WorldWideScience

Sample records for hurried actions escalated

  1. 42 CFR 405.1108 - MAC actions when request for review or escalation is filed.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false MAC actions when request for review or escalation...) Medicare Appeals Council Review § 405.1108 MAC actions when request for review or escalation is filed. (a) Except as specified in paragraphs (c) and (d) of this section, when a party requests that the MAC review...

  2. Escalation of Commitment to an Ineffective Course of Action: The Effect of Feedback Having Negative Implications for Self-Identity.

    Science.gov (United States)

    Brockner, Joel; And Others

    1986-01-01

    Examines entrapment, the process by which organizational decision makers escalate commitment to an ineffective course of action to justify allocation of previous resources. Two laboratory experiments exploring individuals' perceptions of entrapment and its effect on their self identity are described. Also discusses practical theoretical…

  3. Escalation Practices in Automotive Development

    Directory of Open Access Journals (Sweden)

    Tomaž Jurejevčič

    2016-12-01

    Full Text Available Research Question (RQ: In automotive business many risk-involved situations occur and when detected, an escalation process takes place. Although defined and controlled by process guidelines and being supported by experts, escalation brings increased emotional pressure and stress for parties involved. Do escalation processes in automotive industry maintain all implied challenges? Purpose: The purpose of the article is to present current status of escalation processes and gaps between theory and practice cases. Results of the analysis are recommendations of good engineering practice derived also from actual experiences and learned lessons. Method: The method involves analysis of practical cases from automotive development process, lessons learned, anonymous survey of automotive engineers and classification of experiences. Results: Results of the survey have shown that the controlled escalation process for know-how related escalations is needed in order to establish the environment where the team is able to provide new, sometimes unconventional ideas for the problem to be solved. Organization: Presented recommendations and measures enable organization and managers to put the expertise and experiences of employees into action for problem solving during escalation. Originality: In this article some practices are presented that, although simple and some yet seen, with proper adjustment stemming from real life processes give a fruitful settlement of escalations in automotive development business.

  4. Understanding behavior in escalation situations.

    Science.gov (United States)

    Staw, B M; Ross, J

    1989-10-13

    Everyday observation reveals that both individuals and organizations often become overly committed to losing courses of action; in a sense, throwing good money after bad. More than 10 years of research on this escalation problem shows that persistence is associated with at least four major clases of determinants: project, psychological, social, and organizational variables. The influence of these four sets of variables evolves over time, forming a dynamic model of behavior in escalation situations.

  5. Escalation of commitment with transparent future outcomes.

    Science.gov (United States)

    Karlsson, Niklas; Gärling, Tommy; Bonini, Nicolao

    2005-01-01

    A frequent case of irrational decision making is the tendency to escalate commitment to a chosen course of action after unsuccessful prior investments of money, effort, or time (sunk costs). In previous research it is argued that escalation does not occur when future outcomes and alternative investments are transparent. Inconsistent with this argument, in an experiment in which undergraduates were presented fictitious investment problems with sunk costs, escalation was demonstrated when full information was given about investment alternatives and estimates of future returns. Thus, it is indicated that people may escalate despite knowing that it will not make them economically better off. A more comprehensive understanding of escalation requires disentangling people's noneconomic reasons for escalation.

  6. Before escalation: behavioral and affective forecasting in escalation of commitment.

    Science.gov (United States)

    Ku, Gillian

    2008-11-01

    This research examines preinvestment forecasting processes in escalation of commitment, considering two questions: whether individuals are able to accurately predict their behavior and affect in escalation situations and how forecasting processes may be linked to actual escalation. Three experiments demonstrated that individuals underpredicted their escalation and overpredicted their postescalation regret. Two of the experiments also indicated that the less individuals predicted being entrapped, the more they escalated. Counter to expectations, anticipated regret did not predict escalation. The discussion focuses on the theoretical and practical importance of forecasting on escalation and on the importance of understanding both behavioral and affective forecasting effects simultaneously.

  7. Escalate shamefully, de-escalate angrily or gratefully: the influence of discrete emotions on escalation of commitment.

