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Sample records for escalation safety study

  1. Maintenance and Safety Practices of Escalator in Commercial Buildings

    Science.gov (United States)

    Afida Isnaini Janipha, Nurul; Nur Aina Syed Alwee, Sharifah; Ariff, Raihan Mohd; Ismail, Faridah

    2018-02-01

    The escalator is very crucial to transport a person from one place to another. Nevertheless, there are many cases recorded the accidents in relation to escalator. These may occur due to lack of maintenance which leads to systems breakdown, poor safety practices, wear and tear, users’ negligence and others. Thus, proper maintenance systems need to be improvised to prevent and reduce escalator accident in future. This research was aimed to determine the escalator maintenance activities and safety practices in a commercial building. Three case studies were selected within Selangor area. Semi-structured interviews were conducted for collecting data from these three case studies. To achieve the aim of this research, the study was carried out on the maintenance activities, safety practices and cost related to escalator maintenance. As one of the important means of access in building, it is very crucial to increase effectiveness of escalator particularly in commercial building. It is expected that readers will get clear information on the maintenance activities and safety practices of escalator in commercial building.

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

    Science.gov (United States)

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

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

  3. Phase I dose escalation safety study of nanoparticulate paclitaxel (CTI 52010) in normal dogs.

    Science.gov (United States)

    Axiak, Sandra M; Selting, Kim A; Decedue, Charles J; Henry, Carolyn J; Tate, Deborah; Howell, Jahna; Bilof, K James; Kim, Dae Y

    2011-01-01

    Paclitaxel is highly effective in the treatment of many cancers in humans, but cannot be routinely used in dogs as currently formulated due to the exquisite sensitivity of this species to surfactant-solubilizing agents. CTI 52010 is a formulation of nanoparticulate paclitaxel consisting of drug and normal saline. Our objectives were to determine the maximally tolerated dose, dose-limiting toxicities, and pharmacokinetics of CTI 52010 administered intravenously to normal dogs. Three normal adult hound dogs were evaluated by physical examination, complete blood count, chemistry profile, and urinalysis. Dogs were treated with staggered escalating dosages of CTI 52010 with a 28-day washout. All dogs were treated with a starting dosage of 40 mg/m(2), and subsequent dosages were escalated at 50% (dog 1), 100% (dog 2), or 200% (dog 3) with each cycle, to a maximum of 240 mg/m(2). Dogs were monitored by daily physical assessment and weekly laboratory evaluation. Standard criteria were used to grade adverse events. Plasma was collected at regular intervals to determine pharmacokinetics. Dogs were euthanized humanely, and necropsy was performed one week after the last treatment. The dose-limiting toxicity was grade 4 neutropenia and the maximum tolerated dosage was 120 mg/m(2). Grade 1-2 gastrointestinal toxicity was noted at higher dosages. Upon post mortem evaluation, no evidence of organ (liver, kidney, spleen) toxicity was noted. CTI 52010 was well tolerated when administered intravenously to normal dogs. A starting dosage for a Phase I/II trial in tumor-bearing dogs is 80 mg/m(2).

  4. Phase I dose escalation safety study of nanoparticulate paclitaxel (CTI 52010 in normal dogs

    Directory of Open Access Journals (Sweden)

    Axiak SM

    2011-10-01

    Full Text Available Sandra M Axiak1, Kim A Selting1, Charles J Decedue2, Carolyn J Henry1,3, Deborah Tate1, Jahna Howell2, K James Bilof1, Dae Y Kim4 1Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO, USA; 2CritiTech Inc, Lawrence, KS, USA; 3Department of Internal Medicine, Division of Hematology and Oncology; 4Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA Background: Paclitaxel is highly effective in the treatment of many cancers in humans, but cannot be routinely used in dogs as currently formulated due to the exquisite sensitivity of this species to surfactant-solubilizing agents. CTI 52010 is a formulation of nanoparticulate paclitaxel consisting of drug and normal saline. Our objectives were to determine the maximally tolerated dose, dose-limiting toxicities, and pharmacokinetics of CTI 52010 administered intravenously to normal dogs. Methods: Three normal adult hound dogs were evaluated by physical examination, complete blood count, chemistry profile, and urinalysis. Dogs were treated with staggered escalating dosages of CTI 52010 with a 28-day washout. All dogs were treated with a starting dosage of 40 mg/m2, and subsequent dosages were escalated at 50% (dog 1, 100% (dog 2, or 200% (dog 3 with each cycle, to a maximum of 240 mg/m2. Dogs were monitored by daily physical assessment and weekly laboratory evaluation. Standard criteria were used to grade adverse events. Plasma was collected at regular intervals to determine pharmacokinetics. Dogs were euthanized humanely, and necropsy was performed one week after the last treatment. Results: The dose-limiting toxicity was grade 4 neutropenia and the maximum tolerated dosage was 120 mg/m2. Grade 1–2 gastrointestinal toxicity was noted at higher dosages. Upon post mortem evaluation, no evidence of organ (liver, kidney, spleen toxicity was noted. Conclusion: CTI 52010 was well tolerated when administered intravenously to normal dogs. A starting

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

    NARCIS (Netherlands)

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

    2010-01-01

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

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  7. Elevator and Escalator Safety Education for Older Adults.

    Science.gov (United States)

    Hanks, Roma Stovall

    1996-01-01

    In eight focus groups in five cities, older adults identified their concerns about safety on elevators and escalators, often related to misunderstanding of the equipment. Their preferences for delivery of safety information included video/television, pamphlets, discussions, and posters. Educational interventions and modifications for disabilities…

  8. Open-label, dose escalation phase I study in healthy volunteers to evaluate the safety and pharmacokinetics of a human monoclonal antibody to Clostridium difficile toxin A.

    Science.gov (United States)

    Taylor, Claribel P; Tummala, Sanjeev; Molrine, Deborah; Davidson, Lisa; Farrell, Richard J; Lembo, Anthony; Hibberd, Patricia L; Lowy, Israel; Kelly, Ciaran P

    2008-06-25

    Recent data suggest that Clostridium difficile-associated diarrhea is becoming more severe and difficult to treat. Antibody responses to C. difficile toxin A are protective against symptomatic disease and recurrence. We examined the safety and pharmacokinetics (pk) of a novel neutralizing human monoclonal antibody against C. difficile toxin A (CDA1) in healthy adults. Five cohorts with 6 subjects each received a single intravenous infusion of CDA1 at escalating doses of 0.3, 1, 5, 10, and 20 mg/kg. Safety evaluations took place on days 1, 2, 3, 7, 14, 28, and 56 post-infusion. Samples for pk analysis were obtained before and after infusion, and at each safety evaluation. Serum CDA1 antibody concentrations and human anti-human antibody (HAHA) titers were measured with enzyme-linked immunosorbent assays. A noncompartmental model was used for pk analysis. Thirty subjects were enrolled. The median age was 27.5 yrs. There were no serious adverse events (AE) related to CDA1. Twenty-one of the 48 reported non-serious adverse events were possibly related to CDA1, and included transient blood pressure changes requiring no treatment, nasal congestion, headache, abdominal cramps, nausea, and self-limited diarrhea. Serum CDA1 concentrations increased with escalating doses: mean C(max) ranged from 6.82 microg/ml for the 0.3 mg/kg cohort to 511 microg/ml for the 20 mg/kg cohort. The geometric mean values of the half-life of CDA1 ranged between 25.3 and 31.8 days, and the volume of distribution approximated serum. No subject formed detectable HAHA titers. Administration of CDA1 as a single intravenous infusion was safe and well tolerated. C(max) increased proportionally with increasing doses. A randomized study of CDA1 in patients with C. difficile associated diarrhea is underway.

  9. An open-label dose escalation study to evaluate the safety of administration of nonviral stromal cell-derived factor-1 plasmid to treat symptomatic ischemic heart failure.

    Science.gov (United States)

    Penn, Marc S; Mendelsohn, Farrell O; Schaer, Gary L; Sherman, Warren; Farr, Maryjane; Pastore, Joseph; Rouy, Didier; Clemens, Ruth; Aras, Rahul; Losordo, Douglas W

    2013-03-01

    Preclinical studies indicate that adult stem cells induce tissue repair by activating endogenous stem cells through the stromal cell-derived factor-1:chemokine receptor type 4 axis. JVS-100 is a DNA plasmid encoding human stromal cell-derived factor-1. We tested in a phase 1, open-label, dose-escalation study with 12 months of follow-up in subjects with ischemic cardiomyopathy to see if JVS-100 improves clinical parameters. Seventeen subjects with ischemic cardiomyopathy, New York Heart Association class III heart failure, with an ejection fraction ≤40% on stable medical therapy, were enrolled to receive 5, 15, or 30 mg of JVS-100 via endomyocardial injection. The primary end points for safety and efficacy were at 1 and 4 months, respectively. The primary safety end point was a major adverse cardiac event. Efficacy end points were change in quality of life, New York Heart Association class, 6-minute walk distance, single photon emission computed tomography, N-terminal pro-brain natruretic peptide, and echocardiography at 4 and 12 months. The primary safety end point was met. At 4 months, all of the cohorts demonstrated improvements in 6-minute walk distance, quality of life, and New York Heart Association class. Subjects in the 15- and 30-mg dose groups exhibited improvements in 6-minute walk distance (15 mg: median [range]: 41 minutes [3-61 minutes]; 30 mg: 31 minutes [22-74 minutes]) and quality of life (15 mg: -16 points [+1 to -32 points]; 30 mg: -24 points [+17 to -38 points]) over baseline. At 12 months, improvements in symptoms were maintained. These data highlight the importance of defining the molecular mechanisms of stem cell-based tissue repair and suggest that overexpression of stromal cell-derived factor-1 via gene therapy is a strategy for improving heart failure symptoms in patients with ischemic cardiomyopathy.

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

    Science.gov (United States)

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

    2012-04-01

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

  11. Safety and immunogenicity in man of a cell culture derived trivalent live attenuated seasonal influenza vaccine: a Phase I dose escalating study in healthy volunteers.

    Science.gov (United States)

    Heldens, Jacco; Hulskotte, Ellen; Voeten, Theo; Breedveld, Belinda; Verweij, Pierre; van Duijnhoven, Wilbert; Rudenko, Larissa; van Damme, Pierre; van den Bosch, Han

    2014-09-03

    Live attenuated influenza vaccine (LAIV) offers the promise of inducing a variety of immune responses thereby conferring protection to circulating field strains. LAIVs are based on cold adapted and temperature sensitive phenotypes of master donor viruses (MDVs) containing the surface glycoprotein genes of seasonal influenza strains. Two types of MDV lineages have been described, the Ann Arbor lineages and the A/Leningrad/17 and B/USSR/60 lineages. Here the safety and immunogenicity of a Madin Darby Canine Kidney - cell culture based, intranasal LAIV derived from A/Leningrad/17 and B/USSR, was evaluated in healthy influenza non-naive volunteers 18-50 years of age. In a double-blind, randomized, placebo-controlled design, single escalating doses of 1×10(5), 1×10(6), or 1×10(7) tissue culture infectious dose 50% (TCID50) of vaccine containing each of the three influenza virus re-assortants recommended by the World Health Organization for the 2008-2009 season were administered intranasally. A statistically significant geometric mean increase in hemagglutination inhibition titer was reached for influenza strain A/H3N2 after immunization with all doses of LAIV. For the A/H1N1 and B strains, the GMI in HI titer did not increase for any of the doses. Virus neutralization antibody titers showed a similar response pattern. A dose-response effect could not be demonstrated for any of the strains, neither for the HI antibody nor for the VN antibody responses. No influenza like symptoms, no nasal congestions, no rhinorrhea, or other influenza related upper respiratory tract symptoms were observed. In addition, no difference in the incidence or nature of adverse events was found between vaccine and placebo treated subjects. Overall, the results indicated that the LAIV for nasal administration is immunogenic (i.e. able to provoke an immune response) and safe both from the perspective of the attenuated virus and the MDCK cell line from which it was derived, and it warrants

  12. Emergency Department Escalation in Theory and Practice: A Mixed-Methods Study Using a Model of Organizational Resilience.

    Science.gov (United States)

    Back, Jonathan; Ross, Alastair J; Duncan, Myanna D; Jaye, Peter; Henderson, Katherine; Anderson, Janet E

    2017-11-01

    Escalation policies are used by emergency departments (EDs) when responding to an increase in demand (eg, a sudden inflow of patients) or a reduction in capacity (eg, a lack of beds to admit patients). The policies aim to maintain the ability to deliver patient care, without compromising safety, by modifying "normal" processes. The study objective is to examine escalation policies in theory and practice. This was a mixed-method study involving a conceptual analysis of National Health Service escalation policies (n=12) and associated escalation actions (n=92), as well as a detailed ethnographic study of escalation in situ during a 16-month period in a large UK ED (n=30 observations). The conceptual analysis of National Health Service escalation policies found that their use requires the ability to dynamically reconfigure resources (staff and equipment), change work flow, and relocate patients. In practice, it was discovered that when the ED is under pressure, these prerequisites cannot always be attained. Instead, escalation processes were adapted to manage pressures informally. This adaptive need ("work as done") was found to be incompletely specified in policies ("work as imagined"). Formal escalation actions and their implementation in practice differed and varied in their effectiveness. Monitoring how escalation works in practice is essential in understanding whether and how escalation policies help to manage workload. Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  13. Conflict escalation in paediatric services: findings from a qualitative study

    OpenAIRE

    Forbat, Liz; Teuten, Bea; Barclay, Sarah

    2015-01-01

    Objective To explore clinician and family experiences of conflict in paediatric services, in order to map the trajectory of conflict escalation. Design Qualitative interview study, employing extreme-case sampling. Interviews were analysed using an iterative thematic approach to identify common themes regarding the experience and escalation of conflict. Participants Thirty-eight health professionals and eight parents. All participants had direct experience of conflict, including physical assau...

  14. Conflict escalation in paediatric services: findings from a qualitative study.

    Science.gov (United States)

    Forbat, Liz; Teuten, Bea; Barclay, Sarah

    2015-08-01

    To explore clinician and family experiences of conflict in paediatric services, in order to map the trajectory of conflict escalation. Qualitative interview study, employing extreme-case sampling. Interviews were analysed using an iterative thematic approach to identify common themes regarding the experience and escalation of conflict. Thirty-eight health professionals and eight parents. All participants had direct experience of conflict, including physical assault and court proceedings, at the interface of acute and palliative care. Two teaching hospitals, one district general hospital and two paediatric hospices in England, in 2011. Conflicts escalate in a predictable manner. Clearly identifiable behaviours by both clinicians and parents are defined as mild, moderate and severe. Mild describes features like the insensitive use of language and a history of unresolved conflict. Moderate involves a deterioration of trust, and a breakdown of communication and relationships. Severe marks disintegration of working relationships, characterised by behavioural changes including aggression, and a shift in focus from the child's best interests to the conflict itself. Though conflicts may remain at one level, those which escalated tended to move sequentially from one level to the next. Understanding how conflicts escalate provides clinicians with a practical, evidence-based framework to identify the warning signs of conflict in paediatrics. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  15. Open-label, dose-escalation, safety, pharmacokinetic, and pharmacodynamic study of intravenously administered CNF1010 (17-(allylamino)-17-demethoxygeldanamycin [17-AAG]) in patients with solid tumors.

    Science.gov (United States)

    Saif, M W; Erlichman, C; Dragovich, T; Mendelson, D; Toft, D; Burrows, F; Storgard, C; Von Hoff, D

    2013-05-01

    17-(Allylamino)-17-demethoxygeldanamycin (17-AAG) is a benzoquinone ansamycin that binds to and inhibits the Hsp90 family of molecular chaperones leading to the proteasomal degradation of client proteins critical in malignant cell proliferation and survival. We have undertaken a Phase 1 trial of CNF1010, an oil-in-water nanoemulsion of 17-AAG. Patients with advanced solid tumors and adequate organ functions received CNF1010 by 1-h intravenous (IV) infusion, twice a week, 3 out of 4 weeks. Doses were escalated sequentially in single-patient (6 and 12 mg/m(2)/day) and three-to-six-patient (≥25 mg/m(2)/day) cohorts according to a modified Fibonacci's schema. Plasma pharmacokinetic (PK) profiles and biomarkers, including Hsp70 in PBMCs, HER-2 extracellular domain, and IGFBP2 in plasma, were performed. Thirty-five patients were treated at doses ranging from 6 to 225 mg/m(2). A total of 10 DLTs in nine patients (2 events of fatigue, 83 and 175 mg/m(2); shock, abdominal pain, ALT increased, increased transaminases, and pain in extremity at 175 mg/m(2); extremity pain, atrial fibrillation, and metabolic encephalopathy at 225 mg/m(2)) were noted. The PK profile of 17-AAG after the first dose appeared to be linear up to 175 mg/m(2), with a dose-proportional increase in C max and AUC0-inf. Hsp70 induction in PBMCs and inhibition of serum HER-2 neu extracellular domain indicated biological effects of CNF1010 at doses >83 mg/m(2). The maximum tolerated dose was not formally established. Hsp70 induction in PBMCs and inhibition of serum HER-2 neu extracellular domain indicated biological effects. The CNF1010 clinical program is no longer being pursued due to the toxicity profile of the drug and the development of second-generation Hsp90 molecules.

  16. Phase I dose-escalation study to examine the safety and tolerability of LY2603618, a checkpoint 1 kinase inhibitor, administered 1 day after pemetrexed 500 mg/m(2) every 21 days in patients with cancer.

    Science.gov (United States)

    Weiss, Glen J; Donehower, Ross C; Iyengar, Tara; Ramanathan, Ramesh K; Lewandowski, Karen; Westin, Eric; Hurt, Karla; Hynes, Scott M; Anthony, Stephen P; McKane, Scott

    2013-02-01

    This phase I study aims at assessing the safety and tolerability of LY2603618, a selective inhibitor of Checkpoint Kinase 1, in combination with pemetrexed and determining the maximum tolerable dose and the pharmacokinetic parameters. This was an open-label, multicenter, dose-escalation study in patients with advanced solid tumors. Increasing doses of LY2603618 (40-195 mg/m(2)) were combined with 500 mg/m(2) of pemetrexed. LY2603618 was administered on Days 1 and 9 and pemetrexed on Day 8 in a 28-day cycle. For all subsequent 21-day cycles, pemetrexed was administered on Day 1 and LY2603618 on Day 2. Antitumor activity was evaluated as per Response Evaluation Criteria in Solid Tumors 1.0. A total of 31 patients were enrolled into six cohorts (three at 40 mg/m(2) over 4.5-hour infusion, 1-hour infusion in subsequent cohorts: three each at 40 mg/m(2), 70 mg/m(2), and 195 mg/m(2); 13 at 105 mg/m(2); six at 150 mg/m(2)). Four patients experienced a dose-limiting toxicity: diarrhea (105 mg/m(2)); reversible infusion-related reaction (150 mg/m(2)); thrombocytopenia (195 mg/m(2)); and fatigue (195 mg/m(2)). The maximum tolerated dose was defined as 150 mg/m(2). The pharmacokinetic data demonstrated that the exposure of LY2603618 increased in a dose-dependent manner, displayed a suitable half-life for maintaining required human exposures while minimizing the intra- and inter-cycle accumulation, and was unaffected by the pemetrexed administration. The pharmacokinetic-defined biologically efficacious dose was achieved at doses ≥105 mg/m(2). LY2603618 administered approximately 24 h after pemetrexed showed acceptable safety and pharmacokinetic profiles.

  17. Safety and Immunogenicity of EBA-175 RII-NG Malaria Vaccine Administered Intramuscularly in Semi-Immune Adults: A Phase 1, Double-Blinded Placebo Controlled Dosage Escalation Study.

    Directory of Open Access Journals (Sweden)

    Kwadwo A Koram

    Full Text Available The erythrocyte binding antigen region II (EBA-175 RII is a Plasmodium falciparum ligand that mediates erythrocyte invasion and is considered an important malaria vaccine candidate. A phase Ia trial in malaria naïve adults living in the United States found the recombinant non-glycosylated vaccine antigen, EBA-175 RII-NG adjuvanted with aluminium phosphate to be safe, immunogenic and capable of inducing biologically active antibodies that can inhibit parasite growth in vitro. The aim of the current study was to assess the safety and immunogenicity of this vaccine in malaria exposed semi-immune healthy adults living in a malaria endemic country, Ghana. In this double-blinded, placebo controlled, dose escalation phase I trial, eighteen subjects per group received ascending dose concentrations (5 μg, 20 μg or 80 μg of the vaccine intramuscularly at 0, 1 and 6 months, while 6 subjects received placebo (normal saline. The primary end point was the number of subjects experiencing Grade 3 systemic or local adverse events within 14 days post-vaccination. Serious adverse events were assessed throughout the study period. Blood samples for immunological analyses were collected at days 0, 14, 28, 42, 180 and 194. A total of 52 subjects received three doses of the vaccine in the respective groups. No serious adverse events were reported. The majority of all adverse events reported were mild to moderate in severity, with local pain and tenderness being the most common. All adverse events, irrespective of severity, resolved without any sequelae. Subjects who received any of the EBA-175 RII-NG doses had high immunoglobulin G levels which moderately inhibited P. falciparum growth in vitro, compared to those in the placebo group. In conclusion, the EBA-175 RII-NG vaccine was safe, well tolerated and immunogenic in malaria semi-immune Ghanaian adults. Its further development is recommended.ClinicalTrials.gov. Identifier: NCT01026246.

  18. Safety and Immunogenicity of EBA-175 RII-NG Malaria Vaccine Administered Intramuscularly in Semi-Immune Adults: A Phase 1, Double-Blinded Placebo Controlled Dosage Escalation Study.

    Science.gov (United States)

    Koram, Kwadwo A; Adu, Bright; Ocran, Josephine; Karikari, Yaa S; Adu-Amankwah, Susan; Ntiri, Michael; Abuaku, Benjamin; Dodoo, Daniel; Gyan, Ben; Kronmann, Karl C; Nkrumah, Francis

    2016-01-01

    The erythrocyte binding antigen region II (EBA-175 RII) is a Plasmodium falciparum ligand that mediates erythrocyte invasion and is considered an important malaria vaccine candidate. A phase Ia trial in malaria naïve adults living in the United States found the recombinant non-glycosylated vaccine antigen, EBA-175 RII-NG adjuvanted with aluminium phosphate to be safe, immunogenic and capable of inducing biologically active antibodies that can inhibit parasite growth in vitro. The aim of the current study was to assess the safety and immunogenicity of this vaccine in malaria exposed semi-immune healthy adults living in a malaria endemic country, Ghana. In this double-blinded, placebo controlled, dose escalation phase I trial, eighteen subjects per group received ascending dose concentrations (5 μg, 20 μg or 80 μg) of the vaccine intramuscularly at 0, 1 and 6 months, while 6 subjects received placebo (normal saline). The primary end point was the number of subjects experiencing Grade 3 systemic or local adverse events within 14 days post-vaccination. Serious adverse events were assessed throughout the study period. Blood samples for immunological analyses were collected at days 0, 14, 28, 42, 180 and 194. A total of 52 subjects received three doses of the vaccine in the respective groups. No serious adverse events were reported. The majority of all adverse events reported were mild to moderate in severity, with local pain and tenderness being the most common. All adverse events, irrespective of severity, resolved without any sequelae. Subjects who received any of the EBA-175 RII-NG doses had high immunoglobulin G levels which moderately inhibited P. falciparum growth in vitro, compared to those in the placebo group. In conclusion, the EBA-175 RII-NG vaccine was safe, well tolerated and immunogenic in malaria semi-immune Ghanaian adults. Its further development is recommended. ClinicalTrials.gov. Identifier: NCT01026246.

  19. Emergency Department Escalation in Theory and Practice:A Mixed-Methods Study Using a Model of Organizational Resilience

    OpenAIRE

    Back, Jonathan; Ross, Alastair J; Duncan, Myanna D; Jaye, Peter; Henderson, Katherine; Anderson, Janet E

    2017-01-01

    Study objective: Escalation policies are used by emergency departments when responding to an increase in demand (e.g., a sudden inflow of patients) or a reduction in capacity (e.g., a lack of beds to admit patients). The policies aim to maintain the ability to deliver patient care, without compromising safety, by modifying ‘normal’ processes. The study objective was to examine escalation policies in theory and practice. \\ud Methods: This was a mixed-method study, involving: i) a conceptual an...

  20. Early termination of prostate cancer hyperfractionated dose escalation study

    International Nuclear Information System (INIS)

    Forman, Jeffrey D; Porter, Arthur T; Kocheril, Paul; Grignon, David; Orton, Colin

    1996-01-01

    Purpose: This study was initiated to determine the maximum tolerable dose of hyperfractionated radiation in patients with locally advanced prostate cancer. Materials and Methods: Forty-nine patients with locally advanced prostate cancer (T3-T4 Nx, 0, 1 M0 and/or Gleason Score ≥ 8) were treated on the first two steps of a prospective dose-escalation study using hyperfractionated conformal radiotherapy. The first 25 patients received a minimum dose of 78Gy to the clinical tumor volume (CTV) including the prostate, seminal vesicle and a 5mm margin at 1.3Gy b.i.d. The second group (24 patients) received a minimum dose to the CTV of 82.8Gy at 1.15Gy b.i.d. Twenty eight patients received neo-adjuvant hormonal therapy in conjunction with their radiation (8 of 25 patients at 78Gy and 20 of 24 patients at 82.8Gy). Toxicity was scored according to the RTOG grading scale. Efficacy was evaluated by PSA levels and ultrasound guided biopsies. Median follow up was 36 and 18 months for the 78Gy and 82.8Gy dose levels, respectively. Results: No grade 3 or 4 gastrointestinal (GI) or genitourinary (GU) toxicity was noted. At 36 months, the actuarial probability of Grade 2 GI and GU toxicity were 16 and 20%, respectively. Twelve to 18 months following radiation, 41 patients (86%) underwent ultrasound guided biopsy. At 78Gy, 60% of 20 patients had a biopsy which was negative or showed a marked therapeutic effect. At 82.8Gy, these combined rates were 95% in the 21 patients who had biopsies. Nine patients (50%) who did not receive neo-adjuvant hormones had positive biopsies. No patient who received neo-adjuvant hormones plus 78Gy (5 patients) or 82.8Gy (18 patients) had a positive biopsy. Conclusion: Proceeding to the next dose level (87.4Gy) was justified by the lack of severe chronic toxicity. However, in view of the high rate of histologic sterilization when hyperfractionated irradiation was given in conjunction with neo-adjuvant hormonal therapy, it was felt to be unethical to

  1. Safety and clinical outcomes of carbapenem de-escalation as part of an antimicrobial stewardship programme in an ESBL-endemic setting.

    Science.gov (United States)

    Lew, Kaung Yuan; Ng, Tat Ming; Tan, Michelle; Tan, Sock Hoon; Lew, Ee Ling; Ling, Li Min; Ang, Brenda; Lye, David; Teng, Christine B

    2015-04-01

    To evaluate the safety and clinical outcomes of patients who received carbapenem de-escalation as guided by an antimicrobial stewardship programme (ASP) in a setting where ESBL-producing Enterobacteriaceae are endemic. Patients receiving meropenem or imipenem underwent a prospective ASP review for eligibility for de-escalation according to defined institutional guidelines. Patients in whom carbapenem was de-escalated or not de-escalated, representing the acceptance and rejection of the ASP recommendation, respectively, were compared. The primary outcome was the clinical success rate; secondary outcomes included the 30 day readmission and mortality rates, the duration of carbapenem therapy, the incidence of adverse drug reactions due to antimicrobials, the acquisition of carbapenem-resistant Gram-negative bacteria and the occurrence of Clostridium difficile-associated diarrhoea (CDAD). The de-escalation recommendations for 300 patients were evaluated; 204 (68.0%) were accepted. The patient demographics and disease severity were similar. The clinical success rates were similar [de-escalated versus not de-escalated, 183/204 (89.7%) versus 85/96 (88.5%), P=0.84], as was the survival at hospital discharge [173/204 (84.8%) versus 79/96 (82.3%), P=0.58]. In the de-escalated group, the duration of carbapenem therapy was shorter (6 versus 8 days, Pcarbapenem-resistant Acinetobacter baumannii acquisition [4/204 (2.0%) versus 7/96 (7.3%), P=0.042] and there was a lower incidence of CDAD [2/204 (1.0%) versus 4/96 (4.2%), P=0.081]. This study suggests that the ASP-guided de-escalation of carbapenems led to comparable clinical success, fewer adverse effects and a lower incidence of the development of resistance. This approach is safe and practicable, and should be a key component of an ASP. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. STUDY OF PRIVILEGE ESCALATION ATTACK ON ANDROID AND ITS COUNTERMEASURES

    OpenAIRE

    REJO MATHEW

    2012-01-01

    Android is most commonly used platform for smartphones today which boasts of an advanced security model having MAC and sandboxing. These features allow developers and users to restrict the execution of anapplication to the privileges assigned. The exploitation of vulnerabilities of the program is confined within the privilege boundaries of an applications sandbox. Privilege escalation attacks have grown manifold as the use of android systems have increased. Different kinds of mechanisms have ...

  3. Studying the efficacy of escalated dose conformal radiation therapy in prostate carcinoma – Pakistan experience

    Directory of Open Access Journals (Sweden)

    Asad Zamir

    2017-11-01

    Conclusion: Our data were comparable to international studies of dose escalation using 3D and beneficial as compared to conventional radiation therapy delivered by 2D in terms of biochemical failure rate and treatment related toxicity.

  4. Capecitabine based postoperative accelerated chemoradiation of pancreatic carcinoma. A dose-escalation study

    International Nuclear Information System (INIS)

    Morganti, Alessio G.; Picardi, Vincenzo; Ippolito, Edy; Massaccesi, Mariangela; Macchia, Gabriella; Deodato, Francesco; Caravatta, Luciana; Tambaro, Rosa; Mignogna, Samantha; Cellini, Numa; Valentini, Vincenzo; Mattiucci, Gian Carlo; Di Lullo, Liberato; Giglio, Gianfranco; Caprino, Paola; Sofo, Luigi; Ingrosso, Marcello

    2010-01-01

    The objective of this study was to evaluate the safety of escalating up to 55 Gy within five weeks, the dose of external beam radiotherapy to the previous tumor site concurrently with a fixed daily dose of capecitabine, in patients with resected pancreatic cancer. Material and methods. Patients with resected pancreatic carcinoma were eligible for this study. Capecitabine was administered at a daily dose of 1600 mg/m 2 . Regional lymph nodes received a total radiation dose of 45 Gy with 1.8 Gy per fractions. The starting radiation dose to the tumor bed was 50.0 Gy (2.0 Gy/fraction, 25 fractions). Escalation was achieved up to a total dose of 55.0 Gy by increasing the fraction size by 0.2 Gy (2.2 Gy/fraction), while keeping the duration of radiotherapy to five weeks (25 fractions). A concomitant boost technique was used. Dose limiting toxicity (DLT) was defined as any grade>3 hematologic toxicity, grade>2 liver, renal, neurologic, gastrointestinal, or skin toxicity, by RTOG criteria, or any toxicity producing prolonged (> 10 days) radiotherapy interruption. Results and discussion. Twelve patients entered the study (median age: 64 years). In the first cohort (six patients), no patient experienced DLT. Similarly in the second cohort, no DLT occurred. All 12 patients completed the planned regimen of therapy. Nine patients experienced grade 1-2 nausea and/or vomiting. Grade 2 hematological toxicity occurred in four patients. The results of our study indicate that a total radiation dose up to 55.0 Gy/5 weeks can be safely administered to the tumor bed, concurrently with capecitabine (1600 mg/m 2 ) in patients with resected pancreatic carcinoma.

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

    Science.gov (United States)

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

    2018-05-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    DEFF Research Database (Denmark)

    Lassen, U; Nielsen, D L; Sørensen, M

    2012-01-01

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

  8. Authorization request for potential non-compliance with the American Standard Safety Code for Elevators Dumbwaiters and Escalators

    Energy Technology Data Exchange (ETDEWEB)

    Boyd, J.E.

    1964-09-28

    A Third Party inspection of the reactor work platforms was conducted by representatives of the Travelers Insurance Company in 1958. An inspection report submitted by these representatives described hazardous conditions noted and presented a series of recommendations to improve the operational safety of the systems. Project CGI-960, ``C`` & ``D`` Work Platform Safety Improvements -- All Reactors, vas initiated to modify the platforms in compliance with the Third Party recommendations. The American Standard Safety Code for Elevators Dumbwaiters and Escalators (A-17.1) is used as a guide by the Third Party in formulating their recommendations. This code is used because there is no other applicable code for this type of equipment. While the work platforms do not and in some cases can not comply with this code because of operational use, every effort is made to comply with the intent of the code.

  9. Off-label biologic regimens in psoriasis: a systematic review of efficacy and safety of dose escalation, reduction, and interrupted biologic therapy.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Brezinski

    Full Text Available OBJECTIVES: While off-label dosing of biologic treatments may be necessary in selected psoriasis patients, no systematic review exists to date that synthesizes the efficacy and safety of these off-label dosing regimens. The aim of this systematic review is to evaluate efficacy and safety of off-label dosing regimens (dose escalation, dose reduction, and interrupted treatment with etanercept, adalimumab, infliximab, ustekinumab, and alefacept for psoriasis treatment. DATA SOURCES AND STUDY SELECTION: We searched OVID Medline from January 1, 1990 through August 1, 2011 for prospective clinical trials that studied biologic therapy for psoriasis treatment in adults. Individual articles were screened for studies that examined escalated, reduced, or interrupted therapy with etanercept, adalimumab, infliximab, ustekinumab, or alefacept. DATA SYNTHESIS: A total of 23 articles with 12,617 patients matched the inclusion and exclusion criteria for the systematic review. Data were examined for primary and secondary efficacy outcomes and adverse events including infections, malignancies, cardiovascular events, and anti-drug antibodies. The preponderance of data suggests that continuous treatment with anti-TNF agents and anti-IL12/23 agent was necessary for maintenance of disease control. Among non-responders, dose escalation with etanercept, adalimumab, ustekinumab, and alefacept typically resulted in greater efficacy than standard dosing. Dose reduction with etanercept and alefacept resulted in reduced efficacy. Withdrawal of the examined biologics led to an increase in disease activity; efficacy from retreatment did not result in equivalent initial response rates for most biologics. Safety data on off-label dosing regimens are limited. CONCLUSION: Dose escalation in non-responders generally resulted in increased efficacy in the examined biologics used to treat moderate-to-severe psoriasis. Continuous treatment with anti-TNF agents and anti-IL12/23 agent

  10. Dose escalation to rash for erlotinib plus gemcitabine for metastatic pancreatic cancer: the phase II RACHEL study.

    Science.gov (United States)

    Van Cutsem, E; Li, C-P; Nowara, E; Aprile, G; Moore, M; Federowicz, I; Van Laethem, J-L; Hsu, C; Tham, C K; Stemmer, S M; Lipp, R; Zeaiter, A; Fittipaldo, A; Csutor, Z; Klughammer, B; Meng, X; Ciuleanu, T

    2014-11-25

    This phase II, open-label, randomised study evaluated whether patients with metastatic pancreatic cancer receiving erlotinib/gemcitabine derived survival benefits from increasing the erlotinib dose. After a 4-week run-in period (gemcitabine 1000 mg m(-2) once weekly plus erlotinib 100 mg per day), patients with metastatic pancreatic cancer who developed grade 0/1 rash were randomised to receive gemcitabine plus erlotinib dose escalation (150 mg, increasing by 50 mg every 2 weeks (maximum 250 mg); n=71) or gemcitabine plus standard-dose erlotinib (100 mg per day; n=75). The primary end point was to determine whether overall survival (OS) was improved by increasing the erlotinib dose. Secondary end points included progression-free survival (PFS), incidence of grade ⩾2 rash, and safety. Erlotinib dose escalation induced grade ⩾2 rash in 29 out of 71 (41.4%) patients compared with 7 out of 75 (9.3%) patients on standard dose. Efficacy was not significantly different in the dose-escalation arm compared with the standard-dose arm (OS: median 7.0 vs 8.4 months, respectively, hazard ratio (HR), 1.26, 95% confidence interval (CI): 0.88-1.80; P=0.2026; PFS: median 3.5 vs 4.5 months, respectively, HR, 1.09, 95% CI: 0.77-1.54; P=0.6298). Incidence of adverse events was comparable between randomised arms. The erlotinib dose-escalation strategy induced rash in some patients; there was no evidence that the higher dose translated into increased benefit.

  11. Cost escalation in nuclear power

    International Nuclear Information System (INIS)

    Montomery, W.D.; Quirk, J.P.

    1978-01-01

    This report is concerned with the escalation of capital costs of nuclear central station power plants between the early 1960s and the present. The report presents an historical overview of the development of the nuclear power industry and cost escalation in the industry, using existing data on orders and capital costs. New data are presented on regulatory delays in the licensing process, derived from a concurrent study being carried on in the Social Science group at Caltech. The conclusions of the study are that nuclear capital costs have escalated more rapidly than the GNP deflator or the construction industry price index. Prior to 1970, cost increases are related to bottleneck problems in the nuclear construction and supplying industries and the regulatory process; intervenors play only a minor role in cost escalation. After 1970, generic changes introduced into the licensing process by intervenors (including environmental impact reviews, antitrust reviews, more stringent safety standards) dominate the cost escalation picture, with bottlenecks of secondary importance. Recent increases in the time from application for a construction permit to commercial operation are related not only to intervenor actions, but also to suspensions, cancellations or postponements of construction by utilities due to unfavorable demand or financing conditions

  12. A dose-escalation study of combretastatin A4-phosphate in healthy dogs.

    Science.gov (United States)

    Abma, E; Smets, P; Daminet, S; Cornelis, I; De Clercq, K; Ni, Y; Vlerick, L; de Rooster, H

    2018-03-01

    Combretastatin A4-Phosphate (CA4P) is a vascular disrupting agent revealing promising results in cancer treatments for humans. The aim of this study was to investigate the safety and adverse events of CA4P in healthy dogs as a prerequisite to application of CA4P in dogs with cancer. Ten healthy dogs were included. The effects of escalating doses of CA4P on physical, haematological and biochemical parameters, systolic arterial blood pressure, electrocardiogram, echocardiographic variables and general wellbeing were characterised. Three different doses were tested: 50, 75 and 100 mg m -2 . At all 3 CA4P doses, nausea, abdominal discomfort as well as diarrhoea were observed for several hours following administration. Likewise, a low-grade neutropenia was observed in all dogs. Doses of 75 and 100 mg m -2 additionally induced vomiting and elevation of serum cardiac troponine I levels. At 100 mg m -2 , low-grade hypertension and high-grade neurotoxicity were also observed. In healthy dogs, doses up to 75 mg m -2 seem to be well tolerated. The severity of the neurotoxicity observed at 100 mg m -2 , although transient, does not invite to use this dose in canine oncology patients. © 2017 John Wiley & Sons Ltd.

  13. A randomised controlled trial of the efficacy and safety of allopurinol dose escalation to achieve target serum urate in people with gout.

    Science.gov (United States)

    Stamp, Lisa K; Chapman, Peter T; Barclay, Murray L; Horne, Anne; Frampton, Christopher; Tan, Paul; Drake, Jill; Dalbeth, Nicola

    2017-09-01

    To determine the efficacy and safety of allopurinol dose escalation using a treat-to-target serum urate (SU) approach. A randomised, controlled, parallel-group, comparative clinical trial was undertaken. People with gout receiving at least creatinine clearance (CrCL)-based allopurinol dose for ≥1 month and SU ≥6 mg/dL were recruited. Participants were randomised to continue current dose (control) or allopurinol dose escalation for 12 months. In the dose escalation group, allopurinol was increased monthly until SU was gout. Allopurinol dose escalation is well tolerated. ANZCTR12611000845932; Results. 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/.

  14. SYSTEMS-2: A randomised phase II study of radiotherapy dose escalation for pain control in malignant pleural mesothelioma

    Directory of Open Access Journals (Sweden)

    M. Ashton

    2018-01-01

    Full Text Available SYSTEMS-2 is a randomised study of radiotherapy dose escalation for pain control in 112 patients with malignant pleural mesothelioma (MPM. Standard palliative (20 Gy/5# or dose escalated treatment (36 Gy/6# will be delivered using advanced radiotherapy techniques and pain responses will be compared at week 5. Data will guide optimal palliative radiotherapy in MPM.

  15. Narration and Escalation. An Empirical Study of Conflict Narratives

    Directory of Open Access Journals (Sweden)

    Evelyn Gius

    2016-06-01

    Full Text Available This article describes the methodology and the outcomes of an empirical study of conflict narratives. The narratological analysis deployed narratological catego­ries in the structuralist tradition based on Genette and was conducted with the help of the text annotation tool CATMA. The analysis aimed at covering as many narratological phenomena as possible by establishing 14 fields of narrato­logical phenomena that were annotated in a corpus of 39 factual narratives about situations at the workplace with and without conflicts. The evaluation of approximately 28,000 annotations brought to light a series of interrelations be­tween narratological phenomena and the presence or absence of conflicts in the narratives. Additionally, this approach led to the identification of some over­sights of narrative theory by detecting hitherto unnoticed interrelations among narratological concepts.

  16. Dose-Escalation Study for Cardiac Radiosurgery in a Porcine Model

    Energy Technology Data Exchange (ETDEWEB)

    Blanck, Oliver, E-mail: oliver.blanck@uksh.de [Department of Radiation Oncology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); CyberKnife Center Northern Germany, Guestrow (Germany); Bode, Frank [Medical Department II, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Gebhard, Maximilian [Institute of Pathology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Hunold, Peter [Department of Radiology and Nuclear Medicine, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Brandt, Sebastian [Department of Anaesthesiology and Intensive Care Medicine, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Bruder, Ralf [Institute for Robotics and Cognitive Systems, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Grossherr, Martin [Department of Anaesthesiology and Intensive Care Medicine, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Vonthein, Reinhard [Institute of Medical Biometry and Statistics, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Rades, Dirk [Department of Radiation Oncology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Dunst, Juergen [Department of Radiation Oncology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); University Copenhagen (Denmark)

    2014-07-01

    Purpose: To perform a proof-of-principle dose-escalation study to radiosurgically induce scarring in cardiac muscle tissue to block veno-atrial electrical connections at the pulmonary vein antrum, similar to catheter ablation. Methods and Materials: Nine mini-pigs underwent pretreatment magnetic resonance imaging (MRI) evaluation of heart function and electrophysiology assessment by catheter measurements in the right superior pulmonary vein (RSPV). Immediately after examination, radiosurgery with randomized single-fraction doses of 0 and 17.5-35 Gy in 2.5-Gy steps were delivered to the RSPV antrum (target volume 5-8 cm{sup 3}). MRI and electrophysiology were repeated 6 months after therapy, followed by histopathologic examination. Results: Transmural scarring of cardiac muscle tissue was noted with doses ≥32.5 Gy. However, complete circumferential scarring of the RSPV was not achieved. Logistic regressions showed that extent and intensity of fibrosis significantly increased with dose. The 50% effective dose for intense fibrosis was 31.3 Gy (odds ratio 2.47/Gy, P<.01). Heart function was not affected, as verified by MRI and electrocardiogram evaluation. Adjacent critical structures were not damaged, as verified by pathology, demonstrating the short-term safety of small-volume cardiac radiosurgery with doses up to 35 Gy. Conclusions: Radiosurgery with doses >32.5 Gy in the healthy pig heart can induce circumscribed scars at the RSPV antrum noninvasively, mimicking the effect of catheter ablation. In our study we established a significant dose-response relationship for cardiac radiosurgery. The long-term effects and toxicity of such high radiation doses need further investigation in the pursuit of cardiac radiosurgery for noninvasive treatment of atrial fibrillation.

  17. Midwives' experiences of performing maternal observations and escalating concerns: a focus group study.

    Science.gov (United States)

    Jeffery, Justine; Hewison, Alistair; Goodwin, Laura; Kenyon, Sara

    2017-09-02

    For the past decade, Maternal Mortality Reports, published in the United Kingdom every three years, have consistently raised concerns about maternal observations in maternity care. The reports identify that observations are not being done, not being completed fully, are not recorded on Early Warning Score systems, and/or are not escalated appropriately. This has resulted in delays in referral, intervention and increases the risk of maternal morbidity or mortality. However there has been little exploration of the possible reasons for non-completion of maternal observations. The aim of this study was to explore midwives' experiences of performing maternal observations and escalating concerns in rural and urban maternity settings in the West Midlands of England. A qualitative design involving a series of six focus groups with midwives and Supervisors of Midwives was employed to investigate the facilitators of, and barriers to the completion of maternal observations. Eighteen Midwives and 8 Supervisors of Midwives participated in a total of 6 focus groups. Three key themes emerged from the data: (1) Organisation of Maternal Observations (including delegation of tasks to Midwifery Support Workers, variation in their training, the care model used e.g. one to one care, and staffing issues); (2) Prioritisation of Maternal Observations (including the role of professional judgement and concerns expressed by midwives that they did not feel equipped to care for women with complex clinical needs; and (3) Negotiated Escalation (including the inappropriate response from senior staff to use of Modified Early Warning Score systems, and the emotional impact of escalation). A number of organisational and cultural barriers exist to the completion of maternal observations and the escalation of concerns. In order to address these the following actions are recommended: standardised training for Midwifery Support Workers, review of training of midwives to ensure it addresses the

  18. A dose escalation study of concurrent chemoradiation therapy with nedaplatin for cervical cancer

    International Nuclear Information System (INIS)

    Hatae, Masayuki; Takahashi, Takeshi; Kodama, Shoji

    2005-01-01

    Doses of nedaplatin (CDGP) were established for concurrent chemoradiation therapy (CCRT) for cervical cancer, and a collaborative dose escalation study involving 8 hospitals was conducted to investigate the safety and efficacy of this therapy. Radiotherapy was performed according to the standard treatment described in the Regulations of Cervical Carcinoma Treatment. CDGP at 80 mg/m 2 as Level 1 or at 90 mg/m 2 as Level 2 was administered on Days 1 and 29 of treatment. Dose-limiting toxicity (DLT) was observed in 1 of 6 patients receiving 80 mg/m 2 of CDGP and in all 2 patients receiving 90 mg/m 2 of CDGP; therefore, Level 2 was regarded as the maximum tolerated dose (MTD), and Level 1 as the recommended dose. DLT signs consisted of delayed improvement in the leukocyte count in 2 patients and anorexia in 1 patient, suggesting that delayed improvement in the leukocyte count is the main DLT of this combination therapy. The main side effects were digestive disorders such as nausea and anorexia and bone marrow suppression, such as leukopenia, neutropenia, and thrombopenia. Side effects in the Level 1 group were more mild than in the Level 2 group. The efficacy was partial response (PR) or better in all patients. The complete response (CR) rates were 60% (6/10) in the Level 1 group and 50% (1/2) in the Level 2 group; there was no marked difference between the two groups. These results suggest that CCRT involving administration CDGP at 80 mg/m 2 on Days 1 and 29 is safe and effective. (author)

  19. Clinical Outcomes With Dose-Escalated Adaptive Radiation Therapy for Urinary Bladder Cancer: A Prospective Study

    Energy Technology Data Exchange (ETDEWEB)

    Murthy, Vedang, E-mail: vmurthy@actrec.gov.in [Department of Radiation Oncology, Tata Memorial Centre, Parel, Mumbai (India); Masodkar, Renuka; Kalyani, Nikhil; Mahantshetty, Umesh [Department of Radiation Oncology, Tata Memorial Centre, Parel, Mumbai (India); Bakshi, Ganesh; Prakash, Gagan [Department of Surgical Oncology, Tata Memorial Centre, Parel, Mumbai (India); Joshi, Amit; Prabhash, Kumar [Department of Medical Oncology, Tata Memorial Centre, Parel, Mumbai (India); Ghonge, Sujata; Shrivastava, Shyamkishore [Department of Radiation Oncology, Tata Memorial Centre, Parel, Mumbai (India)

    2016-01-01

    Purpose: The purpose of this study was to assess feasibility, clinical outcomes, and toxicity in patients with bladder cancer treated with adaptive, image guided radiation therapy (IGRT) for bladder preservation as a part of trimodality treatment. The role of dose escalation was also studied. Methods and Materials: Forty-four patients with localized bladder cancer were enrolled in a prospective study. They underwent maximal safe resection of bladder tumor and concurrent platinum-based chemotherapy. Patients with large tumors were offered induction chemotherapy. Radiation therapy planning was done using either 3 (n=34) or 6 (n=10) concentrically grown planning target volumes (PTV). Patients received 64 Gy in 32 fractions to the whole bladder and 55 Gy to the pelvic nodes and, if appropriate, a simultaneous integrated boost to the tumor bed to 68 Gy (equivalent dose for 2-Gy fractions assuming α/β of 10 [EQD2]{sub 10} = 68.7 Gy). Daily megavoltage (MV) imaging helped to choose the most appropriate PTV encompassing bladder for the particular day (using plan-of-the-day approach). Results: Most patients (88%) had T2 disease. Sixteen patients (36%) received neoadjuvant chemotherapy. A majority of the patients (73%) received prophylactic nodal irradiation, whereas 55% of the patients received escalated dose to the tumor bed. With a median follow-up of 30 months, the 3-year locoregional control (LRC), disease-free survival, and overall survival (OS) were 78%, 66%, and 67%, respectively. The bladder preservation rate was 83%. LRC (87% vs 68%, respectively, P=.748) and OS (74% vs 60%, respectively, P=.36) rates were better in patients receiving dose escalation. Instances of acute and late Radiation Therapy Oncology Group (RTOG) grade 3 genitourinary toxicity was seen in 5 (11%) and 2 (4%) patients, respectively. There was no acute or late RTOG grade 3 or higher gastrointestinal toxicity. Conclusions: Adaptive IGRT using plan-of-the-day approach for bladder

  20. Clinical Outcomes With Dose-Escalated Adaptive Radiation Therapy for Urinary Bladder Cancer: A Prospective Study

    International Nuclear Information System (INIS)

    Murthy, Vedang; Masodkar, Renuka; Kalyani, Nikhil; Mahantshetty, Umesh; Bakshi, Ganesh; Prakash, Gagan; Joshi, Amit; Prabhash, Kumar; Ghonge, Sujata; Shrivastava, Shyamkishore

    2016-01-01

    Purpose: The purpose of this study was to assess feasibility, clinical outcomes, and toxicity in patients with bladder cancer treated with adaptive, image guided radiation therapy (IGRT) for bladder preservation as a part of trimodality treatment. The role of dose escalation was also studied. Methods and Materials: Forty-four patients with localized bladder cancer were enrolled in a prospective study. They underwent maximal safe resection of bladder tumor and concurrent platinum-based chemotherapy. Patients with large tumors were offered induction chemotherapy. Radiation therapy planning was done using either 3 (n=34) or 6 (n=10) concentrically grown planning target volumes (PTV). Patients received 64 Gy in 32 fractions to the whole bladder and 55 Gy to the pelvic nodes and, if appropriate, a simultaneous integrated boost to the tumor bed to 68 Gy (equivalent dose for 2-Gy fractions assuming α/β of 10 [EQD2] 10  = 68.7 Gy). Daily megavoltage (MV) imaging helped to choose the most appropriate PTV encompassing bladder for the particular day (using plan-of-the-day approach). Results: Most patients (88%) had T2 disease. Sixteen patients (36%) received neoadjuvant chemotherapy. A majority of the patients (73%) received prophylactic nodal irradiation, whereas 55% of the patients received escalated dose to the tumor bed. With a median follow-up of 30 months, the 3-year locoregional control (LRC), disease-free survival, and overall survival (OS) were 78%, 66%, and 67%, respectively. The bladder preservation rate was 83%. LRC (87% vs 68%, respectively, P=.748) and OS (74% vs 60%, respectively, P=.36) rates were better in patients receiving dose escalation. Instances of acute and late Radiation Therapy Oncology Group (RTOG) grade 3 genitourinary toxicity was seen in 5 (11%) and 2 (4%) patients, respectively. There was no acute or late RTOG grade 3 or higher gastrointestinal toxicity. Conclusions: Adaptive IGRT using plan-of-the-day approach for bladder preservation

  1. Hyperfractionated conformal radiotherapy in locally advanced prostate cancer: results of a dose escalation study

    International Nuclear Information System (INIS)

    Forman, Jeffrey D.; Duclos, Marie; Shamsa, Falah; Porter, Arthur T.; Orton, Colin

    1996-01-01

    Purpose: This study was initiated to assess the incidence of chronic complications and histologic and biochemical control following hyperfractionated conformal radiotherapy in patients with locally advanced prostate cancer. Methods and Materials: Between October 1991 and October 1994, 49 patients with locally advanced prostate cancer were entered on the first two dose levels of a prospective dose-escalation study using hyperfractionated three dimensional conformal radiotherapy. The first 25 patients received a minimum tumor dose of 78 Gy to the prostate and seminal vesicles in 6 weeks at 1.3 Gy, b.i.d. No increase in chronic toxicity compared with conventional radiotherapy was noted; therefore, an additional 24 patients were treated to a minimum tumor dose of 82.8 Gy to the prostate and seminal vesicles in 7 weeks at 1.15 Gy, b.i.d. Toxicity was scored according to the Radiation Therapy Oncology Group morbidity grading scale. Efficacy was assessed through scheduled postradiation prostate specific antigen values and ultrasound-guided biopsies. The median follow-up for the entire group was 20 months. Results: The hyperfractionated external radiation was well tolerated with minimal acute morbidity. At 30 months, the actuarial probability of Grade 2 gastrointestinal toxicity was 17%. At 30 months, the actuarial probability of Grade 2 genitourinary toxicity was 16%. There was no statistically significant difference between the two dose levels. No Grade 3 or 4 gastrointestinal or genitourinary toxicity was noted. At 12 months, 84% of patients had a prostate specific antigen ≤ 4; and 53%; ≤ 1 ng/ml. At 12 months, 71% of patients had post radiation biopsies that were either negative (55%) or showed a marked therapeutic effect (16%). Conclusion: The use of hyperfractionated conformal radiotherapy facilitated dose escalation with no increase in chronic toxicity compared to standard doses. The initial tumor response based on prostate specific antigen measurements and

  2. Ewing sarcoma localized on spine: a dose escalation study in child

    International Nuclear Information System (INIS)

    Vogin, G.; Marchesi, V.; Biston, M.C.; Gassa, F.; Amessis, M.; Zefkili, S.; Helfre, S.; De Marzi, L.; Lacroix, F.; Leroy, A.

    2011-01-01

    The authors report the study of dose escalation for the treatment of spinal in two types of Ewing tumours. They used 5 dose levels at the rate of five 1,6 Gy per week. They compare different radiotherapy techniques: three-dimensional conformation radiotherapy, static intensity-modulated conformational radiotherapy, helical tomo-therapy, volume-modulated arc-therapy (VMAT), stereotactic radiotherapy, and proton-therapy (in passive diffusion). It appears that it is possible to safely and efficiently deliver until 70,4 Gy in some Ewing tumours. In child, exclusive radiotherapy might become a local treatment option and would require a clinic trial and comparison with exclusive surgery or post-operative radiotherapy. Short communication

  3. The Role of Inflation and Price Escalation Adjustments in Properly Estimating Program Costs: F-35 Case Study

    Science.gov (United States)

    2016-03-01

    standard practice is to deflate costs to constant dollars (the dependent variable in the analogous regression) using a previously determined price ...I N S T I T U T E F O R D E F E N S E A N A L Y S E S IDA Document D-5489 March 2016 The Role of Inflation and Price Escalation Adjustments in...DFARS 252.227-7013 (a)(16) [Jun 2013]. The Role of Inflation and Price Escalation Adjustments in Properly Estimating Program Costs: F-35 Case Study

  4. Safety of dose escalation by simultaneous integrated boosting radiation dose within the primary tumor guided by 18FDG-PET/CT for esophageal cancer

    International Nuclear Information System (INIS)

    Yu, Wen; Cai, Xu-Wei; Liu, Qi; Zhu, Zheng-Fei; Feng, Wen; Zhang, Qin; Zhang, Ying-Jian; Yao, Zhi-Feng; Fu, Xiao-Long

    2015-01-01

    Purpose: To observe the safety of selective dose boost to the pre-treatment high 18 F-deoxyglucose (FDG) uptake areas of the esophageal GTV. Methods: Patients with esophageal squamous cell carcinoma were treated with escalating radiation dose of 4 levels, with a simultaneous integrated boost (SIB) to the pre-treatment 50% SUVmax area of the primary tumor. Patients received 4 monthly cycles of cisplatin and fluorouracil. Dose-limiting toxicity (DLT) was defined as any Grade 3 or higher acute toxicities causing continuous interruption of radiation for over 1 week. Results: From April 2012 to February 2014, dose has been escalated up to LEVEL 4 (70 Gy). All of the 25 patients finished the prescribed dose without DLT, and 10 of them developed Grade 3 acute esophagitis. One patient of LEVEL 2 died of esophageal hemorrhage within 1 month after completion of radiotherapy, which was not definitely correlated with treatment yet. Late toxicities remained under observation. With median follow up of 8.9 months, one-year overall survival and local control was 69.2% and 77.4%, respectively. Conclusions: Dose escalation in esophageal cancer based on 18 FDG-PET/CT has been safely achieved up to 70 Gy using the SIB technique. Acute toxicities were well tolerated, whereas late toxicities and long-term outcomes deserved further observation

  5. Optimizing cancer radiotheraphy with 2-deoxy-D-glucose. Dose escalation studies in patients with glioblastoma multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Singh, D.; Gupta, J.P. [Dharmshila Cancer Hospital, New Delhi (India); Banerji, A.K. [Vidyasagar Inst. of Mental Health and Neurosciences, New Delhi (India); Dwarakanath, B.S.; Tripathi, R.P.; Mathew, T.L.; Ravindranath, T. [Institute of Nuclear Medicine and Allied Sciences, Delhi (India); Jain, V. [Wright State University, Dayton, OH (United States). Kettering Medical Center

    2005-08-01

    Background and purpose: Higher rates of glucose utilization and glycolysis generally correlate with poor prognosis in several types of malignant tumors. Own earlier studies on model systems demonstrated that the nonmetabolizable glucose analog 2-deoxy-D-glucose (2-DG) could enhance the efficacy of radiotherapy in a dose-dependent manner by selectively sensitizing cancer cells while protecting normal cells. Phase I/II clinical trials indicated that the combination of 2-DG, at an oral dose of 200 mg/kg body weight (BW), with large fractions of {gamma}-radiation was well tolerated in cerebral glioma patients. Since higher 2-DG doses are expected to improve the therapeutic gain, present studies were undertaken to examine the tolerance and safety of escalating 2-DG dose during combined treatment (2-DG + radiotherapy) in glioblastoma multiforme patients. Patients and methods: Untreated patients with histologically proven glioblastoma multiforme (WHO criteria) were included in the study. Seven weekly fractions of {sup 60}C {gamma}-rays (5 Gy/fraction) were delivered to the tumor volume (presurgical CT/MRI evaluation) plus 3 cm margin. Escalating 2-DG doses (200-250-300 mg/kg BW) were administered orally 30 min before irradiation after overnight fasting. Acute toxicity and tolerance were studied by monitoring the vital parameters and side effects. Late radiation damage and treatment responses were studied radiologically and clinically in surviving patients. Results: Transient side effects similar to hypoglycemia were observed in most of the patients. Tolerance and patient compliance to the combined treatment were very good up to a 2-DG dose of 250 mg/kg BW. However, at the higher dose of 300 mg/kg BW, two out of six patients were very restless and could not complete treatment, though significant changes in the vital parameters were not observed even at this dose. No significant damage to the normal brain tissue was observed during follow-up in seven out of ten patients who

  6. Innovative design for a phase 1 trial with intra-patient dose escalation: The Crotoxin study

    Directory of Open Access Journals (Sweden)

    Jacques Medioni

    2017-09-01

    Full Text Available Introduction: Crotoxin has a broad antitumor activity but has shown frequent neurotoxic toxicity. To induce tolerance and limit this toxicity, we propose a new design with intra-patient dose escalation. Methods: A new Dose Limiting Toxicity definition was used. The concept of Target Ceiling Dose was introduced. Results: Dose Limiting Toxicity was the inability to dose escalate twice. Target Ceiling Dose was the highest planned dose to be administered to a patient and could change for patients along time. Recommended Dose was defined similarly as in a (3 + 3 conventional design. Conclusion: This innovant design was used and the clinical trial is now closed for inclusions. Results will be presented later. Keywords: Clinical trial, Phase 1, Intra-patient dose escalation, Cancer

  7. Study and modelling of the escalation phase of a steam explosion

    International Nuclear Information System (INIS)

    Leclerc, Eric

    2000-01-01

    In Severe Accident studies for PWR, large amount of molten corium may be poured into water. There is then a risk of Steam Explosion. After the premixing sequence in which the melt is more or less dispersed into water, a fine fragmentation process may start which can lead to an escalation. Such an event is generally triggered by the destabilization of the vapour film surrounding the hot melt droplets. In this thesis, an attempt to describe all the successive processes leading to this fine fragmentation is presented. First a critical analysis of previous models is performed, allowing to propose a new sequence of events. As in the previous models, the film destabilization leads to the growth of cold liquids peaks induced by Rayleigh Taylor instability. As these peaks have a smaller density than the drop, they do not penetrate into the hot drop. At the cold liquid-hot liquid contacts, transient heat transfer leads to the explosive boiling of a small amount of coolant. The generated local pressurization deform the hot melt interface. This can produce fine fragments from the filaments issued from the melt. Some of them may reach the vapour-coolant interface where intense and rapid vaporization occurs. A large bubble then develops and a new fragmentation sequence may again appear at the bubble collapse. The present model is support by experimental results. (author) [fr

  8. ZD0473 pharmacokinetics in Japanese patients: a Phase I dose-escalation study.

    Science.gov (United States)

    Murakami, H; Tamura, T; Yamada, Y; Yamamoto, N; Ueda, Y; Shimoyama, T; Saijo, N

    2002-12-01

    ZD0473 is new platinum agent that was rationally designed to circumvent platinum resistance and reduce the potential for nephro-and neurotoxicity. This Phase I dose-escalating study investigated the pharmacokinetics, tolerability and efficacy of ZD0473 in Japanese patients with solid, refractory tumours. ZD0473 was administered as a 1-h intravenous infusion every 3 weeks. Nine patients received a total of 16 cycles of ZD0473 (median 1 cycle/patient), with 3 patients treated at each of 3 doses (60, 90, 120 mg/m2). The maximum plasma concentration (C(max)) and the area under the concentration-time curve to infinity (AUC(0-infinity)) increased with dose in a linear fashion for both total platinum and ZD0473 in plasma ultrafiltrate, suggesting that the pharmacokinetics of ZD0473 are linear. Haematological and non-haematological toxicities such as nausea and vomiting were mild (grade 1 or 2) and transient. No clinically significant nephro-, oto- or neurotoxicity was observed. Dose-limiting toxicity (DLT) was not observed and the maximum tolerated dose (MTD) was not identified. ZD0473 treatment showed evidence of disease stabilisation in 3 patients (33%). In conclusion, ZD0473 appears to have linear pharmacokinetics, and an acceptable tolerability profile at doses up to 120 mg/m2 in Japanese patients with refractory solid malignancies. Following evaluation of the data from all the Western trials, the ZD0473 development programme changed and this Japanese trial was stopped.

  9. Efficacy and safety of de-escalation therapy to ertapenem for treatment of infections caused by extended-spectrum-β-lactamase-producing Enterobacteriaceae: an open-label randomized controlled trial.

