and possibly cartilage under controlled culture and loading conditions over long periods of time. The loading device has been designed to work in two main modes, either to apply a specific compressive strain to a trabecular bone cylinder or to apply a specific force and measure the resulting deformation. Presently, precisely machined bone cylinders can be loaded at frequencies between 0.1 Hz to 50 Hz and amplitudes over 7,000�e. The system allows accurate measurement of many mechanical properties of the tissue in real time, including visco-elastic properties. This paper describes the technical components, reproducibility, precision, and the calibration procedures of the loading system. Data on long term culture and mechanical responses to different loading patterns will be published separately.

  9. Long-term optical stimulation of channelrhodopsin-expressing neurons to study network plasticity.

    Science.gov (United States)

    Lignani, Gabriele; Ferrea, Enrico; Difato, Francesco; Amarù, Jessica; Ferroni, Eleonora; Lugarà, Eleonora; Espinoza, Stefano; Gainetdinov, Raul R; Baldelli, Pietro; Benfenati, Fabio

    2013-01-01

    Neuronal plasticity produces changes in excitability, synaptic transmission, and network architecture in response to external stimuli. Network adaptation to environmental conditions takes place in time scales ranging from few seconds to days, and modulates the entire network dynamics. To study the network response to defined long-term experimental protocols, we setup a system that combines optical and electrophysiological tools embedded in a cell incubator. Primary hippocampal neurons transduced with lentiviruses expressing channelrhodopsin-2/H134R were subjected to various photostimulation protocols in a time window in the order of days. To monitor the effects of light-induced gating of network activity, stimulated transduced neurons were simultaneously recorded using multi-electrode arrays (MEAs). The developed experimental model allows discerning short-term, long-lasting, and adaptive plasticity responses of the same neuronal network to distinct stimulation frequencies applied over different temporal windows.

  10. The involvement of long-term serial-order memory in reading development: A longitudinal study.

    Science.gov (United States)

    Bogaerts, Louisa; Szmalec, Arnaud; De Maeyer, Marjolijn; Page, Mike P A; Duyck, Wouter

    2016-05-01

    Recent findings suggest that Hebb repetition learning-a paradigmatic example of long-term serial-order learning-is impaired in adults with dyslexia. The current study further investigated the link between serial-order learning and reading using a longitudinal developmental design. With this aim, verbal and visual Hebb repetition learning performance and reading skills were assessed in 96 Dutch-speaking children who we followed from first through second grade of primary school. We observed a positive association between order learning capacities and reading ability as well as weaker Hebb learning performance in early readers with poor reading skills even at the onset of reading instruction. Hebb learning further predicted individual differences in later (nonword) reading skills. Finally, Hebb learning was shown to explain a significant part of the variance in reading performance above and beyond phonological awareness. These findings highlight the role of serial-order memory in reading ability. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Long Term Performance Study of a Direct Methanol Fuel Cell Fed with Alcohol Blends

    Directory of Open Access Journals (Sweden)

    Eleuterio Mora

    2013-01-01

    Full Text Available The use of alcohol blends in direct alcohol fuel cells may be a more environmentally friendly and less toxic alternative to the use of methanol alone in direct methanol fuel cells. This paper assesses the behaviour of a direct methanol fuel cell fed with aqueous methanol, aqueous ethanol and aqueous methanol/ethanol blends in a long term experimental study followed by modelling of polarization curves. Fuel cell performance is seen to decrease as the ethanol content rises, and subsequent operation with aqueous methanol only partly reverts this loss of performance. It seems that the difference in the oxidation rate of these alcohols may not be the only factor affecting fuel cell performance.

  12. Long-term mortality in patients diagnosed with Listeria monocytogenes meningitis: A Danish nationwide cohort study

    DEFF Research Database (Denmark)

    Roed, Casper; Engsig, Frederik Neess; Omland, Lars Haukali

    2012-01-01

    OBJECTIVES: To determine the long-term mortality, the causes of death and the incidence of cancer in listeria meningitis patients. METHODS: Nationwide, population-based cohort study including all adult patients diagnosed with listeria meningitis from 1977 to 2006 and alive 1 year after diagnosis......, and an age-and gender-matched, population control cohort. Kaplan-Meier tables, Cox regression analysis and cumulative incidence function were used as outcome analyses. RESULTS: We identified 114 listeria meningitis patients and 1026 population controls. The adjusted mortality rate ratio (MRR) for listeria...... meningitis patients the first 5 years of follow-up was 2.35(95% confidence interval (CI) 1.60-3.45) thereafter the MRR was 0.93(95% CI: 0.56-1.55). Listeria meningitis patients had an increased risk of death due to cancer the first 5 years of follow-up, and in the same period patients above 50 years of age...

  13. Aerobic fitness after JDM--a long-term follow-up study

    DEFF Research Database (Denmark)

    Mathiesen, Pernille R; Orngreen, Mette C; Vissing, John

    2013-01-01

    Objectives. It has previously been shown that patients with active JDM have decreased aerobic fitness; however, it is not known whether these patients regain their physical fitness after recovery. The objective of this study was to investigate the long-term outcome of aerobic fitness in patients...... with JDM. We hypothesized that fitness (VO(2max)) is reduced compared with healthy controls in the years after active JDM.Methods. A maximal exercise test was performed using a cycle ergometer. Results were compared with those of sex- and age-matched healthy controls.Results. A total of 36 patients...... year of active disease, VO(2max) was reduced by 0.85 ml/min/kg on average (P fitness. This impairment is directly related to the duration of active disease....

  14. Study on long-term stability of geochemical environments at deep underground

    International Nuclear Information System (INIS)

    Mizuno, Takashi; Iwatsuki, Teruki

    2005-01-01

    Observation and fluid inclusion analysis of fracture filling calcites in granite at the Tono area were conducted to assess long-term stability of geochemical environment at deep underground. The result of observation using SEM and luminoscope shows that precipitation processes of calcite can be divided into four phases (1 to 4) based on their occurrence. (1) Phase 1: indistinct morphology and includes the wall rock fragments. (2) Phase 2: rhombohedral and hexagonal form. (3) Phase 3: elongate rhombohedral form, growth over the layer of phase 2 calcite. (4) Phase 4: small rhombohedral form crystals growth from surface of phase 3 calcite. On Phase 1 calcite, it seems to be hydrothermal origin related to fracture activation. Previous study shows the correlation between the salinity of fluid from which calcite precipitated and morphology of calcite. According to previous studies, the groundwater from which phase 3 calcite precipitated would be the highest salinity such as seawater. Phase 2 and 4 calcite may be precipitated from groundwater with low salinity. On the other hand, fluid inclusions were recognized in phase 2 and 3 calcite. All inclusions indicated mono-phase (liquid phase). These suggest that phase 2 and 3 calcites were precipitated in low-temperature condition. Result of salinity analysis indicates that two groundwaters having different chemical properties had existed during phase 2 and 3 calcite precipitation. Based on these results, geochemical environment had changed by input of high salinity groundwater during Phase 2 and 3 calcite precipitation. It is required to identify the origin of each groundwater in consideration of historical geology for further understanding of long-term hydrochemical condition. (author)

  15. Predictors of Long-Term Healthy Arterial Aging: Coronary Artery Calcium Nondevelopment in the MESA Study.

    Science.gov (United States)

    Whelton, Seamus P; Silverman, Michael G; McEvoy, John W; Budoff, Matthew J; Blankstein, Ron; Eng, John; Blumenthal, Roger S; Szklo, Moyses; Nasir, Khurram; Blaha, Michael J

    2015-12-01

    This study sought to determine the predictors of healthy arterial aging. Long-term nondevelopment of coronary artery calcification (persistent CAC = 0) is a marker of healthy arterial aging. The predictors of this phenotype are not known. We analyzed 1,850 participants from MESA (Multi-Ethnic Study of Atherosclerosis) with baseline CAC = 0 who underwent a follow-up CAC scan at visit 5 (median 9.6 years after baseline). We examined the proportion with persistent CAC = 0 and calculated multivariable relative risks and area under the receiver operating characteristic curve for prediction of this healthy arterial aging phenotype. We found that 55% of participants (n = 1,000) had persistent CAC = 0, and these individuals were significantly more likely to be younger, female, and have fewer traditional risk factors (RF). Participants with an ASCVD (Atherosclerotic Cardiovascular Disease Risk Score) risk score healthy arterial aging than were participants with an ASCVD score ≥7.5%. There was no significant association between the Healthy Lifestyle variables (body mass index, physical activity, Mediterranean diet, and never smoking) and persistent CAC = 0. The area under the receiver operating characteristic curve incorporating age, sex, and ethnicity was 0.65, indicating fair to poor discrimination. No single traditional RF or combination of other risk factors increased the area under the receiver operating characteristic curve by more than 0.05. Whereas participants free of traditional cardiovascular disease RF were significantly more likely to have persistent CAC = 0, there was no single RF or specific low-risk RF phenotype that markedly improved the discrimination of persistent CAC = 0 over demographic variables. Therefore, we conclude that healthy arterial aging may be predominantly influenced by the long-term maintenance of a low cardiovascular disease risk profile or yet to be determined genetic factors rather than the absence of any specific RF cluster identified

  16. Physical activity as a long-term predictor of peak oxygen uptake: the HUNT Study.

    Science.gov (United States)

    Aspenes, Stian Thoresen; Nauman, Javaid; Nilsen, Tom Ivar Lund; Vatten, Lars Johan; Wisløff, Ulrik

    2011-09-01

    A physically active lifestyle and a relatively high level of cardiorespiratory fitness are important for longevity and long-term health. No population-based study has prospectively assessed the association of physical activity levels with long-term peak oxygen uptake (VO(2peak)). 1843 individuals (906 women and 937 men) who were between 18 and 66 yr at baseline and were free from known lung or heart diseases at both baseline (1984-1986) and follow-up (2006-2008) were included in the study. Self-reported physical activity was recorded at both occasions, and VO(2peak) was measured at follow-up. The association of physical activity levels and VO(2peak) was adjusted for age, level of education, smoking status, and weight change from baseline to follow-up, using ANCOVA statistics. The level of physical activity at baseline was strongly associated with VO(2peak) at follow-up 23 yr later in both men and women (Ptrends active at baseline had higher (3.3 and 4.6 mL·kg(-1)·min(-1)) VO(2peak) at follow-up. Women who were inactive at baseline but highly active at follow-up had 3.7 mL·kg(-1)·min(-1) higher VO(2peak) compared with women who were inactive both at baseline and at follow-up. The corresponding comparison in men showed a difference of 5.2 mL·kg(-1)·min(-1) (95% confidence interval = 3.1-7.3) in VO(2peak). Physical activity level at baseline was positively associated with directly measured cardiorespiratory fitness (VO(2peak)) 23 yr later. People who changed from low to high activity during the observation period had substantially higher V˙O(2peak) at follow-up compared with people whose activity remained low.

  17. Long-Term Cognitive Impairment after Hospitalization for Community-Acquired Pneumonia: a Prospective Cohort Study.

    Science.gov (United States)

    Girard, Timothy D; Self, Wesley H; Edwards, Kathryn M; Grijalva, Carlos G; Zhu, Yuwei; Williams, Derek J; Jain, Seema; Jackson, James C

    2018-06-01

    Recent studies suggest older patients hospitalized for community-acquired pneumonia are at risk for new-onset cognitive impairment. The characteristics of long-term cognitive impairment after pneumonia, however, have not been elucidated. To characterize long-term cognitive impairment among adults of all ages hospitalized for community-acquired pneumonia. Prospective cohort study. Adults without severe preexisting cognitive impairment who were hospitalized with community-acquired pneumonia. At enrollment, we estimated baseline cognitive function with the Short Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). At 2- and 12-month follow-up, we assessed cognition using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and tests of executive function, diagnosing cognitive impairment when results were ≥ 1.5 standard deviations below published age-adjusted means for the general population. We also identified subtypes of mild cognitive impairment using standard definitions. We assessed 58 (73%) of 80 patients who survived to 2-month follow-up and 57 (77%) of 74 who survived to 12-month follow-up. The median [range] age of survivors tested was 57 [19-97] years. Only 8 (12%) had evidence of mild cognitive impairment at baseline according to the Short IQCODE, but 21 (38%) at 2 months and 17 (30%) at 12 months had mild cognitive impairment per the RBANS. Moderate-to-severe cognitive impairment was common among adults ≥ 65 years [4/13 (31%) and 5/13 (38%) at 2 and 12 months, respectively] but also affected many of those cognitive domains affected one-third of patients ≥ 65 years old and 20% of younger patients, and another third of survivors had mild cognitive impairment.