    Science.gov (United States)

    Dang, Junhua; Xiao, Shanshan; Liljedahl, Sophie

    2014-08-01

    Decision makers often tend to escalate their commitment when faced with a dilemma of whether to continue a losing course of action. Researchers recently began to investigate the influence of discrete emotions on this decision tendency. However, this work has mainly focused on negative emotions and rarely considered positive emotions, to say nothing of comparing the effects of both of them simultaneously. The current study addresses this need by presenting the results of three experiments that examined the effects of four emotions of both positive and negative valences in escalation situations. Experiment 1 investigated the relationships of three trait emotions (hope, shame, and anger) and escalation of commitment. Experiments 2 and 3 examined the effects of three induced emotions (anger, shame, and gratitude) on escalation of commitment in a student sample and an employee sample, respectively. The results revealed that the effects of discrete emotions in escalation situations are mainly due to their associated differences on the appraisal dimension of responsibility that is related to escalation situations rather than their valence. The theoretical and practical implications are discussed.

  8. Saving electricity in a hurry. Dealing with temporary shortfalls in electricity supplies

    Energy Technology Data Exchange (ETDEWEB)

    none

    2005-07-01

    Blackouts are normally the result of imbalances in electricity supply and demand. A brief blackout is mostly an inconvenience. But persistent shortfalls ? those lasting days, weeks, or months ? can cause economic disruption and danger to human life in our technology-rich societies. Saving Electricity in a Hurry describes some of the recent power shortfalls, from Norway to New Zealand, from Tokyo to Arizona and the policies these regions used to quickly reduce their power consumption. How did the whole country of Sweden cut its power consumption by 4% in only three days? How did California save 14% in only a few months? While the temporary shortfalls in electricity supplies described in this book are relatively rare events, they disproportionately shape future energy policies. Saving Electricity in a Hurry shows that countries can quickly reduce electricity consumption without harming the economy as much as blackouts or unplanned curtailments. The strategies are diverse, unique and often surprisingly cheap. They include mass media campaigns ? where a good joke can save a Megawatt ? improvements in equipment efficiency and quickly adjusting electricity prices. This book explains how California replaced a million traffic signals with energy-saving models, how millions of Tokyo residents raised their thermostat settings, and how New Zealanders took shorter showers, all quickly enough to help avoid imminent blackouts. Finally, it connects these policies to the traditional goal of ?saving electricity slowly?.

  9. Type A behavior pattern and escalating commitment.

    Science.gov (United States)

    Schaubroeck, J; Williams, S

    1993-10-01

    Subjects (N = 98) were randomly assigned to high- and low-responsibility conditions in a commitment-escalation experiment. Global Type A behavior pattern and the underlying dimension of achievement strivings were positively related to the desire to continue the same course of action in the high prior-responsibility condition but not in the low prior-responsibility condition. These findings are discussed in terms of future research into the judgment processes of people with Type A personality and the possible role of escalating commitment in disorders experienced by people with Type A personality.

  10. Learn French In A Hurry Grasp the Basics of Francais Tout De Suite

    CERN Document Server

    Lawless, Laura

    2010-01-01

    Sure, you can blurt out Merci! and Oui! Oui! and Garcon! as well as the next tourist, but in truth your French lacks a certain je ne sais quoi. That just won't do if you're touring the City of Light or sunning in Tahiti or ordering a la carte in a Montreal cafe. Whether you're traveling to a French-speaking country or learning French for business, this pocket-sized primer is your passeport to one of the world's most beautiful-and useful-languages. Learn French in a Hurry features:Common French phrases (days of the week, numbers, letters)Pronunciation and conjugation tips and tricksGrammar made

  11. Significant NRC Enforcement Actions

    Data.gov (United States)

    Nuclear Regulatory Commission — This dataset provides a list of Nuclear Regulartory Commission (NRC) issued significant enforcement actions. These actions, referred to as "escalated", are issued by...

  12. Expo 86: An Escalation Prototype.

    Science.gov (United States)

    Ross, Jerry; Staw, Barry M.