    Science.gov (United States)

    Rattanaumpawan, Pinyo; Werarak, Peerawong; Jitmuang, Anupop; Kiratisin, Pattarachai; Thamlikitkul, Visanu

    2017-03-01

    Carbapenem antibiotics are considered the treatment of choice for serious extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacteria (GNB) infections. The study objectives were to evaluate efficacy and safety of de-escalation therapy to ertapenem for treatment of infections caused by extended-spectrum-β-lactamase-producing Enterobacteriaceae. We conducted a randomized controlled trial of adult patients with documented ESBL-producing Enterobacteriaceae infections who had received any group 2 carbapenem for less than 96 h. In the intervention group, the previously-prescribed group 2 carbapenem was de-escalated to ertapenem. In the control group, the group 2 carbapenem was continued. During June 2011-December 2014, 32 patients were randomized to the de-escalation group and 34 to the control group. Most common sites of infection were urinary tract infection (42%). Characteristics of both groups were comparable. By using a 15% predefined margin, ertapenem was non-inferior to control group regarding the clinical cure rate (%Δ = 14.0 [95% confidence interval: -2.4 to 31.1]), the microbiological eradication rate (%Δ = 4.1 [-5.0 to 13.4]), and the superimposed infection rate (%Δ = -16.5 [-38.4 to 5.3]). Patients in the de-escalation group had a significantly lower 28-day mortality rate (9.4% vs. 29.4%; P = .05), a significantly shorter median length of stay (16.5 days [4.0-73.25] vs. 20.0 days [1.0-112.25]; P = .04), and a significantly lower defined daily dose of carbapenem use (12.9 ± 8.9 vs. 18.4 ± 12.6; P = .05). Ertapenem could be safely used as de-escalation therapy for ESBL-producing Enterobacteriaceae infections, once the susceptibility profiles are known. Future studies are needed to investigate ertapenem efficacy against ESBL-producing Enterobacteriaceae pneumonia to determine its applicability in life-threatening conditions. ClinicalTrials.gov identifier: NCT01297842 . Registered on 14 February 2011. First

  10. Tomotherapy PET-guided dose escalation. A dosimetric feasibility study for patients with malignant pleural mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Maggio, Angelo; Cutaia, Claudia; Di Dia, Amalia; Bresciani, Sara; Miranti, Anna; Poli, Matteo; Stasi, Michele [Candiolo Cancer Institute - FPO, IRCCS, Medical Physics, Turin (Italy); Del Mastro, Elena; Garibaldi, Elisabetta; Gabriele, Pietro [Candiolo Cancer Institute - FPO, IRCCS, Radiotherapy Department, Turin (Italy)

    2016-02-15

    The aim of this study was to investigate whether a safe escalation of the dose to the pleural cavity and PET/CT-positive areas in patients with unresectable malignant pleural mesothelioma (MPM) is possible using helical tomotherapy (HT). We selected 12 patients with MPM. Three planning strategies were investigated. In the first strategy (standard treatment), treated comprised a prescribed median dose to the planning target volume (PTV) boost (PTV{sub 1}) of 64.5 Gy (range: 56 Gy/28 fractions to 66 Gy/30 fractions) and 51 Gy (range: 50.4 Gy/28 fractions to 54 Gy/30 fractions) to the pleura PTV (PTV{sub 2}). Thereafter, for each patient, two dose escalation plans were generated prescribing 62.5 and 70 Gy (2.5 and 2.8 Gy/fraction, respectively) to the PTV{sub 1} and 56 Gy (2.24 Gy/fraction) to the PTV{sub 2}, in 25 fractions. Dose-volume histogram (DVH) constraints and normal tissue complication probability (NTCP) calculations were used to evaluate the differences between the plans. For all plans, the 95 % PTVs received at least 95 % of the prescribed dose. For all patients, it was possible to perform the dose escalation in accordance with the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) constraints for organs at risk (OARs). The average contralateral lung dose was < 8 Gy. NTCP values for OARs did not increase significantly compared with the standard treatment (p > 0.05), except for the ipsilateral lung. For all plans, the lung volume ratio was strongly correlated with the V{sub 20}, V{sub 30}, and V{sub 40} DVHs of the lung (p < 0.0003) and with the lung mean dose (p < 0.0001). The results of this study suggest that by using HT it is possible to safely escalate the dose delivery to at least 62.5 Gy in PET-positive areas while treating the pleural cavity to 56 Gy in 25 fractions without significantly increasing the dose to the surrounding normal organs. (orig.) [German] Ziel war es, zu untersuchen, ob mit der helikalen Tomotherapie (HT) eine

  11. Oral sodium phenylbutyrate in patients with recurrent malignant gliomas: a dose escalation and pharmacologic study.

    Science.gov (United States)

    Phuphanich, Surasak; Baker, Sharyn D; Grossman, Stuart A; Carson, Kathryn A; Gilbert, Mark R; Fisher, Joy D; Carducci, Michael A

    2005-04-01

    We determined the maximum tolerated dose (MTD), toxicity profile, pharmacokinetic parameters, and preliminary efficacy data of oral sodium phenylbutyrate (PB) in patients with recurrent malignant gliomas. Twenty-three patients with supratentorial recurrent malignant gliomas were enrolled on this dose escalation trial. Four dose levels of PB were studied: 9, 18, 27, and 36 g/day. Data were collected to assess toxicity, response, survival, and pharmacokinetics. All PB doses of 9, 18, and 27 g/day were well tolerated. At 36 g/day, two of four patients developed dose-limiting grade 3 fatigue and somnolence. At the MTD of 27 g/day, one of seven patients developed reversible grade 3 somnolence. Median survival from time of study entry was 5.4 months. One patient had a complete response for five years, and no partial responses were noted, which yielded an overall response rate of 5%. Plasma concentrations of 706, 818, 1225, and 1605 muM were achieved with doses of 9, 18, 27, and 36 g/day, respectively. The mean value for PB clearance in this patient population was 22 liters/h, which is significantly higher than the 16 liters/h reported in patients with other malignancies who were not receiving P450 enzyme-inducing anticonvulsant drugs (P = 0.038). This study defines the MTD and recommended phase 2 dose of PB at 27 g/day for heavily pretreated patients with recurrent gliomas. The pharmacology of PB appears to be affected by concomitant administration of P450-inducing anticonvulsants.

  12. Oral sodium phenylbutyrate in patients with recurrent malignant gliomas: A dose escalation and pharmacologic study1

    Science.gov (United States)

    Phuphanich, Surasak; Baker, Sharyn D.; Grossman, Stuart A.; Carson, Kathryn A.; Gilbert, Mark R.; Fisher, Joy D.; Carducci, Michael A.

    2005-01-01

    We determined the maximum tolerated dose (MTD), toxicity profile, pharmacokinetic parameters, and preliminary efficacy data of oral sodium phenylbutyrate (PB) in patients with recurrent malignant gliomas. Twenty-three patients with supratentorial recurrent malignant gliomas were enrolled on this dose escalation trial. Four dose levels of PB were studied: 9, 18, 27, and 36 g/day. Data were collected to assess toxicity, response, survival, and pharmacokinetics. All PB doses of 9, 18, and 27 g/day were well tolerated. At 36 g/day, two of four patients developed dose-limiting grade 3 fatigue and somnolence. At the MTD of 27 g/day, one of seven patients developed reversible grade 3 somnolence. Median survival from time of study entry was 5.4 months. One patient had a complete response for five years, and no partial responses were noted, which yielded an overall response rate of 5%. Plasma concentrations of 706, 818, 1225, and 1605 μM were achieved with doses of 9, 18, 27, and 36 g/day, respectively. The mean value for PB clearance in this patient population was 22 liters/h, which is significantly higher than the 16 liters/h reported in patients with other malignancies who were not receiving P450 enzyme–inducing anticonvulsant drugs (P = 0.038). This study defines the MTD and recommended phase 2 dose of PB at 27 g/day for heavily pretreated patients with recurrent gliomas. The pharmacology of PB appears to be affected by concomitant administration of P450-inducing anticonvulsants. PMID:15831235

  13. {sup 188}Re-HDD/lipiodol therapy for hepatocellular carcinoma: an activity escalation study

    Energy Technology Data Exchange (ETDEWEB)

    Lambert, Bieke; Vos, Filip de; Wiele, Christophe van de [Ghent University Hospital, Nuclear Medicine Division, Gent (Belgium); Bacher, Klaus; Thierens, Hubert [Ghent University, Department of Medical Physics, Gent (Belgium); Defreyne, Luc [Ghent University Hospital, Division of Interventional Radiology, Gent (Belgium); Vlierberghe, Hans van [Ghent University Hospital, Division of Gastroenterology, Gent (Belgium); Jeong, Jae Min [Seoul National University College of Medicine, Department of Nuclear Medicine, Cancer Research Institute, Seoul (Korea); Wang, Rong Fu [Beijing University, Department of Nuclear Medicine, Beijing (China); Meerbeeck, Jan van [Ghent University Hospital, Department of Respiratory Diseases, Gent (Belgium); Smeets, Peter [Ghent University Hospital, Department of Radiology, Gent (Belgium); Troisi, Roberto [Ghent University Hospital, Division of Abdominal Surgery and Liver Transplantation, Gent (Belgium)

    2006-03-15

    The aim of this study was to investigate the feasibility of administering increasing activities of {sup 188}Re-4-hexadecyl-1-2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol/lipiodol ({sup 188}Re-HDD/lipiodol) for the treatment of hepatocellular carcinoma (HCC) in patients with well-compensated cirrhosis. The activity levels were increased by 1.1 GBq/step after a 6-week interval without unacceptable adverse events in at least five consecutive patients. Absorbed doses to the various organs were calculated according to the MIRD formalism, based on three gamma-scintigraphic studies. Response was assessed by means of MRI and alpha-fetoprotein (AFP) monitoring. Thirty-five treatments were carried out in 28 patients. Activities from 4.8 to 7.0 GBq {sup 188}Re-HDD/lipiodol were administered via a transfemoral catheter. The mean absorbed dose to the liver (including tumour) was 7.6{+-}2.2, 9.8{+-}4.9 and 15.2{+-}4.9 Gy for the 4.8-, 5.9- and 7.0-GBq groups, respectively. Treatment was well tolerated at all activity levels. Further escalation of the administered activity was not feasible owing to limitations related to the radiolabelling procedure. Response assessment on MRI showed partial response, stable disease and disease progression in 1, 28 and 2 assessable treatments, respectively. In 8 of 17 treatment sessions with an initially elevated AFP, a reduction ranging from 19% to 97% was observed 6 weeks later. (orig.)

  14. Results of the Phase I Dose-Escalating Study of Motexafin Gadolinium With Standard Radiotherapy in Patients With Glioblastoma Multiforme

    International Nuclear Information System (INIS)

    Ford, Judith M.; Seiferheld, Wendy; Alger, Jeffrey R.; Wu, Genevieve; Endicott, Thyra J.; Mehta, Minesh; Curran, Walter; Phan, See-Chun

    2007-01-01

    Purpose: Motexafin gadolinium (MGd) is a putative radiation enhancer initially evaluated in patients with brain metastases. This Phase I trial studied the safety and tolerability of a 2-6-week course (10-22 doses) of MGd with radiotherapy for glioblastoma multiforme. Methods and Materials: A total of 33 glioblastoma multiforme patients received one of seven MGd regimens starting at 10 doses of 4 mg/kg/d MGd and escalating to 22 doses of 5.3 mg/kg/d MGd (5 or 10 daily doses then three times per week). The National Cancer Institute Cancer Therapy Evaluation Program toxicity and stopping rules were applied. Results: The maximal tolerated dose was 5.0 mg/kg/d MGd (5 d/wk for 2 weeks, then three times per week) for 22 doses. The dose-limiting toxicity was reversible transaminase elevation. Adverse reactions included rash/pruritus (45%), chills/fever (30%), and self-limiting vesiculobullous rash of the thumb and fingers (42%). The median survival of 17.6 months prompted a case-matched analysis. In the case-matched analysis, the MGd patients had a median survival of 16.1 months (n = 31) compared with the matched Radiation Therapy Oncology Group database patients with a median survival of 11.8 months (hazard ratio, 0.43; 95% confidence interval, 0.20-0.94). Conclusion: The maximal tolerated dose of MGd with radiotherapy for glioblastoma multiforme in this study was 5 mg/kg/d for 22 doses (daily for 2 weeks, then three times weekly). The baseline survival calculations suggest progression to Phase II trials is appropriate, with the addition of MGd to radiotherapy with concurrent and adjuvant temozolomide

  15. A phase I study of dose-escalated chemoradiation with accelerated intensity modulated radiotherapy in locally advanced head and neck cancer

    International Nuclear Information System (INIS)

    Guerrero Urbano, Teresa; Clark, Catharine H.; Hansen, Vibeke N.; Adams, Elizabeth J.; A'Hern, Roger; Miles, Elizabeth A.; McNair, Helen; Bidmead, Margaret; Warrington, Alan P.; Dearnaley, David P.; Harrington, Kevin J.; Nutting, Christopher M.

    2007-01-01

    Background and purpose: Intensity modulated radiotherapy (IMRT) allows the delivery of higher and more homogeneous radiation dose to head and neck tumours. This study aims to determine the safety of dose-escalated chemo-IMRT for larynx preservation in locally advanced head and neck cancer. Methods: Patients with T2-4, N1-3, M0 squamous cell carcinoma of the larynx or hypopharynx were treated with a simultaneous-boost IMRT. Two radiation dose levels (DL) were tested: In DL 1, 63 Gy/28F was delivered to primary tumour and involved nodes and 51.8 Gy/28F to elective nodes. In DL 2, the doses were 67.2 Gy/28F and 56 Gy/28F, respectively, representing a 9% dose escalation for the primary. All patients received 2 cycles of neoadjuvant cisplatin and 5-fluorouracil, and concomitant cisplatin. Acute (NCICTCv.2.0) and late toxicity (RTOG and modified LENTSOM) were collected. Results: Thirty patients were entered, 15 in each dose level. All patients completed the treatment schedule. In DL 1, the incidences of acute G3 toxicities were 27% (pain), 20% (radiation dermatitis), 0% (xerostomia) and 67% required gastrostomy tubes. For DL 2 the corresponding incidences were 40%, 20%, 7%, and 87%. G3 dysphagia and pain persisted longer in DL 2. With regard to mucositis, a prolonged healing time for DL 2 was found, with prevalence of G2 of 58% in week 10. No acute grade 4 toxicity was observed. At 6 months, 1 patient in DL 2 had G3 late toxicity (dysphagia). No dose limiting toxicity was found. Complete response rates were 80% in DL 1, and 87% in DL 2. Conclusion: Moderately accelerated chemo-IMRT is safe and feasible with good compliance and acceptable acute toxicity. Dose escalation was possible without a significant difference in acute toxicity. Longer follow-up is required to determine the incidence of late radiation toxicities, and tumour control rates

  16. The Role of Inflation and Price Escalation Adjustments in Properly Estimating Program Costs: F-35 Case Study

    Science.gov (United States)

    2016-04-30

    qÜáêíÉÉåíÜ=^ååì~ä= ^Åèìáëáíáçå=oÉëÉ~êÅÜ= póãéçëáìã= qÜìêëÇ~ó=pÉëëáçåë= sçäìãÉ=ff= = The Role of Inflation and Price Escalation Adjustments in Properly...The Role of Inflation and Price Escalation Adjustments in Properly Estimating Program Costs: F-35 Case Study Stanley Horowitz, Assistant Division...Graduate School of Engineering and Management, Air Force Institute of Technology Cost and Price Collaboration Venkat Rao, Professor, Defense

  17. Integrated boost IMRT with FET-PET-adapted local dose escalation in glioblastomas. Results of a prospective phase II study

    International Nuclear Information System (INIS)

    Piroth, M.D.; Pinkawa, M.; Holy, R.; Forschungszentrum Juelich GmbH

    2012-01-01

    Dose escalations above 60 Gy based on MRI have not led to prognostic benefits in glioblastoma patients yet. With positron emission tomography (PET) using [ 18 F]fluorethyl-L-tyrosine (FET), tumor coverage can be optimized with the option of regional dose escalation in the area of viable tumor tissue. In a prospective phase II study (January 2008 to December 2009), 22 patients (median age 55 years) received radiochemotherapy after surgery. The radiotherapy was performed as an MRI and FET-PET-based integrated-boost intensity-modulated radiotherapy (IMRT). The prescribed dose was 72 and 60 Gy (single dose 2.4 and 2.0 Gy, respectively) for the FET-PET- and MR-based PTV-FET (72 Gy) and PTV-MR (60 Gy) . FET-PET and MRI were performed routinely for follow-up. Quality of life and cognitive aspects were recorded by the EORTC-QLQ-C30/QLQ Brain20 and Mini-Mental Status Examination (MMSE), while the therapy-related toxicity was recorded using the CTC3.0 and RTOG scores. Median overall survival (OS) and disease-free survival (DFS) were 14.8 and 7.8 months, respectively. All local relapses were detected at least partly within the 95% dose volume of PTV-MR (60 Gy) . No relevant radiotherapy-related side effects were observed (excepted alopecia). In 2 patients, a pseudoprogression was observed in the MRI. Tumor progression could be excluded by FET-PET and was confirmed in further MRI and FET-PET imaging. No significant changes were observed in MMSE scores and in the EORTC QLQ-C30/QLQ-Brain20 questionnaires. Our dose escalation concept with a total dose of 72 Gy, based on FET-PET, did not lead to a survival benefit. Acute and late toxicity were not increased, compared with historical controls and published dose-escalation studies. (orig.)

  18. Integrated boost IMRT with FET-PET-adapted local dose escalation in glioblastomas. Results of a prospective phase II study

    Energy Technology Data Exchange (ETDEWEB)

    Piroth, M.D.; Pinkawa, M.; Holy, R. [RWTH Aachen University Hospital (Germany). Dept. of Radiation Oncology; Forschungszentrum Juelich GmbH (DE). Juelich-Aachen Research Alliance (JARA) - Section JARA-Brain] (and others)

    2012-04-15

    Dose escalations above 60 Gy based on MRI have not led to prognostic benefits in glioblastoma patients yet. With positron emission tomography (PET) using [{sup 18}F]fluorethyl-L-tyrosine (FET), tumor coverage can be optimized with the option of regional dose escalation in the area of viable tumor tissue. In a prospective phase II study (January 2008 to December 2009), 22 patients (median age 55 years) received radiochemotherapy after surgery. The radiotherapy was performed as an MRI and FET-PET-based integrated-boost intensity-modulated radiotherapy (IMRT). The prescribed dose was 72 and 60 Gy (single dose 2.4 and 2.0 Gy, respectively) for the FET-PET- and MR-based PTV-FET{sub (72 Gy)} and PTV-MR{sub (60 Gy)}. FET-PET and MRI were performed routinely for follow-up. Quality of life and cognitive aspects were recorded by the EORTC-QLQ-C30/QLQ Brain20 and Mini-Mental Status Examination (MMSE), while the therapy-related toxicity was recorded using the CTC3.0 and RTOG scores. Median overall survival (OS) and disease-free survival (DFS) were 14.8 and 7.8 months, respectively. All local relapses were detected at least partly within the 95% dose volume of PTV-MR{sub (60 Gy)}. No relevant radiotherapy-related side effects were observed (excepted alopecia). In 2 patients, a pseudoprogression was observed in the MRI. Tumor progression could be excluded by FET-PET and was confirmed in further MRI and FET-PET imaging. No significant changes were observed in MMSE scores and in the EORTC QLQ-C30/QLQ-Brain20 questionnaires. Our dose escalation concept with a total dose of 72 Gy, based on FET-PET, did not lead to a survival benefit. Acute and late toxicity were not increased, compared with historical controls and published dose-escalation studies. (orig.)

  19. Does selective pleural irradiation of malignant pleural mesothelioma allow radiation dose escalation. A planning study

    International Nuclear Information System (INIS)

    Botticella, A.; Defraene, G.; Nackaerts, K.; Deroose, C.; Coolen, J.; Nafteux, P.; Vanstraelen, B.; Joosten, S.; Michiels, L.A.W.; Peeters, S.; Ruysscher, D. de

    2017-01-01

    After lung-sparing radiotherapy for malignant pleural mesothelioma (MPM), local failure at sites of previous gross disease represents the dominant form of failure. Our aim is to investigate if selective irradiation of the gross pleural disease only can allow dose escalation. In all, 12 consecutive stage I-IV MPM patients (6 left-sided and 6 right-sided) were retrospectively identified and included. A magnetic resonance imaging-based pleural gross tumor volume (GTV) was contoured. Two sets of planning target volumes (PTV) were generated for each patient: (1) a ''selective'' PTV (S-PTV), originating from a 5-mm isotropic expansion from the GTV and (2) an ''elective'' PTV (E-PTV), originating from a 5-mm isotropic expansion from the whole ipsilateral pleural space. Two sets of volumetric modulated arc therapy (VMAT) treatment plans were generated: a ''selective'' pleural irradiation plan (SPI plan) and an ''elective'' pleural irradiation plan (EPI plan, planned with a simultaneous integrated boost technique [SIB]). In the SPI plans, the average median dose to the S-PTV was 53.6 Gy (range 41-63.6 Gy). In 4 of 12 patients, it was possible to escalate the dose to the S-PTV to >58 Gy. In the EPI plans, the average median doses to the E-PTV and to the S-PTV were 48.6 Gy (range 38.5-58.7) and 49 Gy (range 38.6-59.5 Gy), respectively. No significant dose escalation was achievable. The omission of the elective irradiation of the whole ipsilateral pleural space allowed dose escalation from 49 Gy to more than 58 Gy in 4 of 12 chemonaive MPM patients. This strategy may form the basis for nonsurgical radical combined modality treatment of MPM. (orig.) [de

  20. Anuvasan Basti in escalating dose is an alternative for Snehapana before Vamana and Virechana: Trends from a pilot study

    Directory of Open Access Journals (Sweden)

    Priyadarshani Arvind Kadus

    2014-01-01

    Full Text Available Oral administration of medicated fats (oil or ghee is termed as Snehapana. It is an essential step before Vamana (therapeutic emesis and Virechana (therapeutic purgation. Ayurveda physicians often experience a poor compliance in 10-15% patients for oral administration of medicated fats especially in escalating doses. Incomplete Snehapana sometimes creates a problem for a physician to prepare the patient for these processes. These inconveniences made us think about effective alternatives to counter drawbacks and improve acceptance of Snehapana. The present study was planned to assess the efficacy of Anuvasana Basti (oil enema in escalating doses as an alternative for Snehapana. Anuvasana Basti of medicated sesame oil with rock salt was administered in 10 patients for three to seven days till they showed signs and symptoms of complete Snehana. The symptoms of Snehana like semisolid or loose stools, feeling exhausted without much exertion, lightness of body and oiliness of skin were observed. Though the Snehana symptoms varied in intensity, they were similar as they are produced after oral administration of fats. This trend suggests Anuvasana Basti in escalating dose is an alternative for Snehapana before administration of Shodhana therapy like Vamana or Virechana.

  1. Anuvasan Basti in escalating dose is an alternative for Snehapana before Vamana and Virechana: Trends from a pilot study.

    Science.gov (United States)

    Kadus, Priyadarshani Arvind; Vedpathak, Surendra M

    2014-01-01

    Oral administration of medicated fats (oil or ghee) is termed as Snehapana. It is an essential step before Vamana (therapeutic emesis) and Virechana (therapeutic purgation). Ayurveda physicians often experience a poor compliance in 10-15% patients for oral administration of medicated fats especially in escalating doses. Incomplete Snehapana sometimes creates a problem for a physician to prepare the patient for these processes. These inconveniences made us think about effective alternatives to counter drawbacks and improve acceptance of Snehapana. The present study was planned to assess the efficacy of Anuvasana Basti (oil enema) in escalating doses as an alternative for Snehapana. Anuvasana Basti of medicated sesame oil with rock salt was administered in 10 patients for three to seven days till they showed signs and symptoms of complete Snehana. The symptoms of Snehana like semisolid or loose stools, feeling exhausted without much exertion, lightness of body and oiliness of skin were observed. Though the Snehana symptoms varied in intensity, they were similar as they are produced after oral administration of fats. This trend suggests Anuvasana Basti in escalating dose is an alternative for Snehapana before administration of Shodhana therapy like Vamana or Virechana.

  2. Pharmacogenetic testing for clopidogrel using the rapid INFINITI analyzer: a dose-escalation study.

    Science.gov (United States)

    Gladding, Patrick; White, Harvey; Voss, Jamie; Ormiston, John; Stewart, Jim; Ruygrok, Peter; Bvaldivia, Badi; Baak, Ruth; White, Catherine; Webster, Mark

    2009-11-01

    Our aim was to assess whether a higher clopidogrel maintenance dose has a greater antiplatelet effect in CYP2C19*2 allele carriers compared with noncarriers. Clopidogrel is a prodrug that is biotransformed by the cytochrome P450 enzymes CYP2C19, 2C9, and 3A4, 2B6, 1A2. The CYPC219*2 loss of function variant has been associated with a reduced antiplatelet response to clopidogrel and a 3-fold risk of stent thrombosis. Forty patients on standard maintenance dosage clopidogrel (75 mg), for 9.4 +/- 9.2 weeks, were enrolled into a dose escalation study. Platelet function was assessed at baseline and after 1 week of 150 mg once daily using the VerifyNow platelet function analyzer (Accumetrics Ltd., San Diego, California). Genomic DNA was hybridized to a BioFilmChip microarray on the INFINITI analyzer (AutoGenomics Inc., Carlsbad, California) and analyzed for the CYP19*2, *4, *17, and CYP2C9*2, *3 polymorphisms. Platelet inhibition increased over 1 week, mean +8.6 +/- 13.5% (p = 0.0003). Carriers of the CYP2C19*2 allele had significantly reduced platelet inhibition at baseline (median 18%, range 0% to 72%) compared with wildtype (wt) (median 59%, range 11% to 95%, p = 0.01) and at 1 week (p = 0.03). CYP2C19*2 allele carriers had an increase in platelet inhibition of (mean +9 +/- 11%, p = 0.03) and reduction in platelet reactivity (mean -26 +/- 38 platelet response unit, p = 0.04) with a higher dose. Together CYP2C19*2 and CYP2C9*3 loss of function carriers had a greater change in platelet inhibition with 150 mg daily than wt/wt (+10.9% vs. +0.7%, p = 0.04). Increasing the dose of clopidogrel in patients with nonresponder polymorphisms can increase antiplatelet response. Personalizing clopidogrel dosing using pharmacogenomics may be an effective method of optimizing treatment.

  3. Results of a phase I dose escalation study of eltrombopag in patients with advanced soft tissue sarcoma receiving doxorubicin and ifosfamide

    International Nuclear Information System (INIS)

    Chawla, Sant P; Staddon, Arthur; Hendifar, Andrew; Messam, Conrad A; Patwardhan, Rita; Kamel, Yasser Mostafa

    2013-01-01

    The objective of this Phase I dose escalation study was to explore the safety and tolerability of eltrombopag, an oral, nonpeptide, thrombopoietin receptor agonist, in patients with advanced soft tissue sarcoma (STS) and thrombocytopenia due to treatment with doxorubicin and ifosfamide (AI) combination chemotherapy. Patients aged 18 or older with histologically confirmed, locally advanced or metastatic STS were treated with 1 cycle of AI followed by AI with eltrombopag starting at Cycle 2, using 2 different dosing schedules. The study design included an eltrombopag dose escalation phase starting at 75 mg daily to determine the optimal biological dose (OBD). Eighteen patients were enrolled and 15 received at least 1 dose of chemotherapy; 3 patients withdrew prior to receiving eltrombopag. Seven, 4, and 1 patients received 75 mg, 100 mg, and 150 mg eltrombopag daily, respectively. No dose-limiting toxicities were reported. Due to slow recruitment, the study was closed prior to identifying an OBD. The most common hematologic adverse events (AEs) were thrombocytopenia (80%), neutropenia (73%), and anemia (67%). The most common nonhematologic AEs were fatigue (53%), alanine aminotransferase increased, constipation, and nausea (47% each). Eleven of 12 patients who received eltrombopag completed at least 2 chemotherapy cycles; all had increased platelet counts on Day 1 of Cycle 2 (cycle with eltrombopag) compared to Day 1 of Cycle 1 (cycle without eltrombopag). Although data are limited, safety data were consistent with the known toxicities of AI combination chemotherapy or the side effect profile of eltrombopag seen in other studies. Available data suggest a potential pre- and post-chemotherapy dosing scheme for eltrombopag when administered with AI chemotherapy, and support further investigation of eltrombopag treatment in patients with chemotherapy-induced thrombocytopenia

  4. Methods, safety, and early clinical outcomes of dose escalation using simultaneous integrated and sequential boosts in patients with locally advanced gynecologic malignancies.

    Science.gov (United States)

    Boyle, John; Craciunescu, Oana; Steffey, Beverly; Cai, Jing; Chino, Junzo

    2014-11-01

    To evaluate the safety of dose escalated radiotherapy using a simultaneous integrated boost technique in patients with locally advanced gynecological malignancies. Thirty-nine women with locally advanced gynecological malignancies were treated with intensity modulated radiation therapy utilizing a simultaneous integrated boost (SIB) technique for gross disease in the para-aortic and/or pelvic nodal basins, sidewall extension, or residual primary disease. Women were treated to 45Gy in 1.8Gy fractions to elective nodal regions. Gross disease was simultaneously treated to 55Gy in 2.2Gy fractions (n=44 sites). An additional sequential boost of 10Gy in 2Gy fractions was delivered if deemed appropriate (n=29 sites). Acute and late toxicity, local control in the treated volumes (LC), overall survival (OS), and distant metastases (DM) were assessed. All were treated with a SIB to a dose of 55Gy. Twenty-four patients were subsequently treated with a sequential boost to a median dose of 65Gy. Median follow-up was 18months. Rates of acute>grade 2 gastrointestinal (GI), genitourinary (GU), and hematologic (heme) toxicities were 2.5%, 0%, and 30%, respectively. There were no grade 4 acute toxicities. At one year, grade 1-2 late GI toxicities were 24.5%. There were no grade 3 or 4 late GI toxicities. Rates of grade 1-2 late GU toxicities were 12.7%. There were no grade 3 or 4 late GU toxicities. Dose escalated radiotherapy using a SIB results in acceptable rates of acute toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Adalimumab dose escalation and dose de-escalation success rate and predictors in a large national cohort of Crohn's patients

    NARCIS (Netherlands)

    Baert, Filip; Glorieus, Elien; Reenaers, Cathérine; D'Haens, Geert; Peeters, Harald; Franchimont, Dennis; Dewit, Olivier; Caenepeel, Philippe; Louis, Edouard; van Assche, Gert; D'Heygere, F.; George, C.; van Hootegem, P.; Ilegems, S.; Fontaine, F.; Colard, A.; Schoofs, N.; Belaiche, J.; Louis, E.; Reenaers, C.; van Kemseke, C.; Coche, J. C.; Dewit, O.; Rahier, J. F.; de Reuck, M.; Baert, F.; Decaestecker, J.; de Wulf, D.; Amininejad, L.; Franchimont, D.; van Gossum, A.; Du Ville, L.; Hendrickx, K.; Lepoutre, L.; Vandervoort, J.; van der Spek, P.; Sprengers, D.; van de Mierop, F.; Potvin, P.; Bontems, P.; Moreels, T.; van Outryve, M.; Mana, F.; de Looze, D.; de Vos, M.; Peeters, H.; Ferrante, M.; Rutgeerts, P.; van Assche, G.; Vermeire, S.

    2013-01-01

    Adalimumab is efficacious in inducing and maintaining remission in Crohn's disease but dose escalation is needed in 30-40% after 1 year. Attempts for dose de-escalation have not been studied. This study aimed to assess the need for, predictors, and outcome of dose escalation and de-escalation in a

  6. Dose Escalation Methods in Phase I Cancer Clinical Trials

    OpenAIRE

    Le Tourneau, Christophe; Lee, J. Jack; Siu, Lillian L.

    2009-01-01

    Phase I clinical trials are an essential step in the development of anticancer drugs. The main goal of these studies is to establish the recommended dose and/or schedule of new drugs or drug combinations for phase II trials. The guiding principle for dose escalation in phase I trials is to avoid exposing too many patients to subtherapeutic doses while preserving safety and maintaining rapid accrual. Here we review dose escalation methods for phase I trials, including the rule-based and model-...

  7. Does selective pleural irradiation of malignant pleural mesothelioma allow radiation dose escalation. A planning study

    Energy Technology Data Exchange (ETDEWEB)

    Botticella, A.; Defraene, G. [KU Leuven - University of Leuven, Department of Oncology, Experimental Radiation Oncology, Leuven (Belgium); Nackaerts, K. [KU Leuven - University of Leuven, University Hospitals Leuven, Department of Respiratory Medicine, Leuven (Belgium); Deroose, C. [KU Leuven - University of Leuven, University Hospitals Leuven, Nuclear Medicine, Leuven (Belgium); Coolen, J. [KU Leuven - University of Leuven, University Hospitals Leuven, Radiology Department, Leuven (Belgium); Nafteux, P. [University Hospitals Leuven, Department of Thoracic Surgery, Leuven (Belgium); Vanstraelen, B. [University Hospitals Leuven, Department of Radiation Oncology, Leuven (Belgium); Joosten, S.; Michiels, L.A.W. [Fontys University of Applied Science, Institute Paramedical Studies, Medical Imaging and Radiotherapeutic Techniques, Eindhoven (Netherlands); Peeters, S. [KU Leuven - University of Leuven, Department of Oncology, Experimental Radiation Oncology, Leuven (Belgium); University Hospitals Leuven, Department of Radiation Oncology, Leuven (Belgium); Ruysscher, D. de [KU Leuven - University of Leuven, Department of Oncology, Experimental Radiation Oncology, Leuven (Belgium); Maastricht University Medical Center, GROW - School for Oncology and Developmental Biology, Department of Radiation Oncology (MAASTRO Clinic), Maastricht (Netherlands)

    2017-04-15

    After lung-sparing radiotherapy for malignant pleural mesothelioma (MPM), local failure at sites of previous gross disease represents the dominant form of failure. Our aim is to investigate if selective irradiation of the gross pleural disease only can allow dose escalation. In all, 12 consecutive stage I-IV MPM patients (6 left-sided and 6 right-sided) were retrospectively identified and included. A magnetic resonance imaging-based pleural gross tumor volume (GTV) was contoured. Two sets of planning target volumes (PTV) were generated for each patient: (1) a ''selective'' PTV (S-PTV), originating from a 5-mm isotropic expansion from the GTV and (2) an ''elective'' PTV (E-PTV), originating from a 5-mm isotropic expansion from the whole ipsilateral pleural space. Two sets of volumetric modulated arc therapy (VMAT) treatment plans were generated: a ''selective'' pleural irradiation plan (SPI plan) and an ''elective'' pleural irradiation plan (EPI plan, planned with a simultaneous integrated boost technique [SIB]). In the SPI plans, the average median dose to the S-PTV was 53.6 Gy (range 41-63.6 Gy). In 4 of 12 patients, it was possible to escalate the dose to the S-PTV to >58 Gy. In the EPI plans, the average median doses to the E-PTV and to the S-PTV were 48.6 Gy (range 38.5-58.7) and 49 Gy (range 38.6-59.5 Gy), respectively. No significant dose escalation was achievable. The omission of the elective irradiation of the whole ipsilateral pleural space allowed dose escalation from 49 Gy to more than 58 Gy in 4 of 12 chemonaive MPM patients. This strategy may form the basis for nonsurgical radical combined modality treatment of MPM. (orig.) [German] Beim malignen Pleuramesotheliom (MPM) ist nach lungenschonender Radiotherapie das lokale Scheitern an Stellen eines frueheren, sichtbaren Tumors die dominierende Form des Scheiterns. Unser Ziel ist es, zu untersuchen, ob die selektive

  8. Safety study application guide

    International Nuclear Information System (INIS)

    1993-07-01

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

  9. Phase I dose-escalation and pharmacokinetic study (TED 11576) of cabazitaxel in Japanese patients with castration-resistant prostate cancer.

    Science.gov (United States)

    Mukai, Hirofumi; Takahashi, Shunji; Nozawa, Masahiro; Onozawa, Yusuke; Miyazaki, Jun; Ohno, Keiji; Suzuki, Kazuhiro

    2014-04-01

    The purpose of the study is to analyze the pharmacokinetic (PK) profile of cabazitaxel and evaluate its safety and tolerability as a 1-h IV infusion every 3 weeks in Japanese patients with castration-resistant prostate cancer (CRPC). Seventeen patients were treated with cabazitaxel at doses of 20 and 25 mg/m(2) for PK analyses. Dose escalation was performed only in the absence of dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) was the highest dose at which less than 33 % of the patients developed DLT. Cabazitaxel exhibited a triphasic elimination profile with a long terminal half-life of 116 ± 29.0 or 113 ± 28.0 h after IV infusion of 20 or 25 mg/m(2) cabazitaxel, respectively. The major differences in the PK parameters of cabazitaxel and docetaxel were cabazitaxel's fairly high clearance rate, representing approximately half the hepatic flow, and its large volume of distribution at steady-state conditions. No DLT was observed during Cycle 1. Mild-to-moderate hematological adverse events (AEs), including neutropenia, and other AEs typically associated with taxanes were observed; all AEs were manageable. Cabazitaxel at 25 mg/m(2) every 3 weeks was selected as the MTD in Japanese patients. The PK parameters of cabazitaxel in Japanese CRPC patients were comparable with those previously determined in Caucasian subjects. The safety and tolerability of cabazitaxel were also comparable in both ethnic populations.

  10. Dose escalation without split-course chemoradiation for anal cancer: results of a phase II RTOG study

    International Nuclear Information System (INIS)

    John, Madhu; Pajak, Thomas; Kreig, Richard; Pinover, Wayne H.; Myerson, Robert

    1997-01-01

    PURPOSE: An attempt at radiotherapy (RT) dose escalation (from 45 Gy to 59.6 Gy) in a Radiation Therapy Oncology Group (RTOG) chemoradiation protocol for advanced anal cancers had resulted in an unexpectedly high 1-year colostomy rate (23%) and local failure (The Cancer Journal from Scientific American 2 (4):205-211, 1996). This was felt to be probably secondary to the split course chemoradiation (CR) that was mandated in the protocol. A second phase of this dose escalation study was therefore undertaken without a mandatory split and with an identical RT dose (59.6 Gy) and chemotherapy. MATERIALS AND METHODS: Twenty patients with anal cancers ≥2 cms were treated with a concurrent combination of 59.6 Gy to the pelvis and perineum (1.8 Gy daily, 5 times per week in 33 fractions over 6 (1(2)) weeks) and two cycles of 5 fluorouracil infusion (1000 mg/m 2 over 24 hours for 4 days) and mitomycin C (10 mg/m 2 bolus). A 10 day rest period was allowed only for severe skin reactions. A comparative analysis was made with the 47 patients in the earlier phase of this study who were treated with the identical chemoradiation course but with a mandatory 2-week break at the 36.00 Gy level. RESULTS: Predominant Grade 3 and 4 toxicities in 18 evaluable patients with dermatitis ((14(18)) or 78%), hematologic ((14(18)) or 78%), infection ((3(18)) or 17%) and gastrointestinal ((5(18)) or 28%). There were no fatalities. Nine patients (50%) completed the planned course without a break; 9 others (50%) had their treatments interrupted for a median of 11 days (range 7-19 days) at a median dose of 41.4 Gy (range 32.4 to 48.6 Gy). This compared to (40(47)) patients (85%) who had a 12 day treatment interruption at 36 Gy total dose in a planned break group. One patient had an abdomino-perineal resection (APR) for persistent disease and another for an anal fissure for (2(18)) or 11% 1-year colostomy rate. This was again favorably comparable to 23% 1-year colostomy rate for the earlier group of

  11. A study of the effects of internal organ motion on dose escalation in conformal prostate treatments

    International Nuclear Information System (INIS)

    Happersett, Laura; Mageras, Gig S.; Zelefsky, Michael J.; Burman, Chandra M.; Leibel, Steven A.; Chui Chen; Fuks, Zvi; Bull, Sarah; Ling, C. Clifton; Kutcher, Gerald J.

    2003-01-01

    Background and purpose: To assess the effect of internal organ motion on the dose distributions and biological indices for the target and non-target organs for three different conformal prostate treatment techniques. Materials and methods: We examined three types of treatment plans in 20 patients: (1) a six field plan, with a prescribed dose of 75.6 Gy; (2) the same six field plan to 72 Gy followed by a boost to 81 Gy; and (3) a five field plan with intensity modulated beams delivering 81 Gy. Treatment plans were designed using an initial CT data set (planning) and applied to three subsequent CT scans (treatment). The treatment CT contours were used to represent patient specific organ displacement; in addition, the dose distribution was convolved with a Gaussian distribution to model random setup error. Dose-volume histograms were calculated using an organ deformation model in which the movement between scans of individual points interior to the organs was tracked and the dose accumulated. The tumor control probability (TCP) for the prostate and proximal half of seminal vesicles (clinical target volume, CTV), normal tissue complication probability (NTCP) for the rectum and the percent volume of bladder wall receiving at least 75 Gy were calculated. Results: The patient averaged increase in the planned TCP between plan types 2 and 1 and types 3 and 1 was 9.8% (range 4.9-12.5%) for both, whereas the corresponding increases in treatment TCP were 9.0% (1.3-16%) and 8.1% (-1.3-13.8%). In all patients, plans 2 and 3 (81 Gy) exhibited equal or higher treatment TCP than plan 1 (75.6 Gy). The maximum treatment NTCP for rectum never exceeded the planning constraint and percent volume of bladder wall receiving at least 75 Gy was similar in the planning and treatment scans for all three plans. Conclusion: For plans that deliver a uniform prescribed dose to the planning target volume (PTV) (plan 1), current margins are adequate. In plans that further escalate the dose to part

  12. Comparison of escalating, constant, and reduction energy output in ESWL for renal stones: multi-arm prospective randomized study.

    Science.gov (United States)

    Rabah, Danny M; Mabrouki, Mohamed S; Farhat, Karim H; Seida, Mohamed A; Arafa, Mostafa A; Talic, Riyadh F

    2017-06-01

    This study was designed to find out the optimized energy delivery strategy in Shock Wave Lithotripsy (SWL) that yield to the best stone-free rate (SFR). In this clinical trial, 150 consecutive patients were randomized into three groups: (a) Dose escalation, 1500 SW at 18 kV, followed by 1500 SW at 20 kV then 1500 SW at 22 kV. (b) Constant dose, 4500 SW at 20 kV. All patients undergo plain X-ray film of the urinary tract at day 1, 14, and 90 to assess stone-free rate (SFR) which was defined as no stones or painless fragments less than 4 mm. (c) Dose reduction, 1500 SW at 22 kV, followed by 1500 SW at 20 kV and then 1500 SW at 18 kV. The three treatment groups were comparable in terms of age, sex, stone size and distribution of the kidneys, and the need for Double J stent use. On day 90, the SFR achieved was 82, 90, and 84 % in the escalating, constant, and reduction energy groups, respectively. However, this rate was not statistically significant (x 2  = 1.38, p level = 0.28). At a slow rate of 60 shocks, there was no difference in stone-free rate between different voltages at 1, 14, and 90 days. Our randomized clinical trial showed no statistically significant difference in SFR between the three groups while using the slow SWL rate. Our trial is the first randomized trial comparing the three strategies. As such, a dose adjustment strategy while delivering SWL in slow rate was not recommended.

  13. A double-blind, placebo-controlled, randomised, parallel-group, dose-escalating, repeat dose study in healthy volunteers to evaluate the safety, tolerability, pharmacodynamic effects and pharmacokinetics of the once daily rectal application of NRL001 suppositories for 14 days.

    Science.gov (United States)

    Bell, D; Duffin, A; Jacobs, A; Pediconi, C; Gruss, H J

    2014-03-01

    The 1R,2S stereoisomer of methoxamine hydrochloride, NRL001, is a highly selective α1-adrenoceptor agonist being developed for the local treatment of non-structural faecal incontinence caused by weak internal anal sphincter tone. This study investigated the steady state pharmacokinetics (PK) and safety of 2 g rectal suppositories containing NRL001 in different strengths (7.5, 10, 12.5 or 15 mg). Healthy volunteers aged 18-45 years received 14 daily doses of NRL001 2 g suppositories or matching placebo. In each dose group nine participants received NRL001 and three received placebo. Blood samples to determine NRL001 concentrations were taken on Days 1, 7 and 14. Cardiovascular parameters were collected via electrocardiograms, Holter monitoring (three lead Holter monitor) and vital signs. Forty-eight volunteers were enrolled; 43 completed the study and were included in the PK analysis population. AUC and Cmax broadly increased with increasing dose, Tmax generally occurred between 4.0 and 5.0 h. Although the data did not appear strongly dose proportional, dose proportionality analysis did not provide evidence against dose proportionality as the log(dose) coefficients were not significantly < 1. NRL001 did not accumulate over time for any dose. Increasing NRL001 concentrations were related to changes in vital sign variables, most notably decreased heart rate. The most commonly reported adverse events (AEs) in the active treatment groups were paraesthesia and piloerection. Treatment with NRL001 was generally well tolerated over 14 days once daily dosing and plasma NRL001 did not accumulate over time. Treatment was associated with changes in vital sign variables, most notably decreased heart rate. AEs commonly reported with NRL001 treatment were events indicative of a systemic α-adrenergic effect. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  14. Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination with Docetaxel

    National Research Council Canada - National Science Library

    Vallabhajosula, Shankar

    2007-01-01

    Phase I dose escalation studies with 177Lu-DOTA-huJ591 using dose fractionation regimen will be performed in patients with PCa and who have recurrent and/or metastatic disease. The 177Lu dose (20-45 mCi/m2...

  15. Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination With Docetaxel

    National Research Council Canada - National Science Library

    Vallabhajosula, Shankar

    2006-01-01

    Phase I dose escalation studies with 177Lu-DOTA-huJ591 using dose fractionation regimen will be performed in patients with PCa and who have recurrent and/or metastatic disease. The 177Lu dose (20-45 mCi/m2...

  16. A Phase I-II dose escalation study of fixed-dose rate gemcitabine, oxaliplatin and capecitabine every two weeks in advanced cholangiocarcinomas

    DEFF Research Database (Denmark)

    Lassen, Ulrik V; Jensen, Lars Henrik; Sorensen, Morten

    2011-01-01

    (O) and capecitabine (C), and evaluate the safety and efficacy of this regimen in patients with advanced cholangiocarcinoma (CC). Methods. In the Phase I part of the study a dose-escalation schedule of FDR G, O and C, administered every two weeks, was performed in patients with solid tumours...... and no other treatments or advanced CC. In the Phase II part response rate, toxicity, progression-free survival (PFS) and overall survival was evaluated in patients with newly diagnosed advanced CC. Results. Thirty-six patients entered the Phase I part and G 1 000 mg/m(2) day 1 and 15, O 60 mg/m(2) day 1...... and 15, and C 1 000 mg/m(2) BID day 1-7 and day 15-21 were established as MTD. In the Phase II part, 41 patients with advanced CC were included. Overall response rate was 34% and 51% had stable disease, resulting in a clinical benefit rate of 85%. Grade III and IV adverse events were rare. Median...

  17. Intensity-Modulated Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer: A Dose-Escalation Planning Study

    International Nuclear Information System (INIS)

    Lievens, Yolande; Nulens, An; Gaber, Mousa Amr; Defraene, Gilles; De Wever, Walter; Stroobants, Sigrid; Van den Heuvel, Frank

    2011-01-01

    Purpose: To evaluate the potential for dose escalation with intensity-modulated radiotherapy (IMRT) in positron emission tomography-based radiotherapy planning for locally advanced non-small-cell lung cancer (LA-NSCLC). Methods and Materials: For 35 LA-NSCLC patients, three-dimensional conformal radiotherapy and IMRT plans were made to a prescription dose (PD) of 66 Gy in 2-Gy fractions. Dose escalation was performed toward the maximal PD using secondary endpoint constraints for the lung, spinal cord, and heart, with de-escalation according to defined esophageal tolerance. Dose calculation was performed using the Eclipse pencil beam algorithm, and all plans were recalculated using a collapsed cone algorithm. The normal tissue complication probabilities were calculated for the lung (Grade 2 pneumonitis) and esophagus (acute toxicity, grade 2 or greater, and late toxicity). Results: IMRT resulted in statistically significant decreases in the mean lung (p <.0001) and maximal spinal cord (p = .002 and 0005) doses, allowing an average increase in the PD of 8.6-14.2 Gy (p ≤.0001). This advantage was lost after de-escalation within the defined esophageal dose limits. The lung normal tissue complication probabilities were significantly lower for IMRT (p <.0001), even after dose escalation. For esophageal toxicity, IMRT significantly decreased the acute NTCP values at the low dose levels (p = .0009 and p <.0001). After maximal dose escalation, late esophageal tolerance became critical (p <.0001), especially when using IMRT, owing to the parallel increases in the esophageal dose and PD. Conclusion: In LA-NSCLC, IMRT offers the potential to significantly escalate the PD, dependent on the lung and spinal cord tolerance. However, parallel increases in the esophageal dose abolished the advantage, even when using collapsed cone algorithms. This is important to consider in the context of concomitant chemoradiotherapy schedules using IMRT.

  18. Dose escalation methods in phase I cancer clinical trials.

    Science.gov (United States)

    Le Tourneau, Christophe; Lee, J Jack; Siu, Lillian L

    2009-05-20

    Phase I clinical trials are an essential step in the development of anticancer drugs. The main goal of these studies is to establish the recommended dose and/or schedule of new drugs or drug combinations for phase II trials. The guiding principle for dose escalation in phase I trials is to avoid exposing too many patients to subtherapeutic doses while preserving safety and maintaining rapid accrual. Here we review dose escalation methods for phase I trials, including the rule-based and model-based dose escalation methods that have been developed to evaluate new anticancer agents. Toxicity has traditionally been the primary endpoint for phase I trials involving cytotoxic agents. However, with the emergence of molecularly targeted anticancer agents, potential alternative endpoints to delineate optimal biological activity, such as plasma drug concentration and target inhibition in tumor or surrogate tissues, have been proposed along with new trial designs. We also describe specific methods for drug combinations as well as methods that use a time-to-event endpoint or both toxicity and efficacy as endpoints. Finally, we present the advantages and drawbacks of the various dose escalation methods and discuss specific applications of the methods in developmental oncotherapeutics.

  19. Dose escalation of a curcuminoid formulation

    Directory of Open Access Journals (Sweden)

    Crowell James

    2006-03-01

    Full Text Available Abstract Background Curcumin is the major yellow pigment extracted from turmeric, a commonly-used spice in India and Southeast Asia that has broad anticarcinogenic and cancer chemopreventive potential. However, few systematic studies of curcumin's pharmacology and toxicology in humans have been performed. Methods A dose escalation study was conducted to determine the maximum tolerated dose and safety of a single dose of standardized powder extract, uniformly milled curcumin (C3 Complex™, Sabinsa Corporation. Healthy volunteers were administered escalating doses from 500 to 12,000 mg. Results Seven of twenty-four subjects (30% experienced only minimal toxicity that did not appear to be dose-related. No curcumin was detected in the serum of subjects administered 500, 1,000, 2,000, 4,000, 6,000 or 8,000 mg. Low levels of curcumin were detected in two subjects administered 10,000 or 12,000 mg. Conclusion The tolerance of curcumin in high single oral doses appears to be excellent. Given that achieving systemic bioavailability of curcumin or its metabolites may not be essential for colorectal cancer chemoprevention, these findings warrant further investigation for its utility as a long-term chemopreventive agent.

  20. Dose escalation study of carbon ion radiotherapy for locally advanced carcinoma of the uterine cervix

    International Nuclear Information System (INIS)

    Kato, Shingo; Ohno, Tatsuya; Tsujii, Hirohiko; Nakano, Takashi; Mizoe, Jun-etsu; Kamada, Tadashi; Miyamoto, Tadaaki; Tsuji, Hiroshi; Kato, Hirotoshi; Yamada, Shigeru; Kandatsu, Susumu; Yoshikawa, Kyosan; Ezawa, Hidefumi; Suzuki, Michiya

    2006-01-01

    Purpose: To evaluate the toxicity and efficacy of carbon ion radiotherapy (CIRT) for locally advanced cervical cancer by two phase I/II clinical trials. Methods and Materials: Between June 1995 and January 2000, 44 patients were treated with CIRT. Thirty patients had Stage IIIB disease, and 14 patients had Stage IVA disease. Median tumor size was 6.5 cm (range, 4.2-11.0 cm). The treatment consisted of 16 fractions of whole pelvic irradiation and 8 fractions of local boost. In the first study, the total dose ranged from 52.8 to 72.0 gray equivalents (GyE) (2.2-3.0 GyE per fraction). In the second study, the whole pelvic dose was fixed at 44.8 GyE, and an additional 24.0 or 28.0 GyE was given to the cervical tumor (total dose, 68.8 or 72.8 GyE). Results: No patient developed severe acute toxicity. In contrast, 8 patients developed major late gastrointestinal complications. The doses resulting in major complications were ≥60 GyE. All patients with major complications were surgically salvaged. The 5-year local control rate for patients in the first and second studies was 45% and 79%, respectively. When treated with ≥62.4 GyE, the local control was favorable even for the patients with stage IVA disease (69%) or for those with tumors ≥6.0 cm (64%). Conclusions: In CIRT for advanced cervical cancer, the dose to the intestines should be limited to <60 GyE to avoid major complications. Although the number of patients in this study was small, the results support continued investigation to confirm therapeutic efficacy

  1. 29 CFR 1917.116 - Elevators and escalators.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false Elevators and escalators. 1917.116 Section 1917.116 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) MARINE TERMINALS Terminal Facilities § 1917.116 Elevators and escalators. (a) “Elevator” means a permanent hoisting and lowering...

  2. Escalation of Commitment in the Surgical ICU.

    Science.gov (United States)

    Braxton, Carla C; Robinson, Celia N; Awad, Samir S

    2017-04-01

    Escalation of commitment is a business term that describes the continued investment of resources into a project even after there is objective evidence of the project's impending failure. Escalation of commitment may be a contributor to high healthcare costs associated with critically ill patients as it has been shown that, despite almost certain futility, most ICU costs are incurred in the last week of life. Our objective was to determine if escalation of commitment occurs in healthcare settings, specifically in the surgical ICU. We hypothesize that factors previously identified in business and organizational psychology literature including self-justification, accountability, sunk costs, and cognitive dissonance result in escalation of commitment behavior in the surgical ICU setting resulting in increased utilization of resources and cost. A descriptive case study that illustrates common ICU narratives in which escalation of commitment can occur. In addition, we describe factors that are thought to contribute to escalation of commitment behaviors. Escalation of commitment behavior was observed with self-justification, accountability, and cognitive dissonance accounting for the majority of the behavior. Unlike in business decisions, sunk costs was not as evident. In addition, modulating factors such as personality, individual experience, culture, and gender were identified as contributors to escalation of commitment. Escalation of commitment occurs in the surgical ICU, resulting in significant expenditure of resources despite a predicted and often known poor outcome. Recognition of this phenomenon may lead to actions aimed at more rational decision making and may contribute to lowering healthcare costs. Investigation of objective measures that can help aid decision making in the surgical ICU is warranted.

  3. A phase I dose-escalation study of lenalidomide in combination with gemcitabine in patients with advanced pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Gustav J Ullenhag

    Full Text Available Lenalidomide have both immunomodulatory and anti-angiogenic properties which could confer anti-cancer effects. The aim of this study was to assess the feasibility of combining lenalidomide with the standard treatment gemcitabine in pancreatic cancer patients with advanced disease.Eligible patients had locally advanced or metastatic adenocarcinoma of the pancreas. Patients received lenalidomide days 1-21 orally and gemcitabine 1000 mg/m2 intravenously (days 1, 8 and 15, each 28 day cycle. Three cohorts of lenalidomide were examined (Cohort I = 15 mg, Cohort II = 20 mg and Cohort III = 25 mg daily. The maximum tolerated dose (MTD of lenalidomide given in combination with gemcitabine was defined as the highest dose level at which no more than one out of four (25% subjects experiences a dose-limiting toxicity (DLT. Patients should also be able to receive daily low molecular weight heparin (LMWH (e.g. dalteparin 5000 IU s.c. daily as a prophylactic anticoagulant for venous thromboembolic events (VTEs. Twelve patients (n = 4, n = 3 and n = 5 in cohort I, II and III, respectively were enrolled in this study.Median duration of treatment was 11 weeks (range 1-66, and median number of treatment cycles were three (range 1-14. The only DLT was a cardiac failure grade 3 in cohort III. Frequent treatment-related adverse events (AEs (all grades included neutropenia, leucopenia and fatigue (83% each, but there was no febrile neutropenia; thrombocytopenia (75%; dermatological toxicity (75%; diarrhea and nausea (42% each; and neuropathy (42%.This phase I study demonstrates the feasibility of the combination of lenalidomide and gemcitabine as first-line treatment in patients with advanced pancreatic cancer. The tolerability profile demonstrated in the dose escalation schedule of lenalidomide suggests the dosing of lenalidomide to be 25 mg daily on days 1-21 with standard dosing of gemcitabine and merits further evaluation in a phase II trial.ClinicalTrials.gov NCT

  4. Randomised clinical trial: study of escalating doses of NRL001 given in rectal suppositories of different weights.

    Science.gov (United States)

    Bell, D; Pediconi, C; Jacobs, A

    2014-03-01

    The application of α-adrenoceptor agonists can improve faecal incontinence symptoms. The aim of this study was to investigate the pharmacokinetic and systemic effects of NRL001 administered as different strengths in 1 or 2 g suppositories. This randomised, double-blind, placebo controlled study included 48 healthy subjects. Group 1 consisted of two cohorts of 12 subjects administered either four single doses of 1 or 2 g rectal suppository with either 5, 7.5 or 10 mg NRL001, or matching placebo. Group 2 consisted of two cohorts of 12 subjects administered either four single doses of 1 or 2 g rectal suppository with either 10, 12.5 or 15 mg NRL001, or matching placebo. Doses were given in an escalating manner with placebo at a random position within the sequence. Tmax was at ~4.5 h post-dose for all NRL001 doses. Median AUC0-tz , AUC0-∞ and Cmax increased with increasing dose for both suppository sizes. The estimate of ratios of geometric means comparing 2 g with 1 g suppository, and regression analysis for dose proportionality, was close to 1 for the variables AUC0-tz , AUC0-∞ and Cmax (P > 0.05). For both suppository sizes, 20-min mean pulse rate was significantly decreased compared with placebo with all doses (P < 0.05). Blood pressure decreased overall. There were 144 adverse events (AEs) and no serious AEs reported during the study. All AEs were mild in severity. The regression analysis concluded that the doses were dose proportional. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  5. Phase I dose escalation study of KOS-1584, a novel epothilone, in patients with advanced solid tumors.

    Science.gov (United States)

    Lam, Elaine T; Goel, Sanjay; Schaaf, Larry J; Cropp, Gillian F; Hannah, Alison L; Zhou, Yiqing; McCracken, Barbara; Haley, Brandi I; Johnson, Robert G; Mani, Sridhar; Villalona-Calero, Miguel A

    2012-02-01

    First-in-man study of KOS-1584, a second generation epothilone. Patients with advanced solid malignancies received KOS-1584 every 3 weeks until disease progression. Using a modified Fibonacci dose escalation scheme, one patient was enrolled at each dose level until the first instance of grade 2 toxicity. Thereafter, a standard 3 + 3 design was utilized. Sixty-six patients in 14 cohorts were dosed from 0.8 to 48 mg/m(2). Diarrhea, arthralgias, and encephalopathy were dose-limiting toxicities (DLTs) at doses ≥36 mg/m(2). At the recommended phase II dose (RP2D), the most common adverse effects were peripheral neuropathy (low grade), fatigue, arthralgias/myalgias, and diarrhea (31, 6%). The incidence of neutropenia was low. The overall clearance, volume of distribution, and half-life of KOS-1584 were 11 ± 6.17 L/h/m(2), 327 ± 161 L/m(2), and 21.9 ± 8.75 h, respectively. The half-life for the seco-metabolite (KOS-1891) was 29.6 ± 13.8 h. KOS-1584 exhibited linear pharmacokinetics. A dose-dependent increase in microtubulin bundle formation was observed at doses ≥27 mg/m(2). Two patients achieved partial responses and 24 patients had stable disease (SD). The RP2D of KOS-1584 is 36 mg/m(2). The lack of severe neurologic toxicity, diarrhea, neutropenia, or hypersensitivity reactions; favorable pharmacokinetic profile; and early evidence of activity support further evaluation.

  6. A 12-week dose-escalating study of etelcalcetide (ONO-5163/AMG 416), a novel intravenous calcimimetic, for secondary hyperparathyroidism in Japanese hemodialysis patients
.

    Science.gov (United States)

    Yokoyama, Keitaro; Fukagawa, Masafumi; Shigematsu, Takashi; Akiba, Takashi; Fujii, Akifumi; Odani, Motoi; Akizawa, Tadao

    2017-08-01

    To evaluate dose-escalation of etelcalcetide (ONO-5163/AMG 416), a novel, intravenous (IV), long-acting calcium-sensing receptor agonist, for treatment of secondary hyperparathyroidism (SHPT) in Japanese hemodialysis patients. In this multicenter study, IV injections of etelcalcetide (3 times a week for 12 weeks) were administered, with dose escalation every 4 weeks depending on changes in serum intact parathyroid hormone (iPTH) and corrected calcium (cCa). A total of 24 patients participated in this study. Serum iPTH was reduced in a time- and dose-dependent manner, with reductions (in pg/mL) at 12 weeks of -226.1 ± 125.3, -362.5 ± 161.5, and -412.4 ± 130.2, respectively, for maximum doses of 5, 10, and 15 mg. At the end of the treatment, 50% of patients had serum iPTH levels within the target range (60 - 240 pg/mL). Serum cCa and phosphorus were reduced in parallel with iPTH. Adverse events (AEs) occurred in 20 patients (83.3%). The most frequently observed AEs (> 10%) were either mild or moderate nasopharyngitis (29.2%), decreased serum calcium (16.7%), and vomiting (12.5%). Dose-escalated triweekly etelcalcetide was effective for SHPT in Japanese hemodialysis patients and was satisfactorily tolerated.
.

  7. Probabilistic escalation modelling

    Energy Technology Data Exchange (ETDEWEB)

    Korneliussen, G.; Eknes, M.L.; Haugen, K.; Selmer-Olsen, S. [Det Norske Veritas, Oslo (Norway)

    1997-12-31

    This paper describes how structural reliability methods may successfully be applied within quantitative risk assessment (QRA) as an alternative to traditional event tree analysis. The emphasis is on fire escalation in hydrocarbon production and processing facilities. This choice was made due to potential improvements over current QRA practice associated with both the probabilistic approach and more detailed modelling of the dynamics of escalating events. The physical phenomena important for the events of interest are explicitly modelled as functions of time. Uncertainties are represented through probability distributions. The uncertainty modelling enables the analysis to be simple when possible and detailed when necessary. The methodology features several advantages compared with traditional risk calculations based on event trees. (Author)

  8. Results of a Phase 1 Dose Escalation Study of Intravesical TMX-101 in Patients with Nonmuscle Invasive Bladder Cancer

    NARCIS (Netherlands)

    Falke, Johannes; Lammers, Rianne J. M.; Arentsen, Harm C.; Ravic, Miroslav; Pozzi, Raffaella; Cornel, Erik B.; Vergunst, Henk; de Reijke, Theo M.; Witjes, J. Alfred

    2013-01-01

    Purpose: Imiquimod, a toll like receptor 7 (TLR-7) agonist, is effective as a topical treatment for skin malignancies. TMX-101 is a liquid formulation of imiquimod. In this study we establish a safety profile of TMX-101 in patients with nonmuscle invasive bladder cancer. Materials and Methods: We

  9. Results of a phase 1 dose escalation study of intravesical TMX-101 in patients with nonmuscle invasive bladder cancer

    NARCIS (Netherlands)

    Falke, J.; Lammers, R.; Arentsen, H.C.; Ravic, M.; Pozzi, R.; Cornel, E.B.; Vergunst, H.; Reijke, T.M. de; Witjes, J.A.

    2013-01-01

    PURPOSE: Imiquimod, a toll like receptor 7 (TLR-7) agonist, is effective as a topical treatment for skin malignancies. TMX-101 is a liquid formulation of imiquimod. In this study we establish a safety profile of TMX-101 in patients with nonmuscle invasive bladder cancer. MATERIALS AND METHODS: We

  10. Promoting de-escalation of commitment: a regulatory-focus perspective on sunk costs.

    Science.gov (United States)

    Molden, Daniel C; Hui, Chin Ming

    2011-01-01

    People frequently escalate their commitment to failing endeavors. Explanations for such behavior typically involve loss aversion, failure to recognize other alternatives, and concerns with justifying prior actions; all of these factors produce recommitment to previous decisions with the goal of erasing losses and vindicating these decisions. Solutions to escalation of commitment have therefore focused on external oversight and divided responsibility during decision making to attenuate loss aversion, blindness to alternatives, and justification biases. However, these solutions require substantial resources and have additional adverse effects. The present studies tested an alternative method for de-escalating commitment: activating broad motivations for growth and advancement (promotion). This approach should reduce concerns with loss and increase perceptions of alternatives, thereby attenuating justification motives. In two studies featuring hypothetical financial decisions, activating promotion motivations reduced recommitment to poorly performing investments as compared with both not activating any additional motivations and activating motivations for safety and security (prevention).

  11. A Phase I Dose-Escalation Study of Antibody BI-505 in Relapsed/Refractory Multiple Myeloma

    DEFF Research Database (Denmark)

    Hansson, Markus; Gimsing, Peter; Badros, Ashraf

    2015-01-01

    PURPOSE: This multicenter, first-in-human study evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of BI-505, a human anti-ICAM-1 monoclonal antibody, in advanced relapsed/refractory multiple myeloma patients. EXPERIMENTAL DESIGN: BI-505 was given intravenously, every 2 weeks...... generally mild to moderate, and those attributed to study medication were mostly limited to the first dose and manageable with premedication and slower infusion. No maximum tolerated dose was identified. BI-505's half-life increased with dose while clearance decreased, suggesting target-mediated clearance...