  18. A long-term follow-up study of methotrexate in juvenile localized scleroderma (morphea).

    Science.gov (United States)

    Zulian, Francesco; Vallongo, Cristina; Patrizi, Annalisa; Belloni-Fortina, Anna; Cutrone, Mario; Alessio, Maria; Martino, Silvana; Gerloni, Valeria; Vittadello, Fabio; Martini, Giorgia

    2012-12-01

    Recent studies report that methotrexate (MTX) is beneficial in the treatment of juvenile localized scleroderma (JLS) but little is known about its long-term effectiveness. We assessed the therapeutic role of MTX in children with JLS who were followed up for a prolonged period. A cohort of patients with JLS, previously enrolled in a double-blind, randomized controlled trial and treated with oral MTX (15 mg/m(2)/wk) and prednisone (1 mg/kg/d, maximum 50 mg) for the first 3 months, were prospectively followed up. Lesions were evaluated clinically, with infrared thermography, and by a computerized skin score. Response to treatment was defined as: (1) no new lesions; (2) skin score rate less than 1; and (3) decrease in lesion temperature by at least 10% compared with baseline. Clinical remission (CR) on medication was defined when response was maintained, on treatment, for at least 6 months, and complete CR when response was maintained, without treatment, for at least 6 months. Of 65 patients treated with MTX, 48 (73.8%) were responders, 10 (15.4%) relapsed by 24 months since MTX start, and 7 (10.8%) were lost to follow-up. Among the responders, 35 (72.9%) maintained CR for a mean of 25 months and 13 (27.1%) were in CR on medication. Adverse effects seen in 28 patients (48.3%) were generally mild and never required treatment discontinuation. The use of objective measures not widely available, such as infrared thermography and computerized skin score, makes it difficult to compare data from previous studies. Long-term MTX therapy is beneficial and well tolerated for JLS. Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  19. Study on effects of coupled phenomenon on long-term behavior for crystalline rock (Joint research)

    International Nuclear Information System (INIS)

    Kimoto, Kazushi; Ichikawa, Yasuaki; Matsui, Hiroya

    2017-11-01

    It is important to evaluate the stability of a repository for high-level radioactive waste not only during the design, construction and operation phases, but also during the post-closure period, for time frames likely exceeding several millennia or longer. The rock mass around the tunnels could be deformed through time in response to time dependent behavior such as creep and stress relaxation. On the other hand, it was revealed that chemical reaction of groundwater in rock has an influence on the long-term behavior. Therefore, an evaluation of the microcracks influencing on rock mechanical and chemical coupled phenomena is the issue to understand the past long-term behavior of rock mass. In view of above points, this study has been started as joint research with Okayama University from Fiscal Year 2016. In Fiscal Year 2016, several kinds of elastic wave velocity were measured using ultra sonic sensors and laser Doppler vibrometer to evaluate the anisotropy of different elastic wave in granite. The velocity measurements were carried out focused on transmitted wave and surface wave. The results showed that strong anisotropy was observed in transmitted P-wave velocity while weak anisotropy was observed in transmitted S-wave and group velocity estimated by surface velocity measurement. In addition, data obtained from surface velocity measurement was partitioned into transmitted and reflected waves and analyzed them in detail. It resulted that elastic wave due to mineral particles to compose granite was dispersed; however, significant dispersion was only observed at specific location. For the future study, understanding of the relationship between density and anisotropy of micro cracks also anisotropy and strong dispersion of group velocity is important subject to estimate the geometrical distribution of micro cracks in granitic rock. (author)

  20. Racial differences in long-term adherence to oral antidiabetic drug therapy: a longitudinal cohort study

    Directory of Open Access Journals (Sweden)

    Meigs James B

    2009-02-01

    Full Text Available Abstract Background Adherence to oral antidiabetic medications is often suboptimal. Adherence differences may contribute to health disparities for black diabetes patients, including higher microvascular event rates, greater complication-related disability, and earlier mortality. Methods In this longitudinal retrospective cohort study, we used 10 years of patient-level claims and electronic medical record data (1/1/1992–12/31/2001 to assess differences in short- and long-term adherence to oral antidiabetic medication among 1906 newly diagnosed adults with diabetes (26% black, 74% white in a managed care setting in which all members have prescription drug coverage. Four main outcome measures included: (1 time from diabetes diagnosis until first prescription of oral antidiabetic medication; (2 primary adherence (time from first prescription to prescription fill; (3 time until discontinuation of oral antidiabetic medication from first prescription; and (4 long-term adherence (amount dispensed versus amount prescribed over a 24-month follow-up from first oral antidiabetic medication prescription. Results Black patients were as likely as whites to initiate oral therapy and fill their first prescription, but experienced higher rates of medication discontinuation (HR: 1.8, 95% CI: 1.2, 2.7 and were less adherent over time. These black-white differences increased over the first six months of therapy but stabilized thereafter for patients who initiated on sulfonylureas. Significant black-white differences in adherence levels were constant throughout follow-up for patients initiated on metformin therapy. Conclusion Racial differences in adherence to oral antidiabetic drug therapy persist even with equal access to medication. Early and continued emphasis on adherence from initiation of therapy may reduce persistent racial differences in medication use and clinical outcomes.

  1. Comparative study of long-term outcomes of accelerated and conventional collagen crosslinking for progressive keratoconus.

    Science.gov (United States)

    Males, J J; Viswanathan, D

    2018-01-01

    PurposeTo compare the long-term outcomes of accelerated corneal collagen crosslinking (CXL) to conventional CXL for progressive keratoconus.Patients and methodsComparative clinical study of consecutive progressive keratoconic eyes that underwent either accelerated CXL (9 mW/cm 2 ultraviolet A (UVA) light irradiance for 10 min) or conventional CXL (3 mW/cm 2 UVA light irradiance for 30 min). Eyes with minimum 12 months' follow-up were included. Post-procedure changes in keratometry readings (Flat meridian: K1; steep meridian: K2), central corneal thickness (CCT), best spectacle-corrected visual acuity (BSCVA), and manifest refraction spherical equivalent (MRSE) were analysed.ResultsA total of 42 eyes were included. In all, 21 eyes had accelerated CXL (20.5±5.5 months' follow-up) and 21 eyes had conventional CXL group (20.2±5.6 months' follow-up). In the accelerated CXL group, a significant reduction in K2 (P=0.02), however no significant change in K1 (P=0.35) and CCT (P=0.62) was noted. In the conventional CXL group, a significant reduction was seen in K1 (P=0.01) and K2 (P=0.04), but not in CCT (P=0.95). Although both groups exhibited significant reductions in K2 readings, no noteworthy differences were noted between them (P=0.36). Improvements in BSCVA (accelerated CXL; P=0.22 and conventional CXL; P=0.20) and MRSE (accelerated CXL; P=0.97 and conventional CXL; P=0.54) were noted, however were not significant in either group.ConclusionAccelerated and conventional CXL appear to be effective procedures for stabilising progressive keratoconus in the long-term.

  2. Observed long-term greening of alpine vegetation—a case study in the French Alps

    Science.gov (United States)

    Carlson, Bradley Z.; Corona, Monica C.; Dentant, Cédric; Bonet, Richard; Thuiller, Wilfried; Choler, Philippe

    2017-11-01

    We combined imagery from multiple sources (MODIS, Landsat-5, 7, 8) with land cover data to test for long-term (1984-2015) greening or browning trends of vegetation in a temperate alpine area, the Ecrins National Park, in the context of recent climate change and domestic grazing practices. We showed that over half (56%) of the Ecrins National Park displayed significant increases in peak normalized difference vegetation index (NDVImax) over the last 16 years (2000-2015). Importantly, the highest proportional increases in NDVImax occurred in rocky habitats at high elevations (> 2500 m a.s.l.). While spatial agreement in the direction of change in NDVImax as detected by MODIS and Landsat was high (76% overlap), correlations between log-response ratio values were of moderate strength (approx. 0.3). In the context of above treeline habitats, we found that proportional increases in NDVImax were higher between 1984 and 2000 than between 2000 and 2015, suggesting a slowing of greening dynamics during the recent decade. The timing of accelerated greening prior to 2000 coincided with a pronounced increase in the amount of snow-free growing degree-days that occurred during the 1980s and 1990s. In the case of grasslands and low-shrub habitats, we did not find evidence for a negative effect of grazing on greening trends, possibly due to the low grazing intensity typically found in the study area. We propose that the emergence of a longer and warmer growing season enabled high-elevation plant communities to produce more biomass, and also allowed for plant colonization of habitats previously characterized by long-lasting snow cover. Increasing plant productivity in an alpine context has potential implications for biodiversity trajectories and for ecosystem services in mountain landscapes. The presented evidence for long-term greening trends in a representative region of the European Alps provides the basis for further research on mechanisms of greening in alpine landscapes.

  3. Cadmium toxicity studies under long term-low level exposure (LLE) conditions. I

    International Nuclear Information System (INIS)

    Sabbioni, E.; Marafante, E.; Amantini, L.; Ubertalli, L.; Pietra, R.

    1978-01-01

    A long term-low level exposure (LLE) experiment was conducted on rats to determine the metabolic patterns for realistic dietary levels of cadmium. Male rats fed with 61 ppb of cadmium ad libitum, 50 labelled with 109 Cd radiotracer as cadmium chloride via drinking mineral water and 11 unlabelled via food for 2 years. The diet was characterized in its metal content by neutron activation analysis to obtain the total dietary intake of different elements. The kidney was found to be the tissue with the major concentration of cadmium which accumulated continuously during the experiment. The variation of the accumulation pattern of Cd concentration in the liver and intestine indicated an initial rapid increase of Cd during the first 100 days. After this period an apparent equilibrium was attained in both these tissues until the end of the study. The intracellular distribution of cadmium in kidneys, liver, intestine and pancreas were similar, the cytosol fractions containing about 80% of the cellular cadmium. Dialysis experiments indicated that significant amounts of cadmium were able to be associated with cellular organelles, the mitochondria representing the most important organelle capable of binding cadmium. The cytoplasmatic Cd-profiles obtained at various stages of the experiment showed that the metal was only bound to a low-molecular-weight component, cadmium-binding protein (CdBP), which represents the specific cellular-binding component for cadmium under the long term-low level exposure (LLE) conditions. No significant variations in the concentrations of the elements in different organs were observed in animals supplemented with 109 Cd in respect to 109 Cd untreated controls. (Auth.)

  4. Long-term safety and efficacy of stereotactic radiosurgery for vestibular schwannomas: evaluation of 440 patients more than 10 years after treatment with Gamma Knife surgery.

    Science.gov (United States)

    Hasegawa, Toshinori; Kida, Yoshihisa; Kato, Takenori; Iizuka, Hiroshi; Kuramitsu, Shunichiro; Yamamoto, Takashi

    2013-03-01

    Object Little is known about long-term outcomes, including tumor control and adverse radiation effects, in patients harboring vestibular schwannomas (VSs) treated with stereotactic radiosurgery > 10 years previously. The aim of this study was to confirm whether Gamma Knife surgery (GKS) for VSs continues to be safe and effective > 10 years after treatment. Methods A total of 440 patients with VS (including neurofibromatosis Type 2) treated with GKS between May 1991 and December 2000 were evaluable. Of these, 347 patients (79%) underwent GKS as an initial treatment and 93 (21%) had undergone prior resection. Three hundred fifty-eight patients (81%) had a solid tumor and 82 (19%) had a cystic tumor. The median tumor volume was 2.8 cm(3) and the median marginal dose was 12.8 Gy. Results The median follow-up period was 12.5 years. The actuarial 5- and ≥ 10-year progression-free survival was 93% and 92%, respectively. No patient developed treatment failure > 10 years after treatment. According to multivariate analysis, significant factors related to worse progression-free survival included brainstem compression with a deviation of the fourth ventricle (p 13 Gy) and 100% in the low marginal dose group (≤ 13 Gy). Ten patients (2.3%) developed delayed cyst formation. One patient alone developed malignant transformation, indicating an incidence of 0.3%. Conclusions In this study GKS was a safe and effective treatment for the majority of patients followed > 10 years after treatment. Special attention should be paid to cyst formation and malignant transformation as late adverse radiation effects, although they appeared to be rare. However, it is necessary to collect further long-term follow-up data before making conclusions about the long-term safety and efficacy of GKS, especially for young patients with VSs.