    1986-01-01

    British Columbia remained committed to its decision to host a world's fair (Expo 86) despite rapidly increasing deficit projections. Expo is examined as a prototypical example of the escalation of commitment. Theory is proposed that integrates determinants of escalation from several levels of analysis over time. (CJH)

  13. Escalation of the Space Domain

    Science.gov (United States)

    2015-04-01

    spacepower – what is meant by spacepower and how might its elements be made available for escalation. Chapter 2 Escalation 101 “We sleep safely...its instruments of national power to change the forthcoming behavior of an adversary.21 There are two distinct types of coercion: punishment and...are similar in nature and application to those seen in science fiction moves or on television (i.e., Star Trek) that can provide direct kinetic

  14. 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.

  15. Attribution Bias and Overconfidence in Escalation of Commitment: The Role of Desire to Rectify Past Outcomes

    Science.gov (United States)

    Tine, Delilah Castillo

    2013-01-01

    Escalation of commitment is the voluntary continuation of investing resources into what appears to be a failing course of action whose outcome is uncertain. Investigation into the escalation of commitment phenomenon is important to organizations because such behavior could result in grave economic loss. This research investigates two cognitive…

  16. Understanding Behavior in Escalation Situations.

    Science.gov (United States)

    Staw, Barry M.; Ross, Jerry

    1989-01-01

    The escalation of commitment has been variously labeled the psychology of entrapment, the sunk cost effect, and the too-much-invested-to-quit syndrome. This article reviews the state of research and describes four major determinants: project; psychological; social; and organizational variables. A model is provided. (YP)

  17. Crisis and Escalation in Cyberspace

    Science.gov (United States)

    2012-01-01

    which both sides cannot bear escalation without matching it. Inci- dentally , no state should count on being able to argue that some effect was an...note. Economic theory says that the greater the price of something, the less people will want it: If potato prices rises, people will eat pasta . If

  18. Reducing and exaggerating escalation of commitment by option partitioning.

    Science.gov (United States)

    Kwong, Jessica Y Y; Wong, Kin Fai Ellick

    2014-07-01

    Options under escalation situations can be presented as a general class (e.g., investing in electronic products) or be partitioned into disjunctive suboptions within that class (e.g., investing in MP3 players, portable TV game consoles, and other electronic products). Drawing from the theoretical bases of partition priming and mental accounting, this research found support from 4 experiments that (a) a decision maker's commitment to a failing course of action is exaggerated when the escalation options are partitioned into multiple suboptions, whereas such commitment is reduced when the alternative options are portioned into suboptions, and (b) these partitioning effects are mediated by the subjective utility, including subjective values and probability, of the escalation option.

  19. 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.

  20. 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

    2017-06-26

    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.

  1. Moving Walkways, Escalators, and Elevators

    CERN Document Server

    Cardinal, J; Hurtado, F; Langerman, S; Palop, B

    2007-01-01

    We study a simple geometric model of transportation facility that consists of two points between which the travel speed is high. This elementary definition can model shuttle services, tunnels, bridges, teleportation devices, escalators or moving walkways. The travel time between a pair of points is defined as a time distance, in such a way that a customer uses the transportation facility only if it is helpful. We give algorithms for finding the optimal location of such a transportation facility, where optimality is defined with respect to the maximum travel time between two points in a given set.

  2. Hurry up and wait

    OpenAIRE

    Stephen Kinsella

    2005-01-01

    It is precisely in those fast moving markets that some interim intervention may be needed because of the risk that by the time the case is finally resolved there may have been irreparable harm to the market. Stephen Kinsella (Sidley Austin)

  3. The effects of mortality salience on escalation of commitment.

    Science.gov (United States)

    Yen, Chih-Long; Lin, Chun-Yu

    2012-01-01

    Based on propositions derived from terror management theory (TMT), the current study proposes that people who are reminded of their mortality exhibit a higher degree of self-justification behavior to maintain their self-esteem. For this reason, they could be expected to stick with their previous decisions and invest an increasing amount of resources in those decisions, despite the fact that negative feedback has clearly indicated that they might be on a course toward failure (i.e., "escalation of commitment"). Our experiment showed that people who were reminded of their mortality were more likely to escalate their level of commitment by maintaining their current course of action. Two imaginary scenarios were tested. One of the scenarios involved deciding whether to send additional troops into the battlefield when previous attempts had failed; the other involved deciding whether to continue developing an anti-