  12. A Phase I Dose-Escalation Study (ISIDE-BT-1) of Accelerated IMRT With Temozolomide in Patients With Glioblastoma

    International Nuclear Information System (INIS)

    Morganti, Alessio G.; Balducci, Mario; Salvati, Maurizio; Esposito, Vincenzo; Romanelli, Pantaleo; Ferro, Marica; Calista, Franco; Digesu, Cinzia; Macchia, Gabriella; Ianiri, Massimo; Deodato, Francesco; Cilla, Savino; Piermattei, Angelo M.P.; Valentini, Vincenzo; Cellini, Numa; Cantore, Gian Paolo

    2010-01-01

    Purpose: To determine the maximum tolerated dose (MTD) of fractionated intensity-modulated radiotherapy (IMRT) with temozolomide (TMZ) in patients with glioblastoma. Methods and Materials: A Phase I clinical trial was performed. Eligible patients had surgically resected or biopsy-proven glioblastoma. Patients started TMZ (75 mg/day) during IMRT and continued for 1 year (150-200 mg/day, Days 1-5 every 28 days) or until disease progression. Clinical target volume 1 (CTV1) was the tumor bed ± enhancing lesion with a 10-mm margin; CTV2 was the area of perifocal edema with a 20-mm margin. Planning target volume 1 (PTV1) and PTV2 were defined as the corresponding CTV plus a 5-mm margin. IMRT was delivered in 25 fractions over 5 weeks. Only the dose for PTV1 was escalated (planned dose escalation: 60 Gy, 62.5 Gy, 65 Gy) while maintaining the dose for PTV2 (45 Gy, 1.8 Gy/fraction). Dose limiting toxicities (DLT) were defined as any treatment-related nonhematological adverse effects rated as Grade ≥3 or any hematological toxicity rated as ≥4 by Radiation Therapy Oncology Group (RTOG) criteria. Results: Nineteen consecutive glioblastoma were treated with step-and-shoot IMRT, planned with the inverse approach (dose to the PTV1: 7 patients, 60 Gy; 6 patients, 62.5 Gy; 6 patients, 65 Gy). Five coplanar beams were used to cover at least 95% of the target volume with the 95% isodose line. Median follow-up time was 23 months (range, 8-40 months). No patient experienced DLT. Grade 1-2 treatment-related neurologic and skin toxicity were common (11 and 19 patients, respectively). No Grade >2 late neurologic toxicities were noted. Conclusion: Accelerated IMRT to a dose of 65 Gy in 25 fractions is well tolerated with TMZ at a daily dose of 75 mg.

  13. A Phase I Dose Escalation Study of Hypofractionated IMRT Field-in-Field Boost for Newly Diagnosed Glioblastoma Multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Monjazeb, Arta M., E-mail: arta.monjazeb@ucdmc.ucdavis.edu [U.C. Davis School of Medicine, Department of Radiation Oncology, Sacramento, CA (United States); Ayala, Deandra; Jensen, Courtney [Radiation Oncology, Wake Forest University Health Sciences, Winston-Salem, NC (United States); Case, L. Douglas [Biostatistical Sciences, Wake Forest University Health Sciences, Winston-Salem, NC (United States); Bourland, J. Daniel; Ellis, Thomas L. [Neurosurgery, Wake Forest University Health Sciences, Winston-Salem, NC (United States); McMullen, Kevin P.; Chan, Michael D. [Radiation Oncology, Wake Forest University Health Sciences, Winston-Salem, NC (United States); Tatter, Stephen B. [Neurosurgery, Wake Forest University Health Sciences, Winston-Salem, NC (United States); Lesser, Glen J. [Hematology Oncology, Wake Forest University Health Sciences, Winston-Salem, NC (United States); Shaw, Edward G. [Radiation Oncology, Wake Forest University Health Sciences, Winston-Salem, NC (United States)

    2012-02-01

    Objectives: To describe the results of a Phase I dose escalation trial for newly diagnosed glioblastoma multiforme (GBM) using a hypofractionated concurrent intensity-modulated radiotherapy (IMRT) boost. Methods: Twenty-one patients were enrolled between April 1999 and August 2003. Radiotherapy consisted of daily fractions of 1.8 Gy with a concurrent boost of 0.7 Gy (total 2.5 Gy daily) to a total dose of 70, 75, or 80 Gy. Concurrent chemotherapy was not permitted. Seven patients were enrolled at each dose and dose limiting toxicities were defined as irreversible Grade 3 or any Grade 4-5 acute neurotoxicity attributable to radiotherapy. Results: All patients experienced Grade 1 or 2 acute toxicities. Acutely, 8 patients experienced Grade 3 and 1 patient experienced Grade 3 and 4 toxicities. Of these, only two reversible cases of otitis media were attributable to radiotherapy. No dose-limiting toxicities were encountered. Only 2 patients experienced Grade 3 delayed toxicity and there was no delayed Grade 4 toxicity. Eleven patients requiring repeat resection or biopsy were found to have viable tumor and radiation changes with no cases of radionecrosis alone. Median overall and progression-free survival for this cohort were 13.6 and 6.5 months, respectively. One- and 2-year survival rates were 57% and 19%. At recurrence, 15 patients received chemotherapy, 9 underwent resection, and 5 received radiotherapy. Conclusions: Using a hypofractionated concurrent IMRT boost, we were able to safely treat patients to 80 Gy without any dose-limiting toxicity. Given that local failure still remains the predominant pattern for GBM patients, a trial of dose escalation with IMRT and temozolomide is warranted.

  14. A Phase I Dose Escalation Study of Hypofractionated IMRT Field-in-Field Boost for Newly Diagnosed Glioblastoma Multiforme

    International Nuclear Information System (INIS)

    Monjazeb, Arta M.; Ayala, Deandra; Jensen, Courtney; Case, L. Douglas; Bourland, J. Daniel; Ellis, Thomas L.; McMullen, Kevin P.; Chan, Michael D.; Tatter, Stephen B.; Lesser, Glen J.; Shaw, Edward G.

    2012-01-01

    Objectives: To describe the results of a Phase I dose escalation trial for newly diagnosed glioblastoma multiforme (GBM) using a hypofractionated concurrent intensity-modulated radiotherapy (IMRT) boost. Methods: Twenty-one patients were enrolled between April 1999 and August 2003. Radiotherapy consisted of daily fractions of 1.8 Gy with a concurrent boost of 0.7 Gy (total 2.5 Gy daily) to a total dose of 70, 75, or 80 Gy. Concurrent chemotherapy was not permitted. Seven patients were enrolled at each dose and dose limiting toxicities were defined as irreversible Grade 3 or any Grade 4–5 acute neurotoxicity attributable to radiotherapy. Results: All patients experienced Grade 1 or 2 acute toxicities. Acutely, 8 patients experienced Grade 3 and 1 patient experienced Grade 3 and 4 toxicities. Of these, only two reversible cases of otitis media were attributable to radiotherapy. No dose-limiting toxicities were encountered. Only 2 patients experienced Grade 3 delayed toxicity and there was no delayed Grade 4 toxicity. Eleven patients requiring repeat resection or biopsy were found to have viable tumor and radiation changes with no cases of radionecrosis alone. Median overall and progression-free survival for this cohort were 13.6 and 6.5 months, respectively. One- and 2-year survival rates were 57% and 19%. At recurrence, 15 patients received chemotherapy, 9 underwent resection, and 5 received radiotherapy. Conclusions: Using a hypofractionated concurrent IMRT boost, we were able to safely treat patients to 80 Gy without any dose-limiting toxicity. Given that local failure still remains the predominant pattern for GBM patients, a trial of dose escalation with IMRT and temozolomide is warranted.

  15. Phase 1 Dose Escalation Study of Accelerated Radiation Therapy With Concurrent Chemotherapy for Locally Advanced Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kelsey, Chris R., E-mail: christopher.kelsey@duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Das, Shiva [Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina (United States); Gu, Lin [Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina (United States); Dunphy, Frank R.; Ready, Neal E. [Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States); Marks, Lawrence B. [Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina (United States)

    2015-12-01

    Purpose: To determine the maximum tolerated dose of radiation therapy (RT) given in an accelerated fashion with concurrent chemotherapy using intensity modulated RT. Methods and Materials: Patients with locally advanced lung cancer (non-small cell and small cell) with good performance status and minimal weight loss received concurrent cisplatin and etoposide with RT. Intensity modulated RT with daily image guidance was used to facilitate esophageal avoidance and delivered using 6 fractions per week (twice daily on Fridays with a 6-hour interval). The dose was escalated from 58 Gy to a planned maximum dose of 74 Gy in 4 Gy increments in a standard 3 + 3 trial design. Dose-limiting toxicity (DLT) was defined as acute grade 3-5 nonhematologic toxicity attributed to RT. Results: A total of 24 patients were enrolled, filling all dose cohorts, all completing RT and chemotherapy as prescribed. Dose-limiting toxicity occurred in 1 patient at 58 Gy (grade 3 esophagitis) and 1 patient at 70 Gy (grade 3 esophageal fistula). Both patients with DLTs had large tumors (12 cm and 10 cm, respectively) adjacent to the esophagus. Three additional patients were enrolled at both dose cohorts without further DLT. In the final 74-Gy cohort, no DLTs were observed (0 of 6). Conclusions: Dose escalation and acceleration to 74 Gy with intensity modulated RT and concurrent chemotherapy was tolerable, with a low rate of grade ≥3 acute esophageal reactions.

  16. Phase 1 Study of Dose Escalation in Hypofractionated Proton Beam Therapy for Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gomez, Daniel R., E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gillin, Michael [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao, Zhongxing [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wei, Caimiao [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lin, Steven H.; Swanick, Cameron; Alvarado, Tina; Komaki, Ritsuko; Cox, James D.; Chang, Joe Y. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-07-15

    Background: Many patients with locally advanced non-small cell lung cancer (NSCLC) cannot undergo concurrent chemotherapy because of comorbidities or poor performance status. Hypofractionated radiation regimens, if tolerable, may provide an option to these patients for effective local control. Methods and Materials: Twenty-five patients were enrolled in a phase 1 dose-escalation trial of proton beam therapy (PBT) from September 2010 through July 2012. Eligible patients had histologically documented lung cancer, thymic tumors, carcinoid tumors, or metastatic thyroid tumors. Concurrent chemotherapy was not allowed, but concurrent treatment with biologic agents was. The dose-escalation schema comprised 15 fractions of 3 Gy(relative biological effectiveness [RBE])/fraction, 3.5 Gy(RBE)/fraction, or 4 Gy(RBE)/fraction. Dose constraints were derived from biologically equivalent doses of standard fractionated treatment. Results: The median follow-up time for patients alive at the time of analysis was 13 months (range, 8-28 months). Fifteen patients received treatment to hilar or mediastinal lymph nodes. Two patients experienced dose-limiting toxicity possibly related to treatment; 1 received 3.5-Gy(RBE) fractions and experienced an in-field tracheoesophageal fistula 9 months after PBT and 1 month after bevacizumab. The other patient received 4-Gy(RBE) fractions and was hospitalized for bacterial pneumonia/radiation pneumonitis 4 months after PBT. Conclusion: Hypofractionated PBT to the thorax delivered over 3 weeks was well tolerated even with significant doses to the lungs and mediastinal structures. Phase 2/3 trials are needed to compare the efficacy of this technique with standard treatment for locally advanced NSCLC.

  17. Dose escalation by image-guided intensity-modulated radiotherapy leads to an increase in pain relief for spinal metastases: a comparison study with a regimen of 30 Gy in 10 fractions.

    Science.gov (United States)

    He, Jinlan; Xiao, Jianghong; Peng, Xingchen; Duan, Baofeng; Li, Yan; Ai, Ping; Yao, Min; Chen, Nianyong

    2017-12-22

    Under the existing condition that the optimum radiotherapy regimen for spinal metastases is controversial, this study investigates the benefits of dose escalation by image-guided intensity-modulated radiotherapy (IG-IMRT) with 60-66 Gy in 20-30 fractions for spinal metastases. In the dose-escalation group, each D50 of planning gross tumor volume (PGTV) was above 60 Gy and each Dmax of spinal cord planning organ at risk volume (PRV) was below 48 Gy. The median biological effective dose (BED) of Dmax of spinal cord was lower in the dose-escalation group compared with that in the 30-Gy group (69.70 Gy vs. 83.16 Gy, p pain responses were better in the dose-escalation group than those in the 30-Gy group ( p = 0.005 and p = 0.024), and the complete pain relief rates were respectively 73.69% and 34.29% ( p = 0.006), 73.69% and 41.38% ( p = 0.028) in two compared groups. In the dose-escalation group, there is a trend of a longer duration of pain relief, a longer overall survival and a lower incidence of acute radiation toxicities. No late radiation toxicities were observed in both groups. Dosimetric parameters and clinical outcomes, including pain response, duration of pain relief, radiation toxicities and overall survival, were compared among twenty-five metastatic spinal lesions irradiated with the dose-escalation regimen and among forty-four lesions treated with the 30-Gy regimen. Conventionally-fractionated IG-IMRT for spinal metastases could escalate dose to the vertebral lesions while sparing the spinal cord, achieving a better pain relief without increasing radiation complications.

  18. Nordic studies in reactor safety

    International Nuclear Information System (INIS)

    Pershagen, N.

    1993-01-01

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

  19. A phase I dose escalation study of hypofractionated stereotactic radiotherapy as salvage therapy for persistent or recurrent malignant glioma

    International Nuclear Information System (INIS)

    Hudes, Richard S.; Corn, Benjamin W.; Werner-Wasik, Maria; Andrews, David; Rosenstock, Jeffrey; Thoron, Louisa; Downes, Beverly; Curran, Walter J.

    1999-01-01

    Purpose: A phase I dose escalation of hypofractionated stereotactic radiotherapy (H-SRT) in recurrent or persistent malignant gliomas as a means of increasing the biologically effective dose and decreasing the high rate of reoperation due to toxicity associated with single-fraction stereotactic radiosurgery (SRS) and brachytherapy. Materials and Methods: From November 1994 to September 1996, 25 lesions in 20 patients with clinical and/or imaging evidence of malignant glioma persistence or recurrence received salvage H-SRT. Nineteen patients at the time of initial diagnosis had glioblastoma multiforme (GBM) and one patient had an anaplastic astrocytoma. All of these patients with tumor persistence or recurrence had received initial fractionated radiation therapy (RT) with a mean and median dose of 60 Gy (44.0-72.0 Gy). The median time from completion of initial RT to H-SRT was 3.1 months (0.7-45.5 months). Salvage H-SRT was delivered using daily 3.0-3.5 Gy fractions (fxs). Three different total dose levels were sequentially evaluated: 24.0 Gy/3.0 Gy fxs (five lesions), 30.0 Gy/3.0 Gy fxs (10 lesions), and 35.0 Gy/3.5 Gy fxs (nine lesions). Median treated tumor volume measured 12.66 cc (0.89-47.5 cc). The median ratio of prescription volume to tumor volume was 2.8 (1.4-5.0). Toxicity was judged by RTOG criteria. Response was determined by clinical neurologic improvement, a decrease in steroid dose without clinical deterioration, and/or radiologic imaging. Results: No grade 3 toxicities were observed and no reoperation due to toxicity was required. At the time of analysis, 13 of 20 patients had died. The median survival time from the completion of H-SRT is 10.5 months with a 1-year survival rate of 20%. Neurological improvement was found in 45% of patients. Decreased steroid requirements occurred in 60% of patients. Minor imaging response was noted in 22% of patients. Using Fisher's exact test, response of any kind correlated strongly to total dose (p = 0.0056). None

  20. Whole Brain Irradiation With Hippocampal Sparing and Dose Escalation on Multiple Brain Metastases: A Planning Study on Treatment Concepts

    International Nuclear Information System (INIS)

    Prokic, Vesna; Wiedenmann, Nicole; Fels, Franziska; Schmucker, Marianne; Nieder, Carsten; Grosu, Anca-Ligia

    2013-01-01

    Purpose: To develop a new treatment planning strategy in patients with multiple brain metastases. The goal was to perform whole brain irradiation (WBI) with hippocampal sparing and dose escalation on multiple brain metastases. Two treatment concepts were investigated: simultaneously integrated boost (SIB) and WBI followed by stereotactic fractionated radiation therapy sequential concept (SC). Methods and Materials: Treatment plans for both concepts were calculated for 10 patients with 2-8 brain metastases using volumetric modulated arc therapy. In the SIB concept, the prescribed dose was 30 Gy in 12 fractions to the whole brain and 51 Gy in 12 fractions to individual brain metastases. In the SC concept, the prescription was 30 Gy in 12 fractions to the whole brain followed by 18 Gy in 2 fractions to brain metastases. All plans were optimized for dose coverage of whole brain and lesions, simultaneously minimizing dose to the hippocampus. The treatment plans were evaluated on target coverage, homogeneity, and minimal dose to the hippocampus and organs at risk. Results: The SIB concept enabled more successful sparing of the hippocampus; the mean dose to the hippocampus was 7.55 ± 0.62 Gy and 6.29 ± 0.62 Gy, respectively, when 5-mm and 10-mm avoidance regions around the hippocampus were used, normalized to 2-Gy fractions. In the SC concept, the mean dose to hippocampus was 9.8 ± 1.75 Gy. The mean dose to the whole brain (excluding metastases) was 33.2 ± 0.7 Gy and 32.7 ± 0.96 Gy, respectively, in the SIB concept, for 5-mm and 10-mm hippocampus avoidance regions, and 37.23 ± 1.42 Gy in SC. Conclusions: Both concepts, SIB and SC, were able to achieve adequate whole brain coverage and radiosurgery-equivalent dose distributions to individual brain metastases. The SIB technique achieved better sparing of the hippocampus, especially when a10-mm hippocampal avoidance region was used.

  1. Gemcitabine and paclitaxel associated pneumonitis in non-small cell lung cancer: report of a phase I/II dose-escalating study.

    Science.gov (United States)

    Thomas, A L; Cox, G; Sharma, R A; Steward, W P; Shields, F; Jeyapalan, K; Muller, S; O'Byrne, K J

    2000-12-01

    The aim of this phase I/II dose escalating study was to establish the maximum tolerated dose (MTD) of gemcitabine and paclitaxel given in combination in non-small cell lung cancer (NSCLC). 12 patients with stage IIIB and IV NSCLC received paclitaxel administered intravenously over 1 h followed by gemcitabine given over 30 min on days 1, 8 and 15 every 28 days. Pneumonitis was the principal side-effect observed with 4 patients affected. Of these, 1 experienced grade 3 toxicity after one cycle of treatment and the others had grade 2 toxicity. All 4 cases responded to prednisolone. No other significant toxicities were observed. Of the 8 evaluable patients, 3 had a partial response and 2 had minor responses. The study was discontinued due to this dose-limiting toxicity. The combination of paclitaxel and gemcitabine shows promising antitumour activity in NSCLC, however, this treatment schedule may predispose to pneumonitis.

  2. A phase I open-label dose-escalation study of the anti-HER3 monoclonal antibody LJM716 in patients with advanced squamous cell carcinoma of the esophagus or head and neck and HER2-overexpressing breast or gastric cancer.

    Science.gov (United States)

    Reynolds, Kerry Lynn; Bedard, Philippe L; Lee, Se-Hoon; Lin, Chia-Chi; Tabernero, Josep; Alsina, Maria; Cohen, Ezra; Baselga, José; Blumenschein, George; Graham, Donna M; Garrido-Laguna, Ignacio; Juric, Dejan; Sharma, Sunil; Salgia, Ravi; Seroutou, Abdelkader; Tian, Xianbin; Fernandez, Rose; Morozov, Alex; Sheng, Qing; Ramkumar, Thiruvamoor; Zubel, Angela; Bang, Yung-Jue

    2017-09-12

    Human epidermal growth factor receptor 3 (HER3) is important in maintaining epidermal growth factor receptor-driven cancers and mediating resistance to targeted therapy. A phase I study of anti-HER3 monoclonal antibody LJM716 was conducted with the primary objective to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE), and dosing schedule. Secondary objectives were to characterize safety/tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity. This open-label, dose-finding study comprised dose escalation, followed by expansion in patients with squamous cell carcinoma of the head and neck or esophagus, and HER2-overexpressing metastatic breast cancer or gastric cancer. During dose escalation, patients received LJM716 intravenous once weekly (QW) or every two weeks (Q2W), in 28-day cycles. An adaptive Bayesian logistic regression model was used to guide dose escalation and establish the RDE. Exploratory pharmacodynamic tumor studies evaluated modulation of HER3 signaling. Patients received LJM716 3-40 mg/kg QW and 20 mg/kg Q2W (54 patients; 36 patients at 40 mg/kg QW). No dose-limiting toxicities (DLTs) were reported during dose-escalation. One patient experienced two DLTs (diarrhea, hypokalemia [both grade 3]) in the expansion phase. The RDE was 40 mg/kg QW, providing drug levels above the preclinical minimum effective concentration. One patient with gastric cancer had an unconfirmed partial response; 17/54 patients had stable disease, two lasting >30 weeks. Down-modulation of phospho-HER3 was observed in paired tumor samples. LJM716 was well tolerated; the MTD was not reached, and the RDE was 40 mg/kg QW. Further development of LJM716 is ongoing. Clinicaltrials.gov registry number NCT01598077 (registered on 4 May, 2012).

  3. Hyperfractionated accelerated radiotherapy with concomitant integrated boost of 70-75 Gy in 5 weeks for advanced head and neck cancer. A phase I dose escalation study

    Energy Technology Data Exchange (ETDEWEB)

    Cvek, J.; Skacelikova, E.; Otahal, B.; Halamka, M.; Feltl, D. [University Hospital Ostrava (Czech Republic). Dept. of Oncology; Kubes, J. [University Hospital Bulovka, Prague (Czech Republic). Dept. of Radiation Oncology; Kominek, P. [University Hospital Ostrava (Czech Republic). Dept. of Otolaryngology

    2012-08-15

    Background and purpose: The present study was performed to evaluate the feasibility of a new, 5-week regimen of 70-75 Gy hyperfractionated accelerated radiotherapy with concomitant integrated boost (HARTCIB) for locally advanced, inoperable head and neck cancer. Methods and materials: A total of 39 patients with very advanced, stage IV nonmetastatic head and neck squamous cell carcinoma (median gross tumor volume 72 ml) were included in this phase I dose escalation study. A total of 50 fractions intensity-modulated radiotherapy (IMRT) were administered twice daily over 5 weeks. Prescribed total dose/dose per fraction for planning target volume (PTV{sub tumor}) were 70 Gy in 1.4 Gy fractions, 72.5 Gy in 1.45 Gy fractions, and 75 Gy in 1.5 Gy fractions for 10, 13, and 16 patients, respectively. Uninvolved lymphatic nodes (PTV{sub uninvolved}) were irradiated with 55 Gy in 1.1 Gy fractions using the concomitant integrated boost. Results: Acute toxicity was evaluated according to the RTOG/EORTC scale; the incidence of grade 3 mucositis was 51% in the oral cavity/pharynx and 0% in skin and the recovery time was {<=} 9 weeks for all patients. Late toxicity was evaluated in patients in complete remission according to the RTOG/EORTC scale. No grade 3/4 late toxicity was observed. The 1-year locoregional progression-free survival was 50% and overall survival was 55%. Conclusion: HARTCIB (75 Gy in 5 weeks) is feasible for patients deemed unsuitable for chemoradiation. Acute toxicity was lower than predicted from radiobiological models; duration of dysphagia and confluent mucositis were particularly short. Better conformity of radiotherapy allows the use of more intensive altered fractionation schedules compared with older studies. These results suggest that further dose escalation might be possible when highly conformal techniques (e.g., stereotactic radiotherapy) are used.

  4. Nuclear deterrence: Inherent escalation?

    International Nuclear Information System (INIS)

    Bergbauer, J.R. Jr.

    1993-01-01

    Despite 40 years of peace between the super powers, there is increasing clamor to the effect that nuclear war between the super powers is imminent; or could occur through escalation from a minor conflict; or could result from harsh rhetoric (but only on the part of the U.S.) in the super power dialogue. The factor that is ignored is that a massive nuclear attack would be rational ONLY if that attack could inflict such damage that the other super power could not launch a significant retaliatory nuclear attack. ONLY in this circumstance would there be any profit in launching an initial Strategic Nuclear Attack. This First Strike capability is not now possessed nor projected to be developed by either super power. As long as ANY possible Strategic Nuclear Attack against the national territory of one super power would be insufficient to prevent an equally destructive retaliatory attack, then a Strategic Nuclear Attack would inevitably result in the destruction of both and would be profitless, hence, pointless. This situation describes Mutually Assured Destruction (MAD), the governing conflict paradigm applicable to both super powers. The only convential attack that would even remotely rival the national-destruction potential of a Strategic Nuclear Attack and could cause the attacked power to consider launching a retaliatory Strategic Nuclear Attack would be a massive land-air invasion/occupation of one super power by the other. Since neither super power can successfully execute such a conventional invasion/occupation, this situation is moot. The geo-political environments of the two super powers are so asymmetrical and their military positions so symmetrical that the probability of ANY forseeable situation resulting in their resorting to a Strategic Nuclear Exchange is vanishingly small. It is possible escape the Chicken-Little syndrome and, instead, devote energy to ensuring the maintenance of this favorable, but fragile, world system

  5. A national evaluation of a dissemination and implementation initiative to enhance primary care practice capacity and improve cardiovascular disease care: the ESCALATES study protocol.

    Science.gov (United States)

    Cohen, Deborah J; Balasubramanian, Bijal A; Gordon, Leah; Marino, Miguel; Ono, Sarah; Solberg, Leif I; Crabtree, Benjamin F; Stange, Kurt C; Davis, Melinda; Miller, William L; Damschroder, Laura J; McConnell, K John; Creswell, John

    2016-06-29

    The Agency for Healthcare Research and Quality (AHRQ) launched the EvidenceNOW Initiative to rapidly disseminate and implement evidence-based cardiovascular disease (CVD) preventive care in smaller primary care practices. AHRQ funded eight grantees (seven regional Cooperatives and one independent national evaluation) to participate in EvidenceNOW. The national evaluation examines quality improvement efforts and outcomes for more than 1500 small primary care practices (restricted to those with fewer than ten physicians per clinic). Examples of external support include practice facilitation, expert consultation, performance feedback, and educational materials and activities. This paper describes the study protocol for the EvidenceNOW national evaluation, which is called Evaluating System Change to Advance Learning and Take Evidence to Scale (ESCALATES). This prospective observational study will examine the portfolio of EvidenceNOW Cooperatives using both qualitative and quantitative data. Qualitative data include: online implementation diaries, observation and interviews at Cooperatives and practices, and systematic assessment of context from the perspective of Cooperative team members. Quantitative data include: practice-level performance on clinical quality measures (aspirin prescribing, blood pressure and cholesterol control, and smoking cessation; ABCS) collected by Cooperatives from electronic health records (EHRs); practice and practice member surveys to assess practice capacity and other organizational and structural characteristics; and systematic tracking of intervention delivery. Quantitative, qualitative, and mixed methods analyses will be conducted to examine how Cooperatives organize to provide external support to practices, to compare effectiveness of the dissemination and implementation approaches they implement, and to examine how regional variations and other organization and contextual factors influence implementation and effectiveness. ESCALATES is

  6. Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

    International Nuclear Information System (INIS)

    Vainshtein, Jeffrey M.; Schipper, Matthew; Zalupski, Mark M.; Lawrence, Theodore S.; Abrams, Ross; Francis, Isaac R.; Khan, Gazala; Leslie, William; Ben-Josef, Edgar

    2013-01-01

    Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factors on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression

  7. Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

    Energy Technology Data Exchange (ETDEWEB)

    Vainshtein, Jeffrey M., E-mail: jvainsh@med.umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Schipper, Matthew [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Zalupski, Mark M. [Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States); Lawrence, Theodore S. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Abrams, Ross [Department of Radiation Oncology, Rush Medical Center, Chicago, Illinois (United States); Francis, Isaac R. [Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Khan, Gazala [Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States); Leslie, William [Division of Hematology Oncology, Department of Internal Medicine, Rush Medical Center, Chicago, Illinois (United States); Ben-Josef, Edgar [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2013-05-01

    Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factors on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression

  8. Immunogenicity and safety of the Vi-CRM197 conjugate vaccine against typhoid fever in adults, children, and infants in south and southeast Asia: results from two randomised, observer-blind, age de-escalation, phase 2 trials.

    Science.gov (United States)

    Bhutta, Zulfiqar A; Capeding, Maria Rosario; Bavdekar, Ashish; Marchetti, Elisa; Ariff, Shabina; Soofi, Sajid B; Anemona, Alessandra; Habib, Muhammad A; Alberto, Edison; Juvekar, Sanjay; Khan, Rana M Qasim; Marhaba, Rachid; Ali, Noshad; Malubay, Nelia; Kawade, Anand; Saul, Allan; Martin, Laura B; Podda, Audino

    2014-02-01

    Typhoid vaccination is a public health priority in developing countries where young children are greatly affected by typhoid fever. Because present vaccines are not recommended for children younger than 2 years, the Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM197) for infant immunisation. We aimed to assess the immunogenicity and safety of Vi-CRM197 in participants of various ages in endemic countries in south and southeast Asia. We did two randomised, observer-blind, age de-escalation, phase 2 trials at two sites in Pakistan and India (study A), and at one site in the Philippines (study B), between March 2, 2011, and Aug 9, 2012. Adults aged 18-45 years, children aged 24-59 months, older infants aged 9-12 months, and infants aged 6-8 weeks were randomly assigned (1:1) with a computer-generated randomisation list (block size of four) to receive either 5 μg Vi-CRM197 or 25 μg Vi-polysaccharide vaccine (or 13-valent pneumococcal conjugate vaccine in children younger than 2 years). Both infant populations received Vi-CRM197 concomitantly with vaccines of the Expanded Programme on Immunization (EPI), according to WHO schedule. With the exception of designated study site personnel responsible for vaccine preparation, study investigators, those assessing outcomes, and data analysts were masked to treatment allocation. We specified no a-priori null hypothesis for the immunogenicity or safety objectives and all analyses were descriptive. Analyses were by modified intention-to-treat. These studies are registered with ClinicalTrials.gov, numbers NCT01229176 and NCT01437267. 320 participants were enrolled and vaccinated in the two trials: 200 in study A (all age groups) and 120 in study B (children and infants only), of whom 317 (99%) were included in the modified intention-to-treat analysis. One dose of Vi-CRM197 significantly increased concentrations of anti-Vi antibody in adults (from 113 U/mL [95% CI 67-190] to 208 U/mL [117

  9. Is attention deficit/hyperactivity disorder among men associated with initiation or escalation of substance use at 15-month follow-up? A longitudinal study involving young Swiss men

    NARCIS (Netherlands)

    Vogel, Tanja; Dom, Geert; van de Glind, Geurt; Studer, Joseph; Gmel, Gerhard; Strik, Werner; Moggi, Franz

    2016-01-01

    Young adults with attention deficit/hyperactivity disorder (ADHD) show higher substance use disorder (SUD) prevalence relative to non-ADHD controls; few longitudinal studies have examined the course of substance use with reference to conduct disorder (CD). We compared initiation and escalation of

  10. De-Escalation Strategies in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Early Breast Cancer (BC): Final Analysis of the West German Study Group Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early BC HER2- and Hormone Receptor-Positive Phase II Randomized Trial-Efficacy, Safety, and Predictive Markers for 12 Weeks of Neoadjuvant Trastuzumab Emtansine With or Without Endocrine Therapy (ET) Versus Trastuzumab Plus ET.

    Science.gov (United States)

    Harbeck, Nadia; Gluz, Oleg; Christgen, Matthias; Kates, Ronald Ernest; Braun, Michael; Küemmel, Sherko; Schumacher, Claudia; Potenberg, Jochem; Kraemer, Stefan; Kleine-Tebbe, Anke; Augustin, Doris; Aktas, Bahriye; Forstbauer, Helmut; Tio, Joke; von Schumann, Raquel; Liedtke, Cornelia; Grischke, Eva-Maria; Schumacher, Johannes; Wuerstlein, Rachel; Kreipe, Hans Heinrich; Nitz, Ulrike Anneliese

    2017-09-10

    Purpose Human epidermal growth factor receptor 2 (HER2)-positive/hormone receptor (HR)-positive breast cancer is a distinct subgroup associated with lower chemotherapy sensitivity and slightly better outcome than HER2-positive/HR-negative disease. Little is known about the efficacy of the combination of endocrine therapy (ET) with trastuzumab or with the potent antibody-cytotoxic, anti-HER2 compound trastuzumab emtansine (T-DM1) with or without ET for this subgroup. The West German Study Group trial, ADAPT (Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer) compares pathologic complete response (pCR) rates of T-DM1 versus trastuzumab with ET in early HER2-positive/HR-positive breast cancer. Patients and Methods In this prospective, neoadjuvant, phase II trial, 375 patients with early breast cancer with HER2-positive and HR-positive status (n = 463 screened) were randomly assigned to 12 weeks of T-DM1 with or without ET or to trastuzumab with ET. The primary end point was pCR (ypT0/is/ypN0). Early response was assessed in 3-week post-therapeutic core biopsies (proliferation decrease ≥ 30% Ki-67 or cellularity response). Secondary end points included safety and predictive impact of early response on pCR. Adjuvant therapy followed national standards. Results Baseline characteristics were well balanced among the arms. More than 90% of patients completed the therapy per protocol. pCR was observed in 41.0% of patients treated with T-DM1, 41.5% of patients treated with T-DM1 and ET, and 15.1% with trastuzumab and ET ( P < .001). Early responders (67% of patients with assessable response) achieved pCR in 35.7% compared with 19.8% in nonresponders (odds ratio, 2.2; 95% CI, 1.24 to 4.19). T-DM1 was associated with a significantly higher prevalence of grade 1 to 2 toxicities, especially thrombocytopenia, nausea, and elevation of liver enzymes. Overall toxicity was low; seventeen

  11. Model quality and safety studies

    DEFF Research Database (Denmark)

    Petersen, K.E.

    1997-01-01

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

  12. Stereotactic Body Radiation Therapy Boost After Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer: A Phase 1 Dose Escalation Study

    Energy Technology Data Exchange (ETDEWEB)

    Hepel, Jaroslaw T., E-mail: jhepel@lifespan.org [Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island (United States); Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts (United States); Leonard, Kara Lynne [Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island (United States); Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts (United States); Safran, Howard [Division of Medical Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island (United States); Division of Medical Oncology, Miriam Hospital, Brown University, Providence, Rhode Island (United States); Ng, Thomas [Division of Thoracic Surgery, Rhode Island Hospital, Brown University, Providence, Rhode Island (United States); Taber, Angela [Division of Medical Oncology, Miriam Hospital, Brown University, Providence, Rhode Island (United States); Khurshid, Humera; Birnbaum, Ariel [Division of Medical Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island (United States); Wazer, David E.; DiPetrillo, Thomas [Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island (United States); Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts (United States)

    2016-12-01

    Purpose: Stereotactic body radiation therapy (SBRT) boost to primary and nodal disease after chemoradiation has potential to improve outcomes for advanced non-small cell lung cancer (NSCLC). A dose escalation study was initiated to evaluate the maximum tolerated dose (MTD). Methods and Materials: Eligible patients received chemoradiation to a dose of 50.4 Gy in 28 fractions and had primary and nodal volumes appropriate for SBRT boost (<120 cc and <60 cc, respectively). SBRT was delivered in 2 fractions after chemoradiation. Dose was escalated from 16 to 28 Gy in 2 Gy/fraction increments, resulting in 4 dose cohorts. MTD was defined when ≥2 of 6 patients per cohort experienced any treatment-related grade 3 to 5 toxicity within 4 weeks of treatment or the maximum dose was reached. Late toxicity, disease control, and survival were also evaluated. Results: Twelve patients (3 per dose level) underwent treatment. All treatment plans met predetermined dose-volume constraints. The mean age was 64 years. Most patients had stage III disease (92%) and were medically inoperable (92%). The maximum dose level was reached with no grade 3 to 5 acute toxicities. At a median follow-up time of 16 months, 1-year local-regional control (LRC) was 78%. LRC was 50% at <24 Gy and 100% at ≥24 Gy (P=.02). Overall survival at 1 year was 67%. Late toxicity (grade 3-5) was seen in only 1 patient who experienced fatal bronchopulmonary hemorrhage (grade 5). There were no predetermined dose constraints for the proximal bronchial-vascular tree (PBV) in this study. This patient's 4-cc PBV dose was substantially higher than that received by other patients in all 4 cohorts and was associated with the toxicity observed: 20.3 Gy (P<.05) and 73.5 Gy (P=.07) for SBRT boost and total treatment, respectively. Conclusions: SBRT boost to both primary and nodal disease after chemoradiation is feasible and well tolerated. Local control rates are encouraging, especially at doses ≥24

  13. A Phase 1 Study of Stereotactic Body Radiation Therapy Dose Escalation for Borderline Resectable Pancreatic Cancer After Modified FOLFIRINOX (NCT01446458).

    Science.gov (United States)

    Shaib, Walid L; Hawk, Natalyn; Cassidy, Richard J; Chen, Zhengjia; Zhang, Chao; Brutcher, Edith; Kooby, David; Maithel, Shishir K; Sarmiento, Juan M; Landry, Jerome; El-Rayes, Bassel F

    2016-10-01

    A challenge in borderline resectable pancreatic cancer (BRPC) management is the high rate of positive posterior margins (PM). Stereotactic body radiation therapy (SBRT) allows for higher radiation delivery dose with conformity. This study evaluated the maximal tolerated dose with a dose escalation plan level up to 45 Gy using SBRT in BRPC. A single-institution, 3 + 3 phase 1 clinical trial design was used to evaluate 4 dose levels of SBRT delivered in 3 fractions to the planning target volume (PTV) with a simultaneous in-field boost (SIB) to the PM. Dose level (DL) 1 was 30 Gy to the PTV, and for dose levels 2 through 4 (DL2-DL4) the dose was 36 Gy. The SIB dose to the PM was 6, 6, 7.5, and 9 Gy for DL-1, DL-2, DL-3, and DL-4, respectively. All patients received 4 treatments of modified FOLFIRINOX (fluorouracil, leucovorin, irinotecan, oxaliplatin) before SBRT. Thirteen patients with a median age of 64 years were enrolled. The median follow-up time was 18 months. The locations of the cancer were head (n=12) and uncinate/neck (n=1). One patient did not undergo SBRT. There were no grade 3 or 4 toxicities. Five patients did not undergo resection because of disease progression (1 local, 4 distant); 8 had R0 resection in the PM, and 5 of 8 had vessel reconstruction. Two patients had disease downstaged to T1 and T2 from T3 disease. Four patients are still alive, and 3 are disease free. The median overall survival for resected patients was not reached (9.3: not reached). The SBRT dose of 36 Gy with a 9-Gy SIB to the PM (total 45 Gy) delivered in 3 fractions is safe and well tolerated. The dose-limiting toxicity for a 45-Gy dose was not reached, and further dose escalations are needed in future trials. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study.

    Science.gov (United States)

    Marincek, Nicolas; Jörg, Ann-Catherine; Brunner, Philippe; Schindler, Christian; Koller, Michael T; Rochlitz, Christoph; Müller-Brand, Jan; Maecke, Helmut R; Briel, Matthias; Walter, Martin A

    2013-01-15

    We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle), 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle) and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle) [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1-4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1-158) months, 34 (range: 1-118) months and 29 (range: 1-113) months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59) vs. intermediate dose, p = 0.03) and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79) vs. low dose, p = 0.03). Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. (ClinicalTrials.gov number NCT00978211).

  15. Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study

    Directory of Open Access Journals (Sweden)

    Marincek Nicolas

    2013-01-01

    Full Text Available Abstract Background We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. Methods In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Results Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle, 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1–4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1–158 months, 34 (range: 1–118 months and 29 (range: 1–113 months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59 vs. intermediate dose, p = 0.03 and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79 vs. low dose, p = 0.03. Conclusions Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. (ClinicalTrials.gov number NCT00978211.

  16. A Phase 1 Study of Stereotactic Body Radiation Therapy Dose Escalation for Borderline Resectable Pancreatic Cancer After Modified FOLFIRINOX (NCT01446458)

    International Nuclear Information System (INIS)

    Shaib, Walid L.; Hawk, Natalyn; Cassidy, Richard J.; Chen, Zhengjia; Zhang, Chao; Brutcher, Edith; Kooby, David; Maithel, Shishir K.; Sarmiento, Juan M.; Landry, Jerome; El-Rayes, Bassel F.

    2016-01-01

    Purpose: A challenge in borderline resectable pancreatic cancer (BRPC) management is the high rate of positive posterior margins (PM). Stereotactic body radiation therapy (SBRT) allows for higher radiation delivery dose with conformity. This study evaluated the maximal tolerated dose with a dose escalation plan level up to 45 Gy using SBRT in BRPC. Methods and Materials: A single-institution, 3 + 3 phase 1 clinical trial design was used to evaluate 4 dose levels of SBRT delivered in 3 fractions to the planning target volume (PTV) with a simultaneous in-field boost (SIB) to the PM. Dose level (DL) 1 was 30 Gy to the PTV, and for dose levels 2 through 4 (DL2-DL4) the dose was 36 Gy. The SIB dose to the PM was 6, 6, 7.5, and 9 Gy for DL-1, DL-2, DL-3, and DL-4, respectively. All patients received 4 treatments of modified FOLFIRINOX (fluorouracil, leucovorin, irinotecan, oxaliplatin) before SBRT. Results: Thirteen patients with a median age of 64 years were enrolled. The median follow-up time was 18 months. The locations of the cancer were head (n=12) and uncinate/neck (n=1). One patient did not undergo SBRT. There were no grade 3 or 4 toxicities. Five patients did not undergo resection because of disease progression (1 local, 4 distant); 8 had R0 resection in the PM, and 5 of 8 had vessel reconstruction. Two patients had disease downstaged to T1 and T2 from T3 disease. Four patients are still alive, and 3 are disease free. The median overall survival for resected patients was not reached (9.3: not reached). Conclusion: The SBRT dose of 36 Gy with a 9-Gy SIB to the PM (total 45 Gy) delivered in 3 fractions is safe and well tolerated. The dose-limiting toxicity for a 45-Gy dose was not reached, and further dose escalations are needed in future trials.

  17. A Phase 1 Study of Stereotactic Body Radiation Therapy Dose Escalation for Borderline Resectable Pancreatic Cancer After Modified FOLFIRINOX (NCT01446458)

    Energy Technology Data Exchange (ETDEWEB)

    Shaib, Walid L.; Hawk, Natalyn [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Cassidy, Richard J. [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Chen, Zhengjia; Zhang, Chao [Department of Biostatistics, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Brutcher, Edith [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Kooby, David; Maithel, Shishir K.; Sarmiento, Juan M. [Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Landry, Jerome [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); El-Rayes, Bassel F., E-mail: bassel.el-rayes@emoryhealthcare.org [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

    2016-10-01

    Purpose: A challenge in borderline resectable pancreatic cancer (BRPC) management is the high rate of positive posterior margins (PM). Stereotactic body radiation therapy (SBRT) allows for higher radiation delivery dose with conformity. This study evaluated the maximal tolerated dose with a dose escalation plan level up to 45 Gy using SBRT in BRPC. Methods and Materials: A single-institution, 3 + 3 phase 1 clinical trial design was used to evaluate 4 dose levels of SBRT delivered in 3 fractions to the planning target volume (PTV) with a simultaneous in-field boost (SIB) to the PM. Dose level (DL) 1 was 30 Gy to the PTV, and for dose levels 2 through 4 (DL2-DL4) the dose was 36 Gy. The SIB dose to the PM was 6, 6, 7.5, and 9 Gy for DL-1, DL-2, DL-3, and DL-4, respectively. All patients received 4 treatments of modified FOLFIRINOX (fluorouracil, leucovorin, irinotecan, oxaliplatin) before SBRT. Results: Thirteen patients with a median age of 64 years were enrolled. The median follow-up time was 18 months. The locations of the cancer were head (n=12) and uncinate/neck (n=1). One patient did not undergo SBRT. There were no grade 3 or 4 toxicities. Five patients did not undergo resection because of disease progression (1 local, 4 distant); 8 had R0 resection in the PM, and 5 of 8 had vessel reconstruction. Two patients had disease downstaged to T1 and T2 from T3 disease. Four patients are still alive, and 3 are disease free. The median overall survival for resected patients was not reached (9.3: not reached). Conclusion: The SBRT dose of 36 Gy with a 9-Gy SIB to the PM (total 45 Gy) delivered in 3 fractions is safe and well tolerated. The dose-limiting toxicity for a 45-Gy dose was not reached, and further dose escalations are needed in future trials.

  18. Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study

    Science.gov (United States)

    2013-01-01

    Background We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. Methods In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Results Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle), 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle) and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle) [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1–4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1–158) months, 34 (range: 1–118) months and 29 (range: 1–113) months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59) vs. intermediate dose, p = 0.03) and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79) vs. low dose, p = 0.03). Conclusions Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. Trial registration ClinicalTrials.gov number:NCT00978211 PMID:23320604

  19. Center for Maritime Safety and Health Studies

    Data.gov (United States)

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

  20. Safety analysis and related studies

    International Nuclear Information System (INIS)

    Lelievre, J.

    1979-12-01

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

  1. Improving Escalation of Care: Development and Validation of the Quality of Information Transfer Tool.

    Science.gov (United States)

    Johnston, Maximilian J; Arora, Sonal; Pucher, Philip H; Reissis, Yannis; Hull, Louise; Huddy, Jeremy R; King, Dominic; Darzi, Ara

    2016-03-01

    To develop and provide validity and feasibility evidence for the QUality of Information Transfer (QUIT) tool. Prompt escalation of care in the setting of patient deterioration can prevent further harm. Escalation and information transfer skills are not currently measured in surgery. This study comprised 3 phases: the development (phase 1), validation (phase 2), and feasibility analysis (phase 3) of the QUIT tool. Phase 1 involved identification of core skills needed for successful escalation of care through literature review and 33 semistructured interviews with stakeholders. Phase 2 involved the generation of validity evidence for the tool using a simulated setting. Thirty surgeons assessed a deteriorating postoperative patient in a simulated ward and escalated their care to a senior colleague. The face and content validity were assessed using a survey. Construct and concurrent validity of the tool were determined by comparing performance scores using the QUIT tool with those measured using the Situation-Background-Assessment-Recommendation (SBAR) tool. Phase 3 was conducted using direct observation of escalation scenarios on surgical wards in 2 hospitals. A 7-category assessment tool was developed from phase 1 consisting of 24 items. Twenty-one of 24 items had excellent content validity (content validity index >0.8). All 7 categories and 18 of 24 (P validity. The correlation between the QUIT and SBAR tools used was strong indicating concurrent validity (r = 0.694, P information transfer skills than nurses when faced with a deteriorating patient. A validated tool to assess information transfer for deteriorating surgical patients was developed and tested using simulation and real-time clinical scenarios. It may improve the quality and safety of patient care on the surgical ward.

  2. Phase I dose-escalation study of the c-Met tyrosine kinase inhibitor SAR125844 in Asian patients with advanced solid tumors, including patients with MET-amplified gastric cancer

    OpenAIRE

    Shitara, Kohei; Kim, Tae Min; Yokota, Tomoya; Goto, Masahiro; Satoh, Taroh; Ahn, Jin-Hee; Kim, Hyo Song; Assadourian, Sylvie; Gomez, Corinne; Harnois, Marzia; Hamauchi, Satoshi; Kudo, Toshihiro; Doi, Toshihido; Bang, Yung-Jue

    2017-01-01

    SAR125844 is a potent and selective inhibitor of the c-Met kinase receptor. This was an open-label, phase I, multicenter, dose-escalation, and dose-expansion trial of SAR125844 in Asian patients with solid tumors, a subgroup of whom had gastric cancer and MET amplification (NCT01657214). SAR125844 was administered by intravenous infusion (260–570 mg/m2) on days 1, 8, 15, and 22 of each 28-day cycle. Objectives were to determine the maximum tolerated dose (MTD) and to evaluate SAR125844 safety...

  3. A multicenter dose-escalation study of the analgesic and adverse effects of an oral cannabis extract (Cannador) for postoperative pain management.

    Science.gov (United States)

    Holdcroft, Anita; Maze, Mervyn; Doré, Caroline; Tebbs, Susan; Thompson, Simon

    2006-05-01

    Cannabinoids have dose-related antinociceptive effects in animals. This clinical study aimed to investigate whether a single oral dose of cannabis plant extract (Cannador; Institute for Clinical Research, IKF, Berlin, Germany) could provide pain relief with minimal side effects for postoperative pain. Patients (aged 18-75 yr) were recruited and consented before surgery if patient-controlled analgesia was planned for provision of postoperative pain relief. Each patient received a single dose of 5, 10, or 15 mg Cannador if he or she had at least moderate pain after stopping patient-controlled analgesia. Starting with 5 mg, dose escalation was based on the number of patients requesting rescue analgesia and adverse effects. Pain relief, pain intensity, and side effects were recorded over 6 h and analyzed using tests for trend with dose. Rescue analgesia was requested by all 11 patients (100%) receiving 5 mg, 15 of 30 patient (50%) receiving 10 mg, and 6 of 24 patients (25%) receiving 15 mg Cannador (log rank test for trend in time to rescue analgesia with dose P analgesics without frequent adverse effects.

  4. First-In-Human, Double-Blind, Placebo-Controlled, Randomized, Dose-Escalation Study of BG00010, a Glial Cell Line-Derived Neurotrophic Factor Family Member, in Subjects with Unilateral Sciatica.

    Science.gov (United States)

    Rolan, Paul E; O'Neill, Gilmore; Versage, Eve; Rana, Jitesh; Tang, Yongqiang; Galluppi, Gerald; Aycardi, Ernesto

    2015-01-01

    To evaluate the safety, tolerability, and pharmacokinetics of single doses of BG00010 (neublastin, artemin, enovin) in subjects with unilateral sciatica. This was a single-center, blinded, placebo-controlled, randomized Phase 1 sequential-cohort, dose-escalation study (ClinicalTrials.gov identifier NCT00961766; funded by Biogen Idec). Adults with unilateral sciatica were enrolled at The Royal Adelaide Hospital, Australia. Four subjects were assigned to each of eleven cohorts (intravenous BG00010 0.3, 1, 3, 10, 25, 50, 100, 200, 400, or 800 μg/kg, or subcutaneous BG00010 50 μg/kg) and were randomized 3:1 to receive a single dose of BG00010 or placebo. The primary safety and tolerability assessments were: adverse events; clinical laboratory parameters and vital signs; pain as measured by a Likert rating scale; intra-epidermal nerve fiber density; and longitudinal assessment of quantitative sensory test parameters. Blood, serum, and plasma samples were collected for pharmacokinetic and pharmacodynamic assessments. Subjects were blinded to treatment assignment throughout the study. The investigator was blinded to treatment assignment until the Data Safety Review Committee review of unblinded data, which occurred after day 28. Beyond the planned enrollment of 44 subjects, four additional subjects were enrolled into to the intravenous BG00010 200 μg/kg cohort after one original subject experienced mild generalized pruritus. Therefore, a total of 48 subjects were enrolled between August 2009 and December 2011; all were included in the safety analyses. BG00010 was generally well tolerated: in primary analyses, the most common treatment-emergent adverse events were changes in temperature perception, pruritus, rash, or headache; no trends were observed in clinical laboratory parameters, vital signs, intra-epidermal nerve fiber density, or quantitative sensory testing. BG00010 was not associated with any clear, dose-dependent trends in Likert pain scores. BG00010 was

  5. Mitigation of fire damage and escalation by fireproofing: A risk-based strategy

    International Nuclear Information System (INIS)

    Tugnoli, Alessandro; Cozzani, Valerio; Di Padova, Annamaria; Barbaresi, Tiziana; Tallone, Fabrizio

    2012-01-01

    Passive fire protection by the application of fireproofing materials is a crucial safety barrier in the prevention of the escalation of fire scenarios. Fireproofing improves the capacity of process items and of support structures to maintain their structural integrity during a fire, preventing or at least delaying the collapse of structural elements. Maintenance and cost issues require, however, to apply such protection only where an actual risk of severe fire scenarios is present. Available methodologies for fireproofing application in on-shore installation do not consider the effect of jet-fires. In the present study, a risk-based methodology aimed at the protection from both pool fire and jet fire escalation was developed. The procedure addresses both the prevention of domino effect and the mitigation of asset damage due to the primary fire scenario. The method is mainly oriented to early design application, allowing the identification of fireproofing zones in the initial phases of lay-out definition.

  6. Managing Conflict: Examining Recent PLA Writings on Escalation Control

    Science.gov (United States)

    2016-02-01

    Cleared for Public Release Managing Conflict: Examining Recent PLA Writings on Escalation Control Alison A. Kaufman, Daniel...ANSI Std. Z39.18 i Abstract This study examines how people in China’s People’s Liberation Army ( PLA ) think about and discuss...escalation control in their public writings. It draws on over two dozen PLA writings, most issued since 2008, to explore the current state of PLA

  7. Nanotechnology Safety Self-Study

    Energy Technology Data Exchange (ETDEWEB)

    Grogin, Phillip W. [Los Alamos National Laboratory

    2016-03-29

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

  8. Does e-cigarette use predict cigarette escalation? A longitudinal study of young adult non-daily smokers.

    Science.gov (United States)

    Doran, Neal; Brikmanis, Kristin; Petersen, Angela; Delucchi, Kevin; Al-Delaimy, Wael K; Luczak, Susan; Myers, Mark; Strong, David

    2017-07-01

    Recent studies suggest that e-cigarette use among youth may be associated with increased risk of cigarette initiation. The goal of this study was to test the hypothesis that use of e-cigarettes among young adult non-daily cigarette smokers would be associated with increased cigarette consumption. Participants (n=391; 52% male) were 18-24year-old non-daily cigarette smokers recruited from across California. Cigarette and e-cigarette use were assessed online or via mobile phone every three months for one year between March 2015 and December 2016. Longitudinal negative binomial regression models showed that, adjusted for propensity for baseline e-cigarette use, non-daily smokers who reported more frequent use of e-cigarettes upon study entry reported greater quantity and frequency of cigarette smoking at baseline and greater increases in cigarette quantity over 12months than non-daily cigarette only smokers (psnon-daily smokers, young adults who use e-cigarettes tend to smoke more cigarettes and to do so more frequently. Such individuals may be at greater risk for chronic tobacco use and dependence. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Treatment assignment guesses by study participants in a double-blind dose escalation clinical trial of saw palmetto.

    Science.gov (United States)

    Lee, Jeannette Y; Moore, Page; Kusek, John; Barry, Michael

    2014-01-01

    This report assesses participant perception of treatment assignment in a randomized, double-blind, placebo-controlled trial of saw palmetto for the treatment of benign prostatic hyperplasia (BCM). Participants randomized to receive saw palmetto were instructed to take one 320 mg gelcap daily for the first 24 weeks, two 320 mg gelcaps daily for the second 24 weeks, and three 320 mg gelcaps daily for the third 24 weeks. Study participants assigned to placebo were instructed to take the same number of matching placebo gelcaps in each time period. At 24, 48, and 72 weeks postrandomization, the American Urological Association Symptom Index (AUA-SI) was administered and participants were asked to guess their treatment assignment. The study was conducted at 11 clinical centers in North America. Study participants were men, 45 years and older, with moderate to low severe BPH symptoms, randomized to saw palmetto (N=151) or placebo (N=155). Treatment arms were compared with respect to the distribution of participant guesses of treatment assignment. For participants assigned to saw palmetto, 22.5%, 24.7%, and 29.8% correctly thought they were taking saw palmetto, and 37.3%, 40.0%, and 44.4% incorrectly thought they were on placebo at 24, 48, and 72 weeks, respectively. For placebo participants, 21.8%, 27.4%, and 25.2% incorrectly thought they were on saw palmetto, and 41.6%, 39.9%, and 42.6% correctly thought they were on placebo at 24, 48, and 72 weeks, respectively. The treatment arms did not vary with respect to the distributions of participants who guessed they were on saw palmetto (p=0.823) or placebo (p=0.893). Participants who experienced an improvement in AUA-SI were 2.16 times more likely to think they were on saw palmetto. Blinding of treatment assignment was successful in this study. Improvement in BPH-related symptoms was associated with the perception that participants were taking saw palmetto.

  10. Radioimmunotherapy with Y-90-epratuzumab in patients with previously treated B-cell lymphoma. A fractionated dose-escalation study

    International Nuclear Information System (INIS)

    Linden, O.; Cavallin-Stahl, E.; Tennvall, J.; Hindorf, C.; Olsson, T.; Strand, S.E.; Stenberg, L.; Wingardh, K.

    2002-01-01

    unequivocal CD22 expression, as compared with one of four patients with weak expression, exhibited OR. Tumour CD22 assessments before and during therapy were made in three patients, indicating down regulation of CD22. Conclusion: Radioimmunotherapy using a 2-4 weekly injection schedule with 90 Y-epratuzumab can result in durable OR in patients with various subtypes of B-cell lymphoma. Three weekly infusions 185 MBq/m 2 resulted in only minor haematological toxicity. Unequivocally CD22 expressing lymphoma seems more responsive. Low toxicity as well as evidence of down regulation of CD22 expression during therapy make fractionated treatment with 90 Y-epratuzumab warrants further study

  11. Energy efficient elevators and escalators

    Energy Technology Data Exchange (ETDEWEB)

    Patrao, Carlos; Fong, Joao; Almeida, Anibal de (Dep. Electrical Engineering, Univ. of Coimbra, Coimbra (Portugal)); Rivet, Luc

    2009-07-01

    Elevators and escalators are the crucial element that makes it practical to live and work several floors above ground - more than 4,3 million units are installed in Europe. Due to ageing of the European population the installation of elevators in single family houses is experiencing a significant growth, as well as equipping existing buildings. Elevators use about 4% of the electricity in tertiary sector buildings. High untapped saving potentials exist with respect to energy-efficient technologies, investment decisions and behavioural approaches, in these sectors. This paper presents preliminary results from the IEE project E4, whose overall objective is the improvement of the energy performance of elevators and escalators, in tertiary sector buildings and in multi family residential buildings. The project is characterizing people conveyors electricity consumption in the tertiary sector and in residential buildings in the EU. The installed park is characterised by a survey among elevators national associations in each country. An assessment of the barriers has been made in the first phase of the project and will be presented. Monitoring campaigns in elevators and escalators are being conducted in each country according to a common developed methodology. More than fifty elevators and escalators will be audited. This will allow the collection of load curves (start up, travel up and down, travel full and empty), including the characterization of standby consumption. Standby consumption of an elevator can represent up to 80% of the total energy consumed per year, and can be drastically reduced. This paper presents the preliminary results of the first ten audits performed in Portugal by Isr-UC.

  12. Study of industry safety management

    International Nuclear Information System (INIS)

    Park, Pil Su

    1987-06-01

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

  13. Study on the KALIMER safety approach

    International Nuclear Information System (INIS)

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

    1997-01-01

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

  14. Gemcitabine Plus Radiation Therapy for High-Grade Glioma: Long-Term Results of a Phase 1 Dose-Escalation Study

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Michelle M., E-mail: michekim@med.umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Camelo-Piragua, Sandra [Department of Pathology, University of Michigan, Ann Arbor, Michigan (United States); Schipper, Matthew; Tao, Yebin [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Biostatistics, University of Michigan, Ann Arbor, Michigan (United States); Normolle, Daniel [Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Junck, Larry; Mammoser, Aaron [Department of Neurology, University of Michigan, Ann Arbor, Michigan (United States); Betz, Bryan L. [Department of Pathology, University of Michigan, Ann Arbor, Michigan (United States); Cao, Yue [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan (United States); Kim, Christopher J. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Heth, Jason; Sagher, Oren [Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan (United States); Lawrence, Theodore S. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Tsien, Christina I. [Department of Radiation Oncology, Washington University, St. Louis, Missouri (United States)

    2016-02-01

    Purpose: To evaluate the tolerability and efficacy of gemcitabine plus radiation therapy (RT) in this phase 1 study of patients with newly diagnosed malignant glioma (HGG). Patients and Methods: Between 2004 and 2012, 29 adults with HGG were enrolled. After any extent of resection, RT (60 Gy over 6 weeks) was given concurrent with escalating doses of weekly gemcitabine. Using a time-to-event continual reassessment method, 5 dose levels were evaluated starting at 500 mg/m{sup 2} during the last 2 weeks of RT and advanced stepwise into earlier weeks. The primary objective was to determine the recommended phase 2 dose of gemcitabine plus RT. Secondary objectives included progression-free survival, overall survival (OS), and long-term toxicity. Results: Median follow-up was 38.1 months (range, 8.9-117.5 months); 24 patients were evaluable for toxicity. After 2005 when standard practice changed, patients with World Health Organization grade 4 tumors were no longer enrolled. Median progression-free survival for 22 patients with grade 3 tumors was 26.0 months (95% confidence interval [CI] 15.6-inestimable), and OS was 48.5 months (95% CI 26.8-inestimable). In 4 IDH mutated, 1p/19q codeleted patients, no failures occurred, with all but 1 alive at time of last follow-up. Seven with IDH mutated, non-codeleted tumors with ATRX loss had intermediate OS of 73.5 months (95% CI 32.8-inestimable). Six nonmutated, non-codeleted patients had a median OS of 26.5 months (95% CI 25.4-inestimable). The recommended phase 2 dose of gemcitabine plus RT was 750 mg/m{sup 2}/wk given the last 4 weeks of RT. Dose reductions were most commonly due to grade 3 neutropenia; no grade 4 or 5 toxicities were seen. Conclusions: Gemcitabine concurrent with RT is well-tolerated and yields promising outcomes, including in patients with adverse molecular features. It is a candidate for further study, particularly for poor-prognosis patient subgroups with HGG.

  15. Effect of a simple dose-escalation schedule on tramadol tolerability : assessment in the clinical setting.

    Science.gov (United States)

    Tagarro, I; Herrera, J; Barutell, C; Díez, M C; Marín, M; Samper, D; Busquet, C; Rodríguez, M J

    2005-01-01

    To assess the effect of a very simple dose-escalation schedule on tramadol tolerability in clinical practice. This schedule consists of starting treatment with sustained-release tramadol 50mg twice daily, and escalating the dose around 7 days later to 100mg twice daily. Data from 1925 outpatients with non-malignant chronic pain were collected in this multicentre, prospective, comparative, non-randomised, open, observational study. A total of 1071 patients (55.6%) were included in the dose-escalation group (50mg group) and 854 patients (44.4%) in the control group (sustained-release tramadol 100mg twice daily; 100mg group). The proportion of patients who interrupted tramadol treatment due to the occurrence of adverse reactions was significantly lower in the 50mg group (5.6%) than in the 100mg group (12.6%) [p = 0.001]. In line with this, the proportion of patients who experienced at least one adverse reaction was significantly lower in the 50mg group (18.4%) than in the 100mg group (30.4%) [p = 0.001] and, interestingly, the two most frequently reported adverse reactions, nausea and dizziness, were found with a significantly lower frequency in the 50mg group (p < 0.001). Multivariate analysis showed that the risk of safety-related treatment cessations was 2.3 times higher in the 100mg group than in the 50mg group, and 2.2 times higher in females than in males. The two treatments were equally effective in reducing pain intensity (p = 0.121), measured as a reduction in pain score obtained by means of a visual analogue scale. The instauration of tramadol treatment, starting with sustained-release 50mg capsules twice daily and escalating the dose some days later to 100mg twice daily, was shown to be an effective and easy way to improve tramadol tolerability in clinical practice, whilst maintaining its analgesic efficacy.

  16. Escalation and propagation of thermal detonation in the corium-water systems

    International Nuclear Information System (INIS)

    Melikhov, O.I.; Melikhov, V.I.; Sokolin, A.V.

    2001-01-01

    The thermal detonation taking into account micro-interaction processes model has been applied to study thermal detonation wave escalation and propagation in the corium-water mixture. Transient escalation stage and subsequent steady-state propagation stage of the thermal detonation have been calculated. The essential decrease of the escalation length in comparison with the previous results calculated without micro-interaction concept has been obtained. (authors)

  17. Final toxicity results of a radiation-dose escalation study in patients with non-small-cell lung cancer (NSCLC): Predictors for radiation pneumonitis and fibrosis

    International Nuclear Information System (INIS)

    Kong, F.-M.; Hayman, James A.; Griffith, Kent A.; Kalemkerian, Gregory P.; Arenberg, Douglas; Lyons, Susan; Turrisi, Andrew; Lichter, Allen; Fraass, Benedick; Eisbruch, Avraham; Lawrence, Theodore S.; Haken, Randall K. ten

    2006-01-01

    Purpose: We aimed to report the final toxicity results on a radiation-dose escalation trial designed to test a hypothesis that very high doses of radiation could be safely administered to patients with non-small-cell lung cancer (NSCLC) by quantifying the dose-volume toxicity relationship of the lung. Methods and Materials: A total of 109 patients with unresectable or medically inoperable NSCLC were enrolled and treated with radiation-dose escalation (on the basis of predicted normal-lung toxicity) either alone or with neoadjuvant chemotherapy by use of 3D conformal techniques. Eighty-four patients (77%) received more than 69 Gy, the trial was stopped after the dose reached 103 Gy. Estimated median follow-up was 110 months. Results: There were 17 (14.6%) Grade 2 to 3 pneumonitis and 15 (13.8%) Grade 2 to 3 fibrosis and no Grade 4 to 5 lung toxicity. Multivariate analyses showed them to be (1) not associated with the dose prescribed to the tumor, and (2) significantly (p < 0.001) associated with lung-dosimetric parameters such as the mean lung dose (MLD), volume of lung that received at least 20 Gy (V20), and the normal-tissue complication probability (NTCP) of the lung. If cutoffs are 30% for V20, 20 Gy for MLD, and 10% for NTCP, these factors have positive predictive values of 50% to 71% and negative predictive value of 85% to 89%. Conclusions: With long-term follow-up for toxicity, we have demonstrated that much higher doses of radiation than are traditionally administered can be safely delivered to a majority of patients with NSCLC. Quantitative lung dose-volume toxicity-based dose escalation can form the basis for individualized high-dose radiation treatment to maximize the therapeutic ratio in these patients

  18. Three-Dimensional Conformal Radiation Therapy and Intensity-Modulated Radiation Therapy Combined With Transcatheter Arterial Chemoembolization for Locally Advanced Hepatocellular Carcinoma: An Irradiation Dose Escalation Study

    International Nuclear Information System (INIS)

    Ren Zhigang; Zhao Jiandong; Gu Ke; Chen Zhen; Lin Junhua; Xu Zhiyong; Hu Weigang; Zhou Zhenhua; Liu Luming; Jiang Guoliang

    2011-01-01

    Purpose: To determine the maximum tolerated dose (MTD) of three-dimensional conformal radiation therapy (3DCRT)/intensity-modulated radiation therapy (IMRT) combined with transcatheter arterial chemoembolization for locally advanced hepatocellular carcinoma. Methods and Materials: Patients were assigned to two subgroups based on tumor diameter: Group 1 had tumors <10 cm; Group II had tumors ≥10 cm. Escalation was achieved by increments of 4.0 Gy for each cohort in both groups. Dose-limiting toxicity (DLT) was defined as a grade of ≥3 acute liver or gastrointestinal toxicity or any grade 5 acute toxicity in other organs at risk or radiation-induced liver disease. The dose escalation would be terminated when ≥2 of 8 patients in a cohort experienced DLT. Results: From April 2005 to May 2008, 40 patients were enrolled. In Group I, 11 patients had grade ≤2 acute treatment-related toxicities, and no patient experienced DLT; and in Group II, 10 patients had grade ≤2 acute toxicity, and 1 patient in the group receiving 52 Gy developed radiation-induced liver disease. MTD was 62 Gy for Group I and 52 Gy for Group II. In-field progression-free and local progression-free rates were 100% and 69% at 1 year, and 93% and 44% at 2 years, respectively. Distant metastasis rates were 6% at 1 year and 15% at 2 years. Overall survival rates for 1-year and 2-years were 72% and 62%, respectively. Conclusions: The irradiation dose was safely escalated in hepatocellular carcinoma patients by using 3DCRT/IMRT with an active breathing coordinator. MTD was 62 Gy and 52 Gy for patients with tumor diameters of <10 cm and ≥10 cm, respectively.