  5. 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)

  6. Factors Related to Healthcare Service Quality in Long-term Care Hospitals in South Korea: A Mixed-methods Study.

    Science.gov (United States)

    Sohn, Minsung; Choi, Mankyu

    2017-10-01

    The environment of long-term care hospitals (LTCHs) is critical to the management of the quality of their services and to patient safety, as highlighted by international studies. However, there is a lack of evidence on this topic in South Korea. This study aimed to examine the factors affecting healthcare quality in LTCHs and to explore the effectiveness of their quality management. This study used a mixed methods approach with quantitative data collected in a national survey and qualitative data from semi-structured interviews with practice-based managers. The samples included 725 nationally representative LTCHs in South Korea for the quantitative analysis and 15 administrators for the in-depth interviews. A higher installation rate of patient-safety and hygiene-related facilities and staff with longer-tenures, especially nurses, were more likely to have better healthcare quality and education for both employees and patients. The need for patient-safety- and hygiene-related facilities in LTCHs that serve older adults reflects their vulnerability to certain adverse events (e.g., infections). Consistent and skillful nursing care to improve the quality of LTCHs can be achieved by developing relevant educational programs for staff and patients, thereby strengthening the relationships between them.

  7. 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.)

  8. Book Reviews The Physiology of Reproduction Long-term Studies in ...

    African Journals Online (AJOL)

    classes of ecological phenomena for which long-term stu- dies are .... influenced by processes, interactions and man's activities ... Moving up the evolutionary ladder, George Hughes, .... mary pollinators of most plants, controllers of plant com-.

  9. Long-term exposure to air pollution and asthma hospitalisations in older adults: a cohort study

    DEFF Research Database (Denmark)

    Andersen, Zorana Jovanovic; Bønnelykke, Klaus; Hvidberg, Martin

    2012-01-01

    Exposure to air pollution in early life contributes to the burden of childhood asthma, but it is not clear whether long-term exposure to air pollution can lead to asthma onset or progression in adulthood.......Exposure to air pollution in early life contributes to the burden of childhood asthma, but it is not clear whether long-term exposure to air pollution can lead to asthma onset or progression in adulthood....

  10. Long-term ecological research in the Czech Republic - case study with a 3-year project

    Czech Academy of Sciences Publication Activity Database

    Jelínková, E.; Straškrábová, Viera

    2001-01-01

    Roč. 20, č. 2 (2001), s. 50-56 ISSN 1335-342X. [Long-Term Ecological Research Current State and Perspectives in the Central and Eastern Europe ILTER Regional Workshop /3./. Nitra, 23.05.2000-25.05.2000] R&D Projects: GA ČR GA206/98/0727 Keywords : long-term ecological research * acidification * eutrophication Subject RIV: EH - Ecology, Behaviour Impact factor: 0.192, year: 2001

  11. Study on the system development for evaluating long-term alteration of hydraulic field in Near Field. 3

    International Nuclear Information System (INIS)

    Okutu, Kazuo; Morikawa, Seiji; Taguchi, Katsunori

    2004-02-01

    For the high performance evaluation of reliability of TRU waste repository, the system development for evaluating long-term alteration in consideration of the changes action of barrier materials of hydraulic field in Near Fields is required. In this research, the system development for evaluating the long-term alteration of hydraulic field in near field was examined. The 'Evidential Support logic' for ensuring the long-term stability of the repository was developed and evaluated. Furthermore, the developed chemical/mechanical alteration action analysis system was verified and improved. The system was coupled for the long-term alteration evaluation analysis. The research results of this year are shown below. 1) A logic tree was constructed for the purpose of supporting the high performance evaluation of reliability of a TRU waste repository. The thesis that the long term safety of the TRU waste repository is preserved was ramified into subsidiary theses until all the final theses were supported by objective evidence. The probability of the subsidiary thesis supporting the upper thesis was established by interviewing specialists. The reliability of the thesis was evaluated by applying present knowledge. Furthermore, the sensitivity of the reliability of the highest thesis to increasing reliability of evidence was investigated. Appropriate targets for experiment and analysis were presented based on the sensitivity of evidence. 2) The object of the hydraulic - chemical analysis was determined from the above-mentioned logic tree. The analysis system was improved to perform the 2D analysis. A user interface was developed to simplify the setting of analysis conditions. The system was demonstrated by comparing the results with the experimental results. Furthermore, the system was applied to the near field problem to fix the condition that the safety of the TRU waste repository is preserved. 3) Both the model of bentonite material and the model of cement material were

  12. Psychosexual Development in Men with Congenital Hypogonadotropic Hypogonadism on Long-Term Treatment: A Mixed Methods Study

    Directory of Open Access Journals (Sweden)

    Andrew A. Dwyer, MSN, FNP-BC

    2015-03-01

    Conclusions: CHH men frequently experience psychosexual problems that pose barriers to intimate relationships and initiating sexual activity. These lingering effects cause significant distress and are not ameliorated by long-term treatment. Psychosexual assessment in CHH men with appropriate psychological support and treatment should be warranted in these patients. Dwyer AA, Quinton R, Pitteloud N, and Morin D. Psychosexual development in men with congenital hypogonadotropic hypogonadism on long-term treatment: A mixed methods study. Sex Med 2015;3:32–41.

  13. 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

  14. 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.

  15. Phenomenological study on crystalline rock for evaluating of long-term behavior (Contract research)

    International Nuclear Information System (INIS)

    Okubo, Seisuke; Seno, Yasuhiro; Hirano, Toru; Matsui, Hiroya; Nakama, Shigeo

    2008-08-01

    The Japan Atomic Energy Agency (JAEA) is conducting the Mizunami Underground Research Laboratory (MIU) Project in order to develop comprehensive geological investigation and engineering techniques for deep underground applications (e.g. repository of HLW). The purpose of this study is to contribute to the evaluation of the mechanical stability of a research drift and to plan the future studies. Rock shows time-dependent behavior such as creep/relaxation. For the shaft and gallery of the geological disposal for the radioactive waste, the mechanical stability over a period of thousands of years is demanded not only during construction and operation but also after back-filling. So, to understand the time-dependent behavior of rock is very important for evaluating the long-term mechanical stability. This study is aiming to find out the mechanism of time-dependent behavior of rock such as creep by the precision test, observation and measurement, to develop the evaluating method of long-term behavior of rock mass, and to get the information for planning the study of the Phase III (Operation Phase) at the Mizunami URL. In the previous work conducted before this fiscal year 2007, we improved the testing technique and started test of Toki granite sampled from target site. Furthermore we studied the in-situ measurement method for evaluating the scatter of rock properties. This report describes the results of the works in the fiscal year 2007. In Chapter 1, we described the overview and background of this study. In Chapter 2, the result of continuing creep test of Tage tuff which was started from the fiscal year 1997 was described. Although there was some annual variability, the precious data were obtained. In Chapter 3, the control program for the generalized relaxation test was developed. The generalized relaxation test of Toki granite was conducted in order to get basically data. In Chapter 4, the extended constitutive equation of variable compliance was analytically

  16. Long-term Efficacy, Safety, and Immunogenicity of Biosimilar Infliximab After One Year in a Prospective Nationwide Cohort.

    Science.gov (United States)

    Gonczi, Lorant; Gecse, Krisztina B; Vegh, Zsuzsanna; Kurti, Zsuzsanna; Rutka, Mariann; Farkas, Klaudia; Golovics, Petra A; Lovasz, Barbara D; Banai, Janos; Bene, Laszlo; Gasztonyi, Bea; Kristof, Tunde; Lakatos, Laszlo; Miheller, Pal; Nagy, Ferenc; Palatka, Karoly; Papp, Maria; Patai, Arpad; Salamon, Agnes; Szamosi, Tamas; Szepes, Zoltan; Toth, Gabor T; Vincze, Aron; Szalay, Balazs; Molnar, Tamas; Lakatos, Peter L

    2017-11-01

    It has been previously shown that biosimilar infliximab CT-P13 is effective and safe in inducing remission in inflammatory bowel diseases. We report here the 1-year outcomes from a prospective nationwide inflammatory bowel disease cohort. A prospective, nationwide, multicenter, observational cohort was designed to examine the efficacy and safety of CT-P13 in the induction and maintenance treatment of Crohn's disease (CD) and ulcerative colitis (UC). Demographic data were collected and a harmonized monitoring strategy was applied. Clinical remission, response, and biochemical response were evaluated at weeks 14, 30, and 54, respectively. Safety data were registered. Three hundred fifty-three consecutive inflammatory bowel disease (209 CD and 144 UC) patients were included, of which 229 patients reached the week 54 endpoint at final evaluation. Age at disease onset: 24/28 years (median, interquartile range: 19-34/22-39) in patients with CD/UC. Forty-nine, 53, 48% and 86, 81 and 65% of patients with CD reached clinical remission and response by weeks 14, 30, and 54, respectively. Clinical remission and response rates were 56, 41, 43% and 74, 66, 50% in patients with UC. Clinical efficacy was influenced by previous anti-tumor necrosis factor (TNF) exposure in patients with a drug holiday beyond 1 year. The mean C-reactive protein level decreased significantly in both CD and UC by week 14 and was maintained throughout the 1-year follow-up (both UC/CD: P < 0.001). Thirty-one (8.8%) patients had infusion reactions and 32 (9%) patients had infections. Antidrug antibody positivity rates were significantly higher throughout patients with previous anti-TNF exposure; concomitant azathioprine prevented antidrug antibody formation in anti-TNF-naive patients with CD. Results from this prospective nationwide cohort confirm that CT-P13 is effective and safe in inducing and maintaining long-term remission in both CD and UC. Efficacy was influenced by previous anti-TNF exposure; no

  17. Long-term efficacy and safety of self-intracavernous injection of prostaglandin E1 for treatment of erectile dysfunction in China.

    Science.gov (United States)

    He, L; Wen, J; Jiang, X; Chen, H; Tang, Y

    2011-06-01

    The study evaluated the long-term efficacy and safety profiles of self-intracavernous injection of prostaglandin E1 (PGE1) for erectile dysfunction (ED). Four hundred and sixteen ED patients were treated with self-intracavernous injection of PGE1 from January 1998 to December 2007 in our outpatient service. Follow-up was made to investigate the efficacy and side effects of this treatment. It was found that 261 patients (62.7%) felt satisfied and kept using this treatment due to its advantages of satisfactory efficacy and reasonable expense. Twenty-seven of them (6.5%) got rid of PGE1 treatment after five times injections and did not need any other drugs to maintain satisfactory sexual lives. Two hundred and fourteen (51.4%) patients kept using this treatment for over 1 year, 26 (6.2%) over 5 years, 12 (2.9%) over 8 years and 7 (1.7%) over 10 years. The major complications of self-intracavernous injection of PGE1 include fibrosis of corpus cavernosum (three cases), ecchymosis associated with vascular injury due to injection (23 cases) and pain associated with injection (295 cases). There were no patients displaying priapism. It is concluded that self-intracavernous injection of PGE1 is a safe and effective treatment for ED with various aetiologies and a broad range of severity, and no serious complications were observed after long-term application. © 2011 Blackwell Verlag GmbH.

  18. Occipital Nerve Stimulation for Refractory Chronic Migraine: Results of a Long-Term Prospective Study.

    Science.gov (United States)

    Rodrigo, Dolores; Acin, Pilar; Bermejo, Pedro

    2017-01-01

    Refractory chronic migraine affects approximately 4% of the population worldwide and results in severe pain, lifestyle limitations, and decreased quality of life. Occipital nerve stimulation (ONS) refers to the electric stimulation of the distal branches of greater and lesser occipital nerves; the surgical technique has previously been described and has demonstrated efficacy in the treatment of a wide variety of headache disorders. The aim of this study is to evaluate the long-term efficacy and tolerability of ONS for medically intractable chronic migraine. Prospective, long-term, open-label, uncontrolled observational study. Single public university hospital. Patients who met the International Headache Society criteria for chronic migraine, all of them having been previously treated with other therapeutic alternatives, and who met all inclusion and exclusion criteria for neurostimulation, received the implantation of an ONS system after a positive psychological evaluation and a positive response to a preliminary occipital nerve blockage. The implantation was performed in 2 phases: a 10 day trial with implanted occipital leads connected to an external stimulator and, if more than 50% pain relief was obtained, permanent pulse generator implantation and connection to the previously implanted leads. After the surgery, the patients were thoroughly evaluated annually using different scales: pain Visual Analogue Scale (VAS), number of migraine attacks per month, sleep quality, functionality in social and labor activities, reduction in pain medication, patient satisfaction, tolerability, and reasons for termination. The average follow-up time was 9.4 ± 6.1 years, and 31 patients completed a 7-year follow-up period. Thirty-seven patients were enrolled and classified according to the location and quality of their pain, accompanying symptoms, work status, and psychological effects. Substantial pain reduction was obtained in most patients, and the VAS decreased by 4.9 ± 2

  19. Long-term impairment of the lacrimal glands after radioiodine therapy: a cross-sectional study

    International Nuclear Information System (INIS)

    Zettinig, Georg; Fueger, Barbara J.; Pirich, Christian; Dudczak, Robert; Hanselmayer, Georg; Nepp, Johannes; Hofmann, Andrea

    2002-01-01

    Impairment of the lacrimal glands after external radiation has been well documented, but there are only a few reports on the effects of radioiodine therapy on the lacrimal glands. Long-term effects of high-dose radioiodine therapy on tear secretion have not previously been studied. We investigated 175 eyes of 88 patients with a history of radioiodine therapy for thyroid carcinoma (68 females, 20 males; mean age 55±16 years, range 17-81 years) and compared them with a sex- and age-matched control group (n=39). All patients had been given at least 2.96 GBq iodine-131 (maximal administered activity 22.3 GBq 131 I). An ophthalmological investigation was performed 64±71 months (range 3-317 months) after initial radioiodine therapy by a single ophthalmologist. Lacrimal gland function was evaluated with three different function tests. External eye morphology was considered, and detailed ophthalmological history-taking was performed. Patients with factors known to affect lacrimal gland function (contact lenses, autoimmune disorders, history of additional radiation exposure) were excluded from the study. A total of 81 patients (92%) had at least one abnormal function test indicating impaired lacrimal gland function. Schirmer's tear test was decreased (<10 mm/5 min) in 47 of the 88 patients and definitely abnormal (<5 mm/5 min) in 35 patients. A tear film break-up time of <10 s was found in 78 patients, and 62 patients had a definitely abnormal break-up time of <5 s. The lacrimal lipid layer was impaired in 43 patients. The function tests were all significantly altered in the study group as compared with the controls (P<0.005, P<0.001, P<0.001, respectively). Both subjective symptoms of dry eye (P<0.01) and changes in the external eye morphology (P<0.001) were significantly more prevalent in the study group. Our findings suggest that in the majority of patients, lacrimal gland function may be permanently impaired after high-dose radioiodine therapy. All three layers of the

  20. 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.

  1. A retrospective study of long-term treatment outcomes for reduced vocal intensity in hypokinetic dysarthria

    Directory of Open Access Journals (Sweden)

    Christopher R. Watts

    2016-02-01

    Full Text Available Abstract Background Reduced vocal intensity is a core impairment of hypokinetic dysarthria in Parkinson’s disease (PD. Speech treatments have been developed to rehabilitate the vocal subsystems underlying this impairment. Intensive treatment programs requiring high-intensity voice and speech exercises with clinician-guided prompting and feedback have been established as effective for improving vocal function. Less is known, however, regarding long-term outcomes of clinical benefit in speakers with PD who receive these treatments. Methods A retrospective cohort design was utilized. Data from 78 patient files across a three year period were analyzed. All patients received a structured, intensive program of voice therapy focusing on speaking intent and loudness. The dependent variable for all analyses was vocal intensity in decibels (dBSPL. Vocal intensity during sustained vowel production, reading, and novel conversational speech was compared at pre-treatment, post-treatment, six month follow-up, and twelve month follow-up periods. Results Statistically significant increases in vocal intensity were found at post-treatment, 6 months, and 12 month follow-up periods with intensity gains ranging from 5 to 17 dB depending on speaking condition and measurement period. Significant treatment effects were found in all three speaking conditions. Effect sizes for all outcome measures were large, suggesting a strong degree of practical significance. Conclusions Significant increases in vocal intensity measured at 6 and 12 moth follow-up periods suggested that the sample of patients maintained treatment benefit for up to a year. These findings are supported by outcome studies reporting treatment outcomes within a few months post-treatment, in addition to prior studies that have reported long-term outcome results. The positive treatment outcomes experienced by the PD cohort in this study are consistent with treatment responses subsequent to other treatment

  2. Long-term oxygen therapy in COPD patients: population-based cohort study on mortality

    Directory of Open Access Journals (Sweden)

    Pavlov N

    2018-03-01

    Full Text Available Nikolay Pavlov,1 Alan Gary Haynes,2,3 Armin Stucki,4 Peter Jüni,5 Sebastian Robert Ott1 1Department of Pulmonary Medicine, University Hospital (Inselspital, University of Bern, Bern, Switzerland; 2CTU Bern, University of Bern, Bern, Switzerland; 3Institute of Social and Preventive Medicine (ISPM, University of Bern, Bern, Switzerland; 4Department of Internal Medicine, Spital Thun, Thun, Switzerland; 5Applied Health Research Centre, Li Ka Shing Knowledge Institute of St Michael’s Hospital, Department of Medicine, University of Toronto, Toronto, ON, Canada Purpose: Chronic obstructive pulmonary disease (COPD is the fourth leading cause of death worldwide and is associated with a growing and substantial socioeconomic burden. Long-term oxygen therapy (LTOT, recommended by current treatment guidelines for COPD patients with severe chronic hypoxemia, has shown to reduce mortality in this population. The aim of our study was to assess the standardized mortality ratios of incident and prevalent LTOT users and to identify predictors of mortality. Patients and methods: We conducted a 2-year follow-up population-based cohort study comprising all COPD patients receiving LTOT in the canton of Bern, Switzerland. Comparing age- and sex-adjusted standardized mortality ratios, we examined associations between all-cause mortality and patient characteristics at baseline. To avoid immortal time bias, data for incident (receiving LTOT <6 months and prevalent users were analyzed separately. Results: At baseline, 475 patients (20% incident users, n=93 were receiving LTOT because of COPD (48/100,000 inhabitants. Mortality of incident and prevalent LTOT users was 41% versus 27%, respectively, p<0.007, and standardized mortality ratios were 8.02 (95% CI: 5.64–11.41 versus 5.90 (95% CI: 4.79–7.25, respectively. Type 2 respiratory failure was associated with higher standardized mortality ratios among incident LTOT users (60.57, 95% CI: 11.82–310.45, p=0

  3. Applicability of short-term accelerated biofouling studies to predict long-term biofouling accumulation in reverse osmosis membrane systems

    KAUST Repository

    Sanawar, Huma

    2018-02-02

    Biofouling studies addressing biofouling control are mostly executed in short-term studies. It is unclear whether data collected from these experiments are representative for long-term biofouling as occurring in full-scale membrane systems. This study investigated whether short-term biofouling studies accelerated by biodegradable nutrient dosage to feed water were predictive for long-term biofouling development without nutrient dosage. Since the presence of a feed spacer has an strong effect on the degree of biofouling, this study employed six geometrically different feed spacers. Membrane fouling simulators (MFSs) were operated with the same (i) membrane, (ii) feed flow and (iii) feed water, but with feed spacers varying in geometry. For the short-term experiment, biofilm formation was enhanced by nutrient dosage to the MFS feed water, whereas no nutrient dosage was applied in the long-term experiment. Pressure drop development was monitored to characterize the extent of biofouling, while the accumulated viable biomass content at the end of the experimental run was quantified by adenosine triphosphate (ATP) measurements. Impact of feed spacer geometry on biofouling was compared for the short-term and long-term biofouling study. The results of the study revealed that the feed spacers exhibited the same biofouling behavior for (i) the short-term (9-d) study with nutrient dosage and (ii) the long-term (96-d) study without nutrient dosage. For the six different feed spacers, the accumulated viable biomass content (pg ATP.cm) was roughly the same, but the biofouling impact in terms of pressure drop increase in time was significantly different. The biofouling impact ranking of the six feed spacers was the same for the short-term and long-term biofouling studies. Therefore, it can be concluded that short-term accelerated biofouling studies in MFSs are a representative and suitable approach for the prediction of biofouling in membrane filtration systems after long-term

  4. Radiological evaluation of cartilage after microfracture treatment: A long-term follow-up study

    International Nuclear Information System (INIS)

    Von Keudell, A.; Atzwanger, J.; Forstner, R.; Resch, H.; Hoffelner, T.; Mayer, M.

    2012-01-01

    Introduction: Recent literature revealed good short-term results after microfracturing (MFX) of isolated focal cartilage defects in the knee joint. Study purpose was a long-term evaluation of patients who received MFX through a multimodal approach, correlating clinical scores and morphological pre- and postoperative MRI-scans. Materials and methods: Between 2000 and 2007 158 patients were treated with MFX for focal femoral or tibial defects at our department. Patients with instabilities, secondary surgical intervention, patellofemoral lesions, a plica mediopatellaris or more than one cartilage defect site and age >55 were excluded. 15 patients were included. Minimum postoperative follow-up (FU) was 18 months (18–78 m). Mean age at surgery was 45 years (27–54), mean FU-interval 48 months (18–78 m). Male to female ratio was 9:6. For clinical assessment the Knee Osteoarthritis Outcome Score (KOOS) and Lysholm Score were used, radiological evaluation was performed with radiographs and 3Tesla-MRI. Results: Clinical knee function was rated good to excellent in 1 patient, fair in 2 and poor in 10 patients. 2/15 patients received full knee replacement due to insufficient cartilage repair through MFX during FU period. Evaluation of pre- and postoperative MRI showed good cartilage repair tissue in 1 (7.7%), moderate repair in 2 (15.4%) and poor fill in 10 patients (76.9%). In these 10 patients the defect size increased. Average defect size preoperatively was 187 mm 2 (range 12–800 mm 2 ) and postoperatively 294 mm 2 (40–800 mm 2 ). The KOOS-Pain averaged 60 (39–94), KOOS-Symptoms 60.6 (21–100), KOOS-ADL 69 (21–91), KOOS-Sports 35.7 (5–60) and KOOS-QUL 37.2 (6–81). The average Lysholm Score was 73.9 (58–94). 10 patients showed a varus leg axis deviation (Ø 5.9°), 3 had a neutral alignment. The alignment correlated positively with KOOS and especially with the Lysholm Score. Conclusion: Our study demonstrated that MFX as a treatment option for cartilage

  5. Long-term economic consequences of child maltreatment: a population-based study.

    Science.gov (United States)

    Thielen, Frederick W; Ten Have, Margreet; de Graaf, Ron; Cuijpers, Pim; Beekman, Aartjan; Evers, Silvia; Smit, Filip

    2016-12-01

    Child maltreatment is prognostically associated with long-term detrimental consequences for mental health. These consequences are reflected in higher costs due to health service utilization and productivity losses in adulthood. An above-average sense of mastery can have protective effects in the pathogenesis of mental disorders and thus potentially cushion adverse impacts of maltreatment. This should be reflected in lower costs in individuals with a history of child maltreatment and a high sense of mastery. The aims of the study were to prognostically estimate the excess costs of health service uptake and productivity losses in adults with a history of child maltreatment and to evaluate how mastery may act as an effect modifier. Data were used on 5618 individuals participating in the Netherlands Mental Health Survey and Incidence Study (NEMESIS). We focussed on measures of child maltreatment (emotional neglect, physical, psychological and sexual abuse) and economic costs owing to health-care uptake and productivity losses when people with a history of abuse have grown into adulthood. We evaluated how mastery acted as an effect modifier. Estimates were adjusted for demographics and parental psychopathology. Post-stratification weights were used to account for initial non-response and dropout. Due to the non-normal distribution of the costs data, sample errors, 95 % confidence intervals, and p values were calculated using non-parametric bootstrapping (1000 replications). Exposure to child maltreatment occurs frequently (6.9-24.8 %) and is associated with substantial excess costs in adulthood. To illustrate, adjusted annual excess costs attributable to emotional neglect are €1,360 (95 % CI: 615-215) per adult. Mastery showed a significant effect on these figures: annual costs were €1,608 in those with a low sense of mastery, but only €474 in those with a firmer sense of mastery. Child maltreatment has profound mental health consequences and is associated with

  6. Theoretical study on crystalline rock for evaluating of long-term behavior (Contract research)

    International Nuclear Information System (INIS)