  19. First-in-Man Dose-Escalation Study of the Selective BRAF Inhibitor RG7256 in Patients with BRAF V600-Mutated Advanced Solid Tumors

    DEFF Research Database (Denmark)

    Dienstmann, Rodrigo; Lassen, Ulrik; Cebon, Jonathan

    2016-01-01

    V600-mutated advanced solid tumors. PATIENTS AND METHODS: Patients received RG7256 orally over 8 dose levels from 200 mg once a day (QD) to 2400 mg twice a day (BID) (50-, 100- and 150-mg tablets) using a classic 3 + 3 dose escalation design. RESULTS: In total, 45 patients were enrolled; most (87...... %) had advanced melanoma (94 % BRAF V600E). RG7256 was rapidly absorbed, with limited accumulation and dose-proportional increase in exposure up to 1950 mg BID. The maximal tolerated dose (MTD) was not reached. The most common drug-related adverse events (AEs) were dyspepsia (20 %), dry skin (18 %), rash...

  20. Requirements of a new communication technology for handover and the escalation of patient care: a multi-stakeholder analysis.

    Science.gov (United States)

    Johnston, Maximilian J; King, Dominic; Arora, Sonal; Cooper, Kerri; Panda, Neha Aparajita; Gosling, Rebecca; Singh, Kaushiki; Sanders, Bradley; Cox, Benita; Darzi, Ara

    2014-08-01

    In order to enable safe and efficient information transfer between health care professionals during clinical handover and escalation of care, existing communication technologies must be updated. This study aimed to provide a user-informed guide for the development of an application-based communication system (ABCS), tailored for use in patient handover and escalation of care. Current methods of inter-professional communication in health care along with information system needs for communication technology were identified through literature review. A focus group study was then conducted according to a topic guide developed by health innovation and safety researchers. Fifteen doctors and 11 nurses from three London hospitals participated in a mixture of homogeneous and heterogeneous sessions. The sessions were recorded and transcribed verbatim before being subjected to thematic analysis. Seventeen information system needs were identified from the literature review. Participants identified six themes detailing user perceptions of current communication technology, attitudes to smartphone technology and anticipated requirements of an application produced for handover and escalation of care. Participants were in favour of an ABCS over current methods and expressed enthusiasm for a system with integrated patient information and group-messaging functions. Despite concerns regarding confidentiality and information governance a robust guide for development and implementation of an ABCS was produced, taking input from multiple stakeholders into account. Handover and escalation of care are vital processes for patient safety and communication within these must be optimized. An ABCS for health care professionals would be a welcome innovation and may lead to improvements in patient safety. © 2014 John Wiley & Sons, Ltd.

  1. E4 - Energy efficient elevators and escalators. Monitoring campaign - Germany

    Energy Technology Data Exchange (ETDEWEB)

    Hirzel, Simon; Boege, Christian

    2009-12-15

    A monitoring campaign was carried out within the E4 project as a contribution to improving the understanding of energy consumption and energy efficiency of elevators and escalators in Europe. The aim of this campaign is to broaden the empirical base on the energy consumption of elevators and escalators, to provide publicly available monitoring data and to find hints on system configurations using little energy. Originally, 50 installations were planned to be monitored within the project. In the end, 74 elevators and 7 escalators, i.e. a total of 81 installations, were analyzed in the four countries under study: Portugal, Poland, Italy and Germany. The aim of this document is to summarize the results of the German monitoring campaign with its 14 installations (13 elevators, 1 escalator) and to provide interested readers with some additional information on the campaign. This document has six parts: Second, after the introductory section, some general information on the monitoring methodology is provided as a background for understanding and interpreting the subsequent results. In the third part, information on the monitored elevator installations and their characteristics is given. Part four is concerned with presenting and discussing the results of the monitoring campaign for the elevators while part five shortly presents the results for the monitored escalator. Finally, some conclusions are found in the last part. (orig.)

  2. Nuclear fuel pellet transfer escalator

    International Nuclear Information System (INIS)

    Huggins, T.B. Sr.; Roberts, E.; Edmunds, M.O.

    1991-01-01

    This patent describes a nuclear fuel pellet escalator for loading nuclear fuel pellets into a sintering boat. It comprises a generally horizontally-disposed pellet transfer conveyor for moving pellets in single file fashion from a receiving end to a discharge end thereof, the conveyor being mounted about an axis at its receiving end for pivotal movement to generally vertically move its discharge end toward and away from a sintering boat when placed below the discharge end of the conveyor, the conveyor including an elongated arm swingable vertically about the axis and having an elongated channel recessed below an upper side of the arm and extending between the receiving and discharge ends of the conveyor; a pellet dispensing chute mounted to the arm of the conveyor at the discharge end thereof and extending therebelow such that the chute is carried at the discharge end of the conveyor for generally vertical movement therewith toward and away from the sintering boat

  3. Quantitative assessment of safety barrier performance in the prevention of domino scenarios triggered by fire

    International Nuclear Information System (INIS)

    Landucci, Gabriele; Argenti, Francesca; Tugnoli, Alessandro; Cozzani, Valerio

    2015-01-01

    The evolution of domino scenarios triggered by fire critically depends on the presence and the performance of safety barriers that may have the potential to prevent escalation, delaying or avoiding the heat-up of secondary targets. The aim of the present study is the quantitative assessment of safety barrier performance in preventing the escalation of fired domino scenarios. A LOPA (layer of protection analysis) based methodology, aimed at the definition and quantification of safety barrier performance in the prevention of escalation was developed. Data on the more common types of safety barriers were obtained in order to characterize the effectiveness and probability of failure on demand of relevant safety barriers. The methodology was exemplified with a case study. The results obtained define a procedure for the estimation of safety barrier performance in the prevention of fire escalation in domino scenarios. - Highlights: • We developed a methodology for the quantitative assessment of safety barriers. • We focused on safety barriers aimed at preventing domino effect triggered by fire. • We obtained data on effectiveness and availability of the safety barriers. • The methodology was exemplified with a case study of industrial interest. • The results showed the role of safety barriers in preventing fired domino escalation

  4. Safety, tolerability, and preliminary activity of CUDC-907, a first-in-class, oral, dual inhibitor of HDAC and PI3K, in patients with relapsed or refractory lymphoma or multiple myeloma: an open-label, dose-escalation, phase 1 trial.

    Science.gov (United States)

    Younes, Anas; Berdeja, Jesus G; Patel, Manish R; Flinn, Ian; Gerecitano, John F; Neelapu, Sattva S; Kelly, Kevin R; Copeland, Amanda R; Akins, Amy; Clancy, Myles S; Gong, Lucy; Wang, Jing; Ma, Anna; Viner, Jaye L; Oki, Yasuhiro

    2016-05-01

    Treatment options for patients with relapsed or refractory lymphoma and multiple myeloma are limited. CUDC-907 is an oral, first-in-class, small molecule that is designed to inhibit both histone deacetylase (HDAC) and PI3K enzymes, which are members of common oncogenic pathways in haematological malignancies. We aimed to assess overall safety and preliminary activity in this dose-escalation study of CUDC-907 monotherapy in patients with relapsed or refractory lymphoma and multiple myeloma. This open-label, first-in-man, phase 1 trial recruited adult patients (aged ≥18 years) with lymphoma or multiple myeloma who were refractory to or had relapsed after two or more previous regimens, from four US cancer centres. CUDC-907 was orally administered in a standard 3 + 3 dose-escalation design at four different dosing schedules, to which participants were sequentially assigned as follows: once daily, intermittently (twice or three times weekly; simultaneous enrolment), and daily for 5 days followed by a 2-day break (5/2), in 21-day cycles. Dosing started at 30 mg for the once-daily schedule and 60 mg for other schedules, escalating in 30 mg increments. Patients continued to receive CUDC-907 until disease progression or until other treatment discontinuation criteria were met. The primary objective was to determine the maximum tolerated dose (MTD) and recommended phase 2 dose, assessed in patients who received at least 66% of cycle 1 doses without modification and those who had a dose-limiting toxicity (DLT) in cycle 1 irrespective of dose modification. We assessed safety in all patients who received at least one dose of study drug. This ongoing trial is registered at ClinicalTrials.gov, number NCT01742988. Between Jan 23, 2013, and July 27, 2015, we enrolled 44 patients, of whom ten were sequentially assigned to CUDC-907 once-daily (MTD 60 mg), 12 to twice-weekly (MTD 150 mg), 15 to three-times-weekly (MTD 150 mg), and seven to the 5/2 dosing schedule (MTD 60 mg). 37

  5. A Comparison of Escalating versus Fixed Reinforcement Schedules on Undergraduate Quiz Taking

    Science.gov (United States)

    Mahoney, Amanda

    2017-01-01

    Drug abstinence studies indicate that escalating reinforcement schedules maintain abstinence for longer periods than fixed reinforcement schedules. The current study evaluated whether escalating reinforcement schedules would maintain more quiz taking than fixed reinforcement schedules. During baseline and for the control group, bonus points were…

  6. Water and Wastewater Annual Price Escalation Rates for Selected Cities across the United States

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2017-10-27

    Pacific Northwest National Laboratory conducted this study for the Federal Energy Management Program to identify trends in annual water and wastewater price escalation rates across the United States. This study can be used to inform the selection of an appropriate escalation rates for inclusion in LCCA.

  7. Impact of whole brain radiation therapy on CSF penetration ability of Icotinib in EGFR-mutated non-small cell lung cancer patients with brain metastases: Results of phase I dose-escalation study.

    Science.gov (United States)

    Zhou, Lin; He, Jiazhuo; Xiong, Weijie; Liu, Yongmei; Xiang, Jing; Yu, Qin; Liang, Maozhi; Zhou, Xiaojuan; Ding, Zhenyu; Huang, Meijuan; Ren, Li; Zhu, Jiang; Li, Lu; Hou, Mei; Ding, Lieming; Tan, Fenlai; Lu, You

    2016-06-01

    Whole-brain radiation therapy (WBRT) and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are both treatment options for EGFR-mutated non-small cell lung cancer (NSCLC) patients with brain metastases. However, the dose-escalation toxicity and efficacy of combination therapy, and the effect of WBRT on cerebrospinal fluid (CSF) penetration of EGFR-TKIs are still unclear. EGFR-mutated NSCLC patients with brain metastases were enrolled in this study, and the cohorts were constructed with a 3+3 design. The patients received icotinib with escalating doses (125-625mg, tid), and the concurrent WBRT (37.5Gy/15f/3weeks) started a week later. The CSF penetration rates of icotinib were tested before, immediately after, and 4 weeks after WBRT, respectively. Potential toxicities and benefits from dose-escalation treatment were analyzed. Fifteen patients were included in this study, 3 at each dose level from 125mg-375mg and 6 at 500mg with 3 occurred dose-limiting toxicities. The maximal tolerated dose of icotinib was 375mg tid in this combination therapy. There was a significant correlation between icotinib concentration in the CSF and plasma (R(2)=0.599, Picotinib, from 1.2% to 9.7%, reached a maximum at 375mg (median, 6.1%). There was no significant difference for CSF penetration rates among the three test points (median, 4.1% vs. 2.8% vs. 2.8%, P=0.16). The intracranial objective response rate and median intracranial progression free survival are 80% and 18.9 months. WBRT plus concurrent icotinib is well tolerated in EGFR-mutated NSCLC patients with brain metastases, up to an icotinib dose of 375mg tid. The icotinib CSF concentration seemed to have a potential ceiling effect with the dose escalation, and WBRT seemed to have no significant impact on CSF penetration of icotinib till 4 weeks after the treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Phase I study of continuous MKC-1 in patients with advanced or metastatic solid malignancies using the modified Time-to-Event Continual Reassessment Method (TITE-CRM) dose escalation design.

    Science.gov (United States)

    Tevaarwerk, Amye; Wilding, George; Eickhoff, Jens; Chappell, Rick; Sidor, Carolyn; Arnott, Jamie; Bailey, Howard; Schelman, William; Liu, Glenn

    2012-06-01

    MKC-1 is an oral cell-cycle inhibitor with broad antitumor activity in preclinical models. Clinical studies demonstrated modest antitumor activity using intermittent dosing schedule, however additional preclinical data suggested continuous dosing could be efficacious with additional effects against the mTor/AKT pathway. The primary objectives were to determine the maximum tolerated dose (MTD) and response of continuous MKC-1. Secondary objectives included characterizing the dose limiting toxicities (DLTs) and pharmacokinetics (PK). Patients with solid malignancies were eligible, if they had measurable disease, ECOG PS ≤1, and adequate organ function. Exclusions included brain metastases and inability to receive oral drug. MKC-1 was dosed twice daily, continuously in 28-day cycles. Other medications were eliminated if there were possible drug interactions. Doses were assigned using a TITE-CRM algorithm following enrollment of the first 3 pts. Disease response was assessed every 8 weeks. Between 5/08-9/09, 24 patients enrolled (15 M/9 F, median 58 years, range 44-77). Patients 1-3 received 120 mg/d of MKC-1; patients 4-24 were dosed per the TITE-CRM algorithm: 150 mg [n = 1], 180 [2], 200 [1], 230 [1], 260 [5], 290 [6], 320 [5]. The median time on drug was 8 weeks (range 4-28). The only DLT occurred at 320 mg (grade 3 fatigue). Stable disease occurred at 150 mg/d (28 weeks; RCC) and 320 mg/d (16 weeks; breast, parotid). Escalation halted at 320 mg/d. Day 28 pharmacokinetics indicated absorption and active metabolites. Continuous MKC-1 was well-tolerated; there were no RECIST responses, although clinical benefit occurred in 3/24 pts. Dose escalation stopped at 320 mg/d, and this is the MTD as defined by the CRM dose escalation algorithm; this cumulative dose/cycle exceeds that determined from intermittent dosing studies. A TITE-CRM allowed for rapid dose escalation and was able to account for late toxicities with continuous dosing via a modified algorithm.

  9. Increasing Use of Dose-Escalated External Beam Radiation Therapy for Men With Nonmetastatic Prostate Cancer

    International Nuclear Information System (INIS)

    Swisher-McClure, Samuel; Mitra, Nandita; Woo, Kaitlin; Smaldone, Marc; Uzzo, Robert; Bekelman, Justin E.

    2014-01-01

    Purpose: To examine recent practice patterns, using a large national cancer registry, to understand the extent to which dose-escalated external beam radiation therapy (EBRT) has been incorporated into routine clinical practice for men with prostate cancer. Methods and Materials: We conducted a retrospective observational cohort study using the National Cancer Data Base, a nationwide oncology outcomes database in the United States. We identified 98,755 men diagnosed with nonmetastatic prostate cancer between 2006 and 2011 who received definitive EBRT and classified patients into National Comprehensive Cancer Network (NCCN) risk groups. We defined dose-escalated EBRT as total prescribed dose of ≥75.6 Gy. Using multivariable logistic regression, we examined the association of patient, clinical, and demographic characteristics with the use of dose-escalated EBRT. Results: Overall, 81.6% of men received dose-escalated EBRT during the study period. The use of dose-escalated EBRT did not vary substantially by NCCN risk group. Use of dose-escalated EBRT increased from 70.7% of patients receiving treatment in 2006 to 89.8% of patients receiving treatment in 2011. On multivariable analysis, year of diagnosis and use of intensity modulated radiation therapy were significantly associated with receipt of dose-escalated EBRT. Conclusions: Our study results indicate that dose-escalated EBRT has been widely adopted by radiation oncologists treating prostate cancer in the United States. The proportion of patients receiving dose-escalated EBRT increased nearly 20% between 2006 and 2011. We observed high utilization rates of dose-escalated EBRT within all disease risk groups. Adoption of intensity modulated radiation therapy was strongly associated with use of dose-escalated treatment

  10. Phase I dose-escalation study of the c-Met tyrosine kinase inhibitor SAR125844 in Asian patients with advanced solid tumors, including patients with MET-amplified gastric cancer.

    Science.gov (United States)

    Shitara, Kohei; Kim, Tae Min; Yokota, Tomoya; Goto, Masahiro; Satoh, Taroh; Ahn, Jin-Hee; Kim, Hyo Song; Assadourian, Sylvie; Gomez, Corinne; Harnois, Marzia; Hamauchi, Satoshi; Kudo, Toshihiro; Doi, Toshihido; Bang, Yung-Jue

    2017-10-03

    SAR125844 is a potent and selective inhibitor of the c-Met kinase receptor. This was an open-label, phase I, multicenter, dose-escalation, and dose-expansion trial of SAR125844 in Asian patients with solid tumors, a subgroup of whom had gastric cancer and MET amplification (NCT01657214). SAR125844 was administered by intravenous infusion (260-570 mg/m 2 ) on days 1, 8, 15, and 22 of each 28-day cycle. Objectives were to determine the maximum tolerated dose (MTD) and to evaluate SAR125844 safety and pharmacokinetic profile. Antitumor activity was also assessed. Of 38 patients enrolled (median age 64.0 years), 22 had gastric cancer, including 14 with MET amplification. In the dose-escalation cohort ( N = 19; unselected population, including three patients with MET -amplification [two with gastric cancer and one with lung cancer]), the MTD was not reached, and the recommended dose was established at 570 mg/m 2 . Most frequent treatment-emergent adverse events (AEs) were nausea (36.8%), vomiting (34.2%), decreased appetite (28.9%), and fatigue or asthenia, constipation, and abdominal pains (each 21.1%); none appeared to be dose-dependent. Grade ≥ 3 AEs were observed in 39.5% of patients and considered drug-related in 7.9%. SAR125844 exposure increased slightly more than expected by dose proportionality; dose had no significant effect on clearance. No objective responses were observed in the dose-escalation cohort, with seven patients (three gastric cancer, two colorectal cancer, one breast cancer, and one with cancer of unknown primary origin) having stable disease. Modest antitumor activity was observed at 570 mg/m 2 in the dose-expansion cohort, comprising patients with MET -amplified tumors ( N = 19). Two gastric cancer patients had partial responses, seven patients had stable disease (six gastric cancer and one kidney cancer), and 10 patients had progressive disease. Single-agent SAR125844 administered up to 570 mg/m 2 has acceptable tolerability and modest

  11. Fusion reactor safety studies, FY 1977

    International Nuclear Information System (INIS)

    Darby, J.B. Jr.

    1978-04-01

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

  12. Manifestation of conflict escalation in natural resource management

    NARCIS (Netherlands)

    Yasmi, Y.; Schanz, H.; Salim, A.

    2006-01-01

    Conflict escalation is one of the important aspects to be understood for constructive conflict management. It has been widely discussed in many fields of social study, in particular as it relates inter-individual conflicts. However, this is not the case for natural resource management (NRM). This

  13. Escalating Commitment to a Relationship: The Sexual Harassment Trap.

    Science.gov (United States)

    Williams, Karen B.; Cyr, Ramona R.

    1992-01-01

    Studies divergent sexual harassment perceptions in a case of a perpetrator's gradual sexual advancements and a target's escalating commitment to their relationship, using 60 male and 60 female undergraduates. Males' ratings of sexual harassment decreased when female target participated in increasingly informal friendly interactions. Females'…

  14. Probabilistic studies for a safety assurance program

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  15. Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults.

    Science.gov (United States)

    Brown, Randall T; Nicholas, Christopher R; Cozzi, Nicholas V; Gassman, Michele C; Cooper, Karen M; Muller, Daniel; Thomas, Chantelle D; Hetzel, Scott J; Henriquez, Kelsey M; Ribaudo, Alexandra S; Hutson, Paul R

    2017-12-01

    Psilocybin is a psychedelic tryptamine that has shown promise in recent clinical trials for the treatment of depression and substance use disorders. This open-label study of the pharmacokinetics of psilocybin was performed to describe the pharmacokinetics and safety profile of psilocybin in sequential, escalating oral doses of 0.3, 0.45, and 0.6 mg/kg in 12 healthy adults. Eligible healthy adults received 6-8 h of preparatory counseling in anticipation of the first dose of psilocybin. The escalating oral psilocybin doses were administered at approximately monthly intervals in a controlled setting and subjects were monitored for 24 h. Blood and urine samples were collected over 24 h and assayed by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for psilocybin and psilocin, the active metabolite. The pharmacokinetics of psilocin were determined using both compartmental (NONMEM) and noncompartmental (WinNonlin) methods. No psilocybin was found in plasma or urine, and renal clearance of intact psilocin accounted for less than 2% of the total clearance. The pharmacokinetics of psilocin were linear within the twofold range of doses, and the elimination half-life of psilocin was 3 h (standard deviation 1.1). An extended elimination phase in some subjects suggests hydrolysis of the psilocin glucuronide metabolite. Variation in psilocin clearance was not predicted by body weight, and no serious adverse events occurred in the subjects studied. The small amount of psilocin renally excreted suggests that no dose reduction is needed for subjects with mild-moderate renal impairment. Simulation of fixed doses using the pharmacokinetic parameters suggest that an oral dose of 25 mg should approximate the drug exposure of a 0.3 mg/kg oral dose of psilocybin. Although doses of 0.6 mg/kg are in excess of likely therapeutic doses, no serious physical or psychological events occurred during or within 30 days of any dose. NCT02163707.

  16. Agricultural Terrorism (Agroterror) and Escalation Theory

    National Research Council Canada - National Science Library

    Gooding, Aeneas R

    2007-01-01

    ... credibility terrorist groups must demonstrate a continued ability to conduct operations and inflict significant numbers of casualties on their enemy, maintaining a consistent, if not escalating, level of violence. This thesis uses E...

  17. WE-G-BRB-02: The Role of Program Project Grants in Study of 3D Conformal Therapy, Dose Escalation and Motion Management

    International Nuclear Information System (INIS)

    Fraass, B.

    2015-01-01

    Over the past 20 years the NIH has funded individual grants, program projects grants, and clinical trials which have been instrumental in advancing patient care. The ways that each grant mechanism lends itself to the different phases of translating research into clinical practice will be described. Major technological innovations, such as IMRT and proton therapy, have been advanced with R01-type and P01-type funding and will be discussed. Similarly, the role of program project grants in identifying and addressing key hypotheses on the potential of 3D conformal therapy, normal tissue-guided dose escalation and motion management will be described. An overview will be provided regarding how these technological innovations have been applied to multi-institutional NIH-sponsored trials. Finally, the panel will discuss regarding which research questions should be funded by the NIH to inspire the next advances in radiation therapy. Learning Objectives: Understand the different funding mechanisms of the NIH Learn about research advances that have led to innovation in delivery Review achievements due to NIH-funded program project grants in radiotherapy over the past 20 years Understand example advances achieved with multi-institutional clinical trials NIH

  18. Collaboration and patient safety at an emergency department - a qualitative case study.

    Science.gov (United States)

    Pedersen, Anna Helene Meldgaard; Rasmussen, Kurt; Grytnes, Regine; Nielsen, Kent Jacob

    2018-03-19

    Purpose The purpose of this paper is to examine how conflicts about collaboration between staff at different departments arose during the establishment of a new emergency department and how these conflicts affected the daily work and ultimately patient safety at the emergency department. Design/methodology/approach This qualitative single case study draws on qualitative semi-structured interviews and participant observation. The theoretical concepts "availability" and "receptiveness" as antecedents for collaboration will be applied in the analysis. Findings Close collaboration between departments was an essential precondition for the functioning of the new emergency department. The study shows how a lack of antecedents for collaboration affected the working relation and communication between employees and departments, which spurred negative feelings and reproduced conflicts. This situation was seen as a potential threat for the safety of the emergency patients. Research limitations/implications This study presents a single case study, at a specific point in time, and should be used as an illustrative example of how contextual and situational factors affect the working environment and through that patient safety. Originality/value Few studies provide an in-depth investigation of what actually takes place when collaboration between professional groups goes wrong and escalates, and how problems in collaboration may affect patient safety.

  19. Case study of the effects of public safety regulation on the construction costs of coal-fired and nuclear power plants

    International Nuclear Information System (INIS)

    Morris, C.D.

    1987-01-01

    Regulations intended to reduce the number of accidents at nuclear plants and the discharge of sulfur and particulate wastes at coal-fired power plants have become an important cause of construction cost escalation. Measuring the costs of these regulatory interventions is a difficult research task. The three-unit Bruce Mansfield coal-fired plant and the two-unit Beaver Valley nuclear power station located in Shippingport, Pennsylvania, provide a unique opportunity for a case study of the costs of regulation in the construction of both kinds of plants. The units of each plant were built sequentially over a period of intensifying regulation. The method used to measure the costs of public safety regulation in the construction of each kind of plant is to determine the connections between the issuances of the regulatory agencies (EPA and NRC) and cost escalations of succeeding units. The small cost escalations of the Mansfield 3 unit, in comparison to the massive costs of the Beaver Valley 2 unit, suggest that the design and construction of new coal-fired plants are not disrupted by regulatory interventions nearly as extensively as are nuclear units. Certain technical features of Beaver Valley 2, especially its small size and a design that is identical to the first unit's, further contribute to its cost escalations

  20. Biased information processing in the escalation paradigm: information search and information evaluation as potential mediators of escalating commitment.

    Science.gov (United States)

    Schultze, Thomas; Pfeiffer, Felix; Schulz-Hardt, Stefan

    2012-01-01

    Escalation of commitment denotes decision makers' increased reinvestment of resources in a losing course of action. Despite the relevance of this topic, little is known about how information is processed in escalation situations, that is, whether decision makers who receive negative outcome feedback on their initial decision search for and/or process information biasedly and whether these biases contribute to escalating commitment. Contrary to a widely cited study by E. J. Conlon and J. M. Parks (1987), in 3 experiments, the authors found that biases do not occur on the level of information search. Neither in a direct replication and extension of the original study with largely increased test power (Experiment 1) nor under methodologically improved conditions (Experiments 2 and 3) did decision makers responsible for failure differ from nonresponsible decision makers with regards to information search, and no selective search for information supporting the initial decision or voting for further reinvestment was observed. However, Experiments 3 and 4 show that the evaluation of the previously sought information is biased among participants who were responsible for initiating the course of action. Mediation analyses show that this evaluation bias in favor of reinvestment partially mediated the responsibility effect on escalation of commitment.

  1. To dimension safety valves. Probabilist study

    International Nuclear Information System (INIS)

    Noel, Robert; Couvreur, Denis

    1982-01-01

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

  2. Flammable Gas Safety Self-Study 52827

    Energy Technology Data Exchange (ETDEWEB)

    Glass, George [Los Alamos National Laboratory

    2016-03-17

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

  3. Is attention deficit/hyperactivity disorder among men associated with initiation or escalation of substance use at 15-month follow-up? A longitudinal study involving young Swiss men.

    Science.gov (United States)

    Vogel, Tanja; Dom, Geert; van de Glind, Geurt; Studer, Joseph; Gmel, Gerhard; Strik, Werner; Moggi, Franz

    2016-10-01

    Young adults with attention deficit/hyperactivity disorder (ADHD) show higher substance use disorder (SUD) prevalence relative to non-ADHD controls; few longitudinal studies have examined the course of substance use with reference to conduct disorder (CD). We compared initiation and escalation of substance use at 15-month follow-up in men screened positive or negative for ADHD (ADHD(+) versus ADHD(-) ), controlling for CD presence in early adolescence. Participants were recruited during August 2010 and November 2011 from the census of all young men who have to pass mandatory army conscription from three of six Swiss Army recruitment centres. A two-wave data collection was performed via questionnaires at baseline and 15-month follow-up as a part of the longitudinal Cohort Study on Substance Use Risk Factors. Recruitment centres in Lausanne, Windisch and Mels, responsible for 21 cantons in German- and French-speaking areas of Switzerland. Consecutive sample of 5103 male Swiss Army conscripts who provided informed consent and responded to questionnaires at baseline and 15-month follow-up. Their mean age was 20.0 (standard deviation = 1.21) years at baseline. ADHD and CD were assessed using the adult ADHD Self-Report Scale and the MINI International Neuropsychiatric Interview Plus, respectively, at baseline, and substance use was measured via self-administered substance use questionnaires at baseline and follow-up. Compared with the ADHD(-) group, the ADHD(+) group (n = 215, 4.2%) showed heavier baseline substance use and increased likelihood of alcohol (χ(2)  = 53.96; P cannabis use disorders (χ(2)  = 48.43; P cannabis use in the two groups remained stable from baseline to follow-up (no escalation). The ADHD(+) group was more likely to initiate substance use compared with the ADHD(-) group (higher initiation rates), particularly with amphetamines [odds ratio (OR) = 3.81; 95% confidence interval (CI) = 2.20-6.60; P ADHD medication (OR

  4. Criticality safety basics, a study guide

    Energy Technology Data Exchange (ETDEWEB)

    V. L. Putman

    1999-09-01

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

  5. Criticality safety basics, a study guide

    International Nuclear Information System (INIS)

    Putman, V.L.

    1999-01-01

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

  6. Safety assessment in plant layout design using indexing approach: implementing inherent safety perspective. Part 2-Domino Hazard Index and case study.

    Science.gov (United States)

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

    2008-12-15

    The design of layout plans requires adequate assessment tools for the quantification of safety performance. The general focus of the present work is to introduce an inherent safety perspective at different points of the layout design process. In particular, index approaches for safety assessment and decision-making in the early stages of layout design are developed and discussed in this two-part contribution. Part 1 (accompanying paper) of the current work presents an integrated index approach for safety assessment of early plant layout. In the present paper (Part 2), an index for evaluation of the hazard related to the potential of domino effects is developed. The index considers the actual consequences of possible escalation scenarios and scores or ranks the subsequent accident propagation potential. The effects of inherent and passive protection measures are also assessed. The result is a rapid quantification of domino hazard potential that can provide substantial support for choices in the early stages of layout design. Additionally, a case study concerning selection among various layout options is presented and analyzed. The case study demonstrates the use and applicability of the indices developed in both parts of the current work and highlights the value of introducing inherent safety features early in layout design.

  7. E4 - Energy efficient elevators and escalators. Barriers to and strategies for promoting energy-efficient lift and escalator technologies

    Energy Technology Data Exchange (ETDEWEB)

    Duetschke, Elisabeth; Hirzel, Simon

    2010-02-25

    According to prior findings of the E4 project, considerable savings potential exists both for lifts and escalators that could be realized if appropriate technology is implemented. However, energy-efficient technology is slowly diffusing the market - a phenomenon that could be explained by barriers present in the market. A barrier is defined as a mechanism that inhibits a decision or behavior that appears to be both energy-efficient and economically efficient and thereby prevents investment in energy-efficient technologies. This document has two aims. First, it will identify influential barriers in the European lift and escalator market. This analysis is based on the literature as well as a study including interviews as well as group discussions with relevant stakeholders. Second, strategies and measures to overcome the barriers identified in the first step are outlined. Major barriers to the penetration of energy-efficient technologies identified in this paper include a lack of monitoring energy consumption of installations and a lack of awareness of as well as knowledge about energy-efficient technology. Thus, installations and components are usually chosen without a (comprehensive) assessment of their energy consumption and without considering life-cycle approaches. On top of this, split incentives are a regularly occurring barrier. Various stakeholders are influential in the decisionmaking process about an installation or its components. However, those who will later pay for the energy consumption often are not involved in this process. Moreover, it is important to keep in mind that the number of new lifts and escalators installed each year is relatively low compared to the existing stock. Thus, it is very important to discuss enhancement of energy efficiency also for the existing stock. Based on our analyses, several recommendations are developed in this paper that could contribute to a market transformation in the lift and escalator market. First of all, a

  8. Criticality safety studies at VTT Energy

    International Nuclear Information System (INIS)

    Roine, T.; Anttila, M.

    1995-01-01

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

  9. Post treatment PSA nadirs support continuing dose escalation study in patients with pretreatment PSA levels >10 ng/ml, but not in those with PSA <10 NG/ML

    International Nuclear Information System (INIS)

    Herold, D.H.; Hanlon, A.L.; Movsas, B.; Hanks, G.E.

    1996-01-01

    Purpose: We have recently shown that ICRU reporting point radiation doses above 71 Gy are not associated with improved bNED survival in prostate cancer patients with pretreatment PSA level 20 ng/ml we found a strong correlation between dose and nadir values < 1.0 ng/ml (p=.003) as well as for nadir's < 0.5 ng/ml (p=.04). This dose/nadir effect held at several dose levels, but 74 Gy for nadir values < 1.0 ng/ml and 72 Gy for nadir's < 0.5 ng/ml remained the most significant. 32% of these patients achieved a nadir < 1.0ng/ml and 15% < 0.5ng/ml. Conclusions: This analysis provides strong additional support that patients with pretreatment PSA values of < 10 ng/ml do not benefit from dose escalation beyond an ICRU reporting point dose of 71 Gy. For patients with pretreatment PSA's of 10-19.9 ng/ml there is no dose/nadir response evaluated at a nadir of 1.0 ng/ml; however, there is a borderline effect observed at a nadir of 0.5 ng/ml. Patients with pretreatment PSA's of 20 ng/ml or greater clearly benefit from higher doses as evaluated by PSA nadirs of 1.0 ng/ml, and 0.5 ng/ml. These studies support the continued investigation of dose escalation in treating patients with PSA levels over 10 ng/ml, they do not support continued investigation of dose escalation beyond 71 Gy in patients with pretreatment PSA levels < 10 ng/ml. The failure to demonstrate any dose response for the low PSA group and the finding of only a borderline effect for the intermediate PSA group may be influenced by the relatively small number of patients in our series treated to doses < 70 Gy and the fact that none of our patients were treated to doses below 65.98 Gy. The lower limit of acceptible dose has yet to be defined

  10. Verbal De-escalation of the Agitated Patient: Consensus Statement of the American Association for Emergency Psychiatry Project BETA De-escalation Workgroup.

    Science.gov (United States)

    Richmond, Janet S; Berlin, Jon S; Fishkind, Avrim B; Holloman, Garland H; Zeller, Scott L; Wilson, Michael P; Rifai, Muhamad Aly; Ng, Anthony T

    2012-02-01

    Agitation is an acute behavioral emergency requiring immediate intervention. Traditional methods of treating agitated patients, ie, routine restraints and involuntary medication, have been replaced with a much greater emphasis on a noncoercive approach. Experienced practitioners have found that if such interventions are undertaken with genuine commitment, successful outcomes can occur far more often than previously thought possible. In the new paradigm, a 3-step approach is used. First, the patient is verbally engaged; then a collaborative relationship is established; and, finally, the patient is verbally de-escalated out of the agitated state. Verbal de-escalation is usually the key to engaging the patient and helping him become an active partner in his evaluation and treatment; although, we also recognize that in some cases nonverbal approaches, such as voluntary medication and environment planning, are also important. When working with an agitated patient, there are 4 main objectives: (1) ensure the safety of the patient, staff, and others in the area; (2) help the patient manage his emotions and distress and maintain or regain control of his behavior; (3) avoid the use of restraint when at all possible; and (4) avoid coercive interventions that escalate agitation. The authors detail the proper foundations for appropriate training for de-escalation and provide intervention guidelines, using the "10 domains of de-escalation."

  11. Ewing sarcoma localized on spine: a dose escalation study in child; Sarcome d'Ewing localise au rachis: une etude d'escalade de dose chez l'enfant

    Energy Technology Data Exchange (ETDEWEB)

    Vogin, G.; Marchesi, V. [Centre Alexis-Vautrin, Nancy (France); Biston, M.C.; Gassa, F. [Centre Leon-Berard, Lyon (France); Amessis, M.; Zefkili, S.; Helfre, S. [Institut Curie, Paris (France); De Marzi, L.; Lacroix, F.; Leroy, A. [Institut Curie, Orsay (France)

    2011-10-15

    The authors report the study of dose escalation for the treatment of spinal in two types of Ewing tumours. They used 5 dose levels at the rate of five 1,6 Gy per week. They compare different radiotherapy techniques: three-dimensional conformation radiotherapy, static intensity-modulated conformational radiotherapy, helical tomo-therapy, volume-modulated arc-therapy (VMAT), stereotactic radiotherapy, and proton-therapy (in passive diffusion). It appears that it is possible to safely and efficiently deliver until 70,4 Gy in some Ewing tumours. In child, exclusive radiotherapy might become a local treatment option and would require a clinic trial and comparison with exclusive surgery or post-operative radiotherapy. Short communication

  12. The German reactor safety study

    International Nuclear Information System (INIS)

    Birkhofer, A.

    1980-01-01

    The most important results of the German risk study of a nuclear power plant equipped with a pressurized water reactor were published in August 1979. The main volume of the study with the approach used and the results elaborated has been available for reference since late 1979. Eight technical volumes contain detailed descriptions and documentations of the investigations carried out. The reference facility used as a basis for the technical plant studies was unit B of the Biblis Nuclear Power Station, a KWU PWR of 3750 MW thermal power. This contribution provides more detailed explanations of the methods and the results of the risk study illustrated by examples. The description refers to accident categories and categories of radioactivity releases, probabilities of specific sequences of accident events, and the damage associated with core meltdown accidents as a function of various types of failure. For purposes of evaluation and application of the results the limits in the basic assumptions of the study are referred to. (orig./HP) [de

  13. Study on Fusion Safety Infrastructure using ISAM

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  14. Reply to: Mounting evidence indicates that escalating doses of allopurinol are unnecessary for cardiovascular protection.

    Science.gov (United States)

    Coburn, Brian W; Michaud, Kaleb; Bergman, Debra A; Mikuls, Ted R

    2018-05-08

    We thank Dr. Bredemeier for his comments regarding our manuscript on allopurinol dose escalation and mortality. He raises important evidence to consider in support of an interesting hypothesis that dose escalation may be unnecessary for allopurinol's cardiovascular (CV) protection and may actually be related to adverse CV outcomes. While we agree that evidence exists suggesting that low doses of allopurinol may be sufficient for CV protection, we believe that the studies cited highlight a number of areas where knowledge gaps remain which preclude any definitive conclusions about the effect of dose escalation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. Escalation scenarios initiated by gas explosions on offshore installations. Probabilistic cause and consequence modelling

    Energy Technology Data Exchange (ETDEWEB)

    Eknes, Monika Loeland

    1996-12-31

    This Dr. ing. thesis deals with escalation scenarios initiated by gas explosions on offshore installations. Gas explosions is one of the major hazards to such installations. The objectives were to estimate the probability of ignition and frequency of gas explosions for gas leaks on top sides of offshore installations, and to estimate the response and resistance of components that could result in escalation if they failed. Main fields considered cover risk analysis methodology, gas explosions, simplified escalation models, evaluation of structural consequences, case studies, and guidelines. 107 refs., 33 figs., 33 tabs.

  16. E4 - Energy efficient elevators and escalators. Elevators and escalators in Germany from an energy perspective

    Energy Technology Data Exchange (ETDEWEB)

    Hirzel, Simon; Fleiter, Tobias; Rosende, Daniel

    2010-01-31

    This report aims to provide a brief introduction to the German elevator and escalator market, and gives an aggregated view of current and future developments focusing on energy consumption and energy-related emissions. This update report of January 2010 is an extended version of a report published in April 2009 before the final results from a monitoring campaign carried out within the project were available. During this campaign, 81 installations (74 elevators and 7 escalators) were monitored in terms of energy consumption. In the first section, the structure of the installed German elevator and escalator capacity is presented. The estimates1 were provided courtesy of the two main associations representing elevators and escalators in Germany: the VDMA (Verband Deutscher Maschinen- und Anlagenbau - German Engineering Federation) and the VFA-Interlift e.V. -Verband fuer Aufzugstechnik (Association for Lift Technology). This section is followed by a short description of the German construction sector and its implications for elevators and escalators. The third section describes German electricity production in terms of its environmental impact with the main focus on the carbon dioxide emissions of the national power plants. Then the energy consumption of elevators and escalators in Germany is analyzed, comparing the results to total energy production in Germany.2 The final section summarizes the different aspects and derives indications about the future development of the total energy consumption of elevators and escalators in Germany. (orig.)

  17. The German nuclear power plant safety study

    International Nuclear Information System (INIS)

    1979-01-01

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

  18. Project safety studies - nuclear waste management (PSE)

    International Nuclear Information System (INIS)

    1981-10-01

    The project 'Safety Studies-Nuclear Waste Management' (PSE) is a research project performed by order of the Federal Minister for Research and Technology, the general purpose of which is to deepen and ensure the understanding of the safety aspects of the nuclear waste management and to prepare a risk analysis which will have to be established in the future. Owing to this the project is part of a series of projects which serve the further development of the concept of nuclear waste management and its safety, and which are set up in such a way as to accompany the realization of that concept. This report contains the results of the first stage of the project from 1978 to mid-1981. (orig./RW) [de

  19. Railway safety climate: a study on organizational development.

    Science.gov (United States)

    Cheng, Yung-Hsiang

    2017-09-07

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

  20. Bus safety study : a report to Congress.

    Science.gov (United States)

    2013-11-01

    Section 20021(b) of the Moving Ahead for Progress for the 21st Century (MAP-21) legislation requires the Secretary of Transportation : to submit a report of the results of a Bus Safety Study to the Committee on Banking, Housing, and Urban Affai...

  1. Elephant invasion and escalated depletion of environmental ...

    African Journals Online (AJOL)

    For decades, elephants' invasion is known to be associated with severe environmental consequences leading to escalated depletion o environmental resources (plants, water, wildlife and soil). This paper examined the effects of elephants' activity on the environmental resources inHong and Gombi Local Government areas ...

  2. Pengaruh Framing Effect Sebagai Determinan Escalation of Commitment Dalam Keputusan Investasi: Dampak Dari Working Experiences

    OpenAIRE

    Yahya, Muhammad Nur; Surya, Jen

    2012-01-01

    The prior of research have shown that the framing effect is one of determinant in explaining decisions to escalate commitment to failing projects. However , have not considered whether experience moderates the framing effect on escalation of commitment. This study reports the results of an experiment in which the effect of decision frame of investment performance with negative feedback informatian on judgment to continue project of experienced subjects is compared to inexperienced subjects. F...

  3. Is attention deficit/hyperactivity disorder among men associated with initiation or escalation of substance use at 15‐month follow‐up? A longitudinal study involving young Swiss men

    Science.gov (United States)

    Vogel, Tanja; Dom, Geert; van de Glind, Geurt; Studer, Joseph; Gmel, Gerhard; Strik, Werner

    2016-01-01

    Abstract Background and Aims Young adults with attention deficit/hyperactivity disorder (ADHD) show higher substance use disorder (SUD) prevalence relative to non‐ADHD controls; few longitudinal studies have examined the course of substance use with reference to conduct disorder (CD). We compared initiation and escalation of substance use at 15‐month follow‐up in men screened positive or negative for ADHD (ADHD+ versus ADHD–), controlling for CD presence in early adolescence. Design Participants were recruited during August 2010 and November 2011 from the census of all young men who have to pass mandatory army conscription from three of six Swiss Army recruitment centres. A two‐wave data collection was performed via questionnaires at baseline and 15‐month follow‐up as a part of the longitudinal Cohort Study on Substance Use Risk Factors. Setting Recruitment centres in Lausanne, Windisch and Mels, responsible for 21 cantons in German‐ and French‐speaking areas of Switzerland. Participants Consecutive sample of 5103 male Swiss Army conscripts who provided informed consent and responded to questionnaires at baseline and 15‐month follow‐up. Their mean age was 20.0 (standard deviation = 1.21) years at baseline. Measurements ADHD and CD were assessed using the adult ADHD Self‐Report Scale and the MINI International Neuropsychiatric Interview Plus, respectively, at baseline, and substance use was measured via self‐administered substance use questionnaires at baseline and follow‐up. Findings Compared with the ADHD– group, the ADHD+ group (n = 215, 4.2%) showed heavier baseline substance use and increased likelihood of alcohol (χ2 = 53.96; P cannabis use disorders (χ2 = 48.43; P cannabis use in the two groups remained stable from baseline to follow‐up (no escalation). The ADHD+ group was more likely to initiate substance use compared with the ADHD– group (higher initiation rates), particularly with amphetamines [odds

  4. Studies on Labour Safety in Construction Sites

    Directory of Open Access Journals (Sweden)

    S. Kanchana

    2015-01-01

    Full Text Available Construction industry has accomplished extensive growth worldwide particularly in past few decades. For a construction project to be successful, safety of the structures as well as that of the personnel is of utmost importance. The safety issues are to be considered right from the design stage till the completion and handing over of the structure. Construction industry employs skilled and unskilled labourers subject to construction site accidents and health risks. A proper coordination between contractors, clients, and workforce is needed for safe work conditions which are very much lacking in Indian construction companies. Though labour safety laws are available, the numerous accidents taking place at construction sites are continuing. Management commitment towards health and safety of the workers is also lagging. A detailed literature study was carried out to understand the causes of accidents, preventive measures, and development of safe work environment. This paper presents the results of a questionnaire survey, which was distributed among various categories of construction workers in Kerala region. The paper examines and discusses in detail the total working hours, work shifts, nativity of the workers, number of accidents, and type of injuries taking place in small and large construction sites.

  5. Studies on Labour Safety in Construction Sites

    Science.gov (United States)

    Kanchana, S.; Sivaprakash, P.; Joseph, Sebastian

    2015-01-01

    Construction industry has accomplished extensive growth worldwide particularly in past few decades. For a construction project to be successful, safety of the structures as well as that of the personnel is of utmost importance. The safety issues are to be considered right from the design stage till the completion and handing over of the structure. Construction industry employs skilled and unskilled labourers subject to construction site accidents and health risks. A proper coordination between contractors, clients, and workforce is needed for safe work conditions which are very much lacking in Indian construction companies. Though labour safety laws are available, the numerous accidents taking place at construction sites are continuing. Management commitment towards health and safety of the workers is also lagging. A detailed literature study was carried out to understand the causes of accidents, preventive measures, and development of safe work environment. This paper presents the results of a questionnaire survey, which was distributed among various categories of construction workers in Kerala region. The paper examines and discusses in detail the total working hours, work shifts, nativity of the workers, number of accidents, and type of injuries taking place in small and large construction sites. PMID:26839916

  6. In-depth investigation of escalator riding accidents in heavy capacity MRT stations.

    Science.gov (United States)

    Chi, Chia-Fen; Chang, Tin-Chang; Tsou, Chi-Lin

    2006-07-01

    In 2000, the accident rate for escalator riding was about 0.815 accidents per million passenger trips through Taipei Metro Rapid Transit (MRT) heavy capacity stations. In order to reduce the probability and severity of escalator riding accidents and enhance the safety of passengers, the Drury and Brill model [Drury, C.G., Brill, M., 1983. Human factors in consumer product accident investigation. Hum. Factors 25 (3), 329-342] for in-depth investigation was adopted to analyze the 194 escalator riding accidents in terms of victim, task, product and environment. Prevention measures have been developed based on the major causes of accidents and other related contributing factors. The results from the analysis indicated that the majority of the escalator riding accidents was caused by passengers' carrying out other tasks (38 cases, including carrying luggage 24 cases, looking after accompany persons 9 cases, and 5 others), loss of balance (26 cases, 13.4%), not holding the handrail (20 cases, 10.3%), unhealthy passengers (18 cases, 9.3%), followed by people struck by other passenger (16 cases, 8.2%). For female passengers aged 15-64 years, their rushing for trains accidents could have been prevented by wearing safer footwear or by appropriate signing being provided indicating the location and traveling direction of escalators. Female passengers aged 65 years and above whose accidents were caused by loss of balance, should be encouraged to take the elevator instead. To prevent entrapment injuries, following a stricter design code can be most effective. Further in-depth accident investigation is suggested to cover the activity of the victim prior to the accident, any involved product, the location of the accident on the escalator, any medical treatment, what went wrong, opinion of the respondent on the causes of the accident, and personal characteristics of the passengers. Also, management must trade off productivity and safety appropriately to prevent "Organizational

  7. Safety in the ARIES Tokamak Design Study

    International Nuclear Information System (INIS)

    Herring, J.S.; Wong, C.P.-C.; Cheng, E.T.; Grotz, S.

    1989-01-01

    Safety is one of the primary goals of the ARIES Tokamak Design Study. Public safety goals are the achievement passive safety which is demonstrable in tests that could precede operation and the assurance that releases from accidents be passively limited such that no evacuation plan in necessary. Strategies for safety of the plant investment are factory fabrication, short construction times and a design such that no off-normal operational transient results in damage which could not be repaired in routine maintenance. ARIES-I, the first of three 'visions' of potential tokamak reactors, will use He at 5 MPa as a blanket coolant and SiC/composite ceramic for the first wall and blanket materials. Both the coolant and the structural material were chosen for their low activation, both in the short term after accidents and for long term waste management. The breeder, Li 4 SiO 4 , was also chosen for low activation. Contemporary plasma physics and aggressive technology are used in ARIES-I, which results in very high toroidal fields (24 T maximum at the coil). The stored TF energy will be about 130 GJ. A central concern is the safe discharge of this stored energy under electrical fault conditions and prevention of a failure in the magnet set from propagating into systems containing radioactive inventories. The TF coil system consists of 16 coils, each containing two separate windings powered by two independent power supplies. Arcs and shorts between the two power supply systems and across individual windings have been modeled. In addition, delay or failure in circuit breaker opening has been modeled. The safety impacts of LOCA, LOFA and disruptive events have also been evaluated. 8 refs., 4 figs., 7 tabs

  8. Pressure Safety: Advanced Self-Study 30120

    Energy Technology Data Exchange (ETDEWEB)

    Glass, George [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-02-29

    Pressure Safety Advance Self-Study (Course 30120) consists of an introduction, five modules, and a quiz. To receive credit in UTrain for completing this course, you must score 80% or better on the 15-question quiz (check UTrain). Directions for initiating the quiz are appended to the end of this training manual. This course contains several links to LANL websites. UTrain might not support active links, so please copy links into the address line in your browser.

  9. COLD-SAT feasibility study safety analysis

    Science.gov (United States)

    Mchenry, Steven T.; Yost, James M.

    1991-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yogendra Bhattacharya

    2015-12-01

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

  11. 77 FR 27776 - Safety and Occupational Health Study Section (SOHSS), National Institute for Occupational Safety...

    Science.gov (United States)

    2012-05-11

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

  12. 76 FR 18220 - Safety and Occupational Health Study Section (SOHSS), National Institute for Occupational Safety...

    Science.gov (United States)

    2011-04-01

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

  13. 75 FR 26266 - Safety and Occupational Health Study Section (SOHSS), National Institute for Occupational Safety...

    Science.gov (United States)

    2010-05-11

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

  14. Penile bulb dose and impotence after three-dimensional conformal radiotherapy for prostate cancer on RTOG 9406: Findings from a prospective, multi-institutional, phase I/II dose-escalation study

    International Nuclear Information System (INIS)

    Roach, Mack; Winter, Kathryn; Michalski, Jeffrey M.; Cox, James D.; Purdy, James A.; Bosch, Walter; Lin Xiao; Shipley, William S.

    2004-01-01

    Purpose: To assess the relationship between the dose to the bulb of the penis and the risk of impotence in men treated on Radiation Therapy Oncology Group (RTOG) 9406. Methods and materials: Men enrolled on a Phase I/II dose-escalation study, RTOG 9406, who were reported to be potent at entry and evaluable (n = 158) were selected for inclusion. Follow-up evaluations were scheduled every 3, 4, and 6 months for the first, second, and the third through fifth years, then annually. At each follow-up visit an assessment of potency status was made. Penile structures were defined by a single observer blinded to the potency status, using Web-based, on-line software. The dosimetry for penile structures was calculated at the Quality Assurance Center at Washington University and provided to RTOG Statistical Headquarters to determine whether there was a relationship between dose and impotence. Results: Patients whose median penile dose was ≥52.5 Gy had a greater risk of impotence compared with those receiving <52.5 Gy (p = 0.039). In a multivariate analysis neither age, the dose to the prostate, nor the use of hormonal therapy correlated with the risk of impotence. Conclusions: Dose to the bulb of the penis seems to be associated with the risk of radiation-induced impotence

  15. Preliminary study on improving safety culture in Malaysian nuclear industries

    International Nuclear Information System (INIS)

    Ibrahim, Sabariah Kader; Lee, Y. E.

    2012-01-01

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

  16. Preliminary study on improving safety culture in Malaysian nuclear industries

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-10-15

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

  17. Safety studies concerning nuclear power reactors

    International Nuclear Information System (INIS)

    Bailly, Jean; Pelce, Jacques

    1980-01-01

    The safety of nuclear installations poses different technical problems, whether concerning pressurized water reactors or fast reactors. But investigating methods are closely related and concern, on the one hand, the behavior of shields placed between fuel and outside and, on the other, analysis of accidents. The article is therefore in two parts based on the same plan. Concerning light water reactors, the programme of studies undertaken in France accounts for the research carried out in countries where collaboration agreements exist. Concerning fast reactors, France has the initiative of their studies owing to her technical advance, which explains the great importance of the programmes under way [fr

  18. Pharmacological cardioversion of atrial fibrillation--a double-blind, randomized, placebo-controlled, multicentre, dose-escalation study of AZD1305 given intravenously

    DEFF Research Database (Denmark)

    Rónaszéki, Aladár; Alings, Marco; Egstrup, Kenneth

    2011-01-01

    AZD1305 is a combined ion channel blocker developed for the treatment of atrial fibrillation (AF). The aim of this study was to determine whether AZD1305 was effective in converting AF to sinus rhythm (SR)....

  19. Preliminary Study on the Revision of Nuclear Safety Policy Statement

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  20. Nonresponders to Daily Paroxetine and Another SSRI in Men With Lifelong Premature Ejaculation : A Pharmacokinetic Dose-Escalation Study for a Rare Phenomenon

    NARCIS (Netherlands)

    Janssen, Paddy Kc; Touw, Daan; Schweitzer, Dave H; Waldinger, Marcel D

    PURPOSE: Nonresponse to any selective serotonin reuptake inhibitor (SSRI) treatment is rare. In this study, we aimed to investigate ejaculation delay nonresponse to paroxetine treatment in men with lifelong premature ejaculation (PE) who were also known to be nonresponders to other SSRIs. MATERIALS

  1. Phase I dose escalation, pharmacokinetic and pharmacodynamic study of naptumomab estafenatox alone in patients with advanced cancer and with docetaxel in patients with advanced non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Borghaei, Hossein; Alpaugh, Katherine; Hedlund, Gunnar

    2009-01-01

    recognizing the tumor-associated antigen 5T4. PATIENTS AND METHODS: Patients with non-small-cell lung cancer (NSCLC), pancreatic cancer (PC), and renal cell cancer (RCC) received 5 daily boluses of ABR-217620 (3-month cycles) in escalating doses to determine the maximum-tolerated dose (MTD; ABR-217620 dose...

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

    Science.gov (United States)

    Nielsen, Kent J

    2014-02-01

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

  3. Escalating Health Care Expenditures in Cancer Decedents' Last Year of Life: A Decade of Evidence from a Retrospective Population‐Based Cohort Study in Taiwan

    Science.gov (United States)

    Hung, Yen‐Ni; Liu, Tsang‐Wu; Wen, Fur‐Hsing; Chou, Wen‐Chi

    2017-01-01

    Abstract Background. No population‐based longitudinal studies on end‐of‐life (EOL) expenditures were found for cancer decedents. Methods. This population‐based, retrospective cohort study examined health care expenditures from 2001 to 2010 among 339,546 Taiwanese cancer decedents' last year of life. Individual patient‐level data were linked from administrative datasets. Health care expenditures were converted from Taiwan dollars to U.S. dollars by health‐specific purchasing power parity conversions to account for different health‐purchasing powers. Associations of patient, physician, hospital, and regional factors with EOL care expenditures were evaluated by multilevel linear regression model by generalized estimating equation method. Results. Mean annual EOL care expenditures for Taiwanese cancer decedents increased from 2000 to 2010 from U.S. $49,591 to U.S. $68,773, respectively, with one third of spending occurring in the patients' last month. Increased EOL care expenditures were associated with male gender, younger age, being married, diagnosed with hematological malignancies and cancers other than lung, gastric, and hepatic‐pancreatic cancers, and dying within 7–24 months of diagnosis. Patients spent less at EOL when they had higher comorbidities and metastatic disease, died within 6 months of diagnosis, were under care of oncologists, gastroenterologists, and intensivists, and received care at a teaching hospital with more terminally ill cancer patients. Higher EOL care expenditures were associated with greater EOL care intensity at the primary hospital and regional levels. Conclusion. Taiwanese cancer decedents consumed considerable National Health Insurance disbursements at EOL, totaling more than was consumed in six developed non‐U.S. countries surveyed in 2010. To slow increasing cost and improve EOL cancer care quality, interventions to ensure appropriate EOL care provision should target hospitals and clinicians less experienced in

  4. Dose Escalation and Healthcare Resource Use among Ulcerative Colitis Patients Treated with Adalimumab in English Hospitals: An Analysis of Real-World Data.

    Directory of Open Access Journals (Sweden)

    Christopher M Black

    Full Text Available To describe the real-world use of adalimumab for maintenance treatment of ulcerative colitis (UC and associated healthcare costs in English hospitals.Retrospective cohort study.Analysis of NHS Hospital Episode Statistics linked with pharmacy dispensing data in English hospitals.Adult UC patients receiving ≥240mg during adalimumab treatment induction, subsequently maintained on adalimumab.Frequency and pattern of adalimumab use and dose escalation during maintenance treatment and associated healthcare costs (prescriptions and hospital visits.191 UC patients completed adalimumab treatment induction. 83 (43.46% dose escalated during maintenance treatment by ≥100% (equivalent to weekly dosing (median time to dose escalation: 139 days. 56 patients (67.47% subsequently de-escalated by ≥50% (median time to dose de-escalation: 21 days. Mean all-cause healthcare costs for all patients ≤12 months of index were £13,892. Dose escalators incurred greater mean healthcare costs than non-escalators ≤12 months of index (£14,596 vs. £13,351. Prescriptions accounted for 96.49% of UC-related healthcare costs (£11,090 of £11,494 in all patients.Within the cohort, 43.46% of UC patients escalated their adalimumab dose by ≥100% and incurred greater costs than non-escalators. The apparent underestimation of adalimumab dose escalation in previous studies may have resulted in underestimated costs in healthcare systems.

  5. Risk of neuroblastoma, birth-related characteristics, congenital malformations and perinatal exposures: A pooled analysis of the ESCALE and ESTELLE French studies (SFCE).

    Science.gov (United States)

    Rios, Paula; Bailey, Helen D; Orsi, Laurent; Lacour, Brigitte; Valteau-Couanet, Dominique; Levy, Dominique; Corradini, Nadège; Leverger, Guy; Defachelles, Anne-Sophie; Gambart, Marion; Sirvent, Nicolas; Thebaud, Estelle; Ducassou, Stéphane; Clavel, Jacqueline

    2016-11-01

    Neuroblastoma (NB), an embryonic tumour arising from neural crest cells, is the most common malignancy among infants. The aetiology of NB is largely unknown. We conducted a pooled analysis to explore whether there is an association between NB and preconception and perinatal factors using data from two French national population-based case-control studies. The mothers of 357 NB cases and 1783 controls younger than 6 years, frequency-matched by age and gender, responded to a telephone interview that focused on demographic, socioeconomic and perinatal characteristics, childhood environment, life-style and maternal reproductive history. Unconditional logistic regression was used to estimate pooled odds ratios and 95% confidence intervals. After controlling for matching variables, study of origin and potential confounders, being born either small (OR 1.4 95% CI 1.0-2.0) or large (OR 1.5 95% CI 1.1-2.2) for gestational age and, among children younger than 18 months, having congenital malformations (OR 3.6 95% CI 1.3-8.9), were significantly associated with NB. Inverse associations were observed with breastfeeding (OR 0.7 95% CI 0.5-1.0) and maternal use of any supplements containing folic acid, vitamins or minerals (OR 0.5 95% CI 0.3-0.9) during the preconception period. Our findings reinforce the hypothesis that fetal growth anomalies and congenital malformations may be associated with an increased risk of NB. Further investigations are needed in order to clarify the role of folic acid supplementation and breastfeeding, given their potential importance in NB prevention. © 2016 UICC.

  6. Escalating Health Care Expenditures in Cancer Decedents' Last Year of Life: A Decade of Evidence from a Retrospective Population-Based Cohort Study in Taiwan.

    Science.gov (United States)

    Hung, Yen-Ni; Liu, Tsang-Wu; Wen, Fur-Hsing; Chou, Wen-Chi; Tang, Siew Tzuh

    2017-04-01

    No population-based longitudinal studies on end-of-life (EOL) expenditures were found for cancer decedents. This population-based, retrospective cohort study examined health care expenditures from 2001 to 2010 among 339,546 Taiwanese cancer decedents' last year of life. Individual patient-level data were linked from administrative datasets. Health care expenditures were converted from Taiwan dollars to U.S. dollars by health-specific purchasing power parity conversions to account for different health-purchasing powers. Associations of patient, physician, hospital, and regional factors with EOL care expenditures were evaluated by multilevel linear regression model by generalized estimating equation method. Mean annual EOL care expenditures for Taiwanese cancer decedents increased from 2000 to 2010 from U.S. $49,591 to U.S. $68,773, respectively, with one third of spending occurring in the patients' last month. Increased EOL care expenditures were associated with male gender, younger age, being married, diagnosed with hematological malignancies and cancers other than lung, gastric, and hepatic-pancreatic cancers, and dying within 7-24 months of diagnosis. Patients spent less at EOL when they had higher comorbidities and metastatic disease, died within 6 months of diagnosis, were under care of oncologists, gastroenterologists, and intensivists, and received care at a teaching hospital with more terminally ill cancer patients. Higher EOL care expenditures were associated with greater EOL care intensity at the primary hospital and regional levels. Taiwanese cancer decedents consumed considerable National Health Insurance disbursements at EOL, totaling more than was consumed in six developed non-U.S. countries surveyed in 2010. To slow increasing cost and improve EOL cancer care quality, interventions to ensure appropriate EOL care provision should target hospitals and clinicians less experienced in providing EOL care and those who tend to provide aggressive EOL care to

  7. Phase I dose-escalation study of vinflunine hard capsules administered twice a day for 2 consecutive days every week in patients with advanced/metastatic solid tumors.

    Science.gov (United States)

    Calvo, E; Vermorken, J B; Hiret, S; Rodon, J; Cortes, J; Senellart, H; Van den Brande, J; Dyck, J; Pétain, A; Ferre, P; Bennouna, J

    2012-06-01

    Vinflunine is a new microtubule inhibitor of the vinca-alkaloid family. It is marketed in transitional cell carcinoma of urothelial tract as a 20 min infusion given every 3 weeks in Europe. In this phase I study, vinflunine was administered to patients with advanced malignancies as hard capsules given twice a day on days 1-2 every week, with 3 weeks cycles. Serial blood samples were collected during the first cycle for pharmacokinetic investigations. Thirty-six patients (pts) were treated at 6 dose levels 150 (3 pts), 190 (3 pts), 230 (8 pts), 300 mg/day (6 pts) and then 250 (3 pts) and 270 mg/day (13 pts). The Maximal Tolerated Dose (MTD) was reached at 300 mg/day where 2 patients out of 6 experienced a dose limiting toxicity (febrile neutropenia with diarrhea). The lower dose level of 270 mg/day was the recommended dose (RD), the toxicity profile being mainly anaemia, neutropenia, fatigue and constipation. The pharmacokinetic analysis demonstrated the adequacy of the flat-fixed dosing regimen, as no correlation between clearance of vinflunine and body surface area was evidenced. Blood concentrations and exposure increased with dose, and a pharmacokinetic accumulation was observed, which is consistent with the terminal half-life of the compounds. The inter-individual exposure variability at the RD was 35%. Repeated weekly administration of oral vinflunine is feasible and exhibits a moderate inter-individual PK variability. The MTD was achieved at 300 mg/day given for 2 consecutive days. According to the protocol rules, the RD was established at 270 mg/day.