    Ichikawa, Yasuaki; Seno, Yasuhiro; Sato, Toshinori; Nakama, Shigeo

    2008-03-01

    The Japan Atomic Energy Agency (JAEA) is working on the Project of Mizunami Underground Research Laboratory (MIU). The project aims at developing comprehensive techniques of geological investigation and of construction of deep underground space for a repository of HLW and/or TRU. This study contributes to an estimation of long-term stability of underground spaces. Rock materials commonly show time-dependent behavior such as creep and relaxation. The underground structures for geological disposal of radioactive wastes must keep stable not only during construction and operation but also after closing, and then the long-term stability of rock structures (over thousands of years) is essentially important for designing the structures. The true mechanism of time-dependent behavior of rock materials is not yet clearly understood, though the phenomena are widely known. This study aims at elucidating the scientific truth involved in the time-dependent behavior of rock showing creep and relaxation. We used samples of Toki granite and performed precise tests under laser microscope observation, and then developed theories representing the experimental results. These experimental and theoretical results will be served for the design and construction of the Phase III (Operation Phase) of the MIU Project. This is the report worked out in the fiscal year 2006. In this work we performed the following subjects: 1) Uniaxial and stress relaxation tests under observation of a confocal laser scanning microscope (CLSM) by using granite specimens of MIU. 2) Pressure dissolution experiment by using specimens of single crystal quartz and glass beads. 3) Development of the rate of pressure dissolution of quartz and a homogenization analysis for quartz dissolution. In Chapter 2 CLSM was used to acquire clear three-dimensional images of Mizunami granite specimens for uniaxial and stress relaxation tests, and observed the change of microscale structure including the mineral configuration under

  7. Modeling studies of unsaturated flow with long-term permeability change at Yucca Mountain

    International Nuclear Information System (INIS)

    Zhang Chengyuan; Liu Xiaoyan; Liu Quansheng

    2008-01-01

    The amount of water seeping into the waste emplacement drifts is crucial for the performance of underground nuclear waste repository, since it controls the corrosion rates of waste packages and the mobilization rate of radionuclides. It is limited by water flow through drift vicinity. In the present work we study the potential rates of water flow around drifts as a function of predicted long-term change of permeability at Yucca Mountain, based on a dual-continuum model of the unsaturated flow in fractured rock mass. For stage of DECOVALEX Ⅳ, we used a simplified practical model on unsaturated flow in Yucca Mountain case simulation. These models contain main physical processes that should be considered, including thermal expansion, thermal radiation, water-rock coupling and stress-induced change of permeability. Comparative study with other DECOVALEX team's results shows that they are both good enough and flexible enough to include more physical processes. We can draw the conclusion that it is necessary to model stress-induced changes in permeability and relative processes in future studies, because there are obvious differences (in water saturation and water flux) between simulation cases with and without variable permeability, especially in areas very close to the drift. (authors)

  8. Preliminary study of long-term wind characteristics of the Mexican Yucatan Peninsula

    International Nuclear Information System (INIS)

    Soler-Bientz, Rolando; Watson, Simon; Infield, David

    2009-01-01

    Mexico's Yucatan Peninsula is one of the most promising areas for wind energy development within the Latin American region but no comprehensive assessment of wind resource has been previously published. This research presents a preliminary analysis of the meteorological parameters relevant to the wind resource in order to find patterns in their long-term behaviour and to establish a foundation for subsequent research into the wind power potential of the Yucatan Peninsula. Three meteorological stations with data measured for a period between 10 and 20 years were used in this study. The monthly trends of ambient temperature, atmospheric pressure and wind speed data were identified and are discussed. The directional behaviour of the winds, their frequency distributions and the related Weibull parameters are presented. Wind power densities for the study sites have been estimated and have been shown to be relatively low (wind power class 1), though a larger number of suitable sites needs to be studied before a definitive resource evaluation can be reported.

  9. Long-Term Structural and Functional Myocardial Adaptations in Healthy Living Kidney Donors: A Pilot Study.

    Directory of Open Access Journals (Sweden)

    Diego Bellavia

    Full Text Available Compensatory renal hypertrophy following unilateral nephrectomy (UNX occurs in the remaining kidney. However, the long-term cardiac adaptive process to UNX remains poorly defined in humans. Our goal was to characterize myocardial structure and function in living kidney donors (LKDs, approximately 12 years after UNX.Cardiac function and structure in 15 Italian LKDs, at least 5 years after UNX (median time from donation = 8.4 years was investigated and compared to those of age and sex matched U.S. citizens healthy controls (n = 15. Standard and speckle tracking echocardiography (STE was performed in both LKDs and controls. Plasma angiotensin II, aldosterone, atrial natriuretic peptide (ANP, N terminus pro B-type natriuretic peptide (NT-proBNP, cyclic guanylyl monophosphate (cGMP, and amino-terminal peptide of procollagen III (PIIINP were also collected. Median follow-up was 11.9 years. In LKDs, LV geometry and function by STE were similar to controls, wall thickness and volumes were within normal limits also by CMR. In LKDs, CMR was negative for myocardial fibrosis, but apical rotation and LV torsion obtained by STE were impaired as compared to controls (21.4 ± 7.8 vs 32.7 ± 8.9 degrees, p = 0.04. Serum creatinine and PIIINP levels were increased [1.1 (0.9-1.3 mg/dL, and 5.8 (5.4-7.6] μg/L, respectively, while urinary cGMP was reduced [270 (250-355 vs 581 (437-698 pmol/mL] in LKDs. No LKD developed cardiovascular or renal events during follow-up.Long-term kidney donors have no apparent structural myocardial abnormalities as assessed by contrast enhanced CMR. However, myocardial deformation of the apical segments, as well as apical rotation, and LV torsion are reduced. The concomitant increase in circulating PIIINP level is suggestive of fibrosis. Further studies, focused on US and EU patients are warranted to evaluate whether these early functional modifications will progress to a more compromised cardiac function and structure at a later time.

  10. Long-term outcome of refractory status epilepticus in adults: A retrospective population-based study.

    Science.gov (United States)

    Kantanen, Anne-Mari; Reinikainen, Matti; Parviainen, Ilkka; Kälviäinen, Reetta

    2017-07-01

    Refractory status epilepticus (RSE) is a neurological emergency with significant morbidity and mortality. We aimed to analyze the long-term outcome of intensive care unit (ICU)-treated RSE and super-refractory status epilepticus (SRSE) patients in a population based cohort. A retrospective study of ICU- and anesthesia-treated RSE patients in Kuopio University Hospital's (KUH) special responsibility area hospitals in the central and eastern part of Finland from Jan. 1, 2010 to Dec. 31, 2012 was conducted. KUH's catchment area consists of five hospitals-one university hospital and four central hospitals-and covers a population of 840 000. We included all consecutive adult (16 years or older) RSE patients admitted in the participating ICUs during the 3-year period and excluded patients with postanoxic etiologies. We used a modified Rankin Scale (mRS) as a long-term (1-year) outcome measure: good (mRS 0-3, recovered to baseline function) or poor (mRS 4-6, major functional deficit or death). We identified 75 patients with ICU- and anesthesia-treated RSE, corresponding to an annual incidence of 3.0 (95% confidence interval (CI) 2.4-3.8). 21% of the patients were classified as SRSE, with the annual incidence being 0.6/100 000 (95% CI 0.4-1.0). For RSE, the ICU mortality was 0%, hospital mortality was 7% (95% CI 1.2%-12.8%) (n=5), and one-year mortality was 23% (CI 95% 13.4%-32.5%) (n=17). 48% (n=36) of RSE patients recovered to baseline, and 29% (n=22) showed neurological deficit at 1year. Poor outcome (mRS 4-6) was recorded for 52% (n=39) of the patients. Older age was associated with poorer outcome at 1year (p=0.03). For SRSE, hospital mortality was 6% (n=1) and 1-year mortality was 19% (n=3) (95%CI 0%-38.2%). During 1-year follow-up, nearly 50% of the ICU-treated RSE patients recovered to baseline function, whereas 30% showed new functional defects and 20% died. SRSE does not have a necessarily poorer outcome. The outcome is worse in older patients and in patients with

  11. A prospective cohort study of long-term cognitive changes in older Medicare beneficiaries.

    Science.gov (United States)

    Wolinsky, Fredric D; Bentler, Suzanne E; Hockenberry, Jason; Jones, Michael P; Weigel, Paula A; Kaskie, Brian; Wallace, Robert B

    2011-09-20

    Promoting cognitive health and preventing its decline are longstanding public health goals, but long-term changes in cognitive function are not well-documented. Therefore, we first examined long-term changes in cognitive function among older Medicare beneficiaries in the Survey on Assets and Health Dynamics among the Oldest Old (AHEAD), and then we identified the risk factors associated with those changes in cognitive function. We conducted a secondary analysis of a prospective, population-based cohort using baseline (1993-1994) interview data linked to 1993-2007 Medicare claims to examine cognitive function at the final follow-up interview which occurred between 1995-1996 and 2006-2007. Besides traditional risk factors (i.e., aging, age, race, and education) and adjustment for baseline cognitive function, we considered the reason for censoring (entrance into managed care or death), and post-baseline continuity of care and major health shocks (hospital episodes). Residual change score multiple linear regression analysis was used to predict cognitive function at the final follow-up using data from telephone interviews among 3,021 to 4,251 (sample size varied by cognitive outcome) baseline community-dwelling self-respondents that were ≥ 70 years old, not in managed Medicare, and had at least one follow-up interview as self-respondents. Cognitive function was assessed using the 7-item Telephone Interview for Cognitive Status (TICS-7; general mental status), and the 10-item immediate and delayed (episodic memory) word recall tests. Mean changes in the number of correct responses on the TICS-7, and 10-item immediate and delayed word recall tests were -0.33, -0.75, and -0.78, with 43.6%, 54.9%, and 52.3% declining and 25.4%, 20.8%, and 22.9% unchanged. The main and most consistent risks for declining cognitive function were the baseline values of cognitive function (reflecting substantial regression to the mean), aging (a strong linear pattern of increased decline

  12. Long-Term Use of Everolimus in Patients with Tuberous Sclerosis Complex: Final Results from the EXIST-1 Study.

    Directory of Open Access Journals (Sweden)

    David N Franz

    Full Text Available Everolimus, a mammalian target of rapamycin (mTOR inhibitor, has demonstrated efficacy in treating subependymal giant cell astrocytomas (SEGAs and other manifestations of tuberous sclerosis complex (TSC. However, long-term use of mTOR inhibitors might be necessary. This analysis explored long-term efficacy and safety of everolimus from the conclusion of the EXIST-1 study (NCT00789828.EXIST-1 was an international, prospective, double-blind, placebo-controlled phase 3 trial examining everolimus in patients with new or growing TSC-related SEGA. After a double-blind core phase, all remaining patients could receive everolimus in a long-term, open-label extension. Everolimus was initiated at a dose (4.5 mg/m2/day titrated to a target blood trough of 5-15 ng/mL. SEGA response rate (primary end point was defined as the proportion of patients achieving confirmed ≥50% reduction in the sum volume of target SEGA lesions from baseline in the absence of worsening nontarget SEGA lesions, new target SEGA lesions, and new or worsening hydrocephalus. Of 111 patients (median age, 9.5 years who received ≥1 dose of everolimus (median duration, 47.1 months, 57.7% (95% confidence interval [CI], 47.9-67.0 achieved SEGA response. Of 41 patients with target renal angiomyolipomas at baseline, 30 (73.2% achieved renal angiomyolipoma response. In 105 patients with ≥1 skin lesion at baseline, skin lesion response rate was 58.1%. Incidence of adverse events (AEs was comparable with that of previous reports, and occurrence of emergent AEs generally decreased over time. The most common AEs (≥30% incidence suspected to be treatment-related were stomatitis (43.2% and mouth ulceration (32.4%.Everolimus use led to sustained reduction in tumor volume, and new responses were observed for SEGA and renal angiomyolipoma from the blinded core phase of the study. These findings support the hypothesis that everolimus can safely reverse multisystem manifestations of TSC in a

  13. Determinants of long-term neuropsychological symptoms. The Danish Gulf War Study.

    Science.gov (United States)

    Suadicani, P; Ishøy, T; Guldager, B; Appleyard, M; Gyntelberg, F

    1999-11-01

    Compared with controls, up to six years after their return, Danish Gulf War Veterans have a significantly higher prevalence of self-reported neuropsychological symptoms. Independent associations are found for concentration or memory problems, repeated fits of headache, balance disturbances or fits of dizziness, abnormal fatigue not caused by physical activity, and problems sleeping all night. We investigated whether psychosocial, physical, chemical or biological exposures were associated with these symptoms. This study is a prevalence study using retrospective data on exposure. Some 686 subjects who had been deployed in the Persian Gulf within the period August 2 1990 until December 31 1997 were included; the control group comprised 257 subjects matched according to age, gender and profession. All participants underwent clinical and paraclinical examinations, and were interviewed by a physician based on a completed questionnaire. A clustering of three to five of the above symptoms were found in 21.4% of Gulf War Veterans vs. 6.2% in controls, p work conditions known to be important in civilian life, and also environmental factors, should be improved to minimize the risk of long-term neuropsychological symptoms.