  8. Criticality safety (prospect of study in NUCEF)

    International Nuclear Information System (INIS)

    Itagaki, Masafumi

    1996-01-01

    Experimental studies of criticality safety are under way using STACY and TRACY in NUCEF. Collection of fundamental data on criticality in a solution system is undergoing with STACY to confirm that the likelihood of criticality safety in the system constructed on the assumption of apparatuses in a reprocessing plant is enough large. Whereas some experiments simulating criticality accidents in a reprocessing plant using TRACY were designed to investigate the behaviors of fuel solution and radioactive matters in order to clarify whether it is possible to safely shut them in the facility even if a critical accident occurs. Both STACY and TRACY reached the criticality in 1995. Up to now a series of criticality experiments have been done using STACY with a core tank φ60 cm and the first periodical examination is now under way. On the other hand, we have a plan using TRACY to investigate the behaviors of nuclear heat solution at a criticality accident, and the releasing, transfer and deposition of radioactive materials. After reaching the criticality for the first, the performance verification test has been conducted. The full-scale study using TRACY is planned to begin in the second half of 1996. (M.N.)

  9. Safety Study of Doxicycline in Broiler Chickens

    Directory of Open Access Journals (Sweden)

    Romeo Teodor Cristina

    2010-05-01

    Full Text Available Doxicycline is a structural isomer who meets the European reference standard (Ph.Eur. III 1997:0272 and respect EU Regulations for M.R.L. The good solubility permits high tissular absorption and distribution after administration in drinking water. The aim was to ascertain the clinical effects and tolerance consecutive to risen doses administration, as a part of safety study for this antibiotic in poultry in the respect of current drug testing methodology. The safety study revealed: good local and general tolerance to therapeutic doses (10 mg x kgb.w.-1 and to x2 dose, diarrhoea in lots which received x3 and x5 the therapeutic dose. Comparatively with the Control lot, haemoleucogram doesn’t suffer evident changes the registered values being between the references limits (exception of leucocitary formula. Also it was found an increased creatinin concentration consecutively to x3 and x5 greater doses administration and marked increasing of ASAT level and limited for ALAT’s, comparatively to control lot in the case of E4 lot, but light to reference values. Macro and microscopy revealed for the liver samples: hepatomegaly, diffuse hepatic degenerescence, nuclear heterochromatinization, vacuolar degenerescence; renal changes in nefrons and renal corpuscles, light splenomegaly, caecal sacs distension and brown-yellowish gaseous content to lots E3 and E4.

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  11. De-Escalating the IT-Projects

    Directory of Open Access Journals (Sweden)

    Ghulam Muhammad Kundi

    2007-12-01

    Full Text Available Escalation stickins with an ailing project beyond rational justifications. This happens because in the face of negative feedback, decision makers are strangled between whether to stick with or quit the dying project. Environmental uncertainty has been identified as the root cause of the escalatory behavior. This uncertainty emanates from several sources relating to individual, group, organization and broader environmental factors. This paper argues the premise that effective communication can help create an environment whereby workforce can develop an organized action thereby distributing the responsibility across the whole workforce and not the individuals – leading to the possible reduction of escalatory behavior in IT projects.

  12. The de-escalation of nuclear crises

    International Nuclear Information System (INIS)

    Nation, J.E.

    1992-01-01

    Whether and by what means nations can successfully de-escalate nuclear crises - and avoid the disastrous effects of nuclear war - will remain two of the most critical challenges facing humankind. Whatever the future of superpower relations, the United States, the Soviet Union, and other nations will undoubtedly continue to possess and to threaten the use of nuclear weapons. Moreover, the number of nations with nuclear weapons seems likely to increase. This examines how nations in crises might successfully move back from the brink of nuclear war - and how confidence-building measures might help and hinder the de-escalatory process

  13. A systematic methodology review of phase I radiation dose escalation trials

    International Nuclear Information System (INIS)

    Pijls-Johannesma, Madelon; Mastrigt, Ghislaine van; Hahn, Steve M.; De Ruysscher, Dirk; Baumert, Brigitta G.; Lammering, Guido; Buijsen, Jeroen; Bentzen, Soren M.; Lievens, Yolande; Kramar, Andrew; Lambin, Philippe

    2010-01-01

    Background and purpose: The purpose of this review is to evaluate the methodology used in published phase I radiotherapy (RT) dose escalation trials. A specific emphasis was placed on the frequency of reporting late complications as endpoint. Materials and methods: We performed a systematic literature review using a predefined search strategy to identify all phase I trials reporting on external radiotherapy dose escalation in cancer patients. Results: Fifty-three trials (phase I: n = 36, phase I-II: n = 17) fulfilled the inclusion criteria. Of these, 20 used a modified Fibonacci design for the RT dose escalation, but 32 did not specify a design. Late toxicity was variously defined as >3 months (n = 43) or > 6 months (n = 3) after RT, or not defined (n = 7). In only nine studies the maximum tolerated dose (MTD) was related to late toxicity, while only half the studies reported the minimum follow-up period for dose escalation (n = 26). Conclusion: In phase I RT trials, late complications are often not taken into account and there is currently no consensus on the methodology used for radiation dose escalation studies. We therefore propose a decision-tree algorithm which depends on the endpoint selected and whether a validated early surrogate endpoint is available, in order to choose the most appropriate study design.

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

    International Nuclear Information System (INIS)

    Hasegawa, Naoko; Takano, Kenichi; Hirose, Ayako

    2001-01-01

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

  15. De-escalating and escalating treatments for early-stage breast cancer

    DEFF Research Database (Denmark)

    Curigliano, G; Burstein, H J; P Winer, E

    2017-01-01

    The 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. Treatments were assessed in light of their intensity, duration and side-effects, seeking where appropriate to escal...

  16. Teaching microbiological food safety through case studies

    Directory of Open Access Journals (Sweden)

    Florence Dubois-Brissonnet

    2015-10-01

    Full Text Available Higher education students usually ask for more training based on case studies. This was addressed by designing a specific food safety module (24 hours in which students were shown how to predict microbiological risks in food products i.e. they were asked to determine product shelf-life according to product formulation, preservation methods and consumption habits using predictive microbiology tools. Working groups of four students first identified the main microbiological hazards associated with a specific product. To perform this task, they were given several documents including guides for good hygiene practices, reviews on microbiological hazards in the food sector, flow sheets, etc…  After three-hours of work, the working groups prepared and gave an oral presentation in front of their classmates and professors. This raised comments and discussion that allowed students to adjust their conclusions before beginning the next step of their work. This second step consisted in the evaluation of the safety risk associated with the two major microbiological hazards of the product studied, using predictive microbiology. Students then attended a general lecture on the different tools of predictive microbiology and tutorials (6 hours that made them familiar with the modelling of bacterial growth or inactivation. They applied these tools (9 hours to predict the shelf-life of the studied product according to various scenarios of preservation (refrigeration, water activity, concentration of salt or acid, modified atmosphere, etc… and/or consumption procedures (cooking. The module was concluded by oral presentations of each working group and included student evaluation (3 hours.

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

    International Nuclear Information System (INIS)

    Bertsche, K.; Hoermann, E.

    1991-01-01

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

  18. Qualitative analysis in reliability and safety studies

    International Nuclear Information System (INIS)

    Worrell, R.B.; Burdick, G.R.

    1976-01-01

    The qualitative evaluation of system logic models is described as it pertains to assessing the reliability and safety characteristics of nuclear systems. Qualitative analysis of system logic models, i.e., models couched in an event (Boolean) algebra, is defined, and the advantages inherent in qualitative analysis are explained. Certain qualitative procedures that were developed as a part of fault-tree analysis are presented for illustration. Five fault-tree analysis computer-programs that contain a qualitative procedure for determining minimal cut sets are surveyed. For each program the minimal cut-set algorithm and limitations on its use are described. The recently developed common-cause analysis for studying the effect of common-causes of failure on system behavior is explained. This qualitative procedure does not require altering the fault tree, but does use minimal cut sets from the fault tree as part of its input. The method is applied using two different computer programs. 25 refs

  19. Acceptable risk in reactor safety studies

    International Nuclear Information System (INIS)

    Benjamin, J.R.; Shinozuka, M.; Shah, H.C.

    1975-01-01

    Acceptable risk is defined in terms of its five basic parameters: the hazard or problem; the probability of occurrence; the consequence; the possible alternative actions; and the value system of the community or the society. The problem of consistency in design at a site and between differing sites is discussed and solutions are suggested. Techniques for consistent deterministic and probabilistic setting limits and design standards are illustrated using data from AEC Reactor Safety Study, WASH-1400. The influence of level of consequence is discussed and a general methodology for decision analysis in resource allocation problem is briefly introduced and illustrated. The concept of acceptable risk is put in a quantitative format that can be used by engineers and planners. Bayesian statistical methods are introduced to develop the methodologies

  20. A study on safety climate at nuclear power plants

    International Nuclear Information System (INIS)

    Fukui, Hirokazu; Yoshida, Michio; Yoshiyama, Naohiro

    2001-01-01

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

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

    Science.gov (United States)

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

    2010-10-01

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

  2. Avoiding escalation from play to aggression in adult male rats: The role of ultrasonic calls.

    Science.gov (United States)

    Burke, Candace J; Kisko, Theresa M; Pellis, Sergio M; Euston, David R

    2017-11-01

    Play fighting is most commonly associated with juvenile animals, but in some species, including rats, it can continue into adulthood. Post-pubertal engagement in play fighting is often rougher and has an increased chance of escalation to aggression, making the use of play signals to regulate the encounter more critical. During play, both juvenile and adult rats emit many 50-kHz calls and some of these may function as play facilitating signals. In the present study, unfamiliar adult male rats were introduced in a neutral enclosure and their social interactions were recorded. While all pairs escalated their playful encounters to become rougher, only the pairs in which one member was devocalized escalated to serious biting. A Monte Carlo shuffling technique was used for the analysis of the correlations between the overt playful and aggressive actions performed and the types and frequencies of various 50-kHz calls that were emitted. The analysis revealed that lower frequency (20-30kHz) calls with a flat component maybe particularly critical for de-escalating encounters and so allowing play to continue. Moreover, coordinating calls reciprocally, with either the same call mimicked in close, temporal association or with complementary calls emitted by participants as they engage in complementary actions (e.g., attacking the nape, being attacked on the nape), appeared to be ways with which calls could be potentially used to avoid escalation to aggression and so sustain playful interactions. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Safety

    International Nuclear Information System (INIS)

    1998-01-01

    A brief account of activities carried out by the Nuclear power plants Jaslovske Bohunice in 1997 is presented. These activities are reported under the headings: (1) Nuclear safety; (2) Industrial and health safety; (3) Radiation safety; and Fire protection

  4. Attachment and Jealousy: Understanding the Dynamic Experience of Jealousy Using the Response Escalation Paradigm.

    Science.gov (United States)

    Huelsnitz, Chloe O; Farrell, Allison K; Simpson, Jeffry A; Griskevicius, Vladas; Szepsenwol, Ohad

    2018-04-01

    Jealousy is a complex, dynamic experience that unfolds over time in relationship-threatening situations. Prior research has used retrospective reports that cannot disentangle initial levels and change in jealousy in response to escalating threat. In three studies, we examined responses to the Response Escalation Paradigm (REP)-a 5-stage hypothetical scenario in which individuals are exposed to increasing levels of relationship threat-as a function of attachment orientations. Highly anxious individuals exhibited hypervigilant, slow escalation response patterns, interfered earlier in the REP, felt more jealousy, sadness, and worry when they interfered, and wanted to engage in more vigilant, destructive, and passive behaviors aimed at their partner. Highly avoidant individuals felt more anger when they interfered in the REP and wanted to engage in more partner-focused, destructive behaviors. The REP offers a dynamic method for inducing and examining jealousy and introduces a novel approach to studying other emotional experiences.

  5. A feasibility study for Arizona's roadway safety management process using the Highway Safety Manual and SafetyAnalyst : final report.

    Science.gov (United States)

    2016-07-01

    To enable implementation of the American Association of State Highway Transportation (AASHTO) Highway Safety Manual using : SaftetyAnalyst (an AASHTOWare software product), the Arizona Department of Transportation (ADOT) studied the data assessment :...

  6. Fusion safety studies in Russia in 2003

    Energy Technology Data Exchange (ETDEWEB)

    Kolbasov, B.N. [Russian Research Center ' Kurchatov Institute' , Pl. Kurchatova 1, 123182 Moscow (Russian Federation)]. E-mail: kolbasov@nfi.kiae.ru; Guseva, M.I. [Russian Research Center ' Kurchatov Institute' , Pl. Kurchatova 1, 123182 Moscow (Russian Federation); Khripunov, B.I. [Russian Research Center ' Kurchatov Institute' , Pl. Kurchatova 1, 123182 Moscow (Russian Federation); Martynenko, Yu.V. [Russian Research Center ' Kurchatov Institute' , Pl. Kurchatova 1, 123182 Moscow (Russian Federation); Zimin, A.M. [N.E. Bauman Moscow State Technical University, 2nd Bauman ul. 5, 107005 Moscow (Russian Federation); Stankevich, V.G. [Russian Research Center ' Kurchatov Institute' , Pl. Kurchatova 1, 123182 Moscow (Russian Federation); Svechnikov, N.Yu. [Russian Research Center ' Kurchatov Institute' , Pl. Kurchatova 1, 123182 Moscow (Russian Federation); Bartenev, S.A. [V.G. Khlopin Radium Institute, 2nd Murinskij Prospect 28, 194021 St.-Petersburg (Russian Federation)

    2005-11-15

    The paper presents a review of the fusion safety studies performed in Russia in 2003. Among the findings is the effect of tungsten sputtering by subthreshold energy ions at high temperature, which tends to decrease with irradiation dose. The size distribution of W-erosion products (spherical droplets or flakes) depends on the positioning of the collector. Studies of Be + D(H) films revealed that D/Be ratio in co-deposited Be-D films decreases from 0.15 at 375 K to 0.05 at 575 K. Hydrogen concentration in Be + C films, exposed to acetylene ion flux at 670 K, decreased from 20-24 to 6 at.% with increase in irradiation dose from 10{sup 23} to 10{sup 24} m{sup -2}. The analysis of spectroscopic characteristics of C-D films deposited inside the T-10 tokamak vacuum chamber provides qualitative insight into the physical and chemical reasons behind the preferential retention of the heavier hydrogen isotope in the tokamak erosion films. An extraction scheme for radiochemical reprocessing of activated V-Cr-Ti alloy after a fusion reactor decommissioning was developed and checked experimentally. It takes 48 extraction steps to recover V, Cr and Ti down to an effective dose rate <12.5 {mu}Sv/h, permitting the refabrication of these metals without any biological shielding from ionizing radiation.

  7. Revisiting the cost escalation curse of nuclear power. New lessons from the French experience

    International Nuclear Information System (INIS)

    Escobar Rangel, Lina; Leveque, Francois

    2012-01-01

    Since the first wave of nuclear reactors in 1970 to the construction of Generation III+ reactors in Finland and France in 2005 and 2007 respectively, nuclear power seems to be doomed to a cost escalation curse. In this paper we reexamine this issue for the French nuclear power fleet. Using the construction costs from the Cour des Comptes report, that was publicly available in 2012, we found that previous studies overestimated the cost escalation. Although, it is undeniable that the scale-up ended up in more costly reactors, we found evidence of a learning curve within the same size and type of reactors. This result confirms that standardization is a good direction to look, in order to overcome the cost escalation curse. (authors)

  8. Research on the waiting time of passengers and escalator energy consumption at the railway station

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Wei-wu; Liu, Xiao-yan; Li, Liqing; Shi, Xiangnan; Zhou, Chenn Q. [School of Energy Science and Engineering, Central South University, Changsha 410083 (China)

    2009-12-15

    Based on the Little Formula and the classical queuing model of multi-channel M vertical stroke D vertical stroke n, the relation of the average queue length, the maximum waiting time and the escalator service intensity were identified and the waiting time simulation model was established. With the passenger delivery data at A railway station in China and the probability distribution model of waiting time, a detailed analysis was made on the escalator allocation, power and energy consumption on holidays, ordinary working days and the largest-passengers-volume days; meanwhile, the fixed and variable energy consumption were compared and studied when the waiting time are 5, 10 and 30 s. The result shows that the waiting time settings affect the allocation and the energy consumption of the escalators and the fixed energy consumption takes 70%. (author)

  9. The Citizenship Safety Project: a pilot study.

    Science.gov (United States)

    Frederick, K; Barlow, J

    2006-02-01

    The Government White Paper Saving Lives: Our Healthier Nation (1999) provides a clear indication that accidents are a serious public health problem and have been targeted by the Department of Health as a key area for prevention over the next 10 years. School-based injury prevention programmes have been identified as one of the key settings for the implementation of the White Paper's heath promotion strategies. The Citizen Safety Project (CSP) is a peer-delivered injury prevention programme for Year 10 students (14-15 years) and Year 2 pupils (6-7 years). This paper summarizes the findings of a pilot study that assessed the feasibility of implementing the CSP in schools and of conducting a larger study. Working as part of their Personal Social Health Education lessons, 11 pairs (n = 22) of Year 10 students developed a project to take one accident prevention theme of their choice into a primary school to teach small groups of five or six Year 2 pupils (n = 55). A formative evaluation was conducted, based on interviews with Year 2 and Year 10 teachers (n = 2), and the diaries of Year 10 students. Knowledge of accident prevention and risk awareness was measured in Year 2 pupils using the Draw and Write technique, and impact on Year 10 students was measured using self-esteem and locus of control inventories. Using both statistical and thematic analysis the study concludes that the CSP is well accepted, improves knowledge in Year 2 pupils and boosts confidence in Year 10 students, while concurrently achieving key stage attainment targets. Implications of the study are discussed in terms of future research, as are recommendations with regard to modifications to the project.

  10. 78 FR 64504 - Safety and Occupational Health Study Section (SOHSS), National Institute for Occupational Safety...

    Science.gov (United States)

    2013-10-29

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

  11. 75 FR 5333 - Safety and Occupational Health Study Section (SOHSS), National Institute for Occupational Safety...

    Science.gov (United States)

    2010-02-02

    ...) Place: Embassy Suites Hotel, 1900 Diagonal Road, Alexandria, Virginia 22314, Telephone (703) 684-5900... matters related to the conduct of Study Section business and for the study section to consider safety and...

  12. 77 FR 75633 - Safety and Occupational Health Study Section (SOHSS), National Institute for Occupational Safety...

    Science.gov (United States)

    2012-12-21

    ... (Closed). 8:00 a.m.-5:00 p.m., February 22, 2013 (Closed). Place: Embassy Suites, 1900 Diagonal Road... conduct of Study Section business and for the study section to consider safety and occupational health...

  13. Organic Tanks Safety Program: Waste aging studies

    International Nuclear Information System (INIS)

    Camaioni, D.M.; Samuels, W.D.; Lenihan, B.D.; Clauss, S.A.; Wahl, K.L.; Campbell, J.A.

    1994-11-01

    The underground storage tanks at the Hanford Complex contain wastes generated from many years of plutonium production and recovery processes, and mixed wastes from radiological degradation processes. The chemical changes of the organic materials used in the extraction processes have a direct on several specific safety issues, including potential energy releases from these tanks. This report details the first year's findings of a study charged with determining how thermal and radiological processes may change the composition of organic compounds disposed to the tank. Their approach relies on literature precedent, experiments with simulated waste, and studies of model reactions. During the past year, efforts have focused on the global reaction kinetics of a simulated waste exposed to γ radiation, the reactions of organic radicals with nitrite ion, and the decomposition reactions of nitro compounds. In experiments with an organic tank non-radioactive simulant, the authors found that gas production is predominantly radiolytically induced. Concurrent with gas generation they observe the disappearance of EDTA, TBP, DBP and hexone. In the absence of radiolysis, the TBP readily saponifies in the basic medium, but decomposition of the other compounds required radiolysis. Key organic intermediates in the model are C-N bonded compounds such as oximes. As discussed in the report, oximes and nitro compounds decompose in strong base to yield aldehydes, ketones and carboxylic acids (from nitriles). Certain aldehydes can react in the absence of radiolysis to form H 2 . Thus, if the pathways are correct, then organic compounds reacting via these pathways are oxidizing to lower energy content. 75 refs

  14. Change in Visual Field Progression Following Treatment Escalation in Primary Open-angle Glaucoma.

    Science.gov (United States)

    Aptel, Florent; Bron, Alain M; Lachkar, Yves; Schweitzer, Cédric

    2017-10-01

    To evaluate the effect of treatment escalation on the rate of visual field progression in patients with primary open-angle glaucoma (POAG). Multicenter database study. We reviewed the electronic records of 171 patients with POAG under medical hypotensive treatment who underwent 5 consecutive visits 6 months apart before and after medical treatment escalation or additive laser trabeculoplasty. We calculated the rate of visual field progression (mean deviation change per year) before and after treatment escalation. The mean duration of follow-up was 5.1±0.5 years and the mean number of visual field examinations was 10.2±0.2. In 139 eyes with medical treatment escalation, the rate of progression was significantly reduced [from -0.57 to -0.29 dB/y; P=0.022; intraocular pressure (IOP) reduction 11.1%]. In detail, the rate of progression was significantly reduced after escalation from mono to dual therapy, dual to triple therapy, and from mono to triple therapy (-0.35 to -0.24 dB/y, P=0.018; -1.01 to -0.48 dB/y, P=0.038; -1.04 to -0.35 dB/y, P=0.020, respectively). In 32 eyes with additive laser trabeculoplasty, the rate of progression was significantly reduced (-0.60 to -0.24 dB/y; P=0.014; IOP reduction 9.4%). Medical treatment escalation or additive laser trabeculoplasty significantly reduced the rate of visual field progression in POAG. Larger IOP reduction has a greater probability of reducing glaucoma progression.

  15. Two views of the comparative escalation of nuclear and coal-fired power plant costs

    International Nuclear Information System (INIS)

    Anon.

    1982-01-01

    Doan L. Phung critiques Charles Komanoff's 1981 book Power Plant Cost Escalation, which compares new nuclear plant costs unfavorably with those of new coal plants because of the increase in capital costs. Phung blames prophets of doom who ignore the escalating costs throughout the economy and now focus their anti-nuclear attacks in economic terms. Proposals by Alvin Weinberg and others to concentrate on reactor-safety improvements are used to conclude that these efforts will further expand the capital costs of nuclear plants and make them noncompetitive. Phung questions whether Komanoff's modeling considers enough of the political, regulatory, and technological factors to determine future costs. Komanoff replies by explaining his method of analysis and denying a bias against nuclear power. A postscript by Phung reiterates his criticism of simplistic calculations and extrapolations. 17 references

  16. Heterogeneous FDG-guided dose-escalation for locally advanced NSCLC (the NARLAL2 trial): Design and early dosimetric results of a randomized, multi-centre phase-III study

    DEFF Research Database (Denmark)

    Møller, Ditte Sloth; Nielsen, Tine Bjørn; Brink, Carsten

    2017-01-01

    Background and purpose: Local recurrence is frequent in locally advanced NSCLC and is primarily located in FDG-avid parts of tumour and lymph nodes. Aiming at improving local control without increasing toxicity, we designed a multi-centre phase-III trial delivering inhomogeneous dose-escalation d......Background and purpose: Local recurrence is frequent in locally advanced NSCLC and is primarily located in FDG-avid parts of tumour and lymph nodes. Aiming at improving local control without increasing toxicity, we designed a multi-centre phase-III trial delivering inhomogeneous dose...

  17. Preliminary Results of a Phase 1 Dose-Escalation Trial for Early-Stage Breast Cancer Using 5-Fraction Stereotactic Body Radiation Therapy for Partial-Breast Irradiation

    International Nuclear Information System (INIS)

    Rahimi, Asal; Thomas, Kimberly; Spangler, Ann; Rao, Roshni; Leitch, Marilyn; Wooldridge, Rachel; Rivers, Aeisha; Seiler, Stephen; Albuquerque, Kevin; Stevenson, Stella; Goudreau, Sally; Garwood, Dan; Haley, Barbara; Euhus, David; Heinzerling, John; Ding, Chuxiong; Gao, Ang; Ahn, Chul; Timmerman, Robert

    2017-01-01

    Purpose: To evaluate the tolerability of a dose-escalated 5-fraction stereotactic body radiation therapy for partial-breast irradiation (S-PBI) in treating early-stage breast cancer after partial mastectomy; the primary objective was to escalate dose utilizing a robotic stereotactic radiation system treating the lumpectomy cavity without exceeding the maximum tolerated dose. Methods and Materials: Eligible patients included those with ductal carcinoma in situ or invasive nonlobular epithelial histologies and stage 0, I, or II, with tumor size <3 cm. Patients and physicians completed baseline and subsequent cosmesis outcome questionnaires. Starting dose was 30 Gy in 5 fractions and was escalated by 2.5 Gy total for each cohort to 40 Gy. Results: In all, 75 patients were enrolled, with a median age of 62 years. Median follow-up for 5 cohorts was 49.9, 42.5, 25.7, 20.3, and 13.5 months, respectively. Only 3 grade 3 toxicities were experienced. There was 1 dose-limiting toxicity in the overall cohort. Ten patients experienced palpable fat necrosis (4 of which were symptomatic). Physicians scored cosmesis as excellent or good in 95.9%, 100%, 96.7%, and 100% at baseline and 6, 12, and 24 months after S-PBI, whereas patients scored the same periods as 86.5%, 97.1%, 95.1%, and 95.3%, respectively. The disagreement rates between MDs and patients during those periods were 9.4%, 2.9%, 1.6%, and 4.7%, respectively. There have been no recurrences or distant metastases. Conclusion: Dose was escalated to the target dose of 40 Gy in 5 fractions, with the occurrence of only 1 dose-limiting toxicity. Patients felt cosmetic results improved within the first year after surgery and stereotactic body radiation therapy. Our results show minimal toxicity with excellent cosmesis; however, further follow-up is warranted in future studies. This study is the first to show the safety, tolerability, feasibility, and cosmesis results of a 5-fraction dose-escalated S-PBI treatment for

  18. Preliminary Results of a Phase 1 Dose-Escalation Trial for Early-Stage Breast Cancer Using 5-Fraction Stereotactic Body Radiation Therapy for Partial-Breast Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Rahimi, Asal, E-mail: asal.rahimi@utsouthwestern.edu [University of Texas Southwestern Medical Center, Dallas, Texas (United States); Thomas, Kimberly; Spangler, Ann [University of Texas Southwestern Medical Center, Dallas, Texas (United States); Rao, Roshni; Leitch, Marilyn; Wooldridge, Rachel; Rivers, Aeisha [Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Seiler, Stephen [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Albuquerque, Kevin; Stevenson, Stella [University of Texas Southwestern Medical Center, Dallas, Texas (United States); Goudreau, Sally [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Garwood, Dan [University of Texas Southwestern Medical Center, Dallas, Texas (United States); Haley, Barbara [Department of Medical Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Euhus, David [Department of Surgery, Johns Hopkins University, Baltimore, Maryland (United States); Heinzerling, John [Department of Radiation Oncology, Levine Cancer Institute, Charlotte, North Carolina (United States); Ding, Chuxiong [University of Texas Southwestern Medical Center, Dallas, Texas (United States); Gao, Ang; Ahn, Chul [Department of Statistics, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Timmerman, Robert [University of Texas Southwestern Medical Center, Dallas, Texas (United States)

    2017-05-01

    Purpose: To evaluate the tolerability of a dose-escalated 5-fraction stereotactic body radiation therapy for partial-breast irradiation (S-PBI) in treating early-stage breast cancer after partial mastectomy; the primary objective was to escalate dose utilizing a robotic stereotactic radiation system treating the lumpectomy cavity without exceeding the maximum tolerated dose. Methods and Materials: Eligible patients included those with ductal carcinoma in situ or invasive nonlobular epithelial histologies and stage 0, I, or II, with tumor size <3 cm. Patients and physicians completed baseline and subsequent cosmesis outcome questionnaires. Starting dose was 30 Gy in 5 fractions and was escalated by 2.5 Gy total for each cohort to 40 Gy. Results: In all, 75 patients were enrolled, with a median age of 62 years. Median follow-up for 5 cohorts was 49.9, 42.5, 25.7, 20.3, and 13.5 months, respectively. Only 3 grade 3 toxicities were experienced. There was 1 dose-limiting toxicity in the overall cohort. Ten patients experienced palpable fat necrosis (4 of which were symptomatic). Physicians scored cosmesis as excellent or good in 95.9%, 100%, 96.7%, and 100% at baseline and 6, 12, and 24 months after S-PBI, whereas patients scored the same periods as 86.5%, 97.1%, 95.1%, and 95.3%, respectively. The disagreement rates between MDs and patients during those periods were 9.4%, 2.9%, 1.6%, and 4.7%, respectively. There have been no recurrences or distant metastases. Conclusion: Dose was escalated to the target dose of 40 Gy in 5 fractions, with the occurrence of only 1 dose-limiting toxicity. Patients felt cosmetic results improved within the first year after surgery and stereotactic body radiation therapy. Our results show minimal toxicity with excellent cosmesis; however, further follow-up is warranted in future studies. This study is the first to show the safety, tolerability, feasibility, and cosmesis results of a 5-fraction dose-escalated S-PBI treatment for

  19. Age and workers' perceptions of workplace safety: a comparative study.

    Science.gov (United States)

    Gyekye, Seth Ayim; Salminen, Simo

    2009-01-01

    The study examined the relationship between age and (i) safety perception; (ii) job satisfaction; (iii) compliance with safety management policies; and (iv) accident frequency. Participants were Ghanaian industrial workers (N=320) categorized into 4 age groups: 19-29 years; 30-39 years; 40-50 years; and 51 years and above. Workplace safety perception was assessed with Hayes, Perander, Smecko, and Trask's (1998) 50-item Work Safety Scale (WSS): a scale that effectively captures the dimensions identified by safety experts to influence perceptions of workplace safety. ANOVA was used to test for differences in the mean scores of the 4 groups. Post Hoc analysis revealed differences of statistical significance between the 2 younger cohorts and the 2 older cohorts. The results indicated a positive association between age and safety perception. Older workers had the best perceptions on safety, indicated the highest level of job satisfaction, were the most compliant with safety procedures, and recorded the lowest accident involvement rate. From a practical perspective, understanding age-related perceptions of workplace safety would benefit management's decisions regarding workers' adaptability, general work effectiveness, accident frequency, implementation of safety management policies, and handling of age-related accident characteristics.

  20. A study of passive safety conditions for fast reactor core

    International Nuclear Information System (INIS)

    Shimizu, Akinao

    1991-01-01

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

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

    International Nuclear Information System (INIS)

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

    2014-01-01

    Highlights: •The purpose of this paper is to suggest methodology that can investigate safety issues and provides a case study for Korean fusion DEMO plant. •The concepts of integrated safety assessment methodology (ISAM) that can be applied in addressing regulatory requirements and recognizing safety issues for K-DEMO were emphasized. •Phenomena identification and ranking table (PIRT) was proposed. It can recognize vulnerabilities of systems and identify the gaps in technical areas requiring additional researches. •This work is expected to contribute on the conceptual design of safety features for K-DEMO to design engineers and the guidance for regulatory requirements to licensers. -- Abstract: The purpose of this paper is to suggest methodology that can investigate safety issues and provides a case study for Korean fusion DEMO plant (K-DEMO) as a part of R and D program through the National Fusion Research Institute of Korea. Even though nuclear regulation and licensing framework is well setup due to the operating and design experience of Pressurized Water Reactors (PWRs) since 1970s, the regulatory authority of South Korea has concerns on the challenge of facing new nuclear facilities including K-DEMO due to the differences in systems, materials, and inherent safety feature from conventional PWRs. Even though the follow-up of the ITER license process facilitates to deal with significant safety issues of fusion facilities, a licensee as well as a licenser should identify the gaps between ITER and DEMO in terms of safety issues. First we reviewed the methods of conducting safety analysis for unprecedented nuclear facilities such as Generation IV reactors, particularly very high temperature reactor (VHTR), which is called as integrated safety assessment methodology (ISAM). Second, the analysis for the conceptual design of K-DEMO on the basis of ISAM was conducted. The ISAM consists of five analytical tools to develop the safety requirements from licensee

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-10-15

    Highlights: •The purpose of this paper is to suggest methodology that can investigate safety issues and provides a case study for Korean fusion DEMO plant. •The concepts of integrated safety assessment methodology (ISAM) that can be applied in addressing regulatory requirements and recognizing safety issues for K-DEMO were emphasized. •Phenomena identification and ranking table (PIRT) was proposed. It can recognize vulnerabilities of systems and identify the gaps in technical areas requiring additional researches. •This work is expected to contribute on the conceptual design of safety features for K-DEMO to design engineers and the guidance for regulatory requirements to licensers. -- Abstract: The purpose of this paper is to suggest methodology that can investigate safety issues and provides a case study for Korean fusion DEMO plant (K-DEMO) as a part of R and D program through the National Fusion Research Institute of Korea. Even though nuclear regulation and licensing framework is well setup due to the operating and design experience of Pressurized Water Reactors (PWRs) since 1970s, the regulatory authority of South Korea has concerns on the challenge of facing new nuclear facilities including K-DEMO due to the differences in systems, materials, and inherent safety feature from conventional PWRs. Even though the follow-up of the ITER license process facilitates to deal with significant safety issues of fusion facilities, a licensee as well as a licenser should identify the gaps between ITER and DEMO in terms of safety issues. First we reviewed the methods of conducting safety analysis for unprecedented nuclear facilities such as Generation IV reactors, particularly very high temperature reactor (VHTR), which is called as integrated safety assessment methodology (ISAM). Second, the analysis for the conceptual design of K-DEMO on the basis of ISAM was conducted. The ISAM consists of five analytical tools to develop the safety requirements from licensee

  3. Dose study of the multikinase inhibitor, LY2457546, in patients with relapsed acute myeloid leukemia to assess safety, pharmacokinetics, and pharmacodynamics

    International Nuclear Information System (INIS)

    Wacheck, Volker; Lahn, Michael; Dickinson, Gemma; Füreder, Wolfgang; Meyer, Renata; Herndlhofer, Susanne; Füreder, Thorsten; Dorfner, Georg; Pillay, Sada; André, Valérie; Burkholder, Timothy P; Akunda, Jacqueline K; Flye-Blakemore, Leann; Van Bockstaele, Dirk; Schlenk, Richard F; Sperr, Wolfgang R; Valent, Peter

    2011-01-01

    Acute myeloid leukemia (AML) is a life-threatening malignancy with limited treatment options in chemotherapy-refractory patients. A first-in-human dose study was designed to investigate a safe and biologically effective dose range for LY2457546, a novel multikinase inhibitor, in patients with relapsed AML. In this nonrandomized, open-label, dose escalation Phase I study, LY2457546 was administered orally once a day. Safety, pharmacokinetics, changes in phosphorylation of target kinases in AML blasts, and risk of drug–drug interactions (DDI) were assessed. Five patients were treated at the starting and predicted minimal biologically effective dose of 50 mg/day. The most commonly observed adverse events were febrile neutropenia, epistaxis, petechiae, and headache. The majority of adverse events (81%) were Grade 1 or 2. One patient had generalized muscle weakness (Grade 3), which was deemed to be a dose-limiting toxicity. Notably, the pharmacokinetic profile of LY2457546 showed virtually no elimination of LY2457546 within 24 hours, and thus prevented further dose escalation. No significant DDI were observed. Ex vivo flow cytometry studies showed downregulation of the phosphoproteins, pcKIT, pFLT3, and pS6, in AML blasts after LY2457546 administration. No medically relevant responses were observed in the five treated patients. No biologically effective dose could be established for LY2457546 in chemotherapy-resistant AML patients. Lack of drug clearance prevented safe dose escalation, and the study was terminated early. Future efforts should be made to develop derivatives with a more favorable pharmacokinetic profile

  4. Safety and economic study of special trains

    International Nuclear Information System (INIS)

    Loscutoff, W.V.; Hall, R.J.

    1976-01-01

    A comparative evaluation is being conducted of the safety and economics of special (35 mph and less) and regular trains for shipment of spent fuels. The approach, pertinent considerations, and results to date are discussed. The preliminary conclusion is that special train requirements have potential for only a small reduction in the accident likelihood, while increasing the cost

  5. Combustion Safety Simplified Test Protocol Field Study

    Energy Technology Data Exchange (ETDEWEB)

    Brand, L [Gas Technology Inst., Des Plaines, IL (United States); Cautley, D. [Gas Technology Inst., Des Plaines, IL (United States); Bohac, D. [Gas Technology Inst., Des Plaines, IL (United States); Francisco, P. [Gas Technology Inst., Des Plaines, IL (United States); Shen, L. [Gas Technology Inst., Des Plaines, IL (United States); Gloss, S. [Gas Technology Inst., Des Plaines, IL (United States)

    2015-11-05

    "9Combustions safety is an important step in the process of upgrading homes for energy efficiency. There are several approaches used by field practitioners, but researchers have indicated that the test procedures in use are complex to implement and provide too many false positives. Field failures often mean that the house is not upgraded until after remediation or not at all, if not include in the program. In this report the PARR and NorthernSTAR DOE Building America Teams provide a simplified test procedure that is easier to implement and should produce fewer false positives. A survey of state weatherization agencies on combustion safety issues, details of a field data collection instrumentation package, summary of data collected over seven months, data analysis and results are included. The project provides several key results. State weatherization agencies do not generally track combustion safety failures, the data from those that do suggest that there is little actual evidence that combustion safety failures due to spillage from non-dryer exhaust are common and that only a very small number of homes are subject to the failures. The project team collected field data on 11 houses in 2015. Of these homes, two houses that demonstrated prolonged and excessive spillage were also the only two with venting systems out of compliance with the National Fuel Gas Code. The remaining homes experienced spillage that only occasionally extended beyond the first minute of operation. Combustion zone depressurization, outdoor temperature, and operation of individual fans all provide statistically significant predictors of spillage.

  6. 78 FR 24751 - Safety and Occupational Health Study Section (SOHSS), National Institute for Occupational Safety...

    Science.gov (United States)

    2013-04-26

    ... 14, 2013 (Closed) Place: Embassy Suites, 1900 Diagonal Road, Alexandria, Virginia 22314, Telephone... business and for the study section to consider safety and occupational health-related grant applications...

  7. The development of an inherent safety approach to the prevention of domino accidents.

    Science.gov (United States)

    Cozzani, Valerio; Tugnoli, Alessandro; Salzano, Ernesto

    2009-11-01

    The severity of industrial accidents in which a domino effect takes place is well known in the chemical and process industry. The application of an inherent safety approach for the prevention of escalation events leading to domino accidents was explored in the present study. Reference primary scenarios were analyzed and escalation vectors were defined. Inherent safety distances were defined and proposed as a metric to express the intensity of the escalation vectors. Simple rules of thumb were presented for a preliminary screening of these distances. Swift reference indices for layout screening with respect to escalation hazard were also defined. Two case studies derived from existing layouts of oil refineries were selected to understand the potentialities coming from the application in the methodology. The results evidenced that the approach allows a first comparative assessment of the actual domino hazard in a layout, and the identification of critical primary units with respect to escalation events. The methodology developed also represents a useful screening tool to identify were to dedicate major efforts in the design of add-on measures, optimizing conventional passive and active measures for the prevention of severe domino accidents.

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

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

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

  9. Study on some safety-related aspects of tyre use

    NARCIS (Netherlands)

    Jansen, S.T.H.; Schmeitz, A.J.C.; Maas, S.; Rodarius, C.; Akkermans, L.

    2014-01-01

    The tyre is a key component that affects road safety. The European commission has posted a tender aimed to study what measures on a European level can be taken in relation to the use of tyres to improve road safety. The results of this study, supported by a cost benefit analyses and carried out by

  10. The Effect of Image Compatibility and Escalation of Commitment on Decision Performance

    Directory of Open Access Journals (Sweden)

    Harris K. Turino

    2012-04-01

    Full Text Available This study aims at empirically examining the extent to which Image Theory, initially developed as a theoretical basis for selecting a strategy or a decision, can be a theoretical basis for predicting a decision performance in two opposite frames: positive and negative. Image compatibility are employed to operationalize such a theory and the decision under study is progress decision represented by escalation of commitment. Thus, this study also empirically examines the connection between image compatibility and escalation of commitment as well as escalation of commitment as a mediator of the relationship between image compatibility and decision performance. The research context is Indonesia Stock Exchange (IDX that suffered from crisis in the past year (negative frame yet has been recovered recently (positive frame. The respondents are 229 individual investors in IDX. They are involved in day-to-day decision making (progress decision making with regard to their investment portofolio. The results of this study show that high image compatibility tends to lead to better decision performance in both frames. However, image compatibility may only positively affect the escalation of commitment in positive frame

  11. Randomized, double-blind, crossover study comparing DFN-11 injection (3 mg subcutaneous sumatriptan) with 6 mg subcutaneous sumatriptan for the treatment of rapidly-escalating attacks of episodic migraine.

    Science.gov (United States)

    Cady, Roger K; Munjal, Sagar; Cady, Ryan J; Manley, Heather R; Brand-Schieber, Elimor

    2017-12-01

    A 6-mg dose of SC sumatriptan is the most efficacious and fast-acting acute treatment for migraine, but a 3-mg dose of SC sumatriptan may improve tolerability while maintaining efficacy. This randomized, double-blind, crossover study compared the efficacy and tolerability of 3 mg subcutaneous (SC) sumatriptan (DFN-11) with 6 mg SC sumatriptan in 20 adults with rapidly-escalating migraine attacks. Eligible subjects were randomized (1:1) to treat 1 attack with DFN-11 and matching placebo autoinjector consecutively or 2 DFN-11 autoinjectors consecutively and a second attack similarly but with the alternative dose (3 mg or 6 mg). The proportions of subjects who were pain-free at 60 min postdose, the primary endpoint, were similar following treatment with 3 mg SC sumatriptan and 6 mg SC sumatriptan (50% vs 52.6%, P  =  .87). The proportions of subjects experiencing pain relief (P  ≥  .48); reductions in migraine pain intensity (P  ≥  .78); and relief from nausea, photophobia, or phonophobia (P  ≥  .88) with 3 mg SC sumatriptan and 6 mg SC sumatriptan were similar, as were the mean scores for satisfaction with treatment (M  =  2.6 vs M  =  2.4, P  =  .81) and the mean number of rescue medications used (M  =  .11 vs M  =  .26, P  =  .32). The most common adverse events with the 3- and 6-mg doses were triptan sensations - paresthesia, neck pain, flushing, and involuntary muscle contractions of the neck - and the incidence of adverse events with both doses was similar (32 events total: 3 mg, n  =  14 [44%]; 6 mg, n  =  18 [56%], P  =  .60). Triptan sensations affected 4 subjects with the 6-mg dose only, 1 subject with the 3-mg dose only, and 7 subjects with both sumatriptan doses. Chest pain affected 2 subjects (10%) treated with the 6-mg dose and no subjects (0%) treated with the 3-mg dose of DFN-11. There were no serious adverse events. The 3-mg SC dose

  12. Combustion Safety Simplified Test Protocol Field Study

    Energy Technology Data Exchange (ETDEWEB)

    Brand, L. [Gas Technology Inst., Des Plaines, IL (United States); Cautley, D. [Gas Technology Inst., Des Plaines, IL (United States); Bohac, D. [Gas Technology Inst., Des Plaines, IL (United States); Francisco, P. [Gas Technology Inst., Des Plaines, IL (United States); Shen, L. [Gas Technology Inst., Des Plaines, IL (United States); Gloss, S. [Gas Technology Inst., Des Plaines, IL (United States)

    2015-11-01

    Combustions safety is an important step in the process of upgrading homes for energy efficiency. There are several approaches used by field practitioners, but researchers have indicated that the test procedures in use are complex to implement and provide too many false positives. Field failures often mean that the house is not upgraded until after remediation or not at all, if not include in the program. In this report the PARR and NorthernSTAR DOE Building America Teams provide a simplified test procedure that is easier to implement and should produce fewer false positives. A survey of state weatherization agencies on combustion safety issues, details of a field data collection instrumentation package, summary of data collected over seven months, data analysis and results are included. The project team collected field data on 11 houses in 2015.

  13. SAFETY

    CERN Multimedia

    Niels Dupont

    2013-01-01

    CERN Safety rules and Radiation Protection at CMS The CERN Safety rules are defined by the Occupational Health & Safety and Environmental Protection Unit (HSE Unit), CERN’s institutional authority and central Safety organ attached to the Director General. In particular the Radiation Protection group (DGS-RP1) ensures that personnel on the CERN sites and the public are protected from potentially harmful effects of ionising radiation linked to CERN activities. The RP Group fulfils its mandate in collaboration with the CERN departments owning or operating sources of ionising radiation and having the responsibility for Radiation Safety of these sources. The specific responsibilities concerning "Radiation Safety" and "Radiation Protection" are delegated as follows: Radiation Safety is the responsibility of every CERN Department owning radiation sources or using radiation sources put at its disposition. These Departments are in charge of implementing the requi...

  14. Dose De-escalation of Intrapleural Tissue Plasminogen Activator Therapy for Pleural Infection. The Alteplase Dose Assessment for Pleural Infection Therapy Project.

    Science.gov (United States)

    Popowicz, Natalia; Bintcliffe, Oliver; De Fonseka, Duneesha; Blyth, Kevin G; Smith, Nicola A; Piccolo, Francesco; Martin, Geoffrey; Wong, Donny; Edey, Anthony; Maskell, Nick; Lee, Y C Gary

    2017-06-01

    Intrapleural therapy with a combination of tissue plasminogen activator (tPA) 10 mg and DNase 5 mg administered twice daily has been shown in randomized and open-label studies to successfully manage over 90% of patients with pleural infection without surgery. Potential bleeding risks associated with intrapleural tPA and its costs remain important concerns. The aim of the ongoing Alteplase Dose Assessment for Pleural infection Therapy (ADAPT) project is to investigate the efficacy and safety of dose de-escalation for intrapleural tPA. The first of several planned studies is presented here. To evaluate the efficacy and safety of a reduced starting dose regimen of 5 mg of tPA with 5 mg of DNase administered intrapleurally for pleural infection. Consecutive patients with pleural infection at four participating centers in Australia, the United Kingdom, and New Zealand were included in this observational, open-label study. Treatment was initiated with tPA 5 mg and DNase 5 mg twice daily. Subsequent dose escalation was permitted at the discretion of the attending physician. Data relating to treatment success, radiological and systemic inflammatory changes (blood C-reactive protein), volume of fluid drained, length of hospital stay, and treatment complications were extracted retrospectively from the medical records. We evaluated 61 patients (41 males; age, 57 ± 16 yr). Most patients (n = 58 [93.4%]) were successfully treated without requiring surgery for pleural infection. Treatment success was corroborated by clearance of pleural opacities visualized by chest radiography (from 42% [interquartile range, 22-58] to 16% [8-31] of hemithorax; P < 0.001), increase in pleural fluid drainage (from 175 ml in the 24 h preceding treatment to 2,025 ml [interquartile range, 1,247-2,984] over 72 h of therapy; P <  0.05) and a reduction in blood C-reactive protein (P < 0.05). Seven patients (11.5%) had dose escalation of tPA to 10 mg. Three patients underwent

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

    Directory of Open Access Journals (Sweden)

    Mark Mario Morando

    2018-01-01

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

  16. Safety study of PCC 2140 and ALILOG 21 used as part of safety measurement systems

    International Nuclear Information System (INIS)

    Meriaux, Pierre; Adnot, Serge; Rayrolles, Catherine.

    1978-03-01

    The PCC 2140 and ALILOG 21 equipment may be used at C.E.A. or E.D.F., as part of safety measurement systems. In a study of a similar, but earlier equipment, it was noticed that certain types of failures caused the system to switch to the least sensitive measurement range, which was detrimental to safety. This report analyses failure modes leading to unsafe failures and evaluates the risks ran into taking in account tests during use [fr

  17. A study on safety climate at nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

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

    2001-09-01

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

  18. Advances made in French safety studies on pressurized water reactors

    International Nuclear Information System (INIS)

    Pelce, J.

    1979-01-01

    The programme of French safety studies on reactors is supposed to be known in its main outlines. A few recent results, obtained in different fields are presented. They concern the safety margins evaluation, the contamination transfer and the effect of external aggressions

  19. Audience reactions to peace journalism: How supporters and critics of the Israeli policy process escalation and de-escalation oriented media frames

    Directory of Open Access Journals (Sweden)

    Stephanie Thiel

    2014-04-01

    Full Text Available This paper reports on an experiment that uses the Israeli-Palestinian conflict as a natural laboratory for studying how recipients make sense of escalation vs. de-escalation oriented news articles. The results of the study indicate that media frames and individual frames have both a direct effect and complex interaction effects on participants’ text understanding. Particularly the effect of media war frames diminishes if they are incongruent with participants’ individual frames, and the propaganda function of reports about violence and human casualties can be neutralized if framed according to a peace frame. If participants had a priori positioned themselves in favor of the perpetrator, they may produce reactance, however.

  20. Strategies for Biologic Image-Guided Dose Escalation: A Review

    International Nuclear Information System (INIS)

    Sovik, Aste; Malinen, Eirik; Olsen, Dag Rune

    2009-01-01

    There is increasing interest in how to incorporate functional and molecular information obtained by noninvasive, three-dimensional tumor imaging into radiotherapy. The key issues are to identify radioresistant regions that can be targeted for dose escalation, and to develop radiation dose prescription and delivery strategies providing optimal treatment for the individual patient. In the present work, we review the proposed strategies for biologic image-guided dose escalation with intensity-modulated radiation therapy. Biologic imaging modalities and the derived images are discussed, as are methods for target volume delineation. Different dose escalation strategies and techniques for treatment delivery and treatment plan evaluation are also addressed. Furthermore, we consider the need for response monitoring during treatment. We conclude with a summary of the current status of biologic image-based dose escalation and of areas where further work is needed for this strategy to become incorporated into clinical practice

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

    International Nuclear Information System (INIS)

    Lowe, Andrew; Hayward, Brent

    2006-08-01

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

  2. Safety

    International Nuclear Information System (INIS)

    2001-01-01

    This annual report of the Senior Inspector for the Nuclear Safety, analyses the nuclear safety at EDF for the year 1999 and proposes twelve subjects of consideration to progress. Five technical documents are also provided and discussed concerning the nuclear power plants maintenance and safety (thermal fatigue, vibration fatigue, assisted control and instrumentation of the N4 bearing, 1300 MW reactors containment and time of life of power plants). (A.L.B.)

  3. Deterrence Adrift Mapping Conflict and Escalation in South Asia

    Science.gov (United States)

    2016-06-21

    will paralyze India’s political leadership from authorizing Cold Start in the first place , or at the very least, force India to drastically curb its...Pakistan believes that its willingness to escalate will either deter New Delhi from cross-border adventurism in the first place or achieve some...difficulty calibrating a limited ground offensive in a way that does not precipitate an escalation spiral. In es- sence , India’s quandary reflects one of

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-08-15

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

  5. Contribution of operating feedback to probabilistic safety studies

    International Nuclear Information System (INIS)

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

    1992-03-01

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

  6. Soviet declaratory policy regarding the controllability of escalation

    International Nuclear Information System (INIS)

    Prewitt, J.L.

    1991-01-01

    Three variables were examined for their affect on Soviet views regarding the controllability of escalation. The first was bureaucratic affiliation. It was hypothesized that individuals affiliated with groups which directly controlled weapons would be more likely to support the controllability of escalation than those who were members of groups which did not control weapons. This hypothesis could not be rejected. The second variable was a commentator's rank. It was hypothesized that rank would act in two ways: (1) ideas regarding controlled escalation would appear at lower ranks first; and (2) unique views would be produced by specialized ranks within groups. The rank hypothesis could not be rejected. Certain escalation themes appeared to be presented first by military and civilian writers before being presented by the political leadership. The third variable, image of the West, did not appear to function as theorized. It was hypothesized that hard images of the West would be associated with the rejection of controlled escalation, whereas soft images would be associated with positions suggesting that escalation was controlled through joint US-Soviet cooperation

  7. Exploratory study to evaluate tolerability, safety, and activity of Ashwagandha (Withania somnifera in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Ashwinikumar A Raut

    2012-01-01

    Full Text Available Ashwagandha (Withania somnifera (WS, a "rasayana" drug, is recommended for balavardhan and mamsavardhan. The study was intended to evaluate dose-related tolerability, safety, and activity of WS formulation in normal individuals. The design was prospective, open-labeled, variable doses in volunteers. Eighteen apparently healthy volunteers (12M:6F, age:18-30 years, and BMI: 19-30 were enrolled. After baseline investigations, they received WS capsules (Rx (aqueous extract, 8:1 daily in two divided doses with increase in daily dosage every 10 days for 30 days (750 mg/day x10 days, 1 000 mg/day x 10 days, 1 250 mg/day x 10 days. Volunteers were assessed for symptoms/signs, vital functions, hematological and biochemical organ function tests. Muscle activity was measured by hand grip strength, quadriceps strength, and back extensor force. Exercise tolerance was determined using cycle ergometry. Lean body weight and fat% were computed from skin fold thickness measurement. Adverse events were recorded, as volunteered by the subjects. Repeated measures ANOVA, McNemar′s test, and paired t test were employed. All but one volunteer tolerated WS without any adverse event. One volunteer showed increased appetite, libido, and hallucinogenic effects with vertigo at the lowest dose and was withdrawn from study. In six subjects, improvement in quality of sleep was found. Organ function tests were in normal range before and after the intervention. Reduction in total- and LDL- cholesterol and increase of strength in muscle activity was significant. Total body fat percentage showed a reduction trend. WS, in escalated dose, was tolerated well. The formulation appeared safe and strengthened muscle activity. In view of its traditional Rasayana use, further studies are planned to evaluate potential of this drug in patients of sarcopenia.

  8. Main lessons for FBR safety study from the CABRI experiments

    International Nuclear Information System (INIS)

    Sato, Ikken

    2006-01-01

    CABRI project has been carried out FBR safety study with international cooperation of five nations since 1978. The project consists of four periods such as CABRI-1, CABRI-2, CABRI-FAST and CABRI-RAFT. The objects and the main information for hypothetical core decay accident and safety study of fuel are described. The behavior of core decay accident was studied in the first period (CABRI-1), the safety study of fuel was investigated after the second period (CABRI-2). Change of phenomena at the initial process of core decay accident, comparison between analysis and data of fuel diffusion behavior of neutron horoscope by CABRI-2 experiment, representative in-core experiment under slow TOP conditions, the damaged and undamaged pin under slow TOP conditions, the exterior of CABRI and TREAT and the upper part of CABRI and TREAT reactor are shown. CABRI experiments changed to LWR safety study and a part of TREAT is stated. (S.Y.)

  9. Quality management of pharmacology and safety pharmacology studies

    DEFF Research Database (Denmark)

    Spindler, Per; Seiler, Jürg P

    2002-01-01

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

  10. The advanced neutron source facility: Safety philosophy and studies

    International Nuclear Information System (INIS)

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

    1988-01-01

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

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

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

    2006-01-01

    Jan 1, 2006 ... Book cover Environmental Regulation and Food Safety: Studies of ... are sometimes perceived in developing countries as nontariff barriers to trade. ... In some cases, products that had initially been refused access to a ...

  12. Example of a SWOV (Institute for Road Safety Research) safety study : "Avenida Marginal", Lisbon 1989.

    NARCIS (Netherlands)

    Janssen, S.T.M.C.

    1991-01-01

    This paper describes the accident study on the Marginal Road between Alges and Cascais in Portugal. The aim of this study was to produce a philosophy for a strategy to select the best safety measures out of several which had already been proposed. The general point of departure in this philosophy is

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

    International Nuclear Information System (INIS)

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

    2004-03-01

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

  14. Nitrogen-system safety study: Portsmouth Gaseous Diffusion Plant

    International Nuclear Information System (INIS)

    1982-07-01

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

  15. Safety certification of airborne software: An empirical study

    International Nuclear Information System (INIS)

    Dodd, Ian; Habli, Ibrahim

    2012-01-01

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

  16. Behavior-based safety on construction sites: a case study.

    Science.gov (United States)

    Choudhry, Rafiq M

    2014-09-01

    This work presents the results of a case study and describes an important area within the field of construction safety management, namely behavior-based safety (BBS). This paper adopts and develops a management approach for safety improvements in construction site environments. A rigorous behavioral safety system and its intervention program was implemented and deployed on target construction sites. After taking a few weeks of safety behavior measurements, the project management team implemented the designed intervention and measurements were taken. Goal-setting sessions were arranged on-site with workers' participation to set realistic and attainable targets of performance. Safety performance measurements continued and the levels of performance and the targets were presented on feedback charts. Supervisors were asked to give workers recognition and praise when they acted safely or improved critical behaviors. Observers were requested to have discussions with workers, visit the site, distribute training materials to workers, and provide feedback to crews and display charts. They were required to talk to operatives in the presence of line managers. It was necessary to develop awareness and understanding of what was being measured. In the process, operatives learned how to act safely when conducting site tasks using the designed checklists. Current weekly scores were discussed in the weekly safety meetings and other operational site meetings with emphasis on how to achieve set targets. The reliability of the safety performance measures taken by the company's observers was monitored. A clear increase in safety performance level was achieved across all categories: personal protective equipment; housekeeping; access to heights; plant and equipment, and scaffolding. The research reveals that scores of safety performance at one project improved from 86% (at the end of 3rd week) to 92.9% during the 9th week. The results of intervention demonstrated large decreases in

  17. Efficacy, safety and tolerability of escitalopram in doses up to 50 mg in Major Depressive Disorder (MDD: an open-label, pilot study

    Directory of Open Access Journals (Sweden)

    Crawford Gordon M

    2011-03-01

    Full Text Available Abstract Background Escitalopram is licensed for use at doses up to 20 mg but is used clinically at higher doses. There is limited published data at higher doses and none in the treatment of Major Depressive Disorder (MDD. Methods This open-label, pilot study was designed to investigate the efficacy, safety and tolerability of escitalopram in doses up to 50 mg in MDD. It was conducted in 60 primary care patients with MDD who had not responded to adequate treatment with citalopram. Patients were treated with escalating doses of escitalopram up to 50 mg for up to 32 weeks until they achieved remission (Montgomery-Asberg Depression Rating Scale [MADRS] ≤8 or failed to tolerate the dose. Results Forty-two patients (70% completed the study. Twenty-one patients (35% achieved remission with 8 of the 21 patients (38% needing the 50 mg dose to achieve remission. Median time to remission was 24 weeks and median dose in remission was 30 mg. No significant safety issues were identified although tolerability appeared to decline above a dose of 40 mg with 26% of patients unable to tolerate 50 mg. Twelve (20% patients had adverse events leading to discontinuation. The most common adverse events were headache (35%, nausea, diarrhoea and nasopharyngitis (all 25%. Minor mean weight gain was found during the study, which did not appear to be dose-related. Half of the patients who completed the study chose to continue treatment with escitalopram rather than taper down the dose at 32 weeks. Conclusions Dose escalation with escitalopram above 20 mg may have a useful role in the management of patients with MDD, although further studies are needed to confirm this finding. Trial Registration ClinicalTrials.gov: NCT00785434

  18. Factors associated with escalation and problematic approaches toward public figures.

    Science.gov (United States)

    Meloy, J Reid; James, David V; Mullen, Paul E; Pathé, Michele T; Farnham, Frank R; Preston, Lulu F; Darnley, Brian J

    2011-01-01

    Detailed comparison of factors associated with abnormal approach to the prominent and with escalation from communication to approach has not hitherto been undertaken. This partially reflects the failure of individual studies to adopt compatible terminologies. This study involves a careful dissection of six public figure studies, three involving U.S. politicians, two Hollywood celebrities, and one the British Royal Family. Common findings were unearthed across six headings. Approachers were significantly more likely to exhibit serious mental illness, engage in multiple means of communication, involve multiple contacts/targets, and to incorporate into their communication requests for help. They were significantly less likely to use threatening or antagonistic language in their communications, except in those cases involving security breaches. These results emphasize the importance of integrating mental health findings and preventive measures into risk management. Approach should not be regarded as a single behavioral category and has multiple motivations. Future studies should adopt standard terminology, preferably taken from the general stalking research. © 2010 American Academy of Forensic Sciences.

  19. Angra-1 probabilistic safety study-phase B

    International Nuclear Information System (INIS)

    Fernandes Filho, T.L.; Gibelli, S.M.O.

    1988-05-01

    This study represents the Phase B of the Angra-1 Probabilistic Safety Study and is the the final report prepared for the IAEA under Research Contract No. 3423/R2/RB. The three main items covered in this report are the establishment of interim safety goals, analysis of Angra-1 operational experience and development of emergency procedures to address severe accidents. For establishment of interim safety goals a methodology for calculating consequences and risks associated to the Angra-1 operation was developed based on the available data and codes. The proposed safety goals refer to the individual risk of early fatality for people living in the vicinity of the plant, colective risk of cancer fatalities for people living near the plant, the propobability of core melt occurrence and the probability of dominant accident sequences. (author) [pt

  20. Study Of Safety Management By Using Gis In Coimbatore

    Directory of Open Access Journals (Sweden)

    S. Kanchana

    2015-08-01

    Full Text Available The safety management is very important in the process of construction .The traditional methods of construction safety control cannot meet the construction of big project. To ensure the safety of construction and reduce accidents in the process of construction the current situation and problems we face in construction safety management should be studied first. And then the project risk warning mechanism based on the GIS is constructed according to the problems we faced to achieve visual monitoring and warning of construction safety risk management and to provide decision support for construction. This project aims to develop a web-based spatial decision support system model for proactive health and safety management in linear construction projects. 5 Currently health and safety management is usually performed reactively instead of proactive management since hazard identification and risk assessment is mostly performed on paper based documents that are not effectively used at site. An information system relates to a chain of operations lead to planning the observation and collection of data to storage and analysis of data to the use of derived information in decision-making processes. To create a web-based free and open sourced GIS that can work with different data formats by exchanging and presenting data as a real-time map on web.

  1. Preliminary Study on the Development of Quantitative Safety Culture Index

    International Nuclear Information System (INIS)

    Lee, Young Eal; Kim, Hun Sil; Ahn, Nam Sung

    2005-01-01

    Safety culture is that assembly of characteristics and attitudes in organizations and individuals which establishes that, as an overriding priority, nuclear plant safety issues receive the attention warranted by their significance. Because it needs to be recognized as the most significant consciousness to achieve the nuclear safety performance, Korean government and nuclear power generation company have tried to develop the practical method to improve the safety culture from the long term point view. In this study, based on the site interviews to define the potential issues on organizational behavior for the safe operation and the survey on the level of safety culture of occupied workers are conducted. Survey results are quantified as a few indicators of nuclear safety by the statistical method and it can be simulated by the dynamic modeling as time goes on. Currently index and dynamic modeling are still being developed, however, results can be used to suggest the long term strategy which safety is clearly integrated into all activities in the nuclear organization

  2. The Effect of Image Compatibility and Escalation of Commitment on Decision Performance

    OpenAIRE

    Harris K. Turino; Budi W. Soetjipto

    2012-01-01

    This study aims at empirically examining the extent to which Image Theory, initially developed as a theoretical basis for selecting a strategy or a decision, can be a theoretical basis for predicting a decision performance in two opposite frames: positive and negative. Image compatibility are employed to operationalize such a theory and the decision under study is progress decision represented by escalation of commitment. Thus, this study also empirically examines the connection between imag...

  3. High-dose radiation improved local tumor control and overall survival in patients with inoperable/unresectable non-small-cell lung cancer: Long-term results of a radiation dose escalation study

    International Nuclear Information System (INIS)

    Kong, F.-M.; Haken, Randall K. ten; Schipper, Matthew J.; Sullivan, Molly A.; Chen, Ming; Lopez, Carlos; Kalemkerian, Gregory P.; Hayman, James A.