  14. Study of Spermatogenesis in Wistar Adult Rats Administrated to Long Term of Ruta Graveolens

    Directory of Open Access Journals (Sweden)

    Bazrafkan

    2014-07-01

    Full Text Available Background In Iranian folk medicine Ruta graveolens has been used for female and male contraceptive. There are few studies about the effect of this plant on spermatogenesis. Objectives In this study the effect of long term administration of aqueous extract of RG on spermatogenesis has been investigated. Materials and Methods Animals were allocated into 1 control: which did not receive anything, 2 vehicle which received only normal saline and 3 experiment: which received Ruta extract (300 mg/kg administered by gavage once a day for 100 days. A day after last gavage all the individuals were killed by euthanasia. The right testes and epididymis were extruded. The sperm motility was assessed and classified as progressive, no progressive. Results There was a significant decrease in the number of spermatogonia (P 0.05.The fertilization capacity of sperm of rats in experimental group was significantly lower than other groups (P > 0.05. Conclusions It is concluded that the aqueous extract of Ruta graveolens diminishes the reproductive system activity and might be a useful substance for birth control process.

  15. An agar gel membrane-PDMS hybrid microfluidic device for long term single cell dynamic study.

    Science.gov (United States)

    Wong, Ieong; Atsumi, Shota; Huang, Wei-Chih; Wu, Tung-Yun; Hanai, Taizo; Lam, Miu-Ling; Tang, Ping; Yang, Jian; Liao, James C; Ho, Chih-Ming

    2010-10-21

    Significance of single cell measurements stems from the substantial temporal fluctuations and cell-cell variability possessed by individual cells. A major difficulty in monitoring surface non-adherent cells such as bacteria and yeast is that these cells tend to aggregate into clumps during growth, obstructing the tracking or identification of single-cells over long time periods. Here, we developed a microfluidic platform for long term single-cell tracking and cultivation with continuous media refreshing and dynamic chemical perturbation capability. The design highlights a simple device-assembly process between PDMS microchannel and agar membrane through conformal contact, and can be easily adapted by microbiologists for their routine laboratory use. The device confines cell growth in monolayer between an agar membrane and a glass surface. Efficient nutrient diffusion through the membrane and reliable temperature maintenance provide optimal growth condition for the cells, which exhibited fast exponential growth and constant distribution of cell sizes. More than 24 h of single-cell tracking was demonstrated on a transcription-metabolism integrated synthetic biological model, the gene-metabolic oscillator. Single cell morphology study under alcohol toxicity allowed us to discover and characterize cell filamentation exhibited by different E. coli isobutanol tolerant strains. We believe this novel device will bring new capabilities to quantitative microbiology, providing a versatile platform for single cell dynamic studies.

  16. Study on the weediness of winter wheat in a long-term fertilization field experiment.

    Science.gov (United States)

    Lehoczky, E; Kismányoky, A; Kismányoky, T

    2006-01-01

    The study was carried out in Keszthely, in the long-term fertilization field experiment in April of 2005. In the experiment we had opportunity to compare the weediness in NPK and NPK + FYM* treatments, and we could study the effect of increasing N dosis on the weeds and winter wheat. The weed survey was made on the 20th of April at the end of tillering. For the weed survey used the Balázs-Ujvárosi method. After that we collected all the weeds from the plots per 1 m2. We counted, measured the fresh and dry matter weight of aerial parts. Winter wheat sampels were taken also from all plots (1 running meter per plot). In the experiment 10 weed species were found, 9 annual: Ambrosia artemisiifolia, Consolida regalis, Galium aparine, Lamiunt amplexicaule, Matricaria inodora, Papaver rhoeas, Stellaria media, Veronica hederifolia, Veronica triphyllos, and 1 perennial: Cirsium arvense. Veronica hederifolia was the dominant species in both fertilized plots, Stellaria media has the second highest weed coverage. The manuring treatments, and the N-dosis has important and significantly effect to the weedeness and the biomass production of winter wheat. On the control plots was the relation of biomass weight of weeds the highest. This relation reduced to the effect of N treatments, wich had an favorable effect on the winter wheat.

  17. Severity Stages in Essential Tremor: A Long-Term Retrospective Study Using the Glass Scale

    Directory of Open Access Journals (Sweden)

    Alexandre Gironell

    2015-03-01

    Full Text Available Background:  Few prospective studies have attempted to estimate the rate of decline of essential tremor (ET and these were over a relatively short time period (less than 10 years.  We performed a long-term study of severity stages in ET using the Glass scale scoring system.Methods: Fifty consecutive patients with severe ET were included. We retrospectively obtained Glass Scale scores throughout the patient’s life. Common milestone events were used to help recall changes in tremor severity.Results:  According to the Glass Scale, the age distributions were as follows: score I, 40±17 years, score II, 55±12 years, score III, 64±9 years, and score IV, 69±7 years. A significant negative correlation between age at first symptom and rate of progression was found (r=−0.669, p<0.001. The rate of progression was significantly different (p<0.001 when the first symptom appeared at a younger age (under 40 years of age compared with older age (40 years or older.Discussion:  Our results support the progressive nature of ET. Age at onset was a prognostic factor. The Glass Scale may be a useful tool to determine severity stages during the course of ET in a manner similar to the Hoehn and Yahr Scale for Parkinson’s disease.

  18. Severity Stages in Essential Tremor: A Long-Term Retrospective Study Using the Glass Scale

    Science.gov (United States)

    Gironell, Alexandre; Ribosa-Nogué, Roser; Gich, Ignasi; Marin-Lahoz, Juan; Pascual-Sedano, Berta

    2015-01-01

    Background Few prospective studies have attempted to estimate the rate of decline of essential tremor (ET) and these were over a relatively short time period (less than 10 years). We performed a long-term study of severity stages in ET using the Glass Scale scoring system. Methods Fifty consecutive patients with severe ET were included. We retrospectively obtained Glass Scale scores throughout the patient's life. Common milestone events were used to help recall changes in tremor severity. Results According to the Glass Scale, the age distributions were as follows: score I, 40±17 years, score II, 55±12 years, score III, 64±9 years, and score IV, 69±7 years. A significant negative correlation between age at first symptom and rate of progression was found (r = −0.669, p<0.001). The rate of progression was significantly different (p<0.001) when the first symptom appeared at a younger age (under 40 years of age) compared with older age (40 years or older). Discussion Our results support the progressive nature of ET. Age at onset was a prognostic factor. The Glass Scale may be a useful tool to determine severity stages during the course of ET in a manner similar to the Hoehn and Yahr Scale for Parkinson's disease. PMID:25793146

  19. Continued studies of long-term ecological effects of exposure to uranium

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, W.C.; Miera, F.R. Jr.

    1977-06-01

    Studies of the long-term consequences of exposing terrestrial ecosystems to natural and depleted uranium dispersed during explosives tests at Los Alamos Scientific Laboratory (LASL) and test firing at Eglin Air Force Base (EAFB), Florida, were continued. Soils from EAFB, sampled before and after firing of depleted uranium penetrators against armor plate targets, indicated that the upper (0- to 5-cm-deep) soil usually contained more uranium than lower (5- to 10-cm-deep) soil. However, no significant changes were apparent in samples taken before and after the test firing. E-F explosive testing site at LASL was selected for intensive study of uranium redistribution during its 33-yr use. Highest surface soil (0- to 2.5-cm-deep) uranium concentrations occurred 0 and 10 m from the detonation point and averaged 4500 ppM. Concentrations in surface soil 50 and 200 m from the firing point were usually < 15% of that value. The uranium distribution to 30-cm depths showed significant penetration into the soil. Alluvium collected 250 m from the E-F detonation area in Potrillo Canyon indicated that surface (0- to 2.5-cm-deep) uranium concentrations were about 10% of those at the detonation point, and at 2.8 km they were twice background levels.

  20. US Department of Energy Approach to Probabilistic Evaluation of Long-Term Safety for a Potential Yucca Mountain Repository

    International Nuclear Information System (INIS)

    Dr. R. Dyer; Dr. R. Andrews; Dr. A. Van Luik

    2005-01-01

    Regulatory requirements being addressed in the US geological repository program for spent nuclear fuel and high-level waste disposal specify probabilistically defined mean-value dose limits. These dose limits reflect acceptable levels of risk. The probabilistic approach mandated by regulation calculates a ''risk of a dose,'' a risk of a potential given dose value at a specific time in the future to a hypothetical person. The mean value of the time-dependent performance measure needs to remain below an acceptable level defined by regulation. Because there are uncertain parameters that are important to system performance, the regulation mandates an analysis focused on the mean value of the performance measure, but that also explores the ''full range of defensible and reasonable parameter distributions''...System performance evaluations should not be unduly influenced by...''extreme physical situations and parameter values''. Challenges in this approach lie in defending the scientific basis for the models selected, and the data and distributions sampled. A significant challenge lies in showing that uncertainties are properly identified and evaluated. A single-value parameter has no uncertainty, and where used such values need to be supported by scientific information showing the selected value is appropriate. Uncertainties are inherent in data, but are also introduced by creating parameter distributions from data sets, selecting models from among alternative models, abstracting models for use in probabilistic analysis, and in selecting the range of initiating event probabilities for unlikely events. The goal of the assessment currently in progress is to evaluate the level of risk inherent in moving ahead to the next phase of repository development: construction. During the construction phase, more will be learned to inform a new long-term risk evaluation to support moving to the next phase: accepting waste. Therefore, though there was sufficient confidence of safety

  1. Long-term dose-response studies of inhaled or injected radionuclides

    International Nuclear Information System (INIS)

    Boecker, B.B.; Muggenburg, B.A.; Miller, S.C.; Bradley, P.L.

    1994-01-01

    This report describes the scientific progress in, and current status of, life-span studies of the long-term health risks in Beagle dogs of chronic irradiation from internally deposited radionuclides or from an external source. The reporting period for this document is the 2-year period from October 1, 1991 through September 30, 1993. Studies that were initiated at three different laboratories (Inhalation Toxicology Research Institute, ITRI, University of Utah, and Argonne National Laboratory, ANL) are presented here because they are being completed at ITRI. All living dogs in the Utah-initiated studies were transferred to the ITRI facility for the remainder of their life-span observations and measurements in September 1987. This report is the fourth in a series of reports dealing with the current status and progress of both the Utah and ITRI studies. Other life-span studies involving dogs exposed to gamma radiation from an external source were initiated and conducted for many years at ANL. In 1991, the decision was made to discontinue the chronic irradiation of the remaining living dogs and to transfer all remaining dogs to ITRI for care, clinical observations, and pathological observations at death or euthanasia. This report provides the current status of these dogs. Status reports on the Utah and ITRI studies comprise most of this report. The ITRI-related section presents brief statements of project objectives, the general procedures used in these studies, and some study-specific features for each of the 19 studies being conducted with either beta- or alpha-emitting radionuclides. Dose- and effect-modifying factors being addressed in these studies include total dose, dose rate, LET, solubility, nonuniformity of dose, species, age, sex, health status, and mode of exposure. Recent additions to experimental protocols for studies in which dogs are still alive involve the collection and analysis of tumor tissues using currently available molecular biology techniques

  2. Study of delayed strains for concrete in compression and in tension from early age to long term

    International Nuclear Information System (INIS)

    Hilaire, Adrien

    2014-01-01

    This work aims to study the behaviour of the containment buildings in a nuclear power plant. The gas-proofing of these structures is based on the low conductivity of concrete (the hydraulic conductivity is around 10-11 m/s for a standard concrete). However, if cracks appear, this material property increases and the containment may not be longer guaranteed. In accidental situations, the concrete is protected from cracking by the bi-axial prestressing of the internal safety enclosure. The ageing of the structure may have two main consequences: firstly, the prestress has to remain sufficiently high to counterbalance the tensile stress caused by an accident, secondly, cracking induced by non-accidental loads has to be limited. These aims cannot be satisfied if the behaviour of the concrete is not understood from its manufacturing to the end of the operating life of the nuclear reactor. The lifespan of the structure is broken down into two distinguished periods: on one hand, strong chemo-thermo-mechanical couplings characterise the early age phase, on the other hand, the material is under hydro-mechanical stress during the long term phase. In the proposed modelling, hydration, thermal and hydric transfers are coupled with the mechanical behaviour of the concrete; the main mechanisms are considered. The model is implemented in the software CAST3M: the limited number of parameters facilitate the identification process. In tandem with this work, several experimental tests are realised. Parameters are identified from their results, moreover, some of the experimental observations confirmed the physical mechanisms considered in the model. Because of the complexity of the different phenomenon, this document is built around the following principles. The first part deals with the chemo-thermal couplings at early age and the drying process of concrete at long term: the nature of these two problems is diffusive. This part is focused on the identification of the main parameters of

  3. Studies on the dissolution and long term weathering of spilled crude oils

    Energy Technology Data Exchange (ETDEWEB)

    Mackay, D; Charles, M E; Sumchi, Lee; Lun, R; Ooijen, H van; Romocki, K; Harner, T; Ralfs, M

    1993-04-01

    The development of a laboratory system for the study of the long term behavior of crude oil on a water surface is described. The apparatus consists of a cylindrical glass vessel containing water which is rotated at 33 rpm, thus creating a concave surface in which oil tends to accumulate at the center. Turbulence is induced by a stationary stirrer. Results are described of tests conducted with a number of crude oils and it is concluded that the system is able to create reproducible conditions of controlled evaporation, dissolution, turbulence, photolysis, and oil in water emulsion formation. A major advantage of the system is its simplicity and robustness which permits prolonged exposure of the oil to simulate weathering, over periods of weeks and months. A second system is described which can be used to determine the concentrations of dissolved hydrocarbons under oil slicks by in-situ headspace analysis. A prototype submersible sparger sampling system was devised and tested, and results are presented. It is concluded that the system is a promising and practical method of determining the extent to which dissolved hydrocarbons are present in water at various depths under an oil slick. In both cases it is concluded that the concepts have sufficient merit that further work is justified. Recommendations are made for further research and development which will, it is hoped, enable these systems to be used to investigate aspects of the fate and effects of oil spills at sea. 6 refs., 14 figs., 4 tabs.

  4. A comparative study on prediction methods for China's medium- and long-term coal demand

    International Nuclear Information System (INIS)

    Li, Bing-Bing; Liang, Qiao-Mei; Wang, Jin-Cheng

    2015-01-01

    Given the dominant position of coal in China's energy structure and in order to ensure a safe and stable energy supply, it is essential to perform a scientific and effective prediction of China's medium- and long-term coal demand. Based on the historical data of coal consumption and related factors such as GDP (Gross domestic product), coal price, industrial structure, total population, energy structure, energy efficiency, coal production and urbanization rate from 1987 to 2012, this study compared the prediction effects of five types of models. These models include the VAR (vector autoregressive model), RBF (radial basis function) neural network model, GA-DEM (genetic algorithm demand estimation model), PSO-DEM (particle swarm optimization demand estimation model) and IO (input–output model). By comparing the results of different models with the corresponding actual coal consumption, it is concluded that with a testing period from 2006 to 2012, the PSO-DEM model has a relatively optimal predicted effect on China's total coal demand, where the MAPE (mean absolute percentage error) is close to or below 2%. - Highlights: • The prediction effects of five methods for China's coal demand were compared. • Each model has acceptable prediction results, with MAPE below 5%. • Particle swarm optimization demand estimation model has better forecast efficacy.

  5. Birth Outcomes after the Fukushima Daiichi Nuclear Power Plant Disaster: A Long-Term Retrospective Study

    Science.gov (United States)

    Leppold, Claire; Nomura, Shuhei; Sawano, Toyoaki; Ozaki, Akihiko; Tsubokura, Masaharu; Hill, Sarah; Kanazawa, Yukio; Anbe, Hiroshi

    2017-01-01

    Changes in population birth outcomes, including increases in low birthweight or preterm births, have been documented after natural and manmade disasters. However, information is limited following the 2011 Fukushima Daiichi Nuclear Power Plant Disaster. In this study, we assessed whether there were long-term changes in birth outcomes post-disaster, compared to pre-disaster data, and whether residential area and food purchasing patterns, as proxy measurements of evacuation and radiation-related anxiety, were associated with post-disaster birth outcomes. Maternal and perinatal data were retrospectively collected for all live singleton births at a public hospital, located 23 km from the power plant, from 2008 to 2015. Proportions of low birthweight (increased proportions of low birthweight or preterm births in any year after the disaster (merged post-disaster risk ratio of low birthweight birth: 0.98, 95% confidence interval (CI): 0.64–1.51; and preterm birth: 0.68, 95% CI: 0.38–1.21). No significant associations between birth outcomes and residential area or food purchasing patterns were identified, after adjustment for covariates. In conclusion, no changes in birth outcomes were found in this institution-based investigation after the Fukushima disaster. Further research is needed on the pathways that may exacerbate or reduce disaster effects on maternal and perinatal health. PMID:28534840

  6. Effect of routine repeat transurethral resection for superficial bladder cancer: a long-term observational study.

    Science.gov (United States)

    Grimm, Marc-Oliver; Steinhoff, Christine; Simon, Xenia; Spiegelhalder, Philipp; Ackermann, Rolf; Vogeli, Thomas Alexander

    2003-08-01

    We determined the long-term outcome in patients with superficial bladder cancer (Ta and T1) undergoing routine second transurethral bladder tumor resection (ReTURB) in regard to recurrence and progression. We performed an inception cohort study of 124 consecutive patients with superficial bladder cancer undergoing transurethral resection and routine ReTURB (83) between November 1993 and October 1995 at a German university hospital. Immediately after transurethral resection all lesions were documented on a designed bladder map. ReTURB of the scar from initial resection and other suspicious lesions was performed at a mean of 7 weeks. Patients were followed until recurrence or death, or a minimum of 5 years. Residual tumor was found in 33% of all ReTURB cases, including 27% of Ta and 53% of T1 disease, and in 81% at the initial resection site. Five of the 83 patients underwent radical cystectomy due to ReTURB findings. The estimated risk of recurrence after years 1 to 3 was 18%, 29% and 32%, respectively. After 5 years 63% of the patients undergoing ReTURB were still disease-free (mean recurrence-free survival 62 months, median 87). Progression to muscle invasive disease was observed in only 2 patients (3%) after a mean observation of 61 months. These data suggest a favorable outcome regarding recurrence and progression in patients with superficial bladder cancer who undergo ReTURB. ReTURB is suggested at least in those at high risk when bladder preservation is intended.

  7. Long-Term Experiences of Men with Spinal Cord Injuries in Japan: A Qualitative Study

    Directory of Open Access Journals (Sweden)

    Masakuni Tagaki

    2015-03-01

    Full Text Available The goal of the current study was to examine how Japanese men with long-term spinal cord injuries constructed their post-injury life. To do this, I conducted semi-structured interviews with ten participants who had sustained spinal cord injuries. The interview data was transcribed and analyzed qualitatively using the KJ method, which is widely employed in Japan and has been developed by and named after the founder of the method, the anthropologist Jiro KAWAKITA (1967. The participants led lives similar to able-bodied individuals and tried to find specific positive aspects of their lives that they owed to their disabilities. They also developed collective identities as people with acquired disabilities through their relationships with others having disabilities. To alleviate their sense of loss, the participants also emphasized the unchanged aspects of their pre-injury lives. They understood that their lives were greatly influenced by a socially supportive environment that was regarded as being contingent. They recognized their inability to control the environment and valued the contingencies. URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs150210

  8. The influence of coping styles on long-term employment in multiple sclerosis: A prospective study.

    Science.gov (United States)

    Grytten, Nina; Skår, Anne Br; Aarseth, Jan Harald; Assmus, Jorg; Farbu, Elisabeth; Lode, Kirsten; Nyland, Harald I; Smedal, Tori; Myhr, Kjell Morten

    2017-06-01

    The aim was to investigate predictive values of coping styles, clinical and demographic factors on time to unemployment in patients diagnosed with multiple sclerosis (MS) during 1998-2002 in Norway. All patients ( N = 108) diagnosed with MS 1998-2002 in Hordaland and Rogaland counties, Western Norway, were invited to participate in the long-term follow-up study in 2002. Baseline recordings included disability scoring (Expanded Disability Status Scale (EDSS)), fatigue (Fatigue Severity Scale (FSS)), depression (Beck Depression Inventory (BDI)), and questionnaire assessing coping (the Dispositional Coping Styles Scale (COPE)). Logistic regression analysis was used to identify factors associated with unemployed at baseline, and Cox regression analysis to identify factors at baseline associated with time to unemployment during follow-up. In all, 41 (44%) were employed at baseline. After 13 years follow-up in 2015, mean disease duration of 22 years, 16 (17%) were still employed. Median time from baseline to unemployment was 6 years (±5). Older age at diagnosis, female gender, and depression were associated with patients being unemployed at baseline. Female gender, long disease duration, and denial as avoidant coping strategy at baseline predicted shorter time to unemployment. Avoidant coping style, female gender, and longer disease duration were associated with shorter time to unemployment. These factors should be considered when advising patients on MS and future employment.

  9. Long-term life and partnership satisfaction in infertile patients: a 5-year longitudinal study.

    Science.gov (United States)

    Schanz, Stefan; Reimer, Thorisa; Eichner, Martin; Hautzinger, Martin; Häfner, Hans-Martin; Fierlbeck, Gerhard

    2011-08-01

    To describe the long-term effects of infertility on life and partnership satisfaction. Longitudinal cohort study. A university outpatient andrology and gynecology infertility clinic. 275 men and 272 women treated for infertility between August 2000 and December 2001. None. The Life Satisfaction Questionnaire (FLZ), the Partnership Questionnaire (PFB), and sociodemographic items at baseline (T1) and 5 years later (T2). Compared with a representative sample, our male and female participants had higher Finance and Partnership scores and lower Health scores on the FLZ at T1. They also had markedly higher PFB scores, with the exception of Conflict Behavior. After 5 years (T2), 101 men and 113 women rated the Partnership and Sexuality FLZ subscales as well as all the PFB subscales statistically significantly lower than at baseline. Only the women rated the Self-esteem FLZ subscale lower than at baseline (T1). Participants who became parents had lower Leisure and Partnership FLZ subscale scores, and fathers had lower Finance FLZ subscale scores. Satisfaction declined over 5 years for both men and women, but only in the partnership-related domains. Women were more affected than men. The success of infertility treatment had only a minor influence on a couple's future satisfaction. Copyright © 2011. Published by Elsevier Inc.

  10. Long term multiwavelength studies of the corona/disc connection in AGN

    Science.gov (United States)

    Buisson, D.; Lohfink, A.; Alston, W.; Fabian, A.; Gallo, L.; Kara, E.; Zoghbi, A.; Wilkins, D.; Miller, J.; Cackett, E.

    2017-10-01

    One way of increasing our understanding of AGN is determining the nature of the connection between the optical/UV emitting accretion disc and the X-ray emitting corona. Studies of variability in these two bands are a key tool for gaining insight into the processes involved. We will present results from a sample of long-term AGN monitoring campaigns in the optical, UV and X-ray with Swift. In particular, we will explore UV/optical-X-ray correlations and associated time lags. We will compare these measurements and the UV/optical RMS spectra with theoretical reprocessing models and confront recent claims of the observed lags being longer than those which are expected for a standard thin disc. Additionally, a new Swift monitoring campaign of the z=2 quasar PG 1247+267 allows us to probe the shorter wavelengths at the peak of the accretion disc spectrum, providing information on the region of the disc closest to the black hole. However, not all AGN show such correlations, including IRAS 13224-3809, the subject of a recent 1.5 Ms XMM observation. Using this and other examples, we will explore the possible reasons for the lack of observed correlation.

  11. Estimating Long-Term Care Costs among Thai Elderly: A Phichit Province Case Study

    Directory of Open Access Journals (Sweden)

    Pattaraporn Khongboon

    2018-01-01

    Full Text Available Background. Rural-urban inequality in long-term care (LTC services has been increasing alongside rapid socioeconomic development. This study estimates the average spending on LTC services and identifies the factors that influence the use and cost of LTC for the elderly living in urban and rural areas of Thailand. Methods. The sample comprised 837 elderly aged 60 years drawn from rural and urban areas in Phichit Province. Costs were assessed over a 1-month period. Direct costs of caregiving and indirect costs (opportunity cost method were analyzed. Binary logistic regression was performed to determine which factors affected LTC costs. Results. The total annual LTC spending for rural and urban residents was on average USD 7,285 and USD 7,280.6, respectively. Formal care and informal care comprise the largest share of payments. There was a significant association between rural residents and costs for informal care, day/night care, and home renovation. Conclusions. Even though total LTC expenditures do not seem to vary significantly across rural and urban areas, the fundamental differences between areas need to be recognized. Reorganizing country delivery systems and finding a balance between formal and informal care are alternative solutions.