    2005-01-01

    Purpose: To determine whether high-dose radiation leads to improved outcomes in patients with non-small-cell lung cancer (NSCLC). Methods and Materials: This analysis included 106 patients with newly diagnosed or recurrent Stages I-III NSCLC, treated with 63-103 Gy in 2.1-Gy fractions, using three-dimensional conformal radiation therapy (3D-CRT) per a dose escalation trial. Targets included the primary tumor and any lymph nodes ≥1 cm, without intentionally including negative nodal regions. Nineteen percent of patients (20/106) received neoadjuvant chemotherapy. Patient, tumor, and treatment factors were evaluated for association with outcomes. Estimated median follow-up was 8.5 years. Results: Median survival was 19 months, and 5-year overall survival (OS) was 13%. Multivariate analysis revealed weight loss (p = 0.011) and radiation dose (p = 0.0006) were significant predictors for OS. The 5-year OS was 4%, 22%, and 28% for patients receiving 63-69, 74-84, and 92-103 Gy, respectively. Although presence of nodal disease was negatively associated with locoregional control under univariate analysis, radiation dose was the only significant predictor when multiple variables were included (p = 0.015). The 5-year control rate was 12%, 35%, and 49% for 63-69, 74-84, and 92-103 Gy, respectively. Conclusions: Higher dose radiation is associated with improved outcomes in patients with NSCLC treated in the range of 63-103 Gy

  4. Two experiments focusing on de-escalation oriented coverage of post-war conflicts

    Directory of Open Access Journals (Sweden)

    Wilhelm Kempf

    2005-10-01

    Full Text Available War coverage has a strong bias towards the promotion of conflict escalation and - though less pronounced - this bias often survives in post-war coverage as well. Even after the end of war, only a minority of journalists frame conflict in a firmly de-escalation oriented way. Do they have a chance to reach the public? Will their reports be respected by the audience as more balanced and unbiased? Will they have an impact on the audience's mental models of the conflict? Or will the audience continue to cling to its prejudices and reject news articles which do not affirm the enemy images that emerged during wartime? The present paper investigates these questions by means of two experimental studies. In the first experiment, news articles on three events in former Yugoslavia after the fall of Milosevic were presented to a total of n = 128 subjects, representative of the readership of the German quality press: (1 violent conflicts in Southern Serbia (December 2000, (2 the extradition of Milosevic to The Hague (June, 2001 and (3 the treaty between Serbia and Montenegro (March 2003. For each of the events, four different types of articles were used: moderately escalation oriented articles from prestigious German newspapers (Die Welt, Frankfurter Allgemeine Zeitung, Süddeutsche Zeitung and three variants of these articles, (a with increased escalation-oriented framing, (b with moderate de-escalation oriented framing and (c with more strongly de-escalation oriented framing of the events. Each subject was asked to read one article on each of the three events in chronological order and after each article (a to narrate the reported events in their own words and (b to fill out a questionnaire designed to measure the acceptance of the articles as unbiased, well-balanced, interesting, etc. The subjects' mental models of the reported events were inferred from their narratives by means of quantitative content analysis. The second experiment measured the

  5. A study of RFID application impacts on medical safety.

    Science.gov (United States)

    Chang, She-I; Ou, Chin-Shyh; Ku, Cheng-Yuan; Yang, Morris

    2008-01-01

    With the international reform in medical management systems gaining ground worldwide, hospital management has gradually begun to shift its focus from providing expensive medical treatment to improving medical service quality and patient safety. In this study, we discuss the application of Radio Frequency Identification (RFID) and data integrating technology with the medical service, and examine whether or not this technology can enhance medical safety. We also discuss the possible benefits following the application of the RFID system. The findings show that the application of RFID to hospitals can actually generate benefits, which can be further divided into operational structure benefits, users' structure benefits, and organisational and environmental benefits. However, not all these benefits can achieve medical safety. Among them, only the operator and environmental benefits can play such roles. Nevertheless, the application of RFID can bring hospitals towards the integration of technology benefits and improved medical safety.

  6. Study on operational safety issues in the Japanese disposal concept

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  7. PET-guided dose escalation tomotherapy in malignant pleural mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Fodor, Andrei; Dell' Oca, Italo; Pasetti, Marcella; Di Muzio, Nadia Gisella [San Raffaele Scientific Institute, Milan (Italy). Dept. of Radiotherapy; Fiorino, Claudio; Broggi, Sara; Cattaneo, Giovanni Mauro; Calandrino, Riccardo [San Raffaele Scientific Institute, Milan (Italy). Medical Physics; Gianolli, Luigi [San Raffaele Scientific Institute, Milan (Italy). Dept. of Nuclear Medicine

    2011-11-15

    To test the feasibility of salvage radiotherapy using PET-guided helical tomotherapy in patients with progressive malignant pleural mesothelioma (MPM). A group of 12 consecutive MPM patients was treated with 56 Gy/25 fractions to the planning target volume (PTV); FDG-PET/CT simulation was always performed to include all positive lymph nodes and MPM infiltrations. Subsequently, a second group of 12 consecutive patients was treated with the same dose to the whole pleura adding a simultaneous integrated boost of 62.5 Gy to the FDG-PET/CT positive areas (BTV). Good dosimetric results were obtained in both groups. No grade 3 (RTOG/EORTC) acute or late toxicities were reported in the first group, while 3 cases of grade 3 late pneumonitis were registered in the second group: the duration of symptoms was 2-10 weeks. Median overall survival was 8 months (1.2-50.5 months) and 20 months (4.3-33.8 months) from the beginning of radiotherapy, for groups I and II, respectively (p = 0.19). A significant impact on local relapse from radiotherapy was seen (median time to local relapse: 8 vs 17 months; 1-year local relapse-free rate: 16% vs 81%, p = 0.003). The results of this pilot study support the planning of a phase III study of combined sequential chemoradiotherapy with dose escalation to BTV in patients not able to undergo resection. (orig.)

  8. Error Cost Escalation Through the Project Life Cycle

    Science.gov (United States)

    Stecklein, Jonette M.; Dabney, Jim; Dick, Brandon; Haskins, Bill; Lovell, Randy; Moroney, Gregory

    2004-01-01

    It is well known that the costs to fix errors increase as the project matures, but how fast do those costs build? A study was performed to determine the relative cost of fixing errors discovered during various phases of a project life cycle. This study used three approaches to determine the relative costs: the bottom-up cost method, the total cost breakdown method, and the top-down hypothetical project method. The approaches and results described in this paper presume development of a hardware/software system having project characteristics similar to those used in the development of a large, complex spacecraft, a military aircraft, or a small communications satellite. The results show the degree to which costs escalate, as errors are discovered and fixed at later and later phases in the project life cycle. If the cost of fixing a requirements error discovered during the requirements phase is defined to be 1 unit, the cost to fix that error if found during the design phase increases to 3 - 8 units; at the manufacturing/build phase, the cost to fix the error is 7 - 16 units; at the integration and test phase, the cost to fix the error becomes 21 - 78 units; and at the operations phase, the cost to fix the requirements error ranged from 29 units to more than 1500 units

  9. Canadian Consumer Food Safety Practices and Knowledge: Foodbook Study.

    Science.gov (United States)

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

    2017-10-01

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

  10. Planning ahead: Improving escalation plans before the weekend.

    Science.gov (United States)

    Zarkali, Angeliki; Black, Duncan; Smee, Elizabeth; Deshraj, Anshul; Smallwood, Nicholas

    2014-01-01

    Handover is the system by which responsibility for patient care is transferred between healthcare professionals. A significant aspect of handover is the existence of an escalation plan for each patient in case of deterioration over the weekend. According to the Royal College of Physicians, all patients should have a clear escalation plan documented in the notes before a weekend, since parent medical teams (Consultant team in charge of care) are best placed to make these decisions. If left to on-call teams, at a time of deterioration over a weekend, they might not have all available information, the patient might be unable to be involved in the decisions, and the family might not be consulted. With this is mind, we decided to analyse the existing handover process in a medium sized district general hospital, with the aim of improving the process and the documentation of escalation plans. The results from our retrospective analysis of the system in place revealed a significant lack of documentation of escalation plans in the medical notes. Three sample wards were selected to analyse the current handover system and test proposed measures before hospital-wide implementation. After trialling of a physical handover meeting in addition to the existing intranet system and a proforma for the Friday ward round, the documentation of escalation plans in the patients' notes improved from 9.1% to 41.1%. Based on these results, as well as formal feedback from junior doctors and informal feedback from other staff, the physical handover meeting and Friday ward round proforma will be implemented throughout the Trust. Our interventions led to an improvement in the documentation of escalation plans in our hospital, thus saving precious time in the event of a patient's deterioration. This also ensures that families and patients are involved in the decision making process and kept informed, and reduces the burden for the weekend on-call teams.

  11. Clinical Factors Associated With Dose Escalation of Solifenacin for the Treatment of Overactive Bladder in Real Life Practice

    Directory of Open Access Journals (Sweden)

    Ji-Youn Chun

    2014-03-01

    Full Text Available PurposeTo determine the baseline clinical characteristics associated with dose escalation of solifenacin in patients with overactive bladder (OAB.MethodsWe analyzed the data of patients with OAB (micturition frequency ≥8/day and urgency ≥1/day who were treated with solifenacin and followed up for 24 weeks. According to our department protocol, all the patients kept voiding diaries, and OAB symptom scores (OABSS were monitored at baseline and after 4, 12, and 24 weeks of solifenacin treatment.ResultsIn total, 68 patients (mean age, 60.8±10.0 years were recruited. The dose escalation rate by the end of the study was 41.2%, from 23.5% at 4 weeks and 17.6% at 12 weeks. At baseline, the dose escalator group had significantly more OAB wet patients (53.6% vs. 20.0% and higher total OABSS (10.2±2.4 vs. 7.9±3.5, P=0.032 than the nonescalator group. OAB wet (odds ratio [OR], 4.615; 95% confidence interval [CI], 1.578-13.499; P<0.05 and total OABSS (OR, 1.398; 95% CI, 1.046-1.869; P<0.05 were found to be independently associated with dose escalation.ConclusionsPatients who have urgency urinary incontinence and high total OABSS have a tendency for dose escalation of solifenacin.

  12. Nuclear safety code study. Final report

    International Nuclear Information System (INIS)

    Jackson, C.; Abumansoor, K.; Myers, E.; Jespersen, D.; Cramer, E.; O'Reilly, B.; Carmichael, B.

    1980-06-01

    An unprotected overpower accident in a Liquid Metal Fast Breeder Reactor is studied. A mathematical model and a system of partial differential equations for the temperature are derived. After spatial discretization, a large system of ordinary differential equations is obtained. The steady state version of the equations is solved analytically

  13. Patients for patient safety in China: a cross sectional study.

    Science.gov (United States)

    Zhang, Qiongwen; Li, Yulin; Li, Jing; Mao, Xuanyue; Zhang, Lijuan; Ying, Qinghua; Wei, Xin; Shang, Lili; Zhang, Mingming

    2012-02-01

    To investigate the baseline status of patients' awareness, knowledge, and attitudes to patient safety in China, and to determine the factors that influence patients' involvement in patient safety. We conducted a cross sectional survey using questionnaires adapted from recent studies on patient safety from outside China. The items included medical errors, infection, medication safety, and other aspects of patient safety. The questionnaire included 17 items and 5 domains. The survey was conducted between Jan. 2009 and Dec. 2010 involving 1000 patients from ten grade-A hospitals in seven provinces or cities in China. Most patients from the surgery departments completed the questionnaires voluntarily and anonymously. Five reviewers independently input the data into Microsoft Excel 2003, and the data were double-checked. Data were analyzed using SPSS 15.0 software for differences in the perceptions and attitudes of patients toward patient safety among different genders, ages, and regions. We distributed 1000 questionnaires and collected 959 completed questionnaires (response rate: 96%). Among the respondents, 58% of patients did not know what medical error is. Sixty-five percent of patients wanted disclosure of all medical errors. After errors occurred, 58% of patients wanted explanations of all possible harms that had resulted. Among 187 patients who had experienced medical errors, 83% of patients had sought appropriate legal action. About 52% of patients understood hospital infection, but 28% patients did not know that infections could occur in hospital. Seventy-eight percent of patients thought that medical staff should wash their hands before examining patients. More than half of the patients (68%) were willing to remind the staff of hygiene if they saw unsanitary conditions in a health clinic. Only 14% of patients knew the side effects of medications that they took. The majority of patients surveyed expressed willingness to contribute to patient safety, but their

  14. SU-E-T-622: Identification and Improvement of Patients Eligible for Dose Escalation with Matched Plans

    International Nuclear Information System (INIS)

    Bush, K; Holcombe, C; Kapp, D; Buyyounouski, M; Hancock, S; Xing, L; Atwood, T; King, M

    2014-01-01

    Gy. Conclusion: Patientmatching is a promising method to identify eligible patients, and to assist in creating acceptable plans for dose-escalation. Further study will investigate other disease states. Additionally, the time-savings provided by patientmatching warrants further investigation. The following authors have equity ownership in Siris Medical, Inc: K Bush, TF Atwood

  15. Fire safety study of Dodewaard and Borssele nuclear power plants

    International Nuclear Information System (INIS)

    1988-03-01

    From the nuclear and conventional fire safety audits of both Dutch nuclear power plants performed under supervision of the Nuclear Safety Inspectorate and the Inspectorate for the Fire Services it turns out that the fire safety is sufficient however amenable for improvement. Besides a detailed description of the method of examination, the study 'Fire Safety' contains the results of the audit and 14 respectively 15 recommendations for improvement of the fire safety in Dodewaard and Borssele. The suggested recommendations which are applicable to both power plants are the following: fire fighting training for operators and guards, a complete emergency ventilation system of the control room, increase in the number of detectors and alarms, an increase in the quantity of water available for high-pressure fire fighting, improvement of fire barriers between several redundancies of nuclear safety systems, an investigation and possible improvement of the heat and radiation protection offered by presently used fire fighting suits. For Dodewaard a closed emergency staircase in the reactor building (secondary containment) is deemed necessary for personnel emergency escape routes and continued fire fighting if required

  16. A multicenter prospective randomized study comparing the efficacy of escalating higher biphasic versus low biphasic energy defibrillations in patients presenting with cardiac arrest in the in-hospital environment

    Directory of Open Access Journals (Sweden)

    Anantharaman V

    2017-01-01

    Full Text Available Venkataraman Anantharaman,1 Seow Yian Tay,2 Peter George Manning,3 Swee Han Lim,1 Terrance Siang Jin Chua,4 Mohan Tiru,5 Rabind Antony Charles,1 Vidya Sudarshan1 1Department of Emergency Medicine, Singapore General Hospital, 2Department of Emergency Medicine, Tan Tock Seng Hospital, 3Emergency Medicine Department, National University Hospital, 4Department of Cardiology, National Heart Centre, 5Accident and Emergency Department, Changi General Hospital, Singapore Background: Biphasic defibrillation has been practiced worldwide for >15 years. Yet, consensus does not exist on the best energy levels for optimal outcomes when used in patients with ventricular fibrillation (VF/pulseless ventricular tachycardia (VT.Methods: This prospective, randomized, controlled trial of 235 adult cardiac arrest patients with VF/VT was conducted in the emergency and cardiology departments. One group received low-energy (LE shocks at 150–150–150 J and the other escalating higher-energy (HE shocks at 200–300–360 J. If return of spontaneous circulation (ROSC was not achieved by the third shock, LE patients crossed over to the HE arm and HE patients continued at 360 J. Primary end point was ROSC. Secondary end points were 24-hour, 7-day, and 30-day survival.Results: Both groups were comparable for age, sex, cardiac risk factors, and duration of collapse and VF/VT. Of the 118 patients randomized to the LE group, 48 crossed over to the HE protocol, 24 for persistent VF, and 24 for recurrent VF. First-shock termination rates for HE and LE patients were 66.67% and 64.41%, respectively (P=0.78, confidence interval: 0.65–1.89. First-shock ROSC rates were 25.64% and 29.66%, respectively (P=0.56, confidence interval: 0.46–1.45. The 24-hour, 7-day, and 30-day survival rates were 85.71%, 74.29%, and 62.86% for first-shock ROSC LE patients and 70.00%, 50.00%, and 46.67% for first-shock ROSC HE patients, respectively. Conversion rates for further shocks at 200 J and

  17. Safety of pressurized water reactors: problems and corresponding studies

    International Nuclear Information System (INIS)

    Cogne, F.

    1976-01-01

    The author recalls the safety problems subject to researches in the CEA, either because of their importance or because studies made abroad were not sufficiently developed or were classified or in order to acquire an independent judgement when safety is concerned. Those problems and studies are submitted referring to the 3 existing shields between man and dangerous materials: fuel element can, thermal shield, (pressure vessel and pipes), biological shield of which the behaviour is studied in connection with outside aggressions such as earthquakes, plane crashes, chemical explosions.. [fr

  18. Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Coiffier, Bertrand; Lepretre, Stéphane; Pedersen, Lars Møller

    2008-01-01

    Safety and efficacy of the fully human anti-CD20 monoclonal antibody, ofatumumab, was analyzed in a multicenter dose-escalating study including 33 patients with relapsed or refractory chronic lymphocytic leukemia. Three cohorts of 3 (A), 3 (B), and 27 (C) patients received 4, once weekly, infusio...

  19. Phase I Escalating-Dose Trial of CAR-T Therapy Targeting CEA+ Metastatic Colorectal Cancers.

    Science.gov (United States)

    Zhang, Chengcheng; Wang, Zhe; Yang, Zhi; Wang, Meiling; Li, Shiqi; Li, Yunyan; Zhang, Rui; Xiong, Zhouxing; Wei, Zhihao; Shen, Junjie; Luo, Yongli; Zhang, Qianzhen; Liu, Limei; Qin, Hong; Liu, Wei; Wu, Feng; Chen, Wei; Pan, Feng; Zhang, Xianquan; Bie, Ping; Liang, Houjie; Pecher, Gabriele; Qian, Cheng

    2017-05-03

    Chimeric antigen receptor T (CAR-T) cells have shown promising efficacy in treatment of hematological malignancies, but its applications in solid tumors need further exploration. In this study, we investigated CAR-T therapy targeting carcino-embryonic antigen (CEA)-positive colorectal cancer (CRC) patients with metastases to evaluate its safety and efficacy. Five escalating dose levels (DLs) (1 × 10 5 to 1 × 10 8 /CAR + /kg cells) of CAR-T were applied in 10 CRC patients. Our data showed that severe adverse events related to CAR-T therapy were not observed. Of the 10 patients, 7 patients who experienced progressive disease (PD) in previous treatments had stable disease after CAR-T therapy. Two patients remained with stable disease for more than 30 weeks, and two patients showed tumor shrinkage by positron emission tomography (PET)/computed tomography (CT) and MRI analysis, respectively. Decline of serum CEA level was apparent in most patients even in long-term observation. Furthermore, we observed persistence of CAR-T cells in peripheral blood of patients receiving high doses of CAR-T therapy. Importantly, we observed CAR-T cell proliferation especially in patients after a second CAR-T therapy. Taken together, we demonstrated that CEA CAR-T cell therapy was well tolerated in CEA + CRC patients even in high doses, and some efficacy was observed in most of the treated patients. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  20. CANDU 6 probabilistic safety study summary

    International Nuclear Information System (INIS)

    1988-07-01

    This report summarizes the methodology, phenomenology and results relevent to the assessment of severe events in a CANDU 6 (formerly designated CANDU 600) station. The station design being analysed is based on a CANDU 6 Mark I currently operating in Canada. This evaluation includes event frequency and fission product release assessments but does not include assessment of radiation dose to the public, so that the information is equivalent to a level 2 Probabilistic Risk Assessment (PRA). The study has shown that the predicted overall average frequency for core melt in a CANDU 6 Mark I is 4.4 x 10 -6 events/year. This low frequency is, in large part due to the heavy water moderator which acts as a heat sink, prevents UO 2 melting and maintains core geometry for many events which could otherwise result in a core melt. The consequences for most core melts will be limited to the release of a fraction of noble gases and organic iodides. Other isotopes will be condensed or dissolved in the containment atmosphere and are ultimately retained in the pool of water in the basement where they are unavailable for release. Most core melts (∼ 90%) can be mitigated by operator action so that there is no danger of consequential damage to the containment structure and leak tightness. The frequency and consequences of less likely, more severe core melt sequences are also discussed in this report and shown to be small contributors to public risk

  1. Nuclear safety code study. Final report

    International Nuclear Information System (INIS)

    Jackson, C.; Abumansoor, K.; Myers, E.; Jesperson, D.; Cramer, E.; O'Reilly, B.; Carmichael, B.

    1980-06-01

    An unprotected overpower accident in a Liquid Metal Fast Breeder Reactor is studied. We construct a mathematical model and derive a system of partial differential equations for the temperature. After spatial discretization, we have a large system of ordinary differential equations; the system is stiff. We solve the steady state version of our equations analytically and obtain good agreement with other work. Then we solve the time-dependent problem numerically, using two stiff techniques and one non-stiff technique. The stiff techniques are vastly more efficient than the non-stiff technique. Between the two stiff techniques, the Gear backward differentiation formulas are more efficient than an implicit Runge-Kutta type method. We also compare the use of the full neutron kinetics equations to an approximation called the zero-lifetime system. Use of the zero-lifetime system is thought to make the problem easier to solve. Results indicate this is not true when a good stiff method is used. Thus use of the zero-lifetime system is probably not necessary, and should be avoided

  2. The social process of escalation: a promising focus for crisis management research

    Directory of Open Access Journals (Sweden)

    Bergström Johan

    2012-06-01

    Full Text Available Abstract Background This study identifies a promising, new focus for the crisis management research in the health care domain. After reviewing the literature on health care crisis management, there seems to be a knowledge-gap regarding organisational change and adaption, especially when health care situations goes from normal, to non-normal, to pathological and further into a state of emergency or crisis. Discussion Based on studies of escalating situations in obstetric care it is suggested that two theoretical perspectives (contingency theory and the idea of failure as a result of incomplete interaction tend to simplify the issue of escalation rather than attend to its complexities (including the various power relations among the stakeholders involved. However studying the process of escalation as inherently complex and social allows us to see the definition of a situation as normal or non-normal as an exercise of power in itself, rather than representing a putatively correct response to a particular emergency. Implications The concept of escalation, when treated this way, can help us further the analysis of clinical and institutional acts and competence. It can also turn our attention to some important elements in a class of social phenomenon, crises and emergencies, that so far have not received the attention they deserve. Focusing on organisational choreography, that interplay of potential factors such as power, professional identity, organisational accountability, and experience, is not only a promising focus for future naturalistic research but also for developing more pragmatic strategies that can enhance organisational coordination and response in complex events.

  3. Safety design study of fast breeder reactors in Japan

    International Nuclear Information System (INIS)

    Miura, M.; Inagaki, T.

    1992-01-01

    This paper reports on two fast breeder reactor (FBR) concepts, the tank type and the loop type, that have been studied as possible reactor designs to be used for a demonstration FBR (DFBR). The basic principle fo the DFBR design is to ensure plant safety through a defense-in-depth methodology. Improvements in the seismic and thermal stress designs have been attempted for both reactor concepts. The system design study strives to maximize the reliability of the safety-related systems and to rationalize commercialization of the plant

  4. A study on optimization of the nuclear safety system

    International Nuclear Information System (INIS)

    Lee, Sang Hoon; Koh, Byung Joon; Kim, Jin Soo; Kim, Byoung Do; Cho, Seong Won; Kwon, Seog Kwon; Choi, Kwang Sik

    1986-12-01

    The number of nuclear facilities (nuclear power plants, research reactors, nuclear fuel facilities) under construction or in operation in Korea continues to increase and this has brought about increased importance and concerns toward nuclear safety in Korea. Also, domestic nuclear related organizations are increasingly carrying out the design/construction of nuclear power plants and the development /supply of nuclear fuels. In order to flexibly respond to these changes and to suggest direction to take, it is necessary to re-examine the current nuclear safety regulation system. This study is carried out in two stages and this report describes the results of the analysis and the assessment of the nuclear licencing system of such foreign countries as sweden and German, as the first of the two. In this regard, this study includes the analysis on the backgrounds on the choice of nuclear licensing system, the analysis on the licensing procedures, the analysis on the safety inspection system and the enforcement laws, the analysis on the structure and function of the regulatory, business and research organizations as well as the analysis on the relationship between the safety research and the regulatory duties. In this study, the German safety inspection system and the enforcement procedures and the Swedish nuclear licensing system are analyzed in detail. By comparing and assessing the finding with the current Korea Nuclear Licensing System, this study points out some reform measures of the Korean system that needs to improved. With the changing situations in mind, this study aims to develop the nuclear safety regulation system optimized for Korean situation by re-examining the current regulation system. (Author)

  5. An accelerated dose escalation with a grass pollen allergoid is safe and well-tolerated: a randomized open label phase II trial.

    Science.gov (United States)

    Chaker, A M; Al-Kadah, B; Luther, U; Neumann, U; Wagenmann, M

    2015-01-01

    The number of injections in the dose escalation of subcutaneous immunotherapy (SCIT) is small for some currently used hypoallergenic allergoids, but can still be inconvenient to patients and can impair compliance. The aim of this trial was to compare safety and tolerability of an accelerated to the conventional dose escalation scheme of a grass pollen allergoid. In an open label phase II trial, 122 patients were 1:1 randomized for SCIT using a grass pollen allergoid with an accelerated dose escalation comprising only 4 weekly injections (Group I) or a conventional dose escalation including 7 weekly injections (Group II). Safety determination included the occurrence of local and systemic adverse events. Tolerability was assessed by patients and physicians. Treatment-related adverse events were observed in 22 (36.1 %) patients in Group I and 15 (24.6 %) in Group II. Local reactions were reported by 18 patients in Group I and 11 in Group II. Five Grade 1 systemic reactions (WAO classification) were observed in Group I and 2 in Group II. Grade 2 reactions occurred 3 times in Group I and 2 times in Group II. Tolerability was rated as "good" or "very good" by 53 (86.9 %) patients in Group I and 59 (100 %) in Group II by investigators. Forty-eight patients in Group I (80.0 %) and 54 in Group II (91.5 %) rated tolerability as "good" or "very good". The dose escalation of a grass pollen allergoid can be accelerated with safety and tolerability profiles comparable to the conventional dose escalation.

  6. An Intelligent System for Aggression De-escalation Training

    NARCIS (Netherlands)

    Bosse, T.; Gerritsen, C.; de Man, J.

    2016-01-01

    Artificial Intelligence techniques are increasingly being used to develop smart training applications for professionals in various domains. This paper presents an intelligent training system that enables professionals in the public domain to practice their aggression de-escalation skills. The system

  7. Escalator: An Autonomous Scheduling Scheme for Convergecast in TSCH

    Directory of Open Access Journals (Sweden)

    Sukho Oh

    2018-04-01

    Full Text Available Time Slotted Channel Hopping (TSCH is widely used in the industrial wireless sensor networks due to its high reliability and energy efficiency. Various timeslot and channel scheduling schemes have been proposed for achieving high reliability and energy efficiency for TSCH networks. Recently proposed autonomous scheduling schemes provide flexible timeslot scheduling based on the routing topology, but do not take into account the network traffic and packet forwarding delays. In this paper, we propose an autonomous scheduling scheme for convergecast in TSCH networks with RPL as a routing protocol, named Escalator. Escalator generates a consecutive timeslot schedule along the packet forwarding path to minimize the packet transmission delay. The schedule is generated autonomously by utilizing only the local routing topology information without any additional signaling with other nodes. The generated schedule is guaranteed to be conflict-free, in that all nodes in the network could transmit packets to the sink in every slotframe cycle. We implement Escalator and evaluate its performance with existing autonomous scheduling schemes through a testbed and simulation. Experimental results show that the proposed Escalator has lower end-to-end delay and higher packet delivery ratio compared to the existing schemes regardless of the network topology.

  8. Escalator: An Autonomous Scheduling Scheme for Convergecast in TSCH.

    Science.gov (United States)

    Oh, Sukho; Hwang, DongYeop; Kim, Ki-Hyung; Kim, Kangseok

    2018-04-16

    Time Slotted Channel Hopping (TSCH) is widely used in the industrial wireless sensor networks due to its high reliability and energy efficiency. Various timeslot and channel scheduling schemes have been proposed for achieving high reliability and energy efficiency for TSCH networks. Recently proposed autonomous scheduling schemes provide flexible timeslot scheduling based on the routing topology, but do not take into account the network traffic and packet forwarding delays. In this paper, we propose an autonomous scheduling scheme for convergecast in TSCH networks with RPL as a routing protocol, named Escalator. Escalator generates a consecutive timeslot schedule along the packet forwarding path to minimize the packet transmission delay. The schedule is generated autonomously by utilizing only the local routing topology information without any additional signaling with other nodes. The generated schedule is guaranteed to be conflict-free, in that all nodes in the network could transmit packets to the sink in every slotframe cycle. We implement Escalator and evaluate its performance with existing autonomous scheduling schemes through a testbed and simulation. Experimental results show that the proposed Escalator has lower end-to-end delay and higher packet delivery ratio compared to the existing schemes regardless of the network topology.

  9. A probabilistic safety assessment PEER review: Case study on the use of probabilistic safety assessment for safety decisions

    International Nuclear Information System (INIS)

    1989-10-01

    The purpose of this case study is to illustrate, using an actual example, the organizing and carrying out of an independent peer review of a draft full-scope (level 3) probabilistic safety assessment. The specific findings of the peer review are of less importance than the approach taken, the interaction between sponsor and study team, and the technical and administrative issues that can arise during a peer review. This case study will examine the following issues: how the scope of the peer review was established, based on how it was to be used by the review sponsoring body; how the level of effort was determined, and what this determination meant for the technical quality of the review; how the team of peer reviewers was selected; how the review itself was carried out; what findings were made; what was done with these findings by both the review sponsoring body and the PSA analysis team. 9 refs, 2 figs, 1 tab

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  11. Skills escalator in allied health: a time for reflection and refocus

    Directory of Open Access Journals (Sweden)

    Gilmore LG

    2011-09-01

    Full Text Available Lisa G Gilmore1, Joanne H Morris1, Karen Murphy2, Karen Grimmer-Somers3, Saravana Kumar31The Canberra Hospital, ACT Government Health Directorate, Canberra, ACT; 2ACT Government Health Directorate, Canberra, ACT; 3International Centre for Allied Evidence, University of South Australia, Adelaide, SA, AustraliaAbstract: It is abundantly clear that the health workforce of tomorrow will meet a number of unique challenges. There are a number of drivers for this, including the changing demographics of patients and health professionals, changing working patterns and mobility of the health workforce, evolving models of care, emerging evidence base, altering funding models, and the need to underpin health care service delivery with safety, effectiveness, patient centeredness, efficiency, equity, and timeliness. It is in this time of change that role extension within health disciplines is seen as an important tool to meet some of these challenges. Role extension is viewed as a skills escalator, where practitioners move up the skills escalator within the scope of their discipline, to advance it and then, with training, extend it. Within allied health, in some disciplines, advanced and extended scope of practice initiatives have mushroomed. Often these initiatives have been ad hoc, and opportunistically created in response to local needs and requirements. As these initiatives are local and context-dependent, to date there is very little uniformity or congruency between these initiatives. This has led to variability in implementation, lack of rigorous evaluations and, ultimately, poor long-term sustainability. In this paper, we reflect on a number of key issues, drawing on our own experiences in undertaking such initiatives, which need to be taken into account when considering advanced and extended scope of practice for allied health.Keywords: allied health, skill escalation, extended scope of practice, advanced scope of practice

  12. Elevating standards, improving safety.

    Science.gov (United States)

    Clarke, Richard

    2014-08-01

    In our latest 'technical guidance' article, Richard Clarke, sales and marketing director at one of the UK's leading lift and escalator specialists, Schindler, examines some of the key issues surrounding the specification, maintenance, and operation of lifts in hospitals to help ensure the highest standards of safety and reliability.

  13. A Study on University Student's Perception of Food Safety

    International Nuclear Information System (INIS)

    Koh, K.H.

    2007-01-01

    The present study compared the perception of food safety between students majoring in Food Science and Nutrition and other students who are ordinary food consumers. The importance of factors related to food safety was high in order of pesticide residue (45%), food additives (24%), food pathogens (15%), GM foods (7%), antibiotics (4%) and irradiated foods (4%), and no significant difference was observed according to major(p less than 0.10). Particularly with regard to irradiated food, students majoring in Food Science and Nutrition replied 'no hamful' (21%), 'harmful' (58%) or 'not sure' (21%), showing that more than half of them thought that irradiated food is harmful

  14. Fusion-reactor blanket-material safety-compatibility studies

    International Nuclear Information System (INIS)

    Jeppson, D.W.; Muhlestein, L.D.; Keough, R.F.; Cohen, S.

    1982-11-01

    Blanket material selection for fusion reactors is strongly influenced by the desire to minimize safety and environmental concerns. Blanket material safety compatibility studies are being conducted to identify and characterize blanket-coolant-material interactions under postulated reactor accident conditions. Recently completed scoping compatibility tests indicate that : (1) ternary oxides (LiAlO 2 , Li 2 ZrO 3 , Li 2 SiO 3 , Li 4 SiO 4 and LiTiO 3 ) at postulated blanket operating temperatures are compatible with water coolant, while liquid lithium and Li 7 Pb 2 alloy reactions with water generate heat, aerosol and hydrogen; (2) lithium oxide and Li 17 Pb 83 alloy react mildly with water requiring special precautions to control hydrogen release; (3) liquid lithium reacts substantially, while Li 17 Pb 83 alloy reacts mildly with concrete to produce hydrogen; and (4) liquid lithium-air reactions present some major safety concerns

  15. Calculational study for criticality safety data of fissionable actinides

    International Nuclear Information System (INIS)

    Nojiri, Ichiro; Fukasaku, Yasuhiro.

    1997-01-01

    This study has been carried out to obtain basic criticality safety characteristics of minor actinides nuclides. Criticality safety data of minor actinides nuclides have been surveyed through public literatures. Critical mass of seven nuclides, Np-237, Am-241, Am-242m, Am-243, Cm-243, Cm-244 and Cm-245, have been calculated by using two code systems of criticality safety analysis, SCALE-4 and MCNP4A, under some material and reflector conditions. Some applicable cross-section libraries have been used for each code systems. Calculated data have been compared with each other and with published data. The results of this comparison shows that there is no discrepancy within the computational codes and the calculated data is strongly depend on the cross-section library. (author)

  16. Patients' experiences of safety during haemodialysis treatment - a qualitative study

    NARCIS (Netherlands)

    Lovink, M.H.; Kars, M.C.; Man-van Ginkel, J.M. de; Schoonhoven, L.

    2015-01-01

    AIM: To explore the experiences of safety of adult patients during their haemodialysis treatment. BACKGROUND: Haemodialysis is a complex treatment with a risk for harm that causes anxiety among many patients. To date, no in-depth study of haemodialysis patients' emotional responses to conditions of

  17. Can we avoid high levels of dose escalation for high-risk prostate cancer in the setting of androgen deprivation?

    Science.gov (United States)

    Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

    2016-01-01

    Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve outcomes in patients with high-risk prostate cancer. However, there is little evidence specifically evaluating DE-EBRT for patients with high-risk prostate cancer receiving ADT, particularly for EBRT doses >74 Gy. We aimed to determine whether DE-EBRT >74 Gy improves outcomes for patients with high-risk prostate cancer receiving long-term ADT. Patients with high-risk prostate cancer were treated on an institutional protocol prescribing 3-6 months neoadjuvant ADT and DE-EBRT, followed by 2 years of adjuvant ADT. Between 2006 and 2012, EBRT doses were escalated from 74 Gy to 76 Gy and then to 78 Gy. We interrogated our electronic medical record to identify these patients and analyzed our results by comparing dose levels. In all, 479 patients were treated with a 68-month median follow-up. The 5-year biochemical disease-free survivals for the 74 Gy, 76 Gy, and 78 Gy groups were 87.8%, 86.9%, and 91.6%, respectively. The metastasis-free survivals were 95.5%, 94.5%, and 93.9%, respectively, and the prostate cancer-specific survivals were 100%, 94.4%, and 98.1%, respectively. Dose escalation had no impact on any outcome in either univariate or multivariate analysis. There was no benefit of DE-EBRT >74 Gy in our cohort of high-risk prostate patients treated with long-term ADT. As dose escalation has higher risks of radiotherapy-induced toxicity, it may be feasible to omit dose escalation beyond 74 Gy in this group of patients. Randomized studies evaluating dose escalation for high-risk patients receiving ADT should be considered.

  18. SAFETY

    CERN Multimedia

    M. Plagge, C. Schaefer and N. Dupont

    2013-01-01

    Fire Safety – Essential for a particle detector The CMS detector is a marvel of high technology, one of the most precise particle measurement devices we have built until now. Of course it has to be protected from external and internal incidents like the ones that can occur from fires. Due to the fire load, the permanent availability of oxygen and the presence of various ignition sources mostly based on electricity this has to be addressed. Starting from the beam pipe towards the magnet coil, the detector is protected by flooding it with pure gaseous nitrogen during operation. The outer shell of CMS, namely the yoke and the muon chambers are then covered by an emergency inertion system also based on nitrogen. To ensure maximum fire safety, all materials used comply with the CERN regulations IS 23 and IS 41 with only a few exceptions. Every piece of the 30-tonne polyethylene shielding is high-density material, borated, boxed within steel and coated with intumescent (a paint that creates a thick co...

  19. SAFETY

    CERN Multimedia

    C. Schaefer and N. Dupont

    2013-01-01

      “Safety is the highest priority”: this statement from CERN is endorsed by the CMS management. An interpretation of this statement may bring you to the conclusion that you should stop working in order to avoid risks. If the safety is the priority, work is not! This would be a misunderstanding and misinterpretation. One should understand that “working safely” or “operating safely” is the priority at CERN. CERN personnel are exposed to different hazards on many levels on a daily basis. However, risk analyses and assessments are done in order to limit the number and the gravity of accidents. For example, this process takes place each time you cross the road. The hazard is the moving vehicle, the stake is you and the risk might be the risk of collision between both. The same principle has to be applied during our daily work. In particular, keeping in mind the general principles of prevention defined in the late 1980s. These principles wer...

  20. Knowledge Translation and Patient Safety: The Canadian Adverse Events Study

    OpenAIRE

    Baker, G. Ross; Norton, Peter; Flintoft, Virginia

    2006-01-01

    The Canadian Adverse Events Study was the first national study of adverse events in Canadian hospitals. Learning from the controversy surrounding similar studies in other countries, the team engaged in extensive knowledge translation activities throughout the life of the project. Using meetings, Web-based communication and other tools, the team successfully prepared most Canadian stakeholders for the study’s release, allowing them to develop anticipatory patient safety initiatives. However, u...

  1. Safety benefits from CANDU reactor replacement - a case study

    International Nuclear Information System (INIS)

    Mottram, R.; Millard, J.W.F.; Purdy, P.

    2011-01-01

    Both total core replacement and core retubing have been used in the CANDU industry. For future plant refurbishments, based on experience both in new construction and in recent refurbishments, the concept of total core replacement has been revisited. This builds on practices for replacement of other large plant equipment like boilers. The Bruce CANDU reactors, with their local shield tanks built around the Calandria and containment closely located around that Calandria Shield Tank Assembly (CSTA), are believed to be good candidates for core replacement. A structured process was used to design a replacement CSTA suitable for Bruce A use. The work started with a study of opportunities for safety enhancements in the core. This progressed into design studies and related design assist safety analysis on the reactor. A key element of the work involved consideration of how verified features from later CANDU designs, and from our new reactor design work, could be tailored to fit this replacement core. The replacement reactor core brings in structural improvements in both calandria and end shield, and safety improvements like the natural circulation enhancing moderator cooling layout and further optimized reactivity layouts to improve shutdown system performance. Bruce Power are currently studying the business implications of this and retube techniques as part of preparation for future refurbishments. The work explained in this paper is in the context of the safety related changes and the work to choose and quantify them. (author)

  2. Safety benefits from CANDU reactor replacement. A case study

    International Nuclear Information System (INIS)

    Mottram, R.; Millard, J.W.F.; Purdy, P.

    2011-01-01

    Both total core replacement and core retubing have been used in the CANDU industry. For future plant refurbishments, based on experience both in new construction and in recent refurbishments, the concept of total core replacement has been revisited. This builds on practices for replacement of other large plant equipment like boilers. The Bruce CANDU reactors, with their local shield tanks built around the Calandria and containment closely located around that Calandria Shield Tank Assembly (CSTA), are believed to be good candidates for core replacement. A structured process was used to design a replacement CSTA suitable for Bruce A use. The work started with a study of opportunities for safety enhancements in the core. This progressed into design studies and related design assist safety analysis on the reactor. A key element of the work involved consideration of how verified features from later CANDU designs, and from our new reactor design work, could be tailored to fit this replacement core. The replacement reactor core brings in structural improvements in both calandria and end shield, and safety improvements like the natural circulation enhancing moderator cooling layout and further optimized reactivity layouts to improve shutdown system performance. Bruce Power are currently studying the business implications of this and retube techniques as part of preparation for future refurbishments. The work explained in this paper is in the context of the safety related changes and the work to choose and quantify them. (author)

  3. Safety studies on intravenous administration of oncolytic recombinant vesicular stomatitis virus in purpose-bred beagle dogs.

    Science.gov (United States)

    LeBlanc, Amy K; Naik, Shruthi; Galyon, Gina D; Jenks, Nathan; Steele, Mike; Peng, Kah-Whye; Federspiel, Mark J; Donnell, Robert; Russell, Stephen J

    2013-12-01

    VSV-IFNβ-NIS is a novel recombinant oncolytic vesicular stomatitis virus (VSV) with documented efficacy and safety in preclinical murine models of cancer. To facilitate clinical translation of this promising oncolytic therapy in patients with disseminated cancer, we are utilizing a comparative oncology approach to gather data describing the safety and efficacy of systemic VSV-IFNβ-NIS administration in dogs with naturally occurring cancer. In support of this, we executed a dose-escalation study in purpose-bred dogs to determine the maximum tolerated dose (MTD) of systemic VSV-hIFNβ-NIS, characterize the adverse event profile, and describe routes and duration of viral shedding in healthy, immune-competent dogs. The data indicate that an intravenous dose of 10(10) TCID50 is well tolerated in dogs. Expected adverse events were mild to moderate fever, self-limiting nausea and vomiting, lymphopenia, and oral mucosal lesions. Unexpected adverse events included prolongation of partial thromboplastin time, development of bacterial urinary tract infection, and scrotal dermatitis, and in one dog receiving 10(11) TCID50 (10 × the MTD), the development of severe hepatotoxicity and symptoms of shock leading to euthanasia. Viral shedding data indicate that detectable viral genome in blood diminishes rapidly with anti-VSV neutralizing antibodies detectable in blood as early as day 5 postintravenous virus administration. While low levels of viral genome copies were detectable in plasma, urine, and buccal swabs of dogs treated at the MTD, no infectious virus was detectable in plasma, urine, or buccal swabs at any of the doses tested. These studies confirm that VSV can be safely administered systemically in dogs, justifying the use of oncolytic VSV as a novel therapy for the treatment of canine cancer.

  4. Empirical Analysis of Construction Safety Climate - A Study

    OpenAIRE

    S.V.S.RAJA PRASAD; K.P.REGHUNATH

    2010-01-01

    Safety in the construction industry has always been a major issue. Though much improvement in construction safety has been achieved, the industry still continues to lag behind most other industries with regard to safety. The safety climate of any organization consists of employee’s attitudes towards and perceptions of, health and safety behavior. Construction workers attitudes towards safety are influenced by their perceptions of risk, management, safety rulesand procedures. A measure of safe...

  5. A Study on Drug Safety Monitoring Program in India

    Science.gov (United States)

    Ahmad, A.; Patel, Isha; Sanyal, Sudeepa; Balkrishnan, R.; Mohanta, G. P.

    2014-01-01

    Pharmacovigilance is useful in assuring the safety of medicines and protecting the consumers from their harmful effects. A number of single drugs as well as fixed dose combinations have been banned from manufacturing, marketing and distribution in India. An important issue about the availability of banned drugs over the counter in India is that sufficient adverse drug reactions data about these drugs have not been reported. The most common categories of drugs withdrawn in the last decade were nonsteroidal antiinflammatory drugs (28%), antidiabetics (14.28%), antiobesity (14.28%), antihistamines (14.28%), gastroprokinetic drugs (7.14%), breast cancer and infertility drugs (7.14%), irritable bowel syndrome and constipation drugs (7.14%) and antibiotics (7.14%). Drug withdrawals from market were made mainly due to safety issues involving cardiovascular events (57.14%) and liver damage (14.28%). Majority of drugs have been banned since 3-5 years in other countries but are still available for sale in India. The present study compares the drug safety monitoring systems in the developed countries such as the USA and UK and provides implications for developing a system that can ensure the safety and efficacy of drugs in India. Absence of a gold standard for a drug safety surveillance system, variations in culture and clinical practice across countries makes it difficult for India to completely adopt another country's practices. There should be a multidisciplinary approach towards drug safety that should be implemented throughout the entire duration spanning from drug discovery to usage by consumers. PMID:25425751

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

    International Nuclear Information System (INIS)

    Makino, Maomi; Takano, Kenichi

    2004-01-01

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

  7. Ferrocyanide safety project ferrocyanide aging studies. Final report

    International Nuclear Information System (INIS)

    Lilga, M.A.; Hallen, R.T.; Alderson, E.V.

    1996-06-01

    This final report gives the results of the work conducted by Pacific Northwest National Laboratory (PNNL) from FY 1992 to FY 1996 on the Ferrocyanide Aging Studies, part of the Ferrocyanide Safety Project. The Ferrocyanide Safety Project was initiated as a result of concern raised about the safe storage of ferrocyanide waste intermixed with oxidants, such as nitrate and nitrite salts, in Hanford Site single-shell tanks (SSTs). In the laboratory, such mixtures can be made to undergo uncontrolled or explosive reactions by heating dry reagents to over 200 degrees C. In 1987, an Environmental Impact Statement (EIS), published by the U.S. Department of Energy (DOE), Final Environmental Impact Statement, Disposal of Hanford Defense High-Level Transuranic and Tank Waste, Hanford Site, Richland, Washington, included an environmental impact analysis of potential explosions involving ferrocyanide-nitrate mixtures. The EIS postulated that an explosion could occur during mechanical retrieval of saltcake or sludge from a ferrocyanide waste tank, and concluded that this worst-case accident could create enough energy to release radioactive material to the atmosphere through ventilation openings, exposing persons offsite to a short-term radiation dose of approximately 200 mrem. Later, in a separate study (1990), the General Accounting Office postulated a worst-case accident of one to two orders of magnitude greater than that postulated in the DOE EIS. The uncertainties regarding the safety envelope of the Hanford Site ferrocyanide waste tanks led to the declaration of the Ferrocyanide Unreviewed Safety Question (USQ) in October 1990

  8. Can we avoid high levels of dose escalation for high-risk prostate cancer in the setting of androgen deprivation?

    Directory of Open Access Journals (Sweden)

    Shakespeare TP

    2016-05-01

    Full Text Available Thomas P Shakespeare,1,2 Shea W Wilcox,1 Noel J Aherne1,2 1Department of Radiation Oncology, North Coast Cancer Institute, 2Rural Clinical School, Faculty of Medicine, University of New South Wales, Coffs Harbour, NSW, Australia Aim: Both dose-escalated external beam radiotherapy (DE-EBRT and androgen deprivation therapy (ADT improve outcomes in patients with high-risk prostate cancer. However, there is little evidence specifically evaluating DE-EBRT for patients with high-risk prostate cancer receiving ADT, particularly for EBRT doses >74 Gy. We aimed to determine whether DE-EBRT >74 Gy improves outcomes for patients with high-risk prostate cancer receiving long-term ADT. Patients and methods: Patients with high-risk prostate cancer were treated on an institutional protocol prescribing 3–6 months neoadjuvant ADT and DE-EBRT, followed by 2 years of adjuvant ADT. Between 2006 and 2012, EBRT doses were escalated from 74 Gy to 76 Gy and then to 78 Gy. We interrogated our electronic medical record to identify these patients and analyzed our results by comparing dose levels. Results: In all, 479 patients were treated with a 68-month median follow-up. The 5-year biochemical disease-free survivals for the 74 Gy, 76 Gy, and 78 Gy groups were 87.8%, 86.9%, and 91.6%, respectively. The metastasis-free survivals were 95.5%, 94.5%, and 93.9%, respectively, and the prostate cancer-specific survivals were 100%, 94.4%, and 98.1%, respectively. Dose escalation had no impact on any outcome in either univariate or multivariate analysis. Conclusion: There was no benefit of DE-EBRT >74 Gy in our cohort of high-risk prostate patients treated with long-term ADT. As dose escalation has higher risks of radiotherapy-induced toxicity, it may be feasible to omit dose escalation beyond 74 Gy in this group of patients. Randomized studies evaluating dose escalation for high-risk patients receiving ADT should be considered. Keywords: radiotherapy, IMRT, dose

  9. Safety

    International Nuclear Information System (INIS)

    Jones, P.M.S.

    1987-01-01

    Aspects of fission reactors are considered - control, heat removal and containment. Brief descriptions of the reactor accidents at the SL-1 reactor (1961), Windscale (1957), Browns Ferry (1975), Three Mile Island (1979) and Chernobyl (1986) are given. The idea of inherently safe reactor designs is discussed. Safety assessment is considered under the headings of preliminary hazard analysis, failure mode analysis, event trees, fault trees, common mode failure and probabalistic risk assessments. These latter can result in a series of risk distributions linked to specific groups of fault sequences and specific consequences. A frequency-consequence diagram is shown. Fatal accident incidence rates in different countries including the United Kingdom for various industries are quoted. The incidence of fatal cancers from occupational exposure to chemicals is tabulated. Human factors and the acceptability of risk are considered. (U.K.)

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

    International Nuclear Information System (INIS)

    Shimo, Michikuni

    2002-03-01

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

  11. Radiological safety research for nuclear excavation projects - Interoceanic canal studies

    International Nuclear Information System (INIS)

    Klement, A.W. Jr.

    1969-01-01

    The general radiological problems encountered in nuclear cratering and nuclear excavation projects are discussed. Procedures for assessing radiological problems in such projects are outlined. Included in the discussions are source term, meteorology, fallout prediction and ecological factors. Continuing research requirements as well as pre- and post-excavation studies are important considerations. The procedures followed in the current interoceanic canal feasibility studies provide examples of radiological safety problems, current solutions and needed research. (author)

  12. Radiological safety research for nuclear excavation projects - Interoceanic canal studies

    Energy Technology Data Exchange (ETDEWEB)

    Klement, Jr, A W [U.S. Atomic Energy Commission, Las Vegas, NV (United States)

    1969-07-01

    The general radiological problems encountered in nuclear cratering and nuclear excavation projects are discussed. Procedures for assessing radiological problems in such projects are outlined. Included in the discussions are source term, meteorology, fallout prediction and ecological factors. Continuing research requirements as well as pre- and post-excavation studies are important considerations. The procedures followed in the current interoceanic canal feasibility studies provide examples of radiological safety problems, current solutions and needed research. (author)

  13. Pilot Study on Harmonisation of Reactor Safety in WENRA Countries

    International Nuclear Information System (INIS)

    2003-03-01

    Most of the objectives, set for the Pilot Study, were met. It can be concluded that the methodology was adequate for its purpose. National requirements on selected safety issues have been systematically compared and the major gaps and differences have been identified. Convenient overviews have been provided of differences and similarities between the countries. Furthermore, the conclusions are based on a safety justification and are detailed enough to provide input to a further more detailed analysis on the national level. It was not possible, however, to provide fully verified conclusions about the implementation of the reference levels in the different countries. This has to do with the following constraints on the study: In line with the Terms of Reference, the comparison of formal requirements did not address the more detailed use of criteria and methods to verify compliance. The same requirement could be enforced differently in different regulatory systems, and hence lead to different implementation. The Pilot Study also assessed the implementation, but it was not possible to do this in sufficient detail to identify such differences. The implementation was assessed on the basis of current knowledge of the respective regulatory body, but it was not possible to provide the panels with evidence of the implementation. For these reasons, conclusions about implemented safety provisions in the different countries should be drawn with precaution. The introduction of the panel assessments greatly improved the quality and consistency of the comparison assessments. Uncertainties in the assessments are mainly connected with lack of time to make a detailed analysis in some cases. The reliability of the assessments seems to be sufficient for the objectives of the Pilot Study. The introduction of the IAEA safety standards in the study proved to be helpful and provided confidence in the scope and strictness of the reference levels. This Pilot Study has contributed to

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

    OpenAIRE

    Morando, Mark Mario; Tian, Qingyun; Truong, Long T.; Vu, Hai L.

    2018-01-01

    Autonomous vehicle (AV) technology has advanced rapidly in recent years with some automated features already available in vehicles on the market. AVs are expected to reduce traffic crashes as the majority of crashes are related to driver errors, fatigue, alcohol, or drugs. However, very little research has been conducted to estimate the safety impact of AVs. This paper aims to investigate the safety impacts of AVs using a simulation-based surrogate safety measure approach. To this end, safety...

  15. EPR safety. Consideration of the internal and external hazards in the safety studies

    International Nuclear Information System (INIS)

    Gueguin, H.

    2008-04-01

    The author presents the main points of the Preliminary Safety Report of EDF on the EPR reactor safety. It concerns the considerations of the internal (fire, flood, explosions, pipes failures) and external (earthquakes, airplane falls, explosions, exceptional natural disasters, extreme meteorological conditions) damages. It presents how the safety report takes into account the aggression. (A.L.B.)

  16. Survey of the state of the German safety study

    International Nuclear Information System (INIS)

    Heuser, F.W.; Kotthoff, K.

    1977-01-01

    In spring 1976 the Federal Ministry of Research and Technology has ordered a safety study to assess the risk for a nuclear power plant with a PWR. Giving first a survey on the main subtasks of the study the present state of work and some first results are discussed. Assuming a failure of safety systems a core melt event and a subsequent failure of the containment could occur. Corresponding accident sequences are discussed in some detail. Related hereto the results of some calculations for fission product release with respect to different containment failure modes are given. According to the results obtained so far the consequences of a core melt event can essentially be restricted by the retention function of the containment. (orig.) [de

  17. Overview of the reactor safety study consequence model

    International Nuclear Information System (INIS)

    Wall, I.B.; Yaniv, S.S.; Blond, R.M.; McGrath, P.E.; Church, H.W.; Wayland, J.R.

    1977-01-01

    The Reactor Safety Study (WASH-1400) is a comprehensive assessment of the potential risk to the public from accidents in light water power reactors. The engineering analysis of the plants is described in detail in the Reactor Safety Study: it provides an estimate of the probability versus magnitude of the release of radioactive material. The consequence model, which is the subject of this paper, describes the progression of the postulated accident after the release of the radioactive material from the containment. A brief discussion of the manner in which the consequence calculations are performed is presented. The emphasis in the description is on the models and data that differ significantly from those previously used for these types of assessments. The results of the risk calculations for 100 light water power reactors are summarized

  18. Nuclear Criticality Technology and Safety Project parameter study database

    International Nuclear Information System (INIS)

    Toffer, H.; Erickson, D.G.; Samuel, T.J.; Pearson, J.S.

    1993-03-01

    A computerized, knowledge-screened, comprehensive database of the nuclear criticality safety documentation has been assembled as part of the Nuclear Criticality Technology and Safety (NCTS) Project. The database is focused on nuclear criticality parameter studies. The database has been computerized using dBASE III Plus and can be used on a personal computer or a workstation. More than 1300 documents have been reviewed by nuclear criticality specialists over the last 5 years to produce over 800 database entries. Nuclear criticality specialists will be able to access the database and retrieve information about topical parameter studies, authors, and chronology. The database places the accumulated knowledge in the nuclear criticality area over the last 50 years at the fingertips of a criticality analyst

  19. A study on safety assessment methodology for a vitrification plant

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Y. C.; Lee, G. S.; Choi, Y. C.; Kim, G. H. [Yonsei Univ., Seoul (Korea, Republic of)

    2002-03-15

    In this study, the technical and regulatory status of radioactive waste vitrification technologies in foreign and domestic plants is investigated and analyzed, and then significant factors are suggested which must be contained in the final technical guideline or standard for the safety assessment of vitrification plants. Also, the methods to estimate the stability of vitrified waste forms are suggested with property analysis of them. The contents and scope of the study are summarized as follows : survey of the status on radioactive waste vitrification technologies in foreign and domestic plants, survey of the characterization methodology for radioactive waste form, analysis of stability for vitrified waste forms, survey and analysis of technical standards and regulations concerned with them in foreign and domestic plants, suggestion of significant factors for the safety assessment of vitrification plants, submission of regulated technical standard on radioactive waste vitrification plats.

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

    Science.gov (United States)

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

    2017-03-28

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

  1. Reactor safety study applied to the Forsmark 3 Power Plant

    International Nuclear Information System (INIS)

    Ericsson, G.; Tiren, L.I.

    1978-01-01

    A reactor safety study of the Forsmark 3 BWR power plant has been carried out for the purpose of calculating core melt probabilities using WASH-1400 methods. A sensitivity analysis shows that the calculated core melt probability is changed by approximately a factor of 10 depending on assumptions made with respect to the probability of human error. The importance of the availability of off-site power and the influence of common cause failure is also discussed. (author)

  2. Phase I/II clinical and pharmacokinetic study evaluating a fully human monoclonal antibody against EGFr (HuMax-EGFr) in patients with advanced squamous cell carcinoma of the head and neck

    DEFF Research Database (Denmark)

    Bastholt, Lars; Specht, Lena; Jensen, Kenneth

    2007-01-01

    PURPOSE: To assess safety, tolerability, pharmacokinetics and clinical activity of HuMax-EGFr in patients with SCCHN. PATIENTS AND METHODS: Twenty-eight patients with SCCHN were enrolled. The study comprised a single-dose escalation part for assessment of safety issues followed by a repeat dose e...

  3. Extinction risk escalates in the tropics.

    Directory of Open Access Journals (Sweden)

    Jana C Vamosi

    Full Text Available The latitudinal biodiversity gradient remains one of the most widely recognized yet puzzling patterns in nature. Presently, the high level of extinction of tropical species, referred to as the "tropical biodiversity crisis", has the potential to erode this pattern. While the connection between species richness, extinction, and speciation has long intrigued biologists, these interactions have experienced increased poignancy due to their relevancy to where we should concentrate our conservation efforts. Natural extinction is a phenomenon thought to have its own latitudinal gradient, with lower extinction rates in the tropics being reported in beetles, birds, mammals, and bivalves. Processes that have buffered ecosystems from high extinction rates in the past may also buffer ecosystems against disturbance of anthropogenic origin. While potential parallels between historical and present-day extinction patterns have been acknowledged, they remain only superficially explored and plant extinction patterns have been particularly neglected. Studies on the disappearances of animal species have reached conflicting conclusions, with the rate of extinction appearing either higher or lower in species richness hotspots. Our global study of extinction risk in vascular plants finds disproportionately higher extinction risk in tropical countries, even when indicators of human pressure (GDP, population density, forest cover change are taken into account. Our results are at odds with the notion that the tropics represent a museum of plant biodiversity (places of historically lowered extinction and we discuss mechanisms that may reconcile this apparent contradiction.

  4. Extinction risk escalates in the tropics.

    Science.gov (United States)

    Vamosi, Jana C; Vamosi, Steven M

    2008-01-01

    The latitudinal biodiversity gradient remains one of the most widely recognized yet puzzling patterns in nature. Presently, the high level of extinction of tropical species, referred to as the "tropical biodiversity crisis", has the potential to erode this pattern. While the connection between species richness, extinction, and speciation has long intrigued biologists, these interactions have experienced increased poignancy due to their relevancy to where we should concentrate our conservation efforts. Natural extinction is a phenomenon thought to have its own latitudinal gradient, with lower extinction rates in the tropics being reported in beetles, birds, mammals, and bivalves. Processes that have buffered ecosystems from high extinction rates in the past may also buffer ecosystems against disturbance of anthropogenic origin. While potential parallels between historical and present-day extinction patterns have been acknowledged, they remain only superficially explored and plant extinction patterns have been particularly neglected. Studies on the disappearances of animal species have reached conflicting conclusions, with the rate of extinction appearing either higher or lower in species richness hotspots. Our global study of extinction risk in vascular plants finds disproportionately higher extinction risk in tropical countries, even when indicators of human pressure (GDP, population density, forest cover change) are taken into account. Our results are at odds with the notion that the tropics represent a museum of plant biodiversity (places of historically lowered extinction) and we discuss mechanisms that may reconcile this apparent contradiction.

  5. Phylogenetic escalation and decline of plant defense strategies

    Science.gov (United States)

    Agrawal, Anurag A.; Fishbein, Mark

    2008-01-01

    As the basal resource in most food webs, plants have evolved myriad strategies to battle consumption by herbivores. Over the past 50 years, plant defense theories have been formulated to explain the remarkable variation in abundance, distribution, and diversity of secondary chemistry and other defensive traits. For example, classic theories of enemy-driven evolutionary dynamics have hypothesized that defensive traits escalate through the diversification process. Despite the fact that macroevolutionary patterns are an explicit part of defense theories, phylogenetic analyses have not been previously attempted to disentangle specific predictions concerning (i) investment in resistance traits, (ii) recovery after damage, and (iii) plant growth rate. We constructed a molecular phylogeny of 38 species of milkweed and tested four major predictions of defense theory using maximum-likelihood methods. We did not find support for the growth-rate hypothesis. Our key finding was a pattern of phyletic decline in the three most potent resistance traits (cardenolides, latex, and trichomes) and an escalation of regrowth ability. Our neontological approach complements more common paleontological approaches to discover directional trends in the evolution of life and points to the importance of natural enemies in the macroevolution of species. The finding of macroevolutionary escalating regowth ability and declining resistance provides a window into the ongoing coevolutionary dynamics between plants and herbivores and suggests a revision of classic plant defense theory. Where plants are primarily consumed by specialist herbivores, regrowth (or tolerance) may be favored over resistance traits during the diversification process. PMID:18645183

  6. Learning to make collective decisions: the impact of confidence escalation.

    Science.gov (United States)

    Mahmoodi, Ali; Bang, Dan; Ahmadabadi, Majid Nili; Bahrami, Bahador

    2013-01-01

    Little is known about how people learn to take into account others' opinions in joint decisions. To address this question, we combined computational and empirical approaches. Human dyads made individual and joint visual perceptual decision and rated their confidence in those decisions (data previously published). We trained a reinforcement (temporal difference) learning agent to get the participants' confidence level and learn to arrive at a dyadic decision by finding the policy that either maximized the accuracy of the model decisions or maximally conformed to the empirical dyadic decisions. When confidences were shared visually without verbal interaction, RL agents successfully captured social learning. When participants exchanged confidences visually and interacted verbally, no collective benefit was achieved and the model failed to predict the dyadic behaviour. Behaviourally, dyad members' confidence increased progressively and verbal interaction accelerated this escalation. The success of the model in drawing collective benefit from dyad members was inversely related to confidence escalation rate. The findings show an automated learning agent can, in principle, combine individual opinions and achieve collective benefit but the same agent cannot discount the escalation suggesting that one cognitive component of collective decision making in human may involve discounting of overconfidence arising from interactions.

  7. Escalation with Overdose Control Using Ordinal Toxicity Grades for Cancer Phase I Clinical Trials

    Directory of Open Access Journals (Sweden)

    Mourad Tighiouart

    2012-01-01

    Full Text Available We extend a Bayesian adaptive phase I clinical trial design known as escalation with overdose control (EWOC by introducing an intermediate grade 2 toxicity when assessing dose-limiting toxicity (DLT. Under the proportional odds model assumption of dose-toxicity relationship, we prove that in the absence of DLT, the dose allocated to the next patient given that the previously treated patient had a maximum of grade 2 toxicity is lower than the dose given to the next patient had the previously treated patient exhibited a grade 0 or 1 toxicity at the most. Further, we prove that the coherence properties of EWOC are preserved. Simulation results show that the safety of the trial is not compromised and the efficiency of the estimate of the maximum tolerated dose (MTD is maintained relative to EWOC treating DLT as a binary outcome and that fewer patients are overdosed using this design when the true MTD is close to the minimum dose.

  8. Validation of treatment escalation as a definition of atopic eczema flares.

    Directory of Open Access Journals (Sweden)

    Kim S Thomas

    Full Text Available Atopic eczema (AE is a chronic disease with flares and remissions. Long-term control of AE flares has been identified as a core outcome domain for AE trials. However, it is unclear how flares should be defined and measured.To validate two concepts of AE flares based on daily reports of topical medication use: (i escalation of treatment and (ii days of topical anti-inflammatory medication use (topical corticosteroids and/or calcineurin inhibitors.Data from two published AE studies (studies A (n=336 and B (n=60 were analysed separately. Validity and feasibility of flare definitions were assessed using daily global bother (scale 0 to 10 as the reference standard. Intra-class correlations were reported for continuous variables, and odds ratios and area under the receiver operator characteristic (ROC curve for binary outcome measures.Good agreement was found between both AE flare definitions and change in global bother: area under the ROC curve for treatment escalation of 0.70 and 0.73 in studies A and B respectively, and area under the ROC curve of 0.69 for topical anti-inflammatory medication use (Study A only. Significant positive relationships were found between validated severity scales (POEM, SASSAD, TIS and the duration of AE flares occurring in the previous week - POEM and SASSAD rose by half a point for each unit increase in number of days in flare. Smaller increases were observed on the TIS scale. Completeness of daily diaries was 95% for Study A and 60% for Study B over 16 weeks.Both definitions were good proxy indicators of AE flares. We found no evidence that 'escalation of treatment' was a better measure of AE flares than 'use of topical anti-inflammatory medications'. Capturing disease flares in AE trials through daily recording of medication use is feasible and appears to be a good indicator of long-term control.Current Controlled Trials ISRCTN71423189 (Study A.

  9. A double-blind, randomized controlled trial to compare the effect of biannual peripheral magnetic resonance imaging, radiography and standard of care disease progression monitoring on pharmacotherapeutic escalation in rheumatoid and undifferentiated inflammatory arthritis: study protocol for a randomized controlled trial

    Science.gov (United States)

    2014-01-01

    Background Permanent joint damage is a major consequence of rheumatoid arthritis (RA), the most common and destructive form of inflammatory arthritis. In aggressive disease, joint damage can occur within 6 months from symptom onset. Early, intensive treatment with conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) can delay the onset and progression of joint damage. The primary objective of the study is to investigate the value of magnetic resonance imaging (MRI) or radiography (X-ray) over standard of care as tools to guide DMARD treatment decision-making by rheumatologists for the care of RA. Methods A double-blind, randomized controlled trial has been designed. Rheumatoid and undifferentiated inflammatory arthritis patients will undergo an MRI and X-ray assessment every 6 months. Baseline adaptive randomization will be used to allocate participants to MRI, X-ray, or sham-intervention groups on a background of standard of care. Prognostic markers, treating physician, and baseline DMARD therapy will be used as intervention allocation parameters. The outcome measures in rheumatology RA MRI score and the van der Heijde-modified Sharp score will be used to evaluate the MRI and X-ray images, respectively. Radiologists will score anonymized images for all patients regardless of intervention allocation. Disease progression will be determined based on the study-specific, inter-rater smallest detectable difference. Allocation-dependent, intervention-concealed reports of positive or negative disease progression will be reported to the treating rheumatologist. Negative reports will be delivered for the sham-intervention group. Study-based radiology clinical reports will be provided to the treating rheumatologists for extra-study X-ray requisitions to limit patient radiation exposure as part of diagnostic imaging standard of care. DMARD treatment dose escalation and therapy changes will be measured to evaluate the primary objective. A sample size of

  10. Study design and analysis of automobile bumper for pedestrian safety

    Science.gov (United States)

    Kulkarni, Akash; Vora, Rushabh; Ravi, K.

    2017-11-01

    This paper aims to design and analyse the bumper beam structure, in order to ensure the protection of the pedestrians along with the occupants inside the vehicle. The concern shown towards the pedestrian safety is because, each year about 2,70,000 pedestrians are killed in road accidents that accounts to 22% of the total deaths. From the literature review, it was inferred that the mounting position of bumper and material selection play a crucial role in maximising the pedestrian safety. Hence in this paper, the effects of bumper mounting position and the bumper beam material have been studied, with reference to an explicit dynamic collision involving with a dummy human lower leg set-up. The acceptance of a particular mounting position/material was based on the fact that the maximum stress and deformation induced were less than the yield limits of the human leg form structure (representing the skin, femur and tibia).

  11. French studies and research program in pressurized water reactor safety

    International Nuclear Information System (INIS)

    Duco, J.

    1986-06-01

    The aim of researches developed now in France on water reactor safety is to obtain means and knowledge allowing to control accidental situations, including severe situations beyond design basis accidents. The main studies and researches concerning water reactors and described in this report are the following ones: core cooling accident and prevention of severe accidents, fuel behavior in accidental situation, behavior of the containment building, fission product transfer and releases in case of accident, problems related to equipment aging, and, methodology of risk analysis and ''human factor'' studies. Most of these studies follow an analytic approach of phenomena [fr

  12. Reactor parameters for European economic, safety and environmental studies

    International Nuclear Information System (INIS)

    Hancox, R.; Cooke, P.I.H.; Spears, W.R.

    1990-01-01

    Parameter sets for five 1200 MW e tokamak reactors were developed for the European Study Group on the Environmental, Safety-related and Economic Potential of Fusion Power, showing today's perception of the range of reactors likely to be available as a result of the Commission's fusion programme. On the basis of the cost of generating electricity, relative to a fission reactor, a reference set was chosen and endorsed by the Group for further studies including that on the environmental impact of fusion power. Key physics and technology parameters for the reference reactor are compared with values used in the ITER design, and with those from American studies. (author)

  13. A history of studies on safety of irradiated foods

    International Nuclear Information System (INIS)

    Miyahara, Makoto

    2003-01-01

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

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

    Science.gov (United States)

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

    2013-12-01

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

  15. Plant air systems safety study: Portsmouth Gaseous Diffusion Plant

    International Nuclear Information System (INIS)

    1982-05-01

    The Portsmouth Gaseous Diffusion Plant Air System facilities and operations are reviewed for potential safety problems not covered by standard industrial safety procedures. Information is presented under the following section headings: facility and process description (general); air plant equipment; air distribution system; safety systems; accident analysis; plant air system safety overview; and conclusion

  16. SU-C-BRB-02: Automatic Planning as a Potential Strategy for Dose Escalation for Pancreas SBRT?

    International Nuclear Information System (INIS)

    Wang, S; Zheng, D; Ma, R; Lin, C; Zhu, X; Lei, Y; Enke, C; Zhou, S

    2016-01-01

    Purpose: Stereotactic body radiation therapy (SBRT) has been suggested to provide high rates of local control for locally advanced pancreatic cancer. However, the close proximity of highly radiosensitive normal tissues usually causes the labor-intensive planning process, and may impede further escalation of the prescription dose. The present study evaluates the potential of an automatic planning system as a dose escalation strategy. Methods: Ten pancreatic cancer patients treated with SBRT were studied retrospectively. SBRT was delivered over 5 consecutive fractions with 6 ∼ 8Gy/fraction. Two plans were generated by Pinnacle Auto-Planning with the original prescription and escalated prescription, respectively. Escalated prescription adds 1 Gy/fraction to the original prescription. Manually-created planning volumes were excluded in the optimization goals in order to assess the planning efficiency and quality simultaneously. Critical organs with closest proximity were used to determine the plan normalization to ensure the OAR sparing. Dosimetric parameters including D100, and conformity index (CI) were assessed. Results: Auto-plans directly generate acceptable plans for 70% of the cases without necessity of further improvement, and two more iterations at most are necessary for the rest of the cases. For the pancreas SBRT plans with the original prescription, autoplans resulted in favorable target coverage and PTV conformity (D100 = 96.3% ± 1.48%; CI = 0.88 ± 0.06). For the plans with the escalated prescriptions, no significant target under-dosage was observed, and PTV conformity remains reasonable (D100 = 93.3% ± 3.8%, and CI = 0.84 ± 0.05). Conclusion: Automatic planning, without substantial human-intervention process, results in reasonable PTV coverage and PTV conformity on the premise of adequate OAR sparing for the pancreas SBRT plans with escalated prescription. The results highlight the potential of autoplanning as a dose escalation strategy for pancreas

  17. SU-C-BRB-02: Automatic Planning as a Potential Strategy for Dose Escalation for Pancreas SBRT?

    Energy Technology Data Exchange (ETDEWEB)

    Wang, S; Zheng, D; Ma, R; Lin, C; Zhu, X; Lei, Y; Enke, C; Zhou, S [University of Nebraska Medical Center, Omaha, NE (United States)

    2016-06-15

    Purpose: Stereotactic body radiation therapy (SBRT) has been suggested to provide high rates of local control for locally advanced pancreatic cancer. However, the close proximity of highly radiosensitive normal tissues usually causes the labor-intensive planning process, and may impede further escalation of the prescription dose. The present study evaluates the potential of an automatic planning system as a dose escalation strategy. Methods: Ten pancreatic cancer patients treated with SBRT were studied retrospectively. SBRT was delivered over 5 consecutive fractions with 6 ∼ 8Gy/fraction. Two plans were generated by Pinnacle Auto-Planning with the original prescription and escalated prescription, respectively. Escalated prescription adds 1 Gy/fraction to the original prescription. Manually-created planning volumes were excluded in the optimization goals in order to assess the planning efficiency and quality simultaneously. Critical organs with closest proximity were used to determine the plan normalization to ensure the OAR sparing. Dosimetric parameters including D100, and conformity index (CI) were assessed. Results: Auto-plans directly generate acceptable plans for 70% of the cases without necessity of further improvement, and two more iterations at most are necessary for the rest of the cases. For the pancreas SBRT plans with the original prescription, autoplans resulted in favorable target coverage and PTV conformity (D100 = 96.3% ± 1.48%; CI = 0.88 ± 0.06). For the plans with the escalated prescriptions, no significant target under-dosage was observed, and PTV conformity remains reasonable (D100 = 93.3% ± 3.8%, and CI = 0.84 ± 0.05). Conclusion: Automatic planning, without substantial human-intervention process, results in reasonable PTV coverage and PTV conformity on the premise of adequate OAR sparing for the pancreas SBRT plans with escalated prescription. The results highlight the potential of autoplanning as a dose escalation strategy for pancreas

  18. Premarket safety and efficacy studies for ADHD medications in children.

    Directory of Open Access Journals (Sweden)

    Florence T Bourgeois

    Full Text Available Attention-deficit hyperactivity disorder (ADHD is a chronic condition and pharmacotherapy is the mainstay of treatment, with a variety of ADHD medications available to patients. However, it is unclear to what extent the long-term safety and efficacy of ADHD drugs have been evaluated prior to their market authorization. We aimed to quantify the number of participants studied and their length of exposure in ADHD drug trials prior to marketing.We identified all ADHD medications approved by the Food and Drug Administration (FDA and extracted data on clinical trials performed by the sponsor and used by the FDA to evaluate the drug's clinical efficacy and safety. For each ADHD medication, we measured the total number of participants studied and the length of participant exposure and identified any FDA requests for post-marketing trials.A total of 32 clinical trials were conducted for the approval of 20 ADHD drugs. The median number of participants studied per drug was 75 (IQR 0, 419. Eleven drugs (55% were approved after <100 participants were studied and 14 (70% after <300 participants. The median trial length prior to approval was 4 weeks (IQR 2, 9, with 5 (38% drugs approved after participants were studied <4 weeks and 10 (77% after <6 months. Six drugs were approved with requests for specific additional post-marketing trials, of which 2 were performed.Clinical trials conducted for the approval of many ADHD drugs have not been designed to assess rare adverse events or long-term safety and efficacy. While post-marketing studies can fill in some of the gaps, better assurance is needed that the proper trials are conducted either before or after a new medication is approved.

  19. ROAD ACCIDENT AND SAFETY STUDY IN SYLHET REGION OF BANGLADESH

    Directory of Open Access Journals (Sweden)

    B. K. BANIK

    2011-08-01

    Full Text Available Roads, highways and streets are fundamental infrastructure facilities to provide the transportation for passenger travel and goods movement from one place to another in Sylhet, north–eastern division of Bangladesh with rapid growth of road vehicle, being comparatively developed economic tourist prone area faces severe road traffic accident. Such severe road accidents cause harsh safety hazards on the roads of Sylhet area. This research work presents an overview of the road traffic accident and degraded road safety situation in Sylhet zone which in particular, discusses the key road accident problem characteristics identifying the hazardous roads and spots, most responsible vehicles and related components, conditions of drivers and pedestrians, most victims of accident, effects of accident on society, safety priorities and options available in Sylhet. In this regard, a comprehensive questionnaire survey was conducted on the concerned groups of transportation and detailed accident data was collected from a popular local newspaper. Analysis of the study reveals that Dhaka- Sylhet highway is the most hazardous in road basis and Sylhet Sador thana is the most vulnerable in thana basis in Sylhet region.

  20. Study on occupational safety and health strategy for Taiwan.

    Science.gov (United States)

    Chuang, Kuen-Yuan; Su, Teh-Sheng; Kuo, Chao-Yin; Lin, Chien-Liang; Lin, Han-Yu; Yu, Yi-Chun

    2009-12-01

    The aim of this study was to establish a set of occupational safety and health (OSH) issues and development policies suitable for adoption in Taiwan. A survey was conducted on a sample of 102 experts and 235 industrial work safety personnel in Taiwan for statistical analysis of the general consensus, with the results showing such consensus in 104 individual policy indicators. Our results reveal that the most appropriate targets were considered to be annual 10% reductions in the 'occupational accident disability rate', 'occupational accident injury rate' and 'occupational diseases before 2010'. Responding to the specific question of the appropriate method of achieving a reduction in the number of accidents in Taiwan, the primary consideration for 13.4% of the experts and 10.6% of the industry personnel was 'promoting OSH awareness and enhancing the overall safety culture'. As regards the current OSH policy focus, 11.2% of the experts considered 'improving OSH legislation, standards and systems' to be the most important, whilst 8.9% of the industry personnel felt that 'recognizing work stress, overwork and emerging OSH issues' were the most important.

  1. Prescription safety eyewear: impact studies of lens and frame failure.

    Science.gov (United States)

    Vinger, P F; Woods, T A

    2000-02-01

    To determine if a plano lens could be the test lens for all prescription (Rx) lenses and to investigate why Rx lenses pop out of safety eyewear. Plano and Rx polycarbonate lenses (n = 641) with varying thickness and edge geometry, mounted on steel lens holders, and Rx safety eyewear (n = 128) placed on headforms were impacted with test objects of varying diameter and hardness. Impacts were studied with 500 to 2,000 frames-per-second motion analysis. Plano lenses were at least, or more, prone to failure (dislodgment, perforation, shatter, or crack) than -3.00 or +3.00 lenses of the same minimum thickness. More than 40% of safety frames with removable lenses broke or had lenses pop out when impacted with energies expected in industry and sports. Plano lenses can be used as the test lenses for all Rx lenses made of the same material with the same minimal thickness. The ANSI Z87.1-1989 industrial standard for Rx eyewear is inadequate for sports or other activities with high-impact potential. The best lens-retention system has, as a component, a frame with a bevel perpendicular to a frontal impact force.

  2. Nuclear fuel safety studies by laser pulse heating

    International Nuclear Information System (INIS)

    Viswanadham, C.S.; Kumar, Santosh; Dey, G.K.; Kutty, T.R.G.; Khan, K.B.; Kumar, Arun; Jathar, V.P.; Sahoo, K.C.

    2009-01-01

    The behaviour of nuclear fuels under transient heating conditions is vital to nuclear safety. A laser pulse based heating system to simulate the transient heating conditions experienced by the fuel during reactor accidents like LOCA and RIA is under development at BARC, Mumbai. Some of the concepts used in this system are under testing in pilot studies. This paper describes the results of some pilot studies carried out on unirradiated UO 2 specimens by laser pulse heating, followed by metallography and X-ray diffraction measurements. (author)

  3. Dose-escalated intensity-modulated radiotherapy is feasible and may improve locoregional control and laryngeal preservation in laryngo-hypopharyngeal cancers.

    Science.gov (United States)

    Miah, Aisha B; Bhide, Shreerang A; Guerrero-Urbano, M Teresa; Clark, Catharine; Bidmead, A Margaret; St Rose, Suzanne; Barbachano, Yolanda; A'hern, Roger; Tanay, Mary; Hickey, Jennifer; Nicol, Robyn; Newbold, Kate L; Harrington, Kevin J; Nutting, Christopher M

    2012-02-01

    To determine the safety and outcomes of induction chemotherapy followed by dose-escalated intensity-modulated radiotherapy (IMRT) with concomitant chemotherapy in locally advanced squamous cell cancer of the larynx and hypopharynx (LA-SCCL/H). A sequential cohort Phase I/II trial design was used to evaluate moderate acceleration and dose escalation. Patients with LA-SCCL/H received IMRT at two dose levels (DL): DL1, 63 Gy/28 fractions (Fx) to planning target volume 1 (PTV1) and 51.8 Gy/28 Fx to PTV2; DL2, 67.2 Gy/28 Fx and 56 Gy/28 Fx to PTV1 and PTV2, respectively. Patients received induction cisplatin/5-fluorouracil and concomitant cisplatin. Acute and late toxicities and tumor control rates were recorded. Between September 2002 and January 2008, 60 patients (29 DL1, 31 DL2) with Stage III (41% DL1, 52% DL2) and Stage IV (52% DL1, 48% DL2) disease were recruited. Median (range) follow-up for DL1 was 51.2 (12.1-77.3) months and for DL2 was 36.2 (4.2-63.3) months. Acute Grade 3 (G3) dysphagia was higher in DL2 (87% DL2 vs. 59% DL1), but other toxicities were equivalent. One patient in DL1 required dilatation of a pharyngeal stricture (G3 dysphagia). In DL2, 2 patients developed benign pharyngeal strictures at 1 year. One underwent a laryngo-pharyngectomy and the other a dilatation. No other G3/G4 toxicities were reported. Overall complete response was 79% (DL1) and 84% (DL2). Two-year locoregional progression-free survival rates were 64.2% (95% confidence interval, 43.5-78.9%) in DL1 and 78.4% (58.1-89.7%) in DL2. Two-year laryngeal preservation rates were 88.7% (68.5-96.3%) in DL1 and 96.4% (77.7-99.5%) in DL2. At a mean follow-up of 36 months, dose-escalated chemotherapy-IMRT at DL2 has so far been safe to deliver. In this study, DL2 delivered high rates of locoregional control, progression-free survival, and organ preservation and has been selected as the experimental arm in a Cancer Research UK Phase III study. Copyright © 2012 Elsevier Inc. All rights

  4. Dose-Escalated Intensity-Modulated Radiotherapy Is Feasible and May Improve Locoregional Control and Laryngeal Preservation in Laryngo-Hypopharyngeal Cancers

    International Nuclear Information System (INIS)

    Miah, Aisha B.; Bhide, Shreerang A.; Guerrero-Urbano, M. Teresa; Clark, Catharine; Bidmead, A. Margaret; St Rose, Suzanne; Barbachano, Yolanda; A’Hern, Roger; Tanay, Mary; Hickey, Jennifer; Nicol, Robyn; Newbold, Kate L.; Harrington, Kevin J.; Nutting, Christopher M.

    2012-01-01

    Purpose: To determine the safety and outcomes of induction chemotherapy followed by dose-escalated intensity-modulated radiotherapy (IMRT) with concomitant chemotherapy in locally advanced squamous cell cancer of the larynx and hypopharynx (LA-SCCL/H). Methods and Materials: A sequential cohort Phase I/II trial design was used to evaluate moderate acceleration and dose escalation. Patients with LA-SCCL/H received IMRT at two dose levels (DL): DL1, 63 Gy/28 fractions (Fx) to planning target volume 1 (PTV1) and 51.8 Gy/28 Fx to PTV2; DL2, 67.2 Gy/28 Fx and 56 Gy/28 Fx to PTV1 and PTV2, respectively. Patients received induction cisplatin/5-fluorouracil and concomitant cisplatin. Acute and late toxicities and tumor control rates were recorded. Results: Between September 2002 and January 2008, 60 patients (29 DL1, 31 DL2) with Stage III (41% DL1, 52% DL2) and Stage IV (52% DL1, 48% DL2) disease were recruited. Median (range) follow-up for DL1 was 51.2 (12.1–77.3) months and for DL2 was 36.2 (4.2–63.3) months. Acute Grade 3 (G3) dysphagia was higher in DL2 (87% DL2 vs. 59% DL1), but other toxicities were equivalent. One patient in DL1 required dilatation of a pharyngeal stricture (G3 dysphagia). In DL2, 2 patients developed benign pharyngeal strictures at 1 year. One underwent a laryngo-pharyngectomy and the other a dilatation. No other G3/G4 toxicities were reported. Overall complete response was 79% (DL1) and 84% (DL2). Two-year locoregional progression-free survival rates were 64.2% (95% confidence interval, 43.5–78.9%) in DL1 and 78.4% (58.1–89.7%) in DL2. Two-year laryngeal preservation rates were 88.7% (68.5–96.3%) in DL1 and 96.4% (77.7–99.5%) in DL2. Conclusions: At a mean follow-up of 36 months, dose-escalated chemotherapy–IMRT at DL2 has so far been safe to deliver. In this study, DL2 delivered high rates of locoregional control, progression-free survival, and organ preservation and has been selected as the experimental arm in a Cancer Research UK

  5. Dose-Escalated Intensity-Modulated Radiotherapy Is Feasible and May Improve Locoregional Control and Laryngeal Preservation in Laryngo-Hypopharyngeal Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Miah, Aisha B; Bhide, Shreerang A; Guerrero-Urbano, M Teresa [Head and Neck Unit, The Royal Marsden National Health Service (NHS) Foundation Trust, London (United Kingdom); Institute of Cancer Research, London (United Kingdom); Clark, Catharine; Bidmead, A Margaret [Institute of Cancer Research, London (United Kingdom); Department of Physics, The Royal Marsden NHS Foundation Trust, London (United Kingdom); St Rose, Suzanne; Barbachano, Yolanda; A' Hern, Roger [Department of Statistics, The Royal Marsden NHS Foundation Trust, London (United Kingdom); Tanay, Mary; Hickey, Jennifer; Nicol, Robyn; Newbold, Kate L [Head and Neck Unit, The Royal Marsden National Health Service (NHS) Foundation Trust, London (United Kingdom); Harrington, Kevin J [Head and Neck Unit, The Royal Marsden National Health Service (NHS) Foundation Trust, London (United Kingdom); Institute of Cancer Research, London (United Kingdom); Nutting, Christopher M., E-mail: chris.nutting@rmh.nhs.uk [Head and Neck Unit, The Royal Marsden National Health Service (NHS) Foundation Trust, London (United Kingdom); Institute of Cancer Research, London (United Kingdom)

    2012-02-01

    Purpose: To determine the safety and outcomes of induction chemotherapy followed by dose-escalated intensity-modulated radiotherapy (IMRT) with concomitant chemotherapy in locally advanced squamous cell cancer of the larynx and hypopharynx (LA-SCCL/H). Methods and Materials: A sequential cohort Phase I/II trial design was used to evaluate moderate acceleration and dose escalation. Patients with LA-SCCL/H received IMRT at two dose levels (DL): DL1, 63 Gy/28 fractions (Fx) to planning target volume 1 (PTV1) and 51.8 Gy/28 Fx to PTV2; DL2, 67.2 Gy/28 Fx and 56 Gy/28 Fx to PTV1 and PTV2, respectively. Patients received induction cisplatin/5-fluorouracil and concomitant cisplatin. Acute and late toxicities and tumor control rates were recorded. Results: Between September 2002 and January 2008, 60 patients (29 DL1, 31 DL2) with Stage III (41% DL1, 52% DL2) and Stage IV (52% DL1, 48% DL2) disease were recruited. Median (range) follow-up for DL1 was 51.2 (12.1-77.3) months and for DL2 was 36.2 (4.2-63.3) months. Acute Grade 3 (G3) dysphagia was higher in DL2 (87% DL2 vs. 59% DL1), but other toxicities were equivalent. One patient in DL1 required dilatation of a pharyngeal stricture (G3 dysphagia). In DL2, 2 patients developed benign pharyngeal strictures at 1 year. One underwent a laryngo-pharyngectomy and the other a dilatation. No other G3/G4 toxicities were reported. Overall complete response was 79% (DL1) and 84% (DL2). Two-year locoregional progression-free survival rates were 64.2% (95% confidence interval, 43.5-78.9%) in DL1 and 78.4% (58.1-89.7%) in DL2. Two-year laryngeal preservation rates were 88.7% (68.5-96.3%) in DL1 and 96.4% (77.7-99.5%) in DL2. Conclusions: At a mean follow-up of 36 months, dose-escalated chemotherapy-IMRT at DL2 has so far been safe to deliver. In this study, DL2 delivered high rates of locoregional control, progression-free survival, and organ preservation and has been selected as the experimental arm in a Cancer Research UK Phase III

  6. The safety of treatment options available for gout.

    Science.gov (United States)

    Schlesinger, Naomi

    2017-04-01

    Gout is the most common inflammatory arthritis in humans. Gout treatment includes rapid initiation of anti-inflammatory medications for acute attacks and chronically treating with urate lowering drugs as well as chronic anti-inflammatory prophylaxis. Areas covered: This review aims to provide an overview and discussion of the safety concerns of current treatment options available for gout. Expert opinion: Gout is a curable disease with appropriate treatment. The advent of new therapies provides encouraging opportunities to improve gout management. However, clinicians should be aware of some of the safety concerns of medications used to treat acute and chronic gout. When prescribing medications for gout one has to be mindful of the presence of comorbidities commonly affecting gout patients that may affect drug safety and efficacy, especially in the elderly and in patients treated with multiple drugs. The benefits of gout drugs, usually, outweigh their safety concerns. Studies are needed in gout patients with chronic kidney disease and/or cardiovascular disease, so that escalation of dosing /combination of anti-inflammatory drugs needed to suppress gouty inflammation as well as escalation of dosing/combination of urate lowering drugs needed to achieve target serum urate level will lead to better understanding of gout treatment safety issues.

  7. DOSE-ESCALATED EXTERNAL BEAM RADIOTHERAPY DURING HORMONO-RADIOTHERAPY FOR PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    Yu. V. Gumenetskaya

    2016-01-01

    Full Text Available Introduction. The introduction of modern technologies of conformal external beam radiotherapy (EBRT into clinical practice for the treatment of prostate cancer requires proper quality assurance measures as well as a careful analysis of both the efficacy and toxicity data of treatments. The purpose of this study was to inves- tigate tolerance and the immediate efficacy of conformal dose-escalated EBRT during hormono-radiotherapy for prostate cancer. material and methods. The study involved 156 prostate cancer patients treated with EBRT. Among them, 30 patients received a total dose of 70 Gy, and in 126 patients the total dose was esca- lated to 72-76 Gy (median total dose - 74.0 Gy. Fifty-nine patients received intensity modulated radiation therapy. Results. The prescribed course of treatment was completed in all the patients with prostate cancer. Acute radiation-induced bladder reactions (RTOG were observed in 50 (32.1 % patients, of whom 48 (30.8 % experienced grade I reactions, and 2 (1.3 % experienced grade II reactions. Eighteen (11.5 % patients had radiation-induced rectum reactions, not above grade I. The development of grade II dysuric phenomena necessitated treatment interruption only in two patients. Of 9 (5.8 % patients who had late bladder complica- tions (RTOG/EORTC, 8 (5.1 % patients developed grade I complications, and one (0.6 % patient developed grade II complications. Of 11 (7.1 % patients who had rectum complications, 8 (5.1 % patients developed grade I complications, and 3 (1.9 % patients developed grade II complications. No patients experienced the increase in toxicity of treatment during dose escalation up to a total dose exceeding 70 Gy. During the follow-up period, only one patient developed recurrent disease. Conclusion. The results of our study suggest acceptable levels of toxicity following a continuous course of dose-escalated EBRT given in conjunction with hormono-radiotherapy to prostate cancer patients. Further

  8. Does tariff escalation affect export shares: The case of cotton and coffee in global trade

    OpenAIRE

    Narayanan G, Badri; Khorana, Sangeeta

    2011-01-01

    Many studies show that Tariff Escalation (TE) lowers export shares in many of the processing sectors, given their higher level of protection. However, there are instances when the export shares of processed sectors are higher despite the existence of TE. We examine both these contrasting cases of TE in this paper. On the one hand, there is TE in coffee and coffee products in developing countries, which lead in raw coffee exports and lag in roasted coffee exports. On the other hand, there is a...

  9. Radiobiological Determination of Dose Escalation and Normal Tissue Toxicity in Definitive Chemoradiation Therapy for Esophageal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Warren, Samantha, E-mail: Samantha.warren@oncology.ox.ac.uk [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom); Partridge, Mike [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom); Carrington, Rhys [Velindre Cancer Centre, Velindre Hospital, Cardiff (United Kingdom); Hurt, Chris [Wales Cancer Trials Unit, School of Medicine, Heath Park, Cardiff (United Kingdom); Crosby, Thomas [Velindre Cancer Centre, Velindre Hospital, Cardiff (United Kingdom); Hawkins, Maria A. [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom)

    2014-10-01

    Purpose: This study investigated the trade-off in tumor coverage and organ-at-risk sparing when applying dose escalation for concurrent chemoradiation therapy (CRT) of mid-esophageal cancer, using radiobiological modeling to estimate local control and normal tissue toxicity. Methods and Materials: Twenty-one patients with mid-esophageal cancer were selected from the SCOPE1 database (International Standard Randomised Controlled Trials number 47718479), with a mean planning target volume (PTV) of 327 cm{sup 3}. A boost volume, PTV2 (GTV + 0.5 cm margin), was created. Radiobiological modeling of tumor control probability (TCP) estimated the dose required for a clinically significant (+20%) increase in local control as 62.5 Gy/25 fractions. A RapidArc (RA) plan with a simultaneously integrated boost (SIB) to PTV2 (RA{sub 62.5}) was compared to a standard dose plan of 50 Gy/25 fractions (RA{sub 50}). Dose-volume metrics and estimates of normal tissue complication probability (NTCP) for heart and lungs were compared. Results: Clinically acceptable dose escalation was feasible for 16 of 21 patients, with significant gains (>18%) in tumor control from 38.2% (RA{sub 50}) to 56.3% (RA{sub 62.5}), and only a small increase in predicted toxicity: median heart NTCP 4.4% (RA{sub 50}) versus 5.6% (RA{sub 62.5}) P<.001 and median lung NTCP 6.5% (RA{sub 50}) versus 7.5% (RA{sub 62.5}) P<.001. Conclusions: Dose escalation to the GTV to improve local control is possible when overlap between PTV and organ-at-risk (<8% heart volume and <2.5% lung volume overlap for this study) generates only negligible increase in lung or heart toxicity. These predictions from radiobiological modeling should be tested in future clinical trials.

  10. Safety aspects of geological studies around nuclear installations sites

    International Nuclear Information System (INIS)

    Faure, J.

    1988-01-01

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

  11. Fusion safety studies in Russia from 1996 to 2000

    Energy Technology Data Exchange (ETDEWEB)

    Kolbasov, B.N. E-mail: kolbasov@nfi.kiae.ru; Biryukov, A.Yu.; Davydov, D.A.; Guseva, M.I.; Khripunov, B.I.; Korshunov, S.N.; Martynenko, Yu.V.; Romanov, P.V.; Vasiliev, V.I

    2001-04-01

    The paper is a review of results of some fusion safety studies performed in Russia during 1996-2000 (after the 6th IAEA Technical Committee Meeting on 'Developments in Fusion Safety'). In particular, changes of hydrogen isotope inventory in co-deposited layers on tungsten and graphite under simulation of normal tokamak operation and plasma disruptions are reported. Size distribution of graphite and W-Be-dust under the experiments at issue revealed two maximums. Erosion products were collected within tokamak T-10. Their microstructure and chemical composition were studied and are reported in the paper. Chemical interaction of beryllium powder with steam (in temperature range of 400-600 deg. C) and air (at 500-1000 deg. C) was investigated. Mathematical models describing it were developed. Chemical interaction of Be-powder with carbon was studied too. A dependence of beryllium carbide layer thickness growth versus time at 950 deg. C was found on the basis of the experiments.

  12. Dose escalation of cisplatin with 5-fluorouracil in concurrent chemoradiotherapy for esophageal carcinoma

    International Nuclear Information System (INIS)

    Lin Qiang; Gao Xianshu; Qiao Xueying; Zhou Zhiguo; Zhang Jun; Yang Xiangran; Wan Xin

    2006-01-01

    Objective: To define the maximum-tolerated dose (MTD) and observe the side effect of escalating cisplatin with 5-fluorouracil in concurrent chemoradiotherapy for esophageal carcinoma in Chinese, with toxicity studied. Methods: Previously untreated fifteen Chinese patients suffering from esophageal carcinoma received conventional fractionation radiotherapy, with 5 daily fractions of 2.0 Gy per week. The total radiation dose was 60 Gy. Concurrent chemotherapy dose escalation was given by the relatively safe and kidney-sparing modified Fibonacci sequence. The starting dose was cisplatin 37.5 mg/m 2 D1 and 5-fluorouracil 500 mg/m 2 D1-5, respectively. This regimen was repeated 4 times every 28 days. Escalation dose was cisplatin 7.5 mg/m 2 and 5- fluorouracil 100 mg/m 2 . Every. cohort contained at least 3 patients. If no dose-limiting toxicity(DLT) was observed, the next dose level was opened for entry. These courses were repeated until DLT appeared. MTD was declared as one dose level below which DLT appeared. Results: DLT was defined as grade 3 radiation-induced esophagitis at the level of cisplatin 60 mg/m2, 5-fluorouracil 700 mg/m 2 . MTD was defined as cisplatin 52.5 mg/m 2 , 5- fiuorouracil 700 mg/m 2 . The major side effect were radiation-induced esophagitis, leucopenia, nausea, vomiting and anorexia. Conclusion: Maximun tolerated dose of cisplatin with 5-fiuorouracil in concurrent ehemoradiotherapy in the Chinese people with esophageal carcinoma were eisplatin 52.5 mg/m2 D1,5-fluorouracil 700 mg/m 2 D1-5, repeated 4 times every 28 days. (authors)

  13. Feasibility of extreme dose escalation for glioblastoma multiforme using 4π radiotherapy

    International Nuclear Information System (INIS)

    Nguyen, Dan; Rwigema, Jean-Claude M; Yu, Victoria Y; Kaprealian, Tania; Kupelian, Patrick; Selch, Michael; Lee, Percy; Low, Daniel A; Sheng, Ke

    2014-01-01

    Glioblastoma multiforme (GBM) frequently recurs at the same location after radiotherapy. Further dose escalation using conventional methods is limited by normal tissue tolerance. 4π non-coplanar radiotherapy has recently emerged as a new potential method to deliver highly conformal radiation dose using the C-arm linacs. We aim to study the feasibility of very substantial GBM dose escalation while maintaining normal tissue tolerance using 4π. 11 GBM patients previously treated with volumetric modulated arc therapy (VMAT/RapidArc) on the NovalisTx™ platform to a prescription dose of either 59.4 Gy or 60 Gy were included. All patients were replanned with 30 non-coplanar beams using a 4π radiotherapy platform, which inverse optimizes both beam angles and fluence maps. Four different prescriptions were used including original prescription dose and PTV (4πPTV PD ), 100 Gy to the PTV and GTV (4πPTV 100Gy ), 100 Gy to the GTV only while maintaining prescription dose to the rest of the PTV (4πGTV 100Gy ), and a 5 mm margin expansion plan (4πPTV PD+5mm ). OARs included in the study are the normal brain (brain – PTV), brainstem, chiasm, spinal cord, eyes, lenses, optical nerves, and cochleae. The 4π plans resulted in superior dose gradient indices, as indicated by >20% reduction in the R50, compared to the clinical plans. Among all of the 4π cases, when compared to the clinical plans, the maximum and mean doses were significantly reduced (p < 0.05) by a range of 47.01-98.82% and 51.87-99.47%, respectively, or unchanged (p > 0.05) for all of the non-brain OARs. Both the 4πPTV PD and 4π GTV 100GY plans reduced the mean normal brain mean doses. 4π non-coplanar radiotherapy substantially increases the dose gradient outside of the PTV and better spares critical organs. Dose escalation to 100 Gy to the GTV or additional margin expansion while meeting clinical critical organ dose constraints is feasible. 100 Gy to the PTV result in higher normal brain doses but may

  14. A study on Impact of Safety Culture on Safety Behavior: Moderating effect of Prevention Focus

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Sun Chul; Jung, Su Jin; Choi, Young Sung [KAERI, Daejeon (Korea, Republic of)

    2016-05-15

    In modern society, it has been acknowledged that disasters caused by civilization became inevitable. With growing attention to role of human as one component of the system to cope with accident to prevent disasters, various efforts have been deployed to keep safety. Most of the industries with high hazard have adopted the term as their banner in the efforts to promote safety in their installations and operations. Recently, the Fukushima nuclear power plants(NPPs) accident happened in Japan in 2011 resulted in great impact over the world and have highlighted the importance of safety culture again.

  15. A study on Impact of Safety Culture on Safety Behavior: Moderating effect of Prevention Focus

    International Nuclear Information System (INIS)

    Hwang, Sun Chul; Jung, Su Jin; Choi, Young Sung

    2016-01-01

    In modern society, it has been acknowledged that disasters caused by civilization became inevitable. With growing attention to role of human as one component of the system to cope with accident to prevent disasters, various efforts have been deployed to keep safety. Most of the industries with high hazard have adopted the term as their banner in the efforts to promote safety in their installations and operations. Recently, the Fukushima nuclear power plants(NPPs) accident happened in Japan in 2011 resulted in great impact over the world and have highlighted the importance of safety culture again

  16. The role of human intrusion in the dutch safety study

    International Nuclear Information System (INIS)

    Prij, J.; Weers, A.W.v.; Glasbergen, P.; Slot, A.F.M.

    1989-01-01

    In the Netherlands the OPLA research program in which a large number of possible disposal concepts for radioactive waste is investigated has been carried out recently. The disposal concepts concern three different waste strategies, two disposal techiques and three different types of salt formations. In the OPLA program the post-closure safety of the disposal concepts has been investigated. The paper reviews the role of the human intrusion in this safety study. The hydrological consequences of human activities in the underground are discussed and it has been demonstrated that these effects could be taken into account during the groundwater transport calculations. Four different scenario's for human intrusion in the repository have been studied to obtain an indication of the radiological effects. The results show that extremely high doses may result if, after several hundred years, human beings come into direct contact with highly active waste. For the final assessment the probability that the doses will be received should be calculated. This should be done in a subsequent research

  17. Fire safety case study of a railway tunnel: Smoke evacuation

    Directory of Open Access Journals (Sweden)

    van Maele Karim

    2007-01-01

    Full Text Available When a fire occurs in a tunnel, it is of great importance to assure the safety of the occupants of the tunnel. This is achieved by creating smoke-free spaces in the tunnel through control of the smoke gases. In this paper, results are presented of a study concerning the fire safety in a real scale railway tunnel test case. Numerical simulations are performed in order to examine the possibility of natural ventilation of smoke in inclined tunnels. Several aspects are taken into account: the length of the simulated tunnel section, the slope of the tunnel and the possible effects of external wind at one portal of the tunnel. The Fire Dynamics Simulator of the National Institute of Standards and Technology, USA, is applied to perform the simulations. The simulations show that for the local behavior of the smoke during the early stages of the fire, the slope of the tunnel is of little importance. Secondly, the results show that external wind and/or pressure conditions have a large effect on the smoke gases inside the tunnel. Finally, some idea for the value of the critical ventilation velocity is given. The study also shows that computational fluid dynamics calculations are a valuable tool for large scale, real life complex fire cases. .

  18. Sensitivity analysis of the reactor safety study. Final report

    International Nuclear Information System (INIS)

    Parkinson, W.J.; Rasmussen, N.C.; Hinkle, W.D.

    1979-01-01

    The Reactor Safety Study (RSS) or Wash 1400 developed a methodology estimating the public risk from light water nuclear reactors. In order to give further insights into this study, a sensitivity analysis has been performed to determine the significant contributors to risk for both the PWR and BWR. The sensitivity to variation of the point values of the failure probabilities reported in the RSS was determined for the safety systems identified therein, as well as for many of the generic classes from which individual failures contributed to system failures. Increasing as well as decreasing point values were considered. An analysis of the sensitivity to increasing uncertainty in system failure probabilities was also performed. The sensitivity parameters chosen were release category probabilities, core melt probability, and the risk parameters of early fatalities, latent cancers and total property damage. The latter three are adequate for describing all public risks identified in the RSS. The results indicate reductions of public risk by less than a factor of two for factor reductions in system or generic failure probabilities as high as one hundred. There also appears to be more benefit in monitoring the most sensitive systems to verify adherence to RSS failure rates than to backfitting present reactors. The sensitivity analysis results do indicate, however, possible benefits in reducing human error rates

  19. Novel technology to prepare oral formulations for preclinical safety studies.

    Science.gov (United States)

    Niwa, Toshiyuki; Hashimoto, Naofumi

    2008-02-28

    A novel method to prepare oral formulations, normally suspended dosage form, for preclinical safety studies in animals has been developed using a rotation/revolution mixer. Small hard balls made of zirconia were added to the mixing process to evaluate effectiveness in making a high quality suspension. The driving with balls loaded in the cylindrical container (vessel) of the mixer was quite efficient in dispersing and milling the particles of the active pharmaceutical ingredient (API) in an aqueous medium. The API powder and a small amount of oral aqueous medium (vehicle) were successfully mixed by the spinning motion of the balls in the vessel as though the paste-like suspension was kneaded with a mortar and pestle. It was found that the milled suspension with the mean size of 10-20microm could be prepared, in addition finer milling of less than 10microm could be achieved by selecting the material of vessel. Optimum driving conditions including mixing time, size and quantity of balls, and the standard operational procedure was established using compounds varying in physicochemical properties. The particle size and quantitative analysis by HPLC showed that the resultant suspension was well-milled and highly homogeneous with the nearly intended concentration of API. The proposed method established by this experiment could be applied to the actual safety studies in the real preparation scale of oral suspension.

  20. RAMONA-4B development for SBWR safety studies

    Energy Technology Data Exchange (ETDEWEB)

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

    1993-12-31

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

  1. RAMONA-4B development for SBWR safety studies

    International Nuclear Information System (INIS)

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

    1993-01-01

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

  2. Alberta Environment's weir safety program : options for rehabilitation to improve public safety : a case study of the Calgary weir

    Energy Technology Data Exchange (ETDEWEB)

    Blakely, D [Alberta Environment, Edmonton, AB (Canada)

    2009-07-01

    Alberta Environment Water Management Operations (WMO) owns and operates 46 dams and 800 kilometres of canals in Alberta. The WMO consists of 120 staff and several contract operators to take care of this infrastructure. Most of the infrastructure supplies water for irrigation use, which adds 5 billion dollars to the provincial economy annually. Other water uses include stock watering, domestic use, municipal use, recreational use and habitat. Alberta Environment's weir safety program was also discussed along with options for rehabilitation to improve public safety. A case study of Calgary's Weir Dam on the Bow River was highlighted. A brief history of the dam was offered and safety programs around provincially-owned weirs were discussed. Photographs were included to illustrate some of the additional safety measures at the Calgary weir, such as suspended safety buoys upstream of the boom directing paddlers to the portage trail, and signage on the river that can be activated when the boom is out. Typical river users on the Calgary Bow River and safety history at the Calgary Weir were discussed along with other topics such as the Calgary Bow River weir project criteria; project design progress; pre-feasibility options; scale modelling; final design analysis; construction funding; and proposed changes to the safety program for the new weir configuration. figs.

  3. Multi-channel grouping techniques for conducting reactor safety studies

    International Nuclear Information System (INIS)

    Waltar, A.E.; Wilburn, N.P.

    1975-01-01

    In conducting safety studies for postulated unprotected accidents in an LMFBR system, it is common practice to employ multi-channel coupled neutronics, thermal hydraulics computer programs such as SAS3A or MELT-III. The multichannel feature of such code systems is important if the natural fuel failure incoherencies and the resulting sodium void/fuel motion reactivity feedbacks--which have strong spatial variations--are to be properly modeled. Because of the large amounts of computer time associated with many channel runs, however, there is a strong incentive to conduct parametric studies with as few channels as possible. The paper presented is focused on methods successfully employed to accomplish this end for a study of the hypothetical unprotected transient overpower accident conducted for the FFTF

  4. Prevention and reversal of social stress-escalated cocaine self-administration in mice by intra-VTA CRFR1 antagonism.

    Science.gov (United States)

    Han, Xiao; DeBold, Joseph F; Miczek, Klaus A

    2017-09-01

    A history of brief intermittent social defeat stress can escalate cocaine self-administration and induce long-term adaptations in the mesolimbic dopamine system. Extra-hypothalamic corticotrophin releasing factor (CRF) has been shown to be closely associated with stress-induced escalation of drug use. How repeated stress modulates CRF release in the ventral tegmental area (VTA) and the roles of CRF receptors during different phases of stress-induced cocaine self-administration remain to be defined. The current study examines the roles of CRF and CRF receptor 1 (CRFR1) in escalated intravenous cocaine self-administration after exposure to social defeat stress in mice. First, CRFR1 antagonist (CP 376,395, 15 mg/kg, i.p.) given 30 min prior to each social defeat episode prevented later escalated cocaine self-administration. When CP 376,395 (5 and 15 mg/kg, i.p.) was administered 10 days after the last episode of social stress, the escalation of cocaine intake was dose-dependently reversed. Moreover, socially defeated mice showed increased CRF release in the VTA compared to controls. To further explore the role of CRFR1, CP 376,395 (0.5 and 1 μg/0.2 μl) was infused directly into the VTA before the cocaine self-administration session. Intra-VTA antagonism of CRFR1 was sufficient to reverse social defeat stress-escalated cocaine self-administration. These findings suggest that CRF and CRFR1 exert multiple roles in the response to social stress that are relevant to escalated cocaine self-administration.

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

    International Nuclear Information System (INIS)

    Svensson, Ola; Salo, Ilkka; Allwin, Pernilla

    2004-11-01

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

  6. A study of software safety analysis system for safety-critical software

    International Nuclear Information System (INIS)

    Chang, H. S.; Shin, H. K.; Chang, Y. W.; Jung, J. C.; Kim, J. H.; Han, H. H.; Son, H. S.

    2004-01-01

    The core factors and requirements for the safety-critical software traced and the methodology adopted in each stage of software life cycle are presented. In concept phase, Failure Modes and Effects Analysis (FMEA) for the system has been performed. The feasibility evaluation of selected safety parameter was performed and Preliminary Hazards Analysis list was prepared using HAZOP(Hazard and Operability) technique. And the check list for management control has been produced via walk-through technique. Based on the evaluation of the check list, activities to be performed in requirement phase have been determined. In the design phase, hazard analysis has been performed to check the safety capability of the system with regard to safety software algorithm using Fault Tree Analysis (FTA). In the test phase, the test items based on FMEA have been checked for fitness guided by an accident scenario. The pressurizer low pressure trip algorithm has been selected to apply FTA method to software safety analysis as a sample. By applying CASE tool, the requirements traceability of safety critical system has been enhanced during all of software life cycle phases

  7. Review of light--water reactor safety studies. Volume 3 of health and safety impacts of nuclear, geothermal, and fossil-fuel electric generation in California

    International Nuclear Information System (INIS)

    Nero, A.V.; Farnaam, M.R.K.

    1977-01-01

    This report summarizes and compares important studies of light-water nuclear reactor safety, emphasizing the Nuclear Regulatory Commission's Reactor Safety Study, work on risk assessment funded by the Electric Power Research Institute, and the Report of the American Physical Society study group on light-water reactor safety. These reports treat risk assessment for nuclear power plants and provide an introduction to the basic issues in reactor safety and the needs of the reactor safety research program. Earlier studies are treated more briefly. The report includes comments on the Reactor Safety Study. The manner in which these studies may be used and alterations which would increase their utility are discussed

  8. A study of the international trend and comprehensive enhancement program on the Nuclear Power Plant safety

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Soon Hong; Cho, Nam Jin; Paek, Won Phil [Korea Advanced Institute of Science and Technology, Taejon (Korea, Republic of)

    1990-12-15

    The objectives of this study are as follows : overview of the international trend related to the safety of Nuclear Power Plant(NPPs), study of the present status of NPP safety in Korea in aspects of design, construction and operation, suggestion of the comprehensive program to improve NPP safety in Korea. The results of this study can contribute to improve the safety of existing and future NPPs, and to establish the severe accident policy in Korea.

  9. A study of the international trend and comprehensive enhancement program on the Nuclear Power Plant safety

    International Nuclear Information System (INIS)

    Jang, Soon Hong; Cho, Nam Jin; Paek, Won Phil

    1990-12-01

    The objectives of this study are as follows : overview of the international trend related to the safety of Nuclear Power Plant(NPPs), study of the present status of NPP safety in Korea in aspects of design, construction and operation, suggestion of the comprehensive program to improve NPP safety in Korea. The results of this study can contribute to improve the safety of existing and future NPPs, and to establish the severe accident policy in Korea

  10. EFFECT OF TARIFF ESCALATION ON GHANAIAN COCOA EXPORTS: AN EMPIRICAL PERSPECTIVE

    Directory of Open Access Journals (Sweden)

    Ahmed Abdul Aziz

    2017-01-01

    Full Text Available This study analyses the effects of tariff escalation on Ghanaian cocoa exports in four importing markets: USA, EU, Japan and Malaysia. The study estimates nominal and effective protection coefficients in these markets based on ad-valorem equivalent of applied and bound specific tariffs. Results revealed that, effective protection exists in the Japanese and Malaysian cocoa industries at different stages of processing on both bound and applied tariffs. In contrast, the USA and the EU do not effectively protect their cocoa industries, thus, no tariff escalation on applied tariffs against cocoa imports from Ghana. This study concludes that from a static effect, higher tariffs do have a negative consequence on Ghanaian cocoa exports in these importing countries. From a dynamic perspective however, the relationship between tariff structures in these importing countries and Ghanaian cocoa exports is somewhat ambiguous and each situation has to be viewed on their own merit. A complete elimination of tariffs as a form of trade barrier on Ghanaian cocoa exports does not necessarily imply that Ghana could easily increase its exports of value added cocoa.

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

    Science.gov (United States)

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

    2017-04-01

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

  12. Meteorological aspects of the reactor safety study requiring further study

    International Nuclear Information System (INIS)

    Slinn, W.G.N.

    1981-01-01

    Simple and approximate methods are used in a search for meteorological features that dominate estimates of reactor-accident consequences, and that require more accurate descriptions if consequence estimates are to be more realistic. By considering variations in the source term, it is seen that accidents involving containment-vessel failure dominate both the mean and variance of the distribution of consequences, although this conclusion is subject to uncertainties about plume rise. Research is recommended on the behavior of horizontal, sonic jets, with heat transfer to the ground, and especially during stable atmospheric conditions. Diffusion with fumigation and lofting require further study; use of K-theory and National Weather Service data should be vigorously pursued. Conditional upon an accident occurring, precipitation scavenging appears to dominate the variance of the consequences

  13. Summary of safety evaluation toxicity studies of glufosinate ammonium.

    Science.gov (United States)

    Ebert, E; Leist, K H; Mayer, D

    1990-05-01

    This article reviews the results of toxicity studies to evaluate the safety of the herbicide glufosinate ammonium (GLA) and its formulation (200 g/litre) in laboratory animals. The data show that GLA and its formulation are slightly toxic following oral exposure. In addition, the formulation induced GLA and its formulation are slightly toxic following oral exposure. In addition, the formulation induced slight dermal toxicity and eye irritation. Testing for teratogenicity in rats and rabbits indicated no teratogenic potential, and numerous mutagenicity tests showed GLA to be non-genotoxic. Chronic toxicity testing in rats and dogs yielded no-observable-effect levels of 2 and 5 mg/kg body weight/day, respectively. Oncogenicity studies in rats and mice revealed no carcinogenic potential. On the basis of these toxicity data it is concluded that this herbicide is safe under conditions of recommended use.

  14. Contributions to safety studies for new concepts of nuclear reactors

    International Nuclear Information System (INIS)

    Perdu, F.

    2003-12-01

    The complete study of molten salt reactors, designed for a massive and durable nuclear energy production, must include neutronics, hydraulics and thermal effects. This coupled study, using the MCNP and Trio U codes, is undertaken in the case of the MSRE (molten salt reactor experiment) prototype. The obtained results fit very well the experiment. Their extrapolation suggests ways of improving the safety coefficients of power molten salt reactors. A second part is devoted to accelerator driven subcritical reactors, developed to incinerate radioactive waste.We propose a method to measure the prompt reactivity from the decay following a neutron pulse. It relies only on the distribution of times between generations, which is a characteristic of the reactor. This method is implemented on the results of the MUSE 4 experiment, and the obtained reactivity is accurate within 5%. (author)

  15. Safety of SSRIs during pregnancy: a controlled study.

    Science.gov (United States)

    Altamura, A C; De Gaspari, I F; Rovera, C; Colombo, E M; Mauri, M C; Fedele, L

    2013-01-01

    The objective of our study was to analyze the efficacy and the safety of SSRIs during pregnancy. A group of 30 pregnant women affected by Major Depressive Disorder by SCID I interview (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision criteria) and treated with selective serotonin reuptake inhibitor (SSRI) were included in the study. They were matched to a comparison group of 26 pregnant women. There were no statistically significant differences in any of the pregnancy outcomes of interest between the treated women and comparison group. There was no statistically significant association in newborns of women treated with an SSRI and the control group in the first and fifth minute Apgar score, and no newborns were admitted to neonatal Intensive Care Units. No definitive association between use of SSRIs during pregnancy and an increased risk of birth defects or other adverse outcomes could be found. Copyright © 2012 John Wiley & Sons, Ltd.

  16. Consequence model of the German reactor safety study

    International Nuclear Information System (INIS)

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

    1979-01-01

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

  17. 77 FR 43090 - Safety and Occupational Health Study Section: Notice of Charter Renewal

    Science.gov (United States)

    2012-07-23

    ... Committee Act (Pub. L. 92-463) of October 6, 1972, that the Safety and Occupational Health Study Section... Secretary, Safety and Occupational Health Study Section, Department of Health and Human Services, 1600... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Safety and...

  18. 75 FR 42455 - Safety and Occupational Health Study Section: Notice of Charter Renewal

    Science.gov (United States)

    2010-07-21

    ... Committee Act (Pub. L. 92-463) of October 6, 1972, that the Safety and Occupational Health Study Section... Secretary, Safety and Occupational Health Study Section, Department of Health and Human Services, 1600... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Safety and...

  19. Investor’s Commitment Bias and Escalation of Firm’s Investment Decision

    Directory of Open Access Journals (Sweden)

    Anis JARBOUI

    2012-12-01

    Full Text Available This study examines the reasons of perseverance in firm’s investment decision. It shows the possible influence of three closely related features which are: firm’s financial indicators, investor’s risk profile, and investor’s commitment bias, on a firm’s investment decisions escalation. This study aims to provide evidence as to whether investor considers the financial and risk’s perception features (financial strength and risk profile to persevere his initial investment decision while he notes a high level of commitment bias. The proposed model of this paper uses GLM univariate data analyses to examine this relationship. Investor’s risk profile and his commitment bias have been measured by means of a questionnaire comprising several items. As for the selected sample, it has been composed of some 360 Tunisian individual investors. Our results have revealed that investors pay more attention to keep their psychology comfort than their financial comfort. It exposed the importance of the investor’s commitment bias and its risk perception in explaining investment decision escalation. Moreover results shows that there is strong and significant empirical relationship linking the escalatory behavior in investment decision and the interaction effects between the three independent variables. This means that, in practice, investors consider the three factors simultaneously.

  20. Observational Study on Safety of Prehospital BLS CPAP in Dyspnea.

    Science.gov (United States)

    Sahu, Novneet; Matthews, Patrick; Groner, Kathryn; Papas, Mia A; Megargel, Ross

    2017-12-01

    Introduction Continuous positive airway pressure (CPAP) improves outcomes in patients with respiratory distress. Additional benefits are seen with CPAP application in the prehospital setting. Theoretical safety concerns regarding Basic Life Support (BLS) providers using CPAP exist. In Delaware's (USA) two-tiered Emergency Medical Service (EMS) system, BLS often arrives before Advanced Life Support (ALS). Hypothesis This study fills a gap in literature by evaluating the safety of CPAP applied by BLS prior to ALS arrival. This was a retrospective, observational study using Quality Assurance (QA) data collected from October 2009 through December 2012 throughout a state BLS CPAP pilot program; CPAP training was provided to BLS providers prior to participation. Collected data include pulse-oximetry (spO2), respiratory rate (RR), heart rate (HR), skin color, and Glasgow Coma Score (GCS) before and after CPAP application. Pre-CPAP and post-CPAP values were compared using McNemar's and t-tests. Advanced practitioners evaluated whether CPAP was correctly applied and monitored and whether the patient condition was "improved," "unchanged," or "worsened." Seventy-four patients received CPAP by BLS; CPAP was correctly indicated and applied for all 74 patients. Respiratory status and CPAP were appropriately monitored and documented in the majority of cases (98.6%). A total of 89.2% of patients improved and 4.1% worsened; CPAP significantly reduced the proportion of patients with SpO224, and cyanosis (PCPAP (mean difference [MD]=0.17; 95% CI, -0.49 to 0.83; P=.59). The HR decreased from 115.7 (SD=53) to 105.1 (SD=37) after CPAP (MD=-10.9; 95% CI, -3.2 to -18.6; PCPAP (MD=17.8; 95% CI, 14.2-21.5; PCPAP was indicated, to apply it correctly, and to appropriately monitor the status of these patients. The majority of patients who received CPAP by BLS providers had improvement in their clinical status and vital signs. The findings suggest that CPAP can be safely used by BLS providers

  1. A study on LAN applications in nuclear safety systems

    International Nuclear Information System (INIS)

    Kim, Sung; Lee, Young Ryul; Koo, Jun Mo; Han, Jai Bok

    1995-01-01

    It is a general tendency to digitalize the conventional relay based I and C systems in nuclear power plant. But, the digitalisation of nuclear safety systems has many a difficulty to surmount. The typical one thing of many difficulties is the data communication problem between local controllers and systems. The network architecture built with LAN (Local Area Network) in digital systems of the other industries are general. But in case of nuclear safety systems many considerations in point of safety and license are required to implement it in the field. In this parer, some considerations for applying LAN in nuclear safety systems were reviewed

  2. Present status of nuclear power safety studies in JAERI, 1994

    International Nuclear Information System (INIS)

    1994-10-01

    Securing safety in the development and utilization of nuclear power is the prerequisite, and in order to maintain the safety of nuclear power facilities at level corresponding to the expansion and diversification of nuclear power development and utilization, it is necessary to promote the safety research. The reliable evaluation of environmental effect and the safe disposal of radioactive waste are the indispensable conditions. Japan Atomic Energy Research Institute has carried out the research on the engineering safety of nuclear reactors and nuclear fuel cycle facilities and the research on the environmental safety related to environmental radiation and the treatment and disposal of radioactive waste. In this book, the researches on the safety of reactor fuel, the reliability of reactor machinery and equipment and structures, the thermo-hydraulic behavior of reactors at the time of accidents, the behavior of reactors at the time of severe accidents, the analytical research on the safety of reactors, the researches on the safety of nuclear fuel cycle, the treatment and disposal of radioactive waste, the assessment and analysis of environmental radiation and radioactivity, and the individual researches related to nuclear power safety are reported. (K.I.)

  3. Ferrocyanide Safety Project: Subtask 3.4, Aging Studies

    International Nuclear Information System (INIS)

    Lilga, M.A.; Lumetta, M.R.; Riemath, W.F.; Romine, R.A.; Schiefelbein, G.F.

    1992-11-01

    The Hanford Ferrocyanide Task Team is addressing issues involving ferrocyanide precipitates in single-shell waste storage tanks (SSTs), in particular the storage of waste in a safe manner. This Task Team, composed of researchers from Westinghouse Hanford Company (WHC), Pacific Northwest Laboratory (PNL), and outside consultants, was formed in response to the need for an updated analysis of safety questions about the Hanford ferrocyanide tanks. This annual report gives the results of the work conducted by PNL in FY 1992 on Subtask 3.4, Aging Studies, which is part of Task 3, Chemical Nature of Feffocyanide in Wastes. Subtask 3.4 deals with the aging behavior and solubilization of ferrocyanide tank waste sludges in a basic aqueous environment. Investigated were the effects of pH variation, ionic strength, salts present in SSTS, and gamma radiation on solubilization of vendor-prepared Na 2 NiFe(CN) 6

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-11-15

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

  5. Phylogenetic trends in phenolic metabolism of milkweeds (Asclepias): evidence for escalation.

    Science.gov (United States)

    Agrawal, Anurag A; Salminen, Juha-Pekka; Fishbein, Mark

    2009-03-01

    Although plant-defense theory has long predicted patterns of chemical defense across taxa, we know remarkably little about the evolution of defense, especially in the context of directional phylogenetic trends. Here we contrast the production of phenolics and cardenolides in 35 species of milkweeds (Asclepias and Gomphocarpus). Maximum-likelihood analyses of character evolution revealed three major patterns. First, consistent with the defense-escalation hypothesis, the diversification of the milkweeds was associated with a trend for increasing phenolic production; this pattern was reversed (a declining evolutionary trend) for cardenolides, toxins sequestered by specialist herbivores. Second, phylogenetically independent correlations existed among phenolic classes across species. For example, coumaric acid derivatives showed negatively correlated evolution with caffeic acid derivatives, and this was likely driven by the fact that the former are used as precursors for the latter. In contrast, coumaric acid derivatives were positively correlated with flavonoids, consistent with competition for the precursor p-coumaric acid. Finally, of the phenolic classes, only flavonoids showed correlated evolution (positive) with cardenolides, consistent with a physiological and evolutionary link between the two via malonate. Thus, this study presents a rigorous test of the defense-escalation hypothesis and a novel phylogenetic approach to understanding the long-term persistence of physiological constraints on secondary metabolism.

  6. Growth trajectories of alcohol information processing and associations with escalation of drinking in early adolescence.

    Science.gov (United States)

    Colder, Craig R; O'Connor, Roisin M; Read, Jennifer P; Eiden, Rina D; Lengua, Liliana J; Hawk, Larry W; Wieczorek, William F

    2014-09-01

    This longitudinal study provided a comprehensive examination of age-related changes in alcohol outcome expectancies, subjective evaluation of alcohol outcomes, and automatic alcohol associations in early adolescence. A community sample (52% female, 75% White/non-Hispanic) was assessed annually for 3 years (mean age at the first assessment = 11.6 years). Results from growth modeling suggested that perceived likelihood of positive outcomes increased and that subjective evaluations of these outcomes were more positive with age. Perceived likelihood of negative outcomes declined with age. Automatic alcohol associations were assessed with an Implicit Association Task (IAT), and were predominantly negative, but these negative associations weakened with age. High initial levels of perceived likelihood of positive outcomes at age 11 were associated with escalation of drinking. Perceived likelihood of negative outcomes was associated with low risk for drinking at age 11, but not with changes in drinking. Increases in positive evaluations of positive outcomes were associated with increases in alcohol use. Overall, findings suggest that at age 11, youth maintain largely negative attitudes and perceptions about alcohol, but with the transition into adolescence, there is a shift toward a more neutral or ambivalent view of alcohol. Some features of this shift are associated with escalation of drinking. Our findings point to the importance of delineating multiple aspects of alcohol information processing for extending cognitive models of alcohol use to the early stages of drinking.

  7. Stairs or escalator? Using theories of persuasion and motivation to facilitate healthy decision making.

    Science.gov (United States)

    Suri, Gaurav; Sheppes, Gal; Leslie, Sara; Gross, James J

    2014-12-01

    To encourage an increase in daily activity, researchers have tried a variety of health-related communications, but with mixed results. In the present research-using the stair escalator choice context-we examined predictions derived from the Heuristic Systematic Model (HSM), Self Determination Theory (SDT), and related theories. Specifically, we tested whether (as predicted by HSM) signs that encourage heuristic processing ("Take the Stairs") would have greatest impact when placed at the stair/escalator point of choice (when processing time is limited), whereas signs that encourage systematic processing ("Will You Take the Stairs?") would have greatest impact when placed at some distance from the point of choice (when processing time is less limited). We also tested whether (as predicted by SDT) messages promoting autonomy would be more likely to result in sustained motivated behavior (i.e., stair taking at subsequent uncued choice points) than messages that use commands. A series of studies involving more than 9,000 pedestrians provided support for these predictions. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

  8. De-escalating Antibiotic Use in the Inpatient Setting: Strategies, Controversies, and Challenges.

    Science.gov (United States)

    Daniel Markley, J; Bernard, Shaina; Bearman, Gonzalo; Stevens, Michael P

    2017-04-01

    Antibiotic de-escalation (ADE) is widely accepted as an integral strategy to curtail the global antibiotic resistance crisis. However, there is significant uncertainty regarding the ideal ADE strategy and its true impact on antibiotic resistance. Rapid diagnostic testing has the potential to enhance ADE strategies. Herein, we aim to discuss the current strategies, controversies, and challenges of ADE in the inpatient setting. A consensus definition of ADE remains elusive at this time. Preliminary studies utilizing rapid diagnostic tests including matrix-assisted laser desorption/ionization time of flight (MALDI-TOF), procalcitonin, and other molecular techniques have demonstrated the potential to support ADE strategies. In the absence of evidence-based, highly specific ADE protocols, the likelihood that individual providers will make consistent, often challenging, decisions to de-escalate antibiotic therapy is low. Antimicrobial stewardship programs should support local physicians with ADE and develop innovative ways to integrate ADE into the broader construct of antimicrobial stewardship programs. The evolving field of rapid diagnostics has significant potential to improve ADE strategies, but more research is needed to fully realize this goal.

  9. The potential influence of cell protectors for dose escalation in cancer therapy: an analysis of amifostine

    International Nuclear Information System (INIS)

    McCumber, Linda M.