  12. Describing Long-Term Electricity Demand Scenarios in the Telecommunications Industry: A Case Study of Japan

    Directory of Open Access Journals (Sweden)

    Yusuke Kishita

    2016-01-01

    Full Text Available Due to the rapid expansion of information and communication technology (ICT usage, the telecommunications industry is faced with a challenge to promote green ICT toward achieving a low-carbon society. One critical obstacle in planning long-term strategies for green ICT is the uncertainty of various external factors, such as consumers’ lifestyle and technological advancement. To tackle this issue, this paper employs a scenario planning method to analyze electricity consumption in the telecommunications industry, where both changes in various external factors and energy-saving measures are assumed. We propose a model to estimate future electricity consumption of the telecommunications industry using a statistical approach. In a case study, we describe four scenarios that differ in the diffusion of ICT and the technological advancement of ICT equipment in order to analyze the electricity consumption in Japan’s telecommunications industry to 2030. The results reveal that the electricity consumption in 2030 becomes 0.7–1.6-times larger than the 2012 level (10.7 TWh/year. It is also shown that the most effective measures to reduce the electricity consumption include improving the energy efficiency of IP (Internet Protocol communication equipment and mobile communication equipment.

  13. Long-term monitoring studies of pollutants on public lands: Bald Eagles in the Midwest

    Energy Technology Data Exchange (ETDEWEB)

    Bowerman, W.W. [Eagle Environmental Inc., Haslett, MI (United States)

    1995-12-31

    The role of public agencies to monitor the populations of wildlife species with protected status is paramount to the recovery of these species. Since the early 1960s, the bald eagle (Haliaeetus leucocephalus) populations within the Midwest have been monitored to determine number of breeding pairs, nest occupancy, and success rates. In addition to the reproductive outcome studies, abandoned eggs, blood samples, and feather samples have been collected to determine concentrations of organochlorine pesticides, PCBs, and heavy metals. These surveys give an actual measure of population dynamics of a top-predator species in aquatic systems that integrates the effects of many different environmental pollutants. As concentrations of the organochlorine compounds have declined, bald eagle populations have increased in numbers and their reproductive success has improved. The recovery of this species has not been uniform however. In regions where DDT and PCB concentrations are still above thresholds associated with reproductive impairment, eagles still have impaired reproduction. These areas include the shorelines of the Great Lakes and Voyageurs National Park. Some areas such as the Chippewa National Forest have begun to show declines in reproduction due to density dependent factors. Recent proposals for ecosystem management and reclassification of the bald eagle have led to reduced emphasis for maintaining these long-term data sets. The utility and importance of maintaining surveys of top-predators that can give a measure of population-level effects of pollutants rather than an index will be discussed using examples from the Midwest.

  14. Early aging in Chernobyl clean-up workers: long-term study.

    Science.gov (United States)

    Krasnov, V; Kryukov, V; Samedova, E; Emelianova, I; Ryzhova, I

    2015-01-01

    This paper represents data of long-term open prospective study. 312 male clean-up workers, who participated in elimination of the Chernobyl disaster consequences in 1986-87, were observed and examined in Moscow Research Institute of Psychiatry. The average age of patients was 57,0 ± 6,8 years. All patients were diagnosed with psychoorganic syndrome, caused by combination of different factors, which led to early cerebrovascular pathology, which was confirmed by clinical, neuropsychological, and instrumental examination. Anamnesis and the level of social adaptation were also assayed. Clinical estimation was done with the use of specially developed Clinical Psychopathological Chart. All the symptoms were divided into 4 groups (asthenic, psychovegetative, dysthymic, and cognitive symptom-complexes). No pronounced signs of dementia were observed. The control group included 44 clean-up workers without mental disorders. Predomination of various exogenous factors before and after accident was noted. Therapy included different vasotropic remedies, as well as family therapy, art therapy, and cognitive training. The possibilities of the reverse development of symptoms were statistically proved. The results allow making a conclusion that these disorders could not be explained either by radiation effects or by PTSD but connected with cerebrovascular pathology.

  15. Early Aging in Chernobyl Clean-Up Workers: Long-Term Study

    Directory of Open Access Journals (Sweden)

    V. Krasnov

    2015-01-01

    Full Text Available This paper represents data of long-term open prospective study. 312 male clean-up workers, who participated in elimination of the Chernobyl disaster consequences in 1986-87, were observed and examined in Moscow Research Institute of Psychiatry. The average age of patients was 57,0 ± 6,8 years. All patients were diagnosed with psychoorganic syndrome, caused by combination of different factors, which led to early cerebrovascular pathology, which was confirmed by clinical, neuropsychological, and instrumental examination. Anamnesis and the level of social adaptation were also assayed. Clinical estimation was done with the use of specially developed Clinical Psychopathological Chart. All the symptoms were divided into 4 groups (asthenic, psychovegetative, dysthymic, and cognitive symptom-complexes. No pronounced signs of dementia were observed. The control group included 44 clean-up workers without mental disorders. Predomination of various exogenous factors before and after accident was noted. Therapy included different vasotropic remedies, as well as family therapy, art therapy, and cognitive training. The possibilities of the reverse development of symptoms were statistically proved. The results allow making a conclusion that these disorders could not be explained either by radiation effects or by PTSD but connected with cerebrovascular pathology.

  16. Development of long-term event memory in preverbal infants: an eye-tracking study

    OpenAIRE

    Nakano, Tamami; Kitazawa, Shigeru

    2017-01-01

    The development of long-term event memory in preverbal infants remains elusive. To address this issue, we applied an eye-tracking method that successfully revealed in great apes that they have long-term memory of single events. Six-, 12-, 18- and 24-month-old infants watched a video story in which an aggressive ape-looking character came out from one of two identical doors. While viewing the same video again 24?hours later, 18- and 24-month-old infants anticipatorily looked at the door where ...

  17. Study on mid and long-term strategic plan formulation for newly-constructed NPP

    International Nuclear Information System (INIS)

    Song Lin

    2014-01-01

    Mid and Long-term strategic plan plays a key role for the management of a newly constructed nuclear power company. Among others, process, goals, and risk management, are the primary concerns during plan preparing. The article analyzed these three areas for Fuqing NPP, including the formulating process for the plan, the mid and long-term goal setting of the company, the major risk analysis and countermeasure selection therefore. Through that solutions and suggestions for strategic plan formulation were concluded for newly-constructed NPP. (author)

  18. Long-term proton pump inhibitor therapy and falls and fractures in elderly women: a prospective cohort study.

    Science.gov (United States)

    Lewis, Joshua R; Barre, Deka; Zhu, Kun; Ivey, Kerry L; Lim, Ee Mun; Hughes, Jeff; Prince, Richard L

    2014-11-01

    Proton pump inhibitors (PPIs) are widely used in the elderly. Recent studies have suggested that long-term PPI therapy is associated with fractures in the elderly, however the mechanism remains unknown. We investigated the association between long-term PPI therapy ≥1 year and fracture risk factors including bone structure, falls, and balance-related function in a post hoc analysis of a longitudinal population-based prospective cohort of elderly postmenopausal women and replicated the findings in a second prospective study of falling in elderly postmenopausal women. Long-term PPI therapy was associated with increased risk of falls and fracture-related hospitalizations; adjusted odds ratio (AOR) 2.17; 95% CI, 1.25-3.77; p = 0.006 and 1.95; 95% CI, 1.20-3.16; p = 0.007, respectively. In the replication study, long-term PPI use was associated with an increased risk of self-reported falling; AOR, 1.51; 95% CI, 1.00-2.27; p = 0.049. No association of long-term PPI therapy with bone structure was observed; however, questionnaire-assessed falls-associated metrics such as limiting outdoor activity (p = 0.002) and indoor activity (p = 0.001) due to fear of falling, dizziness (p risk in subjects on long-term PPI therapy. This increase in fracture risk in elderly women, already at high risk of fracture, appears to be mediated via increased falls risk and falling rather than impaired bone structure and should be carefully considered when prescribing long-term PPI therapy. © 2014 American Society for Bone and Mineral Research.

  19. Long-Term Safety of Repeated Blood-Brain Barrier Opening via Focused Ultrasound with Microbubbles in Non-Human Primates Performing a Cognitive Task.

    Science.gov (United States)

    Downs, Matthew E; Buch, Amanda; Sierra, Carlos; Karakatsani, Maria Eleni; Teichert, Tobias; Chen, Shangshang; Konofagou, Elisa E; Ferrera, Vincent P

    2015-01-01

    Focused Ultrasound (FUS) coupled with intravenous administration of microbubbles (MB) is a non-invasive technique that has been shown to reliably open (increase the permeability of) the blood-brain barrier (BBB) in multiple in vivo models including non-human primates (NHP). This procedure has shown promise for clinical and basic science applications, yet the safety and potential neurological effects of long term application in NHP requires further investigation under parameters shown to be efficacious in that species (500 kHz, 200-400 kPa, 4-5 μm MB, 2 minute sonication). In this study, we repeatedly opened the BBB in the caudate and putamen regions of the basal ganglia of 4 NHP using FUS with systemically-administered MB over 4-20 months. We assessed the safety of the FUS with MB procedure using MRI to detect edema or hemorrhaging in the brain. Contrast enhanced T1-weighted MRI sequences showed a 98% success rate for openings in the targeted regions. T2-weighted and SWI sequences indicated a lack edema in the majority of the cases. We investigated potential neurological effects of the FUS with MB procedure through quantitative cognitive testing of' visual, cognitive, motivational, and motor function using a random dot motion task with reward magnitude bias presented on a touchpanel display. Reaction times during the task significantly increased on the day of the FUS with MB procedure. This increase returned to baseline within 4-5 days after the procedure. Visual motion discrimination thresholds were unaffected. Our results indicate FUS with MB can be a safe method for repeated opening of the BBB at the basal ganglia in NHP for up to 20 months without any long-term negative physiological or neurological effects with the parameters used.

  20. 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.

  1. 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

  2. Neonatal hypertension – a long-term pilot follow-up study

    Directory of Open Access Journals (Sweden)

    Chaudhari T

    2013-06-01

    Full Text Available Tejasvi Chaudhari,1 Michael C Falk,2,3 Rajeev Jyoti,2,4 Susan Arney,5 Wendy Burton,5 Alison L Kent1,2 1Department of Neonatology, Canberra Hospital, Woden, ACT, Australia; 2Australian National University Medical School, Canberra, ACT, Australia; 3Department of Nephrology, 4Medical Imaging Department, 5Centre for Newborn Care, Canberra Hospital, Woden, ACT, Australia Background: Neonatal hypertension occurs in up to 3% of neonates, more commonly in those admitted to neonatal intensive care. The aims of this study were to review renal function and renal volumes in children who had a history of neonatal hypertension. Methods: Children with a history of neonatal hypertension from January 2001 to December 2008 were included in the study during 2011. Blood pressure, weight, height, and body mass index were recorded. Renal ultrasound with 3D volume, urine for electrolytes, albumin, ß2 microglobulin, and blood for electrolytes, urea, creatinine, calcium, phosphate, renin, and aldosterone were collected depending on parental consent. Results: Of the 41 neonates with neonatal hypertension, eleven (27% were included in the study (six died; 24 moved interstate or declined involvement. One child (9% was still on antihypertensive medication and one was found to be hypertensive on review. This child had small volume kidneys and albuminuria. Three out of nine renal volume measurements were low (33% and two out of eleven had renal scarring (18%. The six available renin/aldosterone results were normal. Conclusion: This study suggests there are long-term renal and blood pressure implications for neonates with hypertension and ongoing surveillance of blood pressure and renal function should be performed throughout childhood and into early adulthood. Keywords: neonate, hypertension, renal ultrasound, 3D

  3. International study on the long-term efficiency of stormwater infiltration by permeable pavements

    NARCIS (Netherlands)

    Boogaard, Floris; Lucke, T.; Dierkes, Carsten; Wentink, Ronald; Akkerman, Olof

    2015-01-01

    Although permeable pavements have been used all over the world in recent years to infiltrate and treat stormwater, only limited research has been undertaken to investigate and compare the long-term performance of these sustainable urban drainage system devices. This paper presents the results of an