    2004-01-01

    The attempt to increase the therapeutic ratio in an effort to improve survival or quality of life is the goal of modern cancer therapy. It is commonly accepted that local and systemic tumor control would increase if the dose intensity of antineoplastic drugs, radiation therapy, or the combination were increased. Radiation dose escalation using intensity-modulated radiation therapy (IMRT), accelerated or hypofractionated radiation schemes, and multidrug chemotherapy regimens are being used to try to increase tumor kill while inflicting minimal injury to normal tissue. Modern chemoradiation techniques have led to improved local regional control and increased cure rates, but the potentially severe and debilitating adverse effects of the therapies prevent them from reaching the ultimate goal of curing the disease while leaving the patient with a good quality of life. Cell protectants such as amifostine function by reducing the effects of therapy on normal cells while maintaining tumor sensitivity to the therapy. In various studies, amifostine has been analyzed and appears to be a potentially powerful adjuvant to current cancer therapy. Administering amifostine may allow dose escalation with less or equal risk to surrounding normal tissues. This could improve therapeutic efficacy, survival, and quality of life for cancer patients

  10. An Hourly Dose-Escalation Desensitization Protocol for Aspirin-Exacerbated Respiratory Disease.

    Science.gov (United States)

    Chen, Justin R; Buchmiller, Brett L; Khan, David A

    2015-01-01

    Aspirin desensitization followed by maintenance therapy effectively improves symptom control in patients with aspirin exacerbated respiratory disease (AERD). The majority of current desensitization protocols use 3-hour dosing intervals and often require 2 to 3 days to complete. We evaluated hourly dose escalations in a subset of patients with chronic rhinosinusitis, nasal polyps, and asthma who historically reacted to aspirin within 1 hour or were avoiding aspirin with the goal of developing a safe and efficient desensitization protocol. Fifty-seven aspirin desensitizations were performed under the hourly protocol. All patients had refractory nasal polyposis as an indication for aspirin desensitization. The clinical characteristics of each subject were analyzed in relation to aspects of his or her reactions during the procedure. Ninety-eight percent of study patients were successfully treated under the hourly protocol, including those with a history of severe reactions and intubation. None required further medication than is available in an outpatient allergy clinic. A total of 96% of reactors recorded a bronchial or naso-ocular reaction within 1 hour of the preceding dose. Of the total patients on this protocol, 40% were able to complete the procedure in a single day, and 60% within 2 days. Patients with AERD who have a history of symptoms less than 1 hour after aspirin exposure can be safely desensitized with a 1-hour dose-escalation protocol that can often be completed in a single day. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  11. Dose study of the multikinase inhibitor, LY2457546, in patients with relapsed acute myeloid leukemia to assess safety, pharmacokinetics, and pharmacodynamics

    Directory of Open Access Journals (Sweden)

    Wacheck V

    2011-05-01

    Full Text Available Volker Wacheck1, Michael Lahn2, Gemma Dickinson3, Wolfgang Füreder4, Renata Meyer4, Susanne Herndlhofer4, Thorsten Füreder1, Georg Dorfner5, Sada Pillay2, Valérie André6, Timothy P Burkholder7, Jacqueline K Akunda8, Leann Flye-Blakemore9, Dirk Van Bockstaele9, Richard F Schlenk10, Wolfgang R Sperr4, Peter Valent4,111Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel, Vienna, Austria; 2Early Oncology Clinical Investigation, Eli Lilly and Company, Indianapolis, IN, USA; 3Department of Pharmacokinetics, Eli Lilly and Company, Erl Wood Research Centre, Windlesham, Surrey, UK; 4Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Währinger Gürtel, Vienna, Austria; 5Eli Lilly GesmbH, Medical Department, Vienna, Austria; 6Department of Statistics, Eli Lilly and Company, Erl Wood Research Centre, Surrey, UK; 7Discovery Chemistry Research and Technology, Eli Lilly and Company, Indianapolis, IN, USA; 8Nonclinical Toxicology, Eli Lilly and Company, Indianapolis, IN, USA; 9Flow Cytometry and Cell Analysis, Esoterix Clinical Trials Services, Mechelen, Belgium; 10Universitätsklinikum Ulm, Klinik für Innere Medizin III, Ulm, Germany; 11Ludwig Boltzmann Cluster Oncology, Vienna, AustriaBackground: Acute myeloid leukemia (AML is a life-threatening malignancy with limited treatment options in chemotherapy-refractory patients. A first-in-human dose study was designed to investigate a safe and biologically effective dose range for LY2457546, a novel multikinase inhibitor, in patients with relapsed AML.Methods: In this nonrandomized, open-label, dose escalation Phase I study, LY2457546 was administered orally once a day. Safety, pharmacokinetics, changes in phosphorylation of target kinases in AML blasts, and risk of drug–drug interactions (DDI were assessed.Results: Five patients were treated at the starting and predicted minimal biologically effective dose of 50 mg

  12. Radiation Dose Escalation in Esophageal Cancer Revisited: A Contemporary Analysis of the National Cancer Data Base, 2004 to 2012

    Energy Technology Data Exchange (ETDEWEB)

    Brower, Jeffrey V. [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States); Chen, Shuai [Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States); Bassetti, Michael F. [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States); Yu, Menggang [Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States); Harari, Paul M.; Ritter, Mark A. [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States); Baschnagel, Andrew M., E-mail: baschnagel@humonc.wisc.edu [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States)

    2016-12-01

    the INT-0123 trial. Furthermore, these data highlight that many radiation oncologists have not embraced the concept that dose escalation does not improve OS. Although local control, not investigated in the present study, might benefit from dose escalation, novel therapies are needed to improve the OS of patients with esophageal cancer.

  13. An intra-patient dose-escalation study of disodium pamidronate plus radiotherapy versus radiotherapy alone for the treatment of osteolytic metastases. Monitoring of recalcification using image-processing techniques

    Energy Technology Data Exchange (ETDEWEB)

    Vassilis Kouloulias, E. [Dept. of Radiology, Aretaieion Univ. Hospital, Athens (Greece); Dept. of Electrical and Computer Engineering, Inst. of Communication and Computer Systems, National Technical Univ. of Athens (Greece); John Kouvaris, R.; Antypas, C.; Mystakidou, K.; Moulopoulos, A.; Lambros Vlahos, J. [Dept. of Radiology, Aretaieion Univ. Hospital, Athens (Greece); Matsopoulos, G.; Nikolaos Uzunoglu, C. [Dept. of Electrical and Computer Engineering, Inst. of Communication and Computer Systems, National Technical Univ. of Athens (Greece)

    2003-07-01

    Objective: To evaluate the clinical benefit and mainly to monitor quantitatively the recalcification of osteolytic lesions after radiotherapy with or without intravenous infusion of disodium pamidronate (DP) in different doses. Patients and Methods: 42 patients with solitary lytic metastasis in weight-bearing bones were studied. Primary endpoints were the mean value and energy of gray-level histogram in plain radiographs (MVGLH and EGLH) and relative electron density (RED) of CT scans in bone lesions. In eleven patients (group A) the DP dose was increased stepwise from 90 up to 180 mg (flat dose), while in other 15 patients (group B) a flat dose of 180 mg was administered intravenously in 2 h. In both groups, the first session of DP was given concurrently with local radiotherapy (30 Gy in ten fractions, 5 days a week). Another 16 patients (group C) underwent radiotherapy only. Results: Morbidity related to pamidronate was mild. Significant differences from the baseline (p < 0.05, Wilcoxon test) were recorded for MVGLH, EGLH and RED values, regarding all groups. Improvement was significantly higher in patients of group B versus A, while the results of pamidronate groups (A and B) were superior to group C, concerning the above indices (p < 0.05, Mann-Whitney test). Additionally, pamidronate groups had significantly lower skeletal morbidity than group C. Conclusion: The 2-h infusional flat dose of 180 mg every 4 weeks seems to be tolerable and superior to 90 mg regarding palliation and mainly recalcification of osteolytic lesions. Radiotherapy alone is effective but inferior to the combined treatment. Last but not least, the findings of MVGLH, EGLH and RED indicate an important increase in bone mass and bone formation, which was difficult to be identified visually by the experts. (orig.)

  14. Assessment of Safety Condition in One of the Teaching Hospitals in Kermanshah (2015: A Case Study

    Directory of Open Access Journals (Sweden)

    Masod Ghanbari Kakavand

    2016-09-01

    Full Text Available Background & Aims of the Study: Many working conditions-related stress factors that can produce injuries and illnesses are important in hospital environments. So, the health and safety of nurses and patients from workplace-induced injuries and illnesses is important. In this study, we have assessed the safety condition of one of the teaching hospitals in Kermanshah (2015. Materials and Methods: This descriptive and cross-sectional study was conducted in one of the teaching hospital of Kermanshah University of medical sciences. For this aim a checklist was prepared based on the Occupational Safety and Health Administration's standards and Part 3 of the manual of National Building Regulations. These checklists comprised (The final checklist had 239 questions of 9 dimensions various sections of safety including; fire safety, building safety, electrical safety, emergency exit routes safety, heating and cooling equipment safety, operating room and laundry room and salty home safety. Eventually, using SPSS 16 and descriptive statistics, data were analyzed. Results: According to the results of this study, 66.6% of the units had poor safety and 33.4% of them were moderately safe. As well as, only ICU and CCU unit, heating and cooling equipment and operational room showed moderate compliance with safety requirements and other sections were poorly complied. Conclusion: The results of this study showed that safety conditions of hospital were not at favorable level. These poor safety statues can jeopardize patients and hospital personnel. Thus some interventions such as improvement of working conditions, compliance with safety acts and implementation of health, safety and environmental management system would be necessary.

  15. Key aspects in managing safety when working with multiple contractors: A case study

    NARCIS (Netherlands)

    Drupsteen, L.; Rasmussen, H.B.; Ustailieva, E.; Kampen, J. van

    2015-01-01

    Working with multiple contractors in a shared workplace can introduce and increase safety risks due to complexity. The aim of this study was to explore how safety issues are recognized in a specific case and to identify whether clients and contractors perceive problems similarly. The safety issues

  16. The study on safety facility criteria for radioactive waste repository

    International Nuclear Information System (INIS)

    Lee, S. H.; Choi, M. H.; Han, S. H. and others

    1992-12-01

    The radioactive waste repository are necessary to install the engineered safety systems to secure the safety for operation of the repository in the event of fire and earthquake. Since the development of safety facility criteria requires a thorough understanding about the characteristics of the engineered safety systems, we should investigate by means of literature survey and visit SKB. In particular, definition, composition of the systems, functional requirement of the systems, engineered safety systems of foreign countries, system design, operation and maintenance requirement should be investigated : fire protection system, ventilation system, drainage system, I and C system, electric system, radiation monitoring system. This proposed criteria consist of purpose, scope of application, ventilation system, fire protection system, drainage system, electric system and this proposed criteria can be applied as a basic reference for the final criteria

  17. Brain Magnetic Resonance Elastography on Healthy Volunteers: A Safety Study

    International Nuclear Information System (INIS)

    Guang-Rui Liu; Pei-Yi Gao; Yan Lin; Jing Xue; Xiao-Chun Wang; Bin-Bin Sui; Li Ma; Zhi-Nong Xi; Qin Bai; Hao Shen

    2009-01-01

    Background: Magnetic resonance elastography (MRE) is a recently developed imaging technique that can directly visualize and quantitatively measure tissue elasticity. Purpose: To evaluate the safety of brain MRE on human subjects. Material and Methods: The study included 20 healthy volunteers. MRE sequence scan (drive signal not applied to external force actuator) and MRE study were separately performed on each volunteer at an interval of more than 24 hours. The heart rate and blood pressure of each volunteer were measured immediately before and after MRE sequence scan and MRE study. Electroencephalography (EEG) was also performed within 2 hours after each scan. The volunteers were asked about their experience of the two scans. Randomized-block analysis of variance (ANOVA) was used to analyze the data of blood pressure and heart rate. Paired t test was used to analyze the data of the two EEG examinations. The volunteers were followed up 1 week after the examination. Results: All procedures were performed on each volunteer, and no one complained of obvious discomfort. No related adverse events were reported during follow-up. There was no statistically significant difference in heart rate or blood pressure. There was a statistically significant difference (P<0.05) in EEG results in the right temporoparietal region. Increased power was found in the theta, delta, alpha, and beta2 bands. No brain injury was detected by the EEG examinations. Conclusion: Based on the study results, brain MRE examinations are safe to perform on human subjects

  18. Maintaining and Researching Port Safety: A Case Study of the Port of Kaohsiung

    OpenAIRE

    Tseng, Po-Hsing.; Pilcher, Nick.

    2017-01-01

    Maintaining port safety in full conformity with IMO standards is a requisite for every port and country. To do this, understanding the challenges and human factors involved is key. To date, much research has shed valuable light on these factors and considered how to address them. One aspect that is often noted is that both maintaining port safety and researching port safety presents numerous challenges. This paper considers both these aspects in the context of a case study of port safety in K...

  19. Study on safety subsidiary objective of nuclear power plant in USA

    International Nuclear Information System (INIS)

    Chen Yan; Zhang Chunming; Fu Zhiwei; Song Wei; Li Chaojun; Wang Zhe; Zuo Jiaxu

    2013-01-01

    This paper reviewed the development of the quantitative safety objective and subsidiary objective in USA. The expressions of CDF and LERF were obtained according to NUREG-1150. The relationship between the subsidiary objective and the quantitative safety objective was derived. The method was compared with that used in NUREG-1860. The requirements of safety objective for the future nuclear power plant and the development of probabilistic safety analysis (PSA) technology in USA were studied and can be used as reference in China. (authors)

  20. An integrative review of patient safety in studies on the care and safety of patients with communication disabilities in hospital.

    Science.gov (United States)

    Hemsley, Bronwyn; Georgiou, Andrew; Hill, Sophie; Rollo, Megan; Steel, Joanne; Balandin, Susan

    2016-04-01

    To review the research literature on the experiences of patients with communication disabilities in hospital according to the Generic Model of patient safety. In 2014 and 2015, we searched four scientific databases for studies with an aim or result relevant to safety of hospital patients with communication disabilities. The review included 27 studies. A range of adverse event types were outlined in qualitative research. Little detail was provided about contributing or protective factors for safety incidents in hospital for these patients or the impact of the incidents on the patient or organisations involved. Further research addressing the safety of patients with communication disabilities is needed. Sufficient detail is required to identify the nature, timing, and detection of incidents; factors that contribute to or prevent adverse events; and detail the impact of the adverse events. In order to provide safe and effective care to people with communication disabilities in hospital, a priority for health and disability services must be the design and evaluation of ecologically appropriate and evidence-based interventions to improve patient care, communication, and reduce the risk of costly and harmful patient safety incidents. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. The impact of health and safety committees. A study based on survey, interview, and Occupational Safety and Health Administration data.

    Science.gov (United States)

    Boden, L I; Hall, J A; Levenstein, C; Punnett, L

    1984-11-01

    In a study conducted to determine if the existence of a joint labor-management health and safety committee (HSC) was correlated with either the number of Occupational Safety and Health Administration (OSHA) complaints or hazardousness, as measured by OSHA serious citations, virtually no effect could be detected in a sample of 127 Massachusetts manufacturing firms. At a sample of 13 firms, interviews of HSC members were conducted. Committee attributes and perceptions about committee effectiveness were compared with the number of OSHA complaints and serious citations. There were fewer complaints and fewer serious citations at firms with HSCs that were perceived as effective. Results of the study suggest that the objective attributes of the committee may be less important to its success than the commitment of management and labor to solving workplace safety problems.

  2. Process Inherent Ultimate Safety (PIUS) reactor evaluation study: Final report

    International Nuclear Information System (INIS)

    1987-02-01

    This report presents the results of an independent study by United Engineers and Constructors (UNITED) of the SECURE-P Process Inherent Ultimate Safety (PIUS) Reactor Concept which is presently under development by the Swedish light water reactor vendor ASEA-ATOM of Vasteras, Sweden. This study was performed to investigate whether there is any realistic basis for believing that the PIUS reactor could be a viable competitor in the US energy market in the future. Assessments were limited to the technical, economic and licensing aspects of PIUS. Socio-political issues, while certainly important in answering this question, are so broad and elusive that it was considered that addressing them with the limited perspective of one small group from one company would be of questionable value and likely be misleading. Socio-political issues aside, the key issue is economics. For this reason, the specific objectives of this study were to determine if the estimated PIUS plant cost will be competitive in the US market and to identify and evaluate the technical and licensing risks that might make PIUS uneconomical or otherwise unacceptable

  3. Safety studies on LOCA for N.S. Mutsu

    International Nuclear Information System (INIS)

    Kawasaki, Masayuki; Yaguchi, Shinnosuke

    1978-01-01

    A number of safety studies are under way concerning the reactor plant of N.S. Mutsu. One such study relates to Loss of Coolant Accidents (LOCA), which has been conducted to cover mainly the two subjects of experiments to ascertain the integrity of stainless steel fuel cladding under the action of the Emergency Core Cooling System (ECCS), and analysis of containment integrity following a LOCA. The stainless steel cladding tests were conducted to test swelling, rupture, oxidation and compression characteristics. Few reports are known to have been published in this domain, so that the present results should prove useful for future studies related to ECCS evaluation analyses on stainless steel fuel cladding. The containment integrity analysis covered variations of containment pressure and temperature following a LOCA, performed separately for short- and long-term periods. Estimates were also made on the changes in the hydrogen concentration present inside the containment after a LOCA. The results obtained should serve in determining the characteristic response to LOCA of marine reactor plants

  4. A study for safety and health management problem of semiconductor industry in Taiwan.

    Science.gov (United States)

    Chao, Chin-Jung; Wang, Hui-Ming; Feng, Wen-Yang; Tseng, Feng-Yi

    2008-12-01

    The main purpose of this study is to discuss and explore the safety and health management in semiconductor industry. The researcher practically investigates and interviews the input, process and output of the safety and health management of semiconductor industry by using the questionnaires and the interview method which is developed according to the framework of the OHSAS 18001. The result shows that there are six important factors for the safety and health management in Taiwan semiconductor industry. 1. The company should make employee clearly understand the safety and health laws and standards. 2. The company should make the safety and health management policy known to the public. 3. The company should put emphasis on the pursuance of the safety and health management laws. 4. The company should prevent the accidents. 5. The safety and health message should be communicated sufficiently. 6. The company should consider safety and health norm completely.

  5. Status of the EU test blanket systems safety studies

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  6. Status of the EU test blanket systems safety studies

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-10-15

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

  7. Present status of nuclear power safety studies in JAERI

    International Nuclear Information System (INIS)

    1989-01-01

    Japan Atomic Energy Research Institute carries out the safety research required for ensuring safety accompanying the development and utilization of atomic energy, dividing the roles with industrial circules, universities and other public research institutes. First, it carries out the research based on the yearly program of safety research, in which the subjects of safety research that the state should execute are decided. Next, it carries out a series of the safety verification test on atomic energy facilities entrusted by the state using the special account for power source development promotion countermeasures. Besides, it carries out the safety research on the specific subjects entrusted by outside organizations. The object and range of atomic energy safety at present are roughly divided into four fields, that is, nuclear power stations, nuclear fuel facilities, waste treatment and disposal, and environmental radioactivity. In order to advance the research effectively, in addition to the generalization department and the execution department, various committees are organized. In 1988, about 260 persons engaged in these four research fields, and the budget for fiscal year 1988 was about 17.4 billion yen. (K.I.)

  8. Progress in the development of methodology for fusion safety systems studies

    International Nuclear Information System (INIS)

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

    1994-01-01

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

  9. Optimization of tolerability and efficacy of the novel dual amylin and calcitonin receptor agonist KBP-089 through dose escalation and combination with a GLP-1 analog

    DEFF Research Database (Denmark)

    Gydesen, Sofie; Andreassen, Kim Vietz; Hjuler, Sara Toftegaard

    2017-01-01

    , and the following treatment with 2.5, 10, and 40 µg/kg resulted in an ~15% vehicle-corrected weight loss, a corresponding reduction in adipose tissue (AT), and, in all treatment groups, improved oral glucose tolerance (P weight evenly with no significant...... second day obtained equal weight loss at study end, albeit with an uneven reduction in both food intake and body weight in rats dosed every second day. In a 4-fold dose escalation, KBP-089 induced a transient reduction in food intake at every escalation step, with reducing magnitude over time...... reduction in food intake at either escalation step. KBP-089 (1.25 µg/kg) and liraglutide (50 µg/kg) reduced 24-h food intake by 29% and 37% compared with vehicle, respectively; however, when they were combined, 24-h food intake was reduced by 87%. Chronically, KBP-089 (1.25 µg/kg) and liraglutide (50 µg...

  10. Study on application of safety checklist in preventive maintenance activities

    International Nuclear Information System (INIS)

    Shi Jin; Chen Song; Liu Jingquan

    2013-01-01

    The paper describes the principles and the characteristics of safety checklist as a risk evaluation method. Examples of application of safety checklists to preventive maintenance activities such as criteria comparison and checkup items in place in nuclear power plants are illustrated in details with issues appeared in the checklist establishment. Checklist has a good application in the RCM analysis or in the actual preventive maintenance program for Chashma Nuclear Power Plant indicated by concrete instances. In the light of safety checklist which is used to sustain preventive maintenance as a simple and applicable risk analysis approach, we can get deep knowledge of risks of nuclear power plant to perfect preventive maintenance activities. (authors)

  11. Understanding the Emotional Aspects of Escalation of Commitment: The Role of Negative Affect

    Science.gov (United States)

    Wong, Kin Fai Ellick; Yik, Michelle; Kwong, Jessica Y. Y.

    2006-01-01

    Despite the importance of understanding the emotional aspects of organizational decision making, prior research has paid scant attention to the role of emotion in escalation of commitment. This article attempts to fill this gap by examining the relationship between negative affect and escalation of commitment. Results showed that regardless of…

  12. Contractors’ Attitude towards Enhancing Safety Performance: Case Study on Construction Firms in Penang

    Directory of Open Access Journals (Sweden)

    Ulang N. Md

    2014-01-01

    Full Text Available A qualitative study was conducted to investigate the contractors’ attitude towards enhancing the safety performance in construction site. Despite the fact that there are many safety initiatives established by the government, the rates of accidents are still in a critically high condition. Thus the purpose of this research is to study the contractors’ attitude towards enhancing the implementation of safety management system in construction site in order to increase the safety awareness of construction practitioners in construction site and improve the safety condition of construction sites. This study is conducted through oral interviews with the construction practitioners, and visual inspection of construction sites. The attitudes of contractors are evaluated from 3 aspects: Contractors’ efforts in implement and enforce the safety rules, Contractors efforts in overcoming the rate of accidents, and Reasons given by the contractors for not implement safety law.

  13. Bridging probabilistic safety assessment studies with information Management System

    International Nuclear Information System (INIS)

    Luanco, E. M.

    2010-01-01

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

  14. Probabilistic seismic safety study of an existing nuclear power plant

    International Nuclear Information System (INIS)

    Kennedy, R.P.; Cornell, C.A.; Kaplan, S.; Perla, H.F.

    1980-01-01

    This study was conducted as part of an overall safety study of the Oyster Creek nuclear power plant. The earthquake hazard was considered as an initiating event that could result in radioactive release from the site as a result of core melt. The probability of earthquake initiated releases were compared with the probability of releases due to other initiating events. Three steps are necessary to evaluate the probability of earthquake initiated core melt. (1) estimate the ground motion (peak ground acceleration) and uncertainty in this estimate as functions of annual probability of occurrence; (2) estimate the conditional probability of failure and its uncertainty for structures, equipment, piping, controls, etc., as functions of ground acceleration; and (3) combine these estimates to obtain probabilities of earthquake induced failure and uncertainties in such estimates to be used in event trees, system models, and fault trees for evaluating the probability of earthquake induced core melt. This paper concentrates on the first two steps with emphasis on step 2. The major difference between the work presented and previous papers is the development and use of uncertainty estimates for both the ground motion probability estimates and the conditional probability of failure estimates. (orig.)

  15. Measuring mobile patient safety information system success: an empirical study.

    Science.gov (United States)

    Jen, Wen-Yuan; Chao, Chia-Cheng

    2008-10-01

    The Health Risk Reminders and Surveillance (HRRS) system was designed to deliver critical abnormal test results of severely ill patients from Laboratory, Radiology, and Pathology departments to physicians within 5 min using cell phone text messages. This paper explores the success of the HRRS system. This study employed an augmented version of the DeLone and McLean IS success model. Seven variables (system quality, information quality, system use, user satisfaction, mobile healthcare anxiety, impact on the individual and impact on the organization) were used to evaluate the success of the HRRS system. The interrelationships between the seven variables were hypothesized and the hypotheses were empirically tested. The results indicate that the information quality of the HRRS system is positively associated with both system use and user satisfaction. In addition, system use is positively associated with user satisfaction, which is also positively associated with mobile healthcare anxiety. Moreover, results indicate that impact on the individual is positively associated with both user satisfaction and mobile healthcare anxiety. Finally, the impact of the organization is positively associated with impact on the individual. The results of the study provide an expanded understanding of the factors that contribute to mobile patient safety information system (IS) success. Implications of the relationship between system use and physician mobile healthcare anxiety are discussed.

  16. Nuclear power and the public safety: a study in regulation

    International Nuclear Information System (INIS)

    Rolph, E.S.

    1979-01-01

    The large-scale introduction of new substances and new technologies into our habitat has been cause for growing alarm. Over the past decade we have come to rely more and more on government regulation to protect us from the hidden dangers of these new products. But how can a regulatory authority set standards when there are enormous uncertainties about consequences of use. How can it satisfy a large, pluralistic society where some take risks easily and others do not. How can it provide the stability needed by industrial decision makers, yet maintain the flexibility to change as information or circumstances change. As the history of the Atomic Energy Commission dramatically illustrates, these are very real problems. And this study of the evolution of AEC's policies, practices, and effectiveness from its creation in 1954 to its demise in 1974 provides an illuminating exploration of the interaction of technical development, economic imperatives, and regulatory mandate. In conclusions drawn from her incisive analysis of the AEC experience, Rolph notes that regulatory bodies must: recognize their political identity; they must be open and responsive; have strong, aggressive information gathering capabilities; and be prepared to pace the evolution and commercial use of the technology they control. Although this study concentrates on a single agency, it explores issues and draws lessons probably common to most regulatory authorities responsible for public safety

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  18. Motorcycle safety device investigation: A case study on airbags

    Indian Academy of Sciences (India)

    analysis methods for research evaluation of rider crash protective devices fitted to ... The safety evaluation is then based on simulation of the 200 impact types. ... with recording of ISO 13232 car-front impact tests to evaluate the qualitative.

  19. Can we avoid dose escalation for intermediate-risk prostate cancer in the setting of short-course neoadjuvant androgen deprivation?

    Science.gov (United States)

    Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

    2016-01-01

    Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve the outcomes in patients with intermediate-risk prostate cancer. Despite this, there are only few reports evaluating DE-EBRT for patients with intermediate-risk prostate cancer receiving neoadjuvant ADT, and virtually no studies investigating dose escalation >74 Gy in this setting. We aimed to determine whether DE-EBRT >74 Gy improved the outcomes for patients with intermediate-risk prostate cancer who received neoadjuvant ADT. In our institution, patients with intermediate-risk prostate cancer were treated with neoadjuvant ADT and DE-EBRT, with doses sequentially increasing from 74 Gy to 76 Gy and then to 78 Gy between 2006 and 2012. We identified 435 patients treated with DE-EBRT and ADT, with a median follow-up of 70 months. For the 74 Gy, 76 Gy, and 78 Gy groups, five-year biochemical disease-free survival rates were 95.0%, 97.8%, and 95.3%, respectively; metastasis-free survival rates were 99.1%, 100.0%, and 98.6%, respectively; and prostate cancer-specific survival rate was 100% for all three dose levels. There was no significant benefit for dose escalation either on univariate or multivariate analysis for any outcome. There was no benefit for DE-EBRT >74 Gy in our cohort of intermediate-risk prostate cancer patients treated with neoadjuvant ADT. Given the higher risks of toxicity associated with dose escalation, it may be feasible to omit dose escalation in this group of patients. Randomized studies evaluating dose de-escalation should be considered.

  20. Dose-escalated simultaneous integrated-boost treatment of prostate cancer patients via helical tomotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Geier, M.; Astner, S.T.; Duma, M.N.; Putzhammer, J.; Winkler, C.; Molls, M.; Geinitz, H. [Technische Univ. Muenchen (Germany). Klinik und Poliklinik fuer Strahlentherapie und Radiologische Onkologie; Jacob, V. [Universitaetsklinikum Freiburg (Germany). Klinik fuer Strahlenheilkunde; Nieder, C. [Nordland Hospital, Bodoe (Norway). Dept. of Oncology and Palliative Care; Tromsoe Univ. (Norway). Inst. of Clinical Medicine

    2012-05-15

    The goal of this work was to assess the feasibility of moderately hypofractionated simultaneous integrated-boost intensity-modulated radiotherapy (SIB-IMRT) with helical tomotherapy in patients with localized prostate cancer regarding acute side effects and dose-volume histogram data (DVH data). Acute side effects and DVH data were evaluated of the first 40 intermediate risk prostate cancer patients treated with a definitive daily image-guided SIB-IMRT protocol via helical tomotherapy in our department. The planning target volume including the prostate and the base of the seminal vesicles with safety margins was treated with 70 Gy in 35 fractions. The boost volume containing the prostate and 3 mm safety margins (5 mm craniocaudal) was treated as SIB to a total dose of 76 Gy (2.17 Gy per fraction). Planning constraints for the anterior rectal wall were set in order not to exceed the dose of 76 Gy prescribed to the boost volume. Acute toxicity was evaluated prospectively using a modified CTCAE (Common Terminology Criteria for Adverse Events) score. SIB-IMRT allowed good rectal sparing, although the full boost dose was permitted to the anterior rectal wall. Median rectum dose was 38 Gy in all patients and the median volumes receiving at least 65 Gy (V65), 70 Gy (V70), and 75 Gy (V75) were 13.5%, 9%, and 3%, respectively. No grade 4 toxicity was observed. Acute grade 3 toxicity was observed in 20% of patients involving nocturia only. Grade 2 acute intestinal and urological side effects occurred in 25% and 57.5%, respectively. No correlation was found between acute toxicity and the DVH data. This institutional SIB-IMRT protocol using daily image guidance as a precondition for smaller safety margins allows dose escalation to the prostate without increasing acute toxicity. (orig.)

  1. Impact of individual resilience and safety climate on safety performance and psychological stress of construction workers: A case study of the Ontario construction industry.

    Science.gov (United States)

    Chen, Yuting; McCabe, Brenda; Hyatt, Douglas

    2017-06-01

    The construction industry has hit a plateau in terms of safety performance. Safety climate is regarded as a leading indicator of safety performance; however, relatively little safety climate research has been done in the Canadian construction industry. Safety climate may be geographically sensitive, thus it is necessary to examine how the construct of safety climate is defined and used to improve safety performance in different regions. On the other hand, more and more attention has been paid to job related stress in the construction industry. Previous research proposed that individual resilience may be associated with a better safety performance and may help employees manage stress. Unfortunately, few empirical research studies have examined this hypothesis. This paper aims to examine the role of safety climate and individual resilience in safety performance and job stress in the Canadian construction industry. The research was based on 837 surveys collected in Ontario between June 2015 and June 2016. Structural equation modeling (SEM) techniques were used to explore the impact of individual resilience and safety climate on physical safety outcomes and on psychological stress among construction workers. The results show that safety climate not only affected construction workers' safety performance but also indirectly affected their psychological stress. In addition, it was found that individual resilience had a direct negative impact on psychological stress but had no impact on physical safety outcomes. These findings highlight the roles of both organizational and individual factors in individual safety performance and in psychological well-being. Construction organizations need to not only monitor employees' safety performance, but also to assess their employees' psychological well-being. Promoting a positive safety climate together with developing training programs focusing on improving employees' psychological health - especially post-trauma psychological

  2. Study on high reliability safety valve for railway vehicle

    Science.gov (United States)

    Zhang, Xuan; Chen, Ruikun; Zhang, Shixi; Xu, BuDu

    2017-09-01

    Now, the realization of most of the functions of the railway vehicles rely on compressed air, so the demand for compressed air is growing higher and higher. This safety valve is a protection device for pressure limitation and pressure relief in an air supply system of railway vehicles. I am going to introduce the structure, operating principle, research and development process of the safety valve designed by our company in this document.

  3. Image-guided adaptive radiation therapy (IGART): Radiobiological and dose escalation considerations for localized carcinoma of the prostate

    International Nuclear Information System (INIS)

    Song, William; Schaly, Bryan; Bauman, Glenn; Battista, Jerry; Van Dyk, Jake

    2005-01-01

    The goal of this work was to evaluate the efficacy of various image-guided adaptive radiation therapy (IGART) techniques to deliver and escalate dose to the prostate in the presence of geometric uncertainties. Five prostate patients with 15-16 treatment CT studies each were retrospectively analyzed. All patients were planned with an 18 MV, six-field conformal technique with a 10 mm margin size and an initial prescription of 70 Gy in 35 fractions. The adaptive strategy employed in this work for patient-specific dose escalation was to increase the prescription dose in 2 Gy-per-fraction increments until the rectum normal tissue complication probability (NTCP) reached a level equal to that of the nominal plan NTCP (i.e., iso-NTCP dose escalation). The various target localization techniques simulated were: (1) daily laser-guided alignment to skin tattoo marks that represents treatment without image-guidance, (2) alignment to bony landmarks with daily portal images, and (3) alignment to the clinical target volume (CTV) with daily CT images. Techniques (1) and (3) were resimulated with a reduced margin size of 5 mm to investigate further dose escalation. When delivering the original clinical prescription dose of 70 Gy in 35 fractions, the 'CTV registration' technique yielded the highest tumor control probability (TCP) most frequently, followed by the 'bone registration' and 'tattoo registration' techniques. However, the differences in TCP among the three techniques were minor when the margin size was 10 mm (≤1.1%). Reducing the margin size to 5 mm significantly degraded the TCP values of the 'tattoo registration' technique in two of the five patients, where a large difference was found compared to the other techniques (≤11.8%). The 'CTV registration' technique, however, did maintain similar TCP values compared to their 10 mm margin counterpart. In terms of normal tissue sparing, the technique producing the lowest NTCP varied from patient to patient. Reducing the

  4. Safety Features of Material and Personnel Movement Devices. Module SH-25. Safety and Health.

    Science.gov (United States)

    Center for Occupational Research and Development, Inc., Waco, TX.

    This student module on safety features of material and personnel movement devices is one of 50 modules concerned with job safety and health. This module covers safe conditions and operating practices for conveyors, elevators, escalators, moving walks, manlifts, forklifts, and motorized hand trucks. Following the introduction, 10 objectives (each…

  5. Adolescents' Perceptions of Safety at School and Their Solutions for Enhancing Safety and Reducing School Violence: A Rural Case Study.

    Science.gov (United States)

    deLara, Ellen

    An exploratory study of a small rural high school in upstate New York investigated students' perceptions of safety at school and empowered students to develop solutions to school violence. A mixed-methods approach drew on action research, youth-based phenomenology, and a general systems frame of reference. Data collection included two surveys of…

  6. Subgroup analysis of patients with localized prostate cancer treated within the Dutch-randomized dose escalation trial

    International Nuclear Information System (INIS)

    Al-Mamgani, Abrahim; Heemsbergen, Wilma D.; Levendag, Peter C.; Lebesque, Joos V.

    2010-01-01

    Purpose: To investigate the effect of dose escalation within prognostic risk groups in prostate cancer. Patients and methods: Between 1997 and 2003, 664 patients with localized prostate cancer were randomly assigned to receive 68- or 78-Gy of radiotherapy. Two prognostic models were examined: a risk group model (low-, intermediate-, and high-risk) and PSA-level groupings. High-risk patients with hormonal therapy (HT) were analyzed separately. Outcome variable was freedom from failure (FFF) (clinical failure or PSA nadir + 2 μg/L). Results: In relation to the advantage of high-dose radiotherapy, intermediate-risk patients benefited most from dose escalation. However no significant heterogeneity could be demonstrated between the risk groups. For two types of PSA-level groupings: PSA 8 μg/L, the test for heterogeneity was significant (p = 0.03 and 0.05, respectively). Patients with PSA 8-18 μg/L (n = 297, HR = 0.59) derived the greatest benefit from dose escalation. No heterogeneity could be demonstrated for high-risk patients with and without HT. Conclusion: Intermediate-risk group derived the greatest benefit for dose escalation. However, from this trial no indication was found to exclude low-risk or high-risk patients from high-dose radiotherapy. Patients could be selected for high-dose radiotherapy based on PSA-level groupings: for patients with a PSA < 8 μg/L high-dose radiotherapy is probably not indicated, but should be confirmed in other randomized studies.

  7. Escalation research: Providing new frontiers for applying behavior analysis to organizational behavior

    Science.gov (United States)

    Goltz, Sonia M.

    2000-01-01

    Decision fiascoes such as escalation of commitment, the tendency of decision makers to “throw good money after bad,” can have serious consequences for organizations and are therefore of great interest in applied research. This paper discusses the use of behavior analysis in organizational behavior research on escalation. Among the most significant aspects of behavior-analytic research on escalation is that it has indicated that both the patterns of outcomes that decision makers have experienced for past decisions and the patterns of responses that they make are critical for understanding escalation. This research has also stimulated the refinement of methods by researchers to better assess decision making and the role reinforcement plays in it. Finally, behavior-analytic escalation research has not only indicated the utility of reinforcement principles for predicting more complex human behavior but has also suggested some additional areas for future exploration of decision making using behavior analysis. PMID:22478347

  8. Assessment of Electrical Safety Beliefs and Practices: A Case Study

    Directory of Open Access Journals (Sweden)

    S. Boubaker

    2017-12-01

    Full Text Available In this paper, the electrical safety beliefs and practices in Hail region, Saudi Arabia, have been assessed. Based on legislative recommendations and rules applied in Saudi Arabia, on official statistics regarding the electricity-caused accidents and on the analysis of more than 200 photos captured in Hail (related to electrical safety, a questionnaire composed of 36 questions (10 for the respondents information, 16 for the home safety culture and 10 for the electrical devices purchasing culture has been devised and distributed to residents. 228 responses have been collected and analyzed. Using a scale similar to the one adopted for a university student GPA calculation, the electrical safety level (ESL in Hail region has been found to be 0.76 (in a scale of 4 points which is a very low score and indicates a poor electrical safety culture. Several recommendations involving different competent authorities have been proposed. Future work will concern the assessment of safety in industrial companies in Hail region.

  9. Ferrocyanide safety project ferrocyanide aging studies FY 1995 annual report

    International Nuclear Information System (INIS)

    Lilga, M.A.; Alderson, E.V.; Hallen, R.T.

    1995-09-01

    This annual report gives the results of the work conducted by the Pacific Northwest Laboratory in FY 1995 on Task 3 of the Ferrocyanide Safety Project, Ferrocyanide Aging Studies. Aging refers to the dissolution and hydrolysis of simulated Hanford ferrocyanide waste in alkaline aqueous solutions by radiolytic and chemical means. The ferrocyanide simulant primarily used in these studies was dried In-Farm-1B, Rev. 7, prepared by Westinghouse Hanford Company to simulate the waste generated when the In-Farm flowsheet was used to remove radiocesium from waste supernates in single-shell tanks at the Hanford Site. In the In-Farm flowsheet, nickel ion and ferrocyanide anion were added to waste supernates to precipitate sodium nickel ferrocyanide, Na 2 NiFe(CN) 6 , and co-precipitate radiocesium. Once the radiocesium was removed, supernates were pumped from the tanks, and new wastes from cladding removal processes or from evaporators were added. These new wastes were typically highly caustic, having hydroxide ion concentrations of over 1 M and as high as 4 M. The Aging Studies task is investigating reactions this caustic waste may have had with the precipitated ferrocyanide waste in a radiation field. In previous Aging Studies research, Na 2 NiFe(CN) 6 in simulants was shown to dissolve in basic solutions, forming insoluble Ni(OH) 2 and soluble Na 4 Fe(CN) 6 . The influence on solubility of base strength, sodium ion concentration, anions, and temperature was previously investigated. The results may indicate that even ferrocyanide sludge that did not come into direct contact with highly basic wastes may also have aged significantly

  10. A phase I dose escalation trial of AXP107-11, a novel multi-component crystalline form of genistein, in combination with gemcitabine in chemotherapy-naive patients with unresectable pancreatic cancer.

    Science.gov (United States)

    Löhr, Johannes-Matthias; Karimi, Masoud; Omazic, Brigitta; Kartalis, Nikolaos; Verbeke, Caroline Sabine; Berkenstam, Anders; Frödin, Jan-Erik

    2016-01-01

    AXP107-11 is a novel, multi-component crystalline form of the naturally occurring compound genistein. AXP107-11 has improved physiochemical properties and oral bioavailability compared to the natural form of genistein, and it is possible that combining AXP107-11 with chemotherapy may increase the effect and reduce chemoresistance. The purpose of this dose escalation phase Ib study was to assess the safety, maximum tolerated dose (MTD) and pharmacokinetics (PK) of AXP107-11 in combination with gemcitabine in treatment-naïve patients with inoperable pancreatic carcinoma. AXP107-11 was given orally in escalating doses (400 mg-1600 mg daily) in combination with standard gemcitabine treatment (1000 mg/m(2)/week) for the first seven of eight weeks and thereafter for a maximum of four × four-week treatment cycles. PK, safety, MTD and efficacy of AXP107-11 in combination with gemcitabine were evaluated. Sixteen patients were enrolled and received AXP107-11. The maximum concentration in serum of unconjugated (free) genistein was 1 μM. Neither dose-limiting toxicities (DLTs) nor signs of hematological or non-hematological toxicities related to AXP107-11 were observed over a period ranging from 0.7 to 13.2 months. The median overall survival time was 4.9 months (range 1.5-19.5 months). Seven patients (44%) survived longer than six months and 19% were alive at the one-year follow-up. Treatment of pancreatic cancer patients with AXP107-11 in combination with gemcitabine resulted in a favorable PK-profile with high serum levels without signs of either hematological or non-hematological toxicity. Accordingly, we suggest further studies with AXP107-11 in pancreatic cancer patients. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  11. Safety of the yellow Fever vaccine: a retrospective study.

    Science.gov (United States)

    Nordin, James D; Parker, Emily D; Vazquez-Benitez, Gabriela; Kharbanda, Elyse O; Naleway, Allison; Marcy, S Michael; Molitor, Beth; Kuckler, Leslie; Baggs, James

    2013-01-01

    Yellow fever (YF) vaccine is considered safe; however, severe illness and death following vaccination have been reported. Vaccine Safety Datalink (VSD) and US Department of Defense (DoD) data were used to identify adverse reactions following YF vaccination. Within the VSD, YF-vaccine-exposed subjects were compared to age-, site-, and gender-matched unexposed subjects. YF-vaccine-exposed DoD subjects were studied using a risk-interval design. For both cohorts, ICD-9 codes were analyzed for allergic and local reactions, mild systemic reactions, and possible visceral and neurologic adverse events (AEs). The VSD cohort received 47,159 doses from 1991 through 2006. The DoD cohort received 1.12 million doses from 1999 through 2007. Most subjects received other vaccines simultaneously. In the VSD cohort, rates of allergic, local, and mild systemic reactions were not statistically different between YF-vaccine-exposed and -unexposed subjects. In the DoD, there was an increased risk for outpatient allergic events in the period following vaccination with YF and other vaccines rate ratios [RR 3.85, 95% confidence interval (CI) 3.35-4.41] but with no increased risk for inpatient allergic reactions. In both cohorts, inpatient ICD-9 codes for visceral events were significantly less common following vaccination; inpatient codes for neurologic events were less common in the VSD YF-vaccine-exposed adult cohort, but did not differ between exposed and unexposed periods in the DoD. In the DoD, one fatal case of YF-vaccine-associated viscerotropic disease (YF-vaccine-AVD) was detected. The estimated death rate was 0.89 for 1,000,000 YF vaccine doses (95% CI 0.12-6.31/1,000,000 doses). No YF vaccine-associated deaths occurred in the VSD. In these closed cohorts we did not detect increased risk for visceral or neurologic events following YF vaccination. The death rate following YF vaccine was consistent with previous reports. These data support current recommendations for use of YF

  12. Electronic Cigarettes Efficacy and Safety at 12 Months: Cohort Study.

    Directory of Open Access Journals (Sweden)

    Lamberto Manzoli

    Full Text Available To evaluate the safety and efficacy as a tool of smoking cessation of electronic cigarettes (e-cigarettes, directly comparing users of e-cigarettes only, smokers of tobacco cigarettes only, and smokers of both.Prospective cohort study. Final results are expected in 2019, but given the urgency of data to support policies on electronic smoking, we report the results of the 12-month follow-up.Direct contact and structured questionnaires by phone or via internet.Adults (30-75 years were included if they were smokers of ≥1 tobacco cigarette/day (tobacco smokers, users of any type of e-cigarettes, inhaling ≥50 puffs weekly (e-smokers, or smokers of both tobacco and e-cigarettes (dual smokers. Carbon monoxide levels were tested in a sample of those declaring tobacco smoking abstinence.Sustained smoking abstinence from tobacco smoking at 12 months, reduction in the number of tobacco cigarettes smoked daily.We used linear and logistic regression, with region as cluster unit.Follow-up data were available for 236 e-smokers, 491 tobacco smokers, and 232 dual smokers (overall response rate 70.8%. All e-smokers were tobacco ex-smokers. At 12 months, 61.9% of the e-smokers were still abstinent from tobacco smoking; 20.6% of the tobacco smokers and 22.0% of the dual smokers achieved tobacco abstinence. Adjusting for potential confounders, tobacco smoking abstinence or cessation remained significantly more likely among e-smokers (adjusted OR 5.19; 95% CI: 3.35-8.02, whereas adding e-cigarettes to tobacco smoking did not enhance the likelihood of quitting tobacco and did not reduce tobacco cigarette consumption. E-smokers showed a minimal but significantly higher increase in self-rated health than other smokers. Non significant differences were found in self-reported serious adverse events (eleven overall.Adding e-cigarettes to tobacco smoking did not facilitate smoking cessation or reduction. If e-cigarette safety will be confirmed, however, the use of e

  13. A safety study on the wet storage of spent fuel

    International Nuclear Information System (INIS)

    Chun, Kwan Sik; Whang, Joo Ho; Lee, Hoo Kun; Choi, Jong Won; Lee, Jong Geun

    1989-02-01

    This study is to provide data related with a basic design of the spent fuel storage facility in the field of radiation and to establish the safety assessment methodology of away from reactor spent fuel storage facility. This is in progress and continue upto the year of 1991. The mathematical model which predict the quantity of environmental release of fission and corrosion products from spent fuel received and stored in wet storage facility operated in normal conditions was prepared. The decay characteristic of domestic spent fuels are analysed and then the coefficients for the prediction of the decay heat by simple formular was determined. This correlations could predict decay heat of spent fuel with ±10% difference from ORIGEN2 results. The release factor of cobalt out of PWR spent fuel in PIE pool is 7.97 x 10-12∼8.49 x 10-11 Ci/ sec-rod, which appears to be linear without being connected with the types of fuel defects, but that of cesium varies with the defect type and the exposure time in water. In water condition, release factor of uranium out of CANDU fuel pellets appears to be about 5 x 10-8/day, whose tendency is similar to that of cesium of the latter half of the exposure time of water. (Author)

  14. A study on safety measure of LMR coolant

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Sung Tai; Choi, Y D; Choi, J H; Kim, T J; Jeong, K C; Kwon, S W; Kim, B H; Jeong, J Y; Park, J H; Kim, K R; Jo, B R

    1997-08-01

    A study on safety measures of LMR coolant showed the results as follows: 1. Sodium fire characteristics. A. Sodium pool temp., gas temp., oxygen concentration calculated by flame combustion model were generally higher than those calculated by surface combustion model. B. Basic and detail designs for medium sodium fire test facility were carried out and medium sodium fire test facility was constructed. 2. Sodium/Cover gas purification technology. A. Construction and operation of calibration loop. B. Purification analysis and conceptual design of the packing for a cold trap. 3. Analysis of sodium-water reaction characteristics. We have investigated the characteristics analysis for micro and small leaks phenomena, development of the computer code for analysis of initial and quasi steady-state spike pressures to analyze large leak accident. Also, water mock-up test facility for the analysis of large leak accident phenomena was designed and manufactured. 4. Development of water leak detection technology. Detection signals were appeared when the hydrogen detector is operated to Ar-H{sub 2} gas system. The technology for the passive acoustic detection with respect to large leakage of water into sodium media was reviewed. And water mock-up test equipment and instrument system were designed and constructed. (author). 19 refs., 45 tabs., 52 figs.

  15. A study on safety measure of LMR coolant

    International Nuclear Information System (INIS)

    Hwang, Sung Tai; Choi, Y. D.; Choi, J. H.; Kim, T. J.; Jeong, K. C.; Kwon, S. W.; Kim, B. H.; Jeong, J. Y.; Park, J. H.; Kim, K. R.; Jo, B. R.

    1997-08-01

    A study on safety measures of LMR coolant showed the results as follows: 1. Sodium fire characteristics. A. Sodium pool temp., gas temp., oxygen concentration calculated by flame combustion model were generally higher than those calculated by surface combustion model. B. Basic and detail designs for medium sodium fire test facility were carried out and medium sodium fire test facility was constructed. 2. Sodium/Cover gas purification technology. A. Construction and operation of calibration loop. B. Purification analysis and conceptual design of the packing for a cold trap. 3. Analysis of sodium-water reaction characteristics. We have investigated the characteristics analysis for micro and small leaks phenomena, development of the computer code for analysis of initial and quasi steady-state spike pressures to analyze large leak accident. Also, water mock-up test facility for the analysis of large leak accident phenomena was designed and manufactured. 4. Development of water leak detection technology. Detection signals were appeared when the hydrogen detector is operated to Ar-H 2 gas system. The technology for the passive acoustic detection with respect to large leakage of water into sodium media was reviewed. And water mock-up test equipment and instrument system were designed and constructed. (author). 19 refs., 45 tabs., 52 figs

  16. Abstract of results of safety study. Nuclear fuel cycle field in fiscal 2003

    International Nuclear Information System (INIS)

    2004-11-01

    This report descried the results of studies of nuclear fuel cycle field (nuclear fuel facilities, seismic design, all subjects of environmental radiation and waste disposal, and subjects on nuclear fuel cycle in probabilistic safety assessment) in fiscal 2003 on the basis of the principle project of safety study (from fiscal 2001 to 2005). It consists of four chapters; the first chapter is outline of the principle of project, the second is objects and subjects of safety study in the nuclear fuel cycle field, the third list of questionnaire of results of safety study and the forth investigation of results of safety study in fiscal 2003. There are 49 lists, which include 22 reports on the nuclear fuel facility, one on the seismic design, 4 on the probabilistic safety assessment, 7 on the environmental radiation and 15 on the waste disposal. (S.Y.)

  17. Metallographic assessment of Al-12Si high-pressure die casting escalator steps.

    Science.gov (United States)

    Vander Voort, George Frederic; Suárez-Peña, Beatriz; Asensio-Lozano, Juan

    2014-10-01

    A microstructural characterization study was performed on high-pressure die cast specimens extracted from escalator steps manufactured from an Al-12 wt.% Si alloy designed for structural applications. Black and white, color light optical imaging and scanning electron microscopy techniques were used to conduct the microstructural analysis. Most regions in the samples studied contained globular-rosette primary α-Al grains surrounded by an Al-Si eutectic aggregate, while primary dendritic α-Al grains were present in the surface layer. This dendritic microstructure was observed in the regions where the melt did not impinge directly on the die surface during cavity filling. Consequently, microstructures in the surface layer were nonuniform. Utilizing physical metallurgy principles, these results were analyzed in terms of the applied pressure and filling velocity during high-pressure die casting. The effects of these parameters on solidification at different locations of the casting are discussed.

  18. Can we avoid dose escalation for intermediate-risk prostate cancer in the setting of short-course neoadjuvant androgen deprivation?

    Directory of Open Access Journals (Sweden)

    Shakespeare TP

    2016-03-01

    Full Text Available Thomas P Shakespeare,1,2 Shea W Wilcox,1 Noel J Aherne1,2 1Department of Radiation Oncology, North Coast Cancer Institute, 2Faculty of Medicine, Rural Clinical School, The University of New South Wales, Coffs Harbour, New South Wales, Australia Background: Both dose-escalated external beam radiotherapy (DE-EBRT and androgen deprivation therapy (ADT improve the outcomes in patients with intermediate-risk prostate cancer. Despite this, there are only few reports evaluating DE-EBRT for patients with intermediate-risk prostate cancer receiving neoadjuvant ADT, and virtually no studies investigating dose escalation >74 Gy in this setting. We aimed to determine whether DE-EBRT >74 Gy improved the outcomes for patients with intermediate-risk prostate cancer who received neoadjuvant ADT. Findings: In our institution, patients with intermediate-risk prostate cancer were treated with neoadjuvant ADT and DE-EBRT, with doses sequentially increasing from 74 Gy to 76 Gy and then to 78 Gy between 2006 and 2012. We identified 435 patients treated with DE-EBRT and ADT, with a median follow-up of 70 months. For the 74 Gy, 76 Gy, and 78 Gy groups, five-year biochemical disease-free survival rates were 95.0%, 97.8%, and 95.3%, respectively; metastasis-free survival rates were 99.1%, 100.0%, and 98.6%, respectively; and prostate cancer-specific survival rate was 100% for all three dose levels. There was no significant benefit for dose escalation either on univariate or multivariate analysis for any outcome. Conclusion: There was no benefit for DE-EBRT >74 Gy in our cohort of intermediate-risk prostate cancer patients treated with neoadjuvant ADT. Given the higher risks of toxicity associated with dose escalation, it may be feasible to omit dose escalation in this group of patients. Randomized studies evaluating dose de-escalation should be considered. Keywords: radiotherapy, IMRT, dose, dose escalation, dose de-escalation, androgen deprivation therapy

  19. Triptan safety during pregnancy: a Norwegian population registry study

    International Nuclear Information System (INIS)

    Nezvalová-Henriksen, Kateřina; Spigset, Olav; Nordeng, Hedvig

    2013-01-01

    Knowledge on triptan safety during pregnancy remains limited to their class effect or studies on sumatriptan. Our aim was to evaluate the individual effect of four most frequently used triptans on several pregnancy outcomes. We used the Norwegian prescription database to access information on triptans redeemed by pregnant women living in Norway between 2004 and 2007. This database was linked to the Medical Birth Registry of Norway covering every institutional delivery in Norway and providing information on pregnancy, delivery, maternal and neonatal health. Estimates of associations with pregnancy outcomes were obtained by Generalised Estimation Equations analysis. Of the 181,125 women in our study, 1,465 (0.8 %) redeemed triptans during pregnancy, and 1,095 (0.6 %) redeemed triptans before pregnancy only (disease comparison group). The population comparison group comprised the remaining 178,565 women. Using this group as reference, we found no associations between triptan redemption during pregnancy and congenital malformations. Second trimester redemption was associated with postpartum haemorrhage (adjusted OR 1.57; 95 % CI 1.19–2.07). The disease comparison group had an increased risk of major congenital malformations (adjusted OR 1.48; 95 % CI 1.11–1.97), low birth weight (adjusted OR 1.39; 95 % CI 1.08–1.81), and preterm birth (adjusted OR 1.30; 95 % CI 1.06–1.60). The association of triptans with postpartum hemorrhage could be attributable to decreased platelet agreeability occurring in severe migraine. Likewise, the increased risk of major congenital malformations and other adverse pregnancy outcomes in the disease comparison group might be attributable to migraine severity

  20. Nuclear safety

    International Nuclear Information System (INIS)

    Tarride, Bruno

    2015-10-01

    The author proposes an overview of methods and concepts used in the nuclear industry, at the design level as well as at the exploitation level, to ensure an acceptable safety level, notably in the case of nuclear reactors. He first addresses the general objectives of nuclear safety and the notion of acceptable risk: definition and organisation of nuclear safety (relationships between safety authorities and operators), notion of acceptable risk, deterministic safety approach and main safety principles (safety functions and confinement barriers, concept of defence in depth). Then, the author addresses the safety approach at the design level: studies of operational situations, studies of internal and external aggressions, safety report, design principles for important-for-safety systems (failure criterion, redundancy, failure prevention, safety classification). The next part addresses safety during exploitation and general exploitation rules: definition of the operation domain and of its limits, periodic controls and tests, management in case of incidents, accidents or aggressions

  1. Simulation study of coal mine safety investment based on system dynamics

    Institute of Scientific and Technical Information of China (English)

    Tong Lei; Dou Yuanyuan

    2014-01-01

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

  2. Patient safety challenges in a case study hospital--of relevance for transfusion processes?

    Science.gov (United States)

    Aase, Karina; Høyland, Sindre; Olsen, Espen; Wiig, Siri; Nilsen, Stein Tore

    2008-10-01

    The paper reports results from a research project with the objective of studying patient safety, and relates the finding to safety issues within transfusion medicine. The background is an increased focus on undesired events related to diagnosis, medication, and patient treatment in general in the healthcare sector. The study is designed as a case study within a regional Norwegian hospital conducting specialised health care services. The study includes multiple methods such as interviews, document analysis, analysis of error reports, and a questionnaire survey. Results show that the challenges for improved patient safety, based on employees' perceptions, are hospital management support, reporting of accidents/incidents, and collaboration across hospital units. Several of these generic safety challenges are also found to be of relevance for a hospital's transfusion service. Positive patient safety factors are identified as teamwork within hospital units, a non-punitive response to errors, and unit manager's actions promoting safety.

  3. Avelumab for metastatic or locally advanced previously treated solid tumours (JAVELIN Solid Tumor): a phase 1a, multicohort, dose-escalation trial.

    Science.gov (United States)

    Heery, Christopher R; O'Sullivan-Coyne, Geraldine; Madan, Ravi A; Cordes, Lisa; Rajan, Arun; Rauckhorst, Myrna; Lamping, Elizabeth; Oyelakin, Israel; Marté, Jennifer L; Lepone, Lauren M; Donahue, Renee N; Grenga, Italia; Cuillerot, Jean-Marie; Neuteboom, Berend; Heydebreck, Anja von; Chin, Kevin; Schlom, Jeffrey; Gulley, James L

    2017-05-01

    Avelumab (MSB0010718C) is a human IgG1 monoclonal antibody that binds to PD-L1, inhibiting its binding to PD-1, which inactivates T cells. We aimed to establish the safety and pharmacokinetics of avelumab in patients with solid tumours while assessing biological correlatives for future development. This open-label, single-centre, phase 1a, dose-escalation trial (part of the JAVELIN Solid Tumor trial) assessed four doses of avelumab (1 mg/kg, 3 mg/kg, 10 mg/kg, and 20 mg/kg), with dose-level cohort expansions to provide additional safety, pharmacokinetics, and target occupancy data. This study used a standard 3 + 3 cohort design and assigned patients sequentially at trial entry according to the 3 + 3 dose-escalation algorithm and depending on the number of dose-limiting toxicities during the first 3-week assessment period (the primary endpoint). Patient eligibility criteria included age 18 years or older, Eastern Cooperative Oncology Group performance status 0-1, metastatic or locally advanced previously treated solid tumours, and adequate end-organ function. Avelumab was given as a 1-h intravenous infusion every 2 weeks. Patients in the dose-limiting toxicity analysis set were assessed for the primary endpoint of dose-limiting toxicity, and all patients enrolled in the dose-escalation part were assessed for the secondary endpoints of safety (treatment-emergent and treatment-related adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0), pharmacokinetic and pharmacodynamic profiles (immunological effects), best overall response by Response Evaluation Criteria, and antidrug antibody formation. The population for the pharmacokinetic analysis included a subset of patients with rich pharmacokinetic samples from two selected disease-specific expansion cohorts at the same study site who had serum samples obtained at multiple early timepoints. This trial is registered with ClinicalTrials.gov, number NCT

  4. Socio-technological study for establishing comprehensive nuclear safety system

    International Nuclear Information System (INIS)

    Furuta, Kazuo; Kanno, Taro; Yagi, Ekou; Shuto, Yuki

    2003-01-01

    This paper presents an overview and preliminary results of a research project on social-technology for nuclear safety, which started in October 2001. In particular, emergency response preparedness against nuclear disaster and consensus development will be discussed. The architecture of an emergency response simulator will be given, which is for assessing design of disaster prevention systems. A conceptual model of evacuation behavior of a resident has been constructed from analysis of past disaster cases. As for consensus development, deliberation spaces of actual committee meetings were constructed by analyzing transcripts of the meetings based on an opinion schema. A model of consensus development process has been proposed from the traces of participants' opinions over the deliberation spaces. Such a socio-technological approach will be useful not only for nuclear safety but also for safety of non-nuclear domains and human activities of a high hazard potential; it is expected to contribute to establishing risk-aware society of the future. (author)

  5. Automated Mixed Traffic Vehicle (AMTV) technology and safety study

    Science.gov (United States)

    Johnston, A. R.; Peng, T. K. C.; Vivian, H. C.; Wang, P. K.

    1978-01-01

    Technology and safety related to the implementation of an Automated Mixed Traffic Vehicle (AMTV) system are discussed. System concepts and technology status were reviewed and areas where further development is needed are identified. Failure and hazard modes were also analyzed and methods for prevention were suggested. The results presented are intended as a guide for further efforts in AMTV system design and technology development for both near term and long term applications. The AMTV systems discussed include a low speed system, and a hybrid system consisting of low speed sections and high speed sections operating in a semi-guideway. The safety analysis identified hazards that may arise in a properly functioning AMTV system, as well as hardware failure modes. Safety related failure modes were emphasized. A risk assessment was performed in order to create a priority order and significant hazards and failure modes were summarized. Corrective measures were proposed for each hazard.

  6. STUDY ON SAFETY TECHNOLOGY SCHEME OF THE UNMANNED HELICOPTER

    Directory of Open Access Journals (Sweden)

    Z. Lin

    2013-08-01

    Full Text Available Nowadays the unmanned helicopter is widely used for its' unique strongpoint, however, the high failure rate of unmanned helicopter seriously limits its further application and development. For solving the above problems, in this paper, the reasons for the high failure rate of unmanned helicopter is analyzed and the corresponding solution schemes are proposed. The main problem of the failure cause of the unmanned helicopter is the aircraft engine fault, and the failure cause of the unmanned helicopter is analyzed particularly. In order to improving the safety performance of unmanned helicopter system, the scheme of adding the safety parachute system to the unmanned helicopter system is proposed and introduced. These schemes provide the safety redundancy of the unmanned helicopter system and lay on basis for the unmanned helicopter applying into residential areas.

  7. A study on methodologies for assessing safety critical network's risk impact on Nuclear Power Plant

    International Nuclear Information System (INIS)

    Lim, T. J.; Lee, H. J.; Park, S. K.; Seo, S. J.

    2006-08-01

    The objectives of this project is to investigate and study existing reliability analysis techniques for communication networks in order to develop reliability analysis models for Nuclear Power Plant's safety-critical networks. It is necessary to make a comprehensive survey of current methodologies for communication network reliability. Major outputs of the first year study are design characteristics of safety-critical communication networks, efficient algorithms for quantifying reliability of communication networks, and preliminary models for assessing reliability of safety-critical communication networks

  8. Case studies in food microbiology for food safety and quality

    National Research Council Canada - National Science Library

    Royal Society of Chemistry (Great Britain); Pawsey, Rosa K

    2002-01-01

    ... to engage in the learning process, and in so doing learn techniques for learning, and subsequently for applying knowledge. This has been more interesting for me, the teacher, and I think for the students too. This book has grown from my ten years teaching food microbiology and hygiene to post-graduate students in Food Safety and Control at South Bank University, London. It was the decade during which, in the UK, the national policies behind the management of food safety changed rapidly, and this me...

  9. Criticality safety study of shutdown diffusion cascade coolers

    International Nuclear Information System (INIS)

    Paschal, L.S.; Basoglu, B.; Bentley, C.L.; Dunn, M.E.

    1996-01-01

    Gaseous diffusion plants use cascade coolers in the production of highly enriched uranium (HEU) to remove heat from the enriched stream of UF 6 . The cascade coolers operate like shell and tube heat exchangers with the UF 6 on the shell side and Freon on the tube side. Recirculating cooling water (RCW) in condensers is used to cool the Freon. A criticality safety analysis was previously performed for cascade coolers during normal operation. The purpose of this paper is to evaluate several different hypothetical accidents regarding RCW ingress into the cooler to determine whether criticality safety concerns exist

  10. The early toxicity of escalated versus standard dose conformal radiotherapy with neo-adjuvant androgen suppression for patients with localised prostate cancer: Results from the MRC RT01 trial (ISRCTN47772397)

    International Nuclear Information System (INIS)

    Dearnaley, David P.; Sydes, Matthew R.; Langley, Ruth E.; Graham, John D.; Huddart, Robert A.; Syndikus, Isabel; Matthews, John H.L.; Scrase, Christopher D.; Jose, Chakiath C.; Logue, John; Stephens, Richard J.

    2007-01-01

    Background: Five-year disease-free survival rates for localised prostate cancer following standard doses of conventional radical external beam radiotherapy are around 80%. Conformal radiotherapy (CFRT) raises the possibility that radiotherapy doses can be increased and long-term efficacy outcomes improved, with safety an important consideration. Methods: MRC RT01 is a randomised controlled trial of 862 men with localised prostate cancer comparing Standard CFRT (64 Gy/32 f) versus Escalated CFRT (74 Gy/37 f), both administered with neo-adjuvant androgen suppression. Early toxicity was measured using physician-reported instruments (RTOG, LENT/SOM, Royal Marsden Scales) and patient-reported questionnaires (MOS SF-36, UCLA Prostate Cancer Index, FACT-P). Results: Overall early radiotherapy toxicity was similar, apart from increased bladder, bowel and sexual toxicity, in the Escalated Group during a short immediate post-radiotherapy period. Toxicity in both groups had abated by week 12. Using RTOG Acute Toxicity scores, cumulative Grade ≥2 bladder and bowel toxicity was 38% and 30% for Standard Group and 39% and 33% in Escalated Group, respectively. Urinary frequency (Royal Marsden Scale) improved in both groups from pre-androgen suppression to 6 months post-radiotherapy (p < 0.001), but bowel and sexual functioning deteriorated. This pattern was supported by patient-completed assessments. Six months after starting radiotherapy the incidence of RTOG Grade ≥2 side-effects was low (<1%); but there were six reports of rectal ulceration (6 Escalated Group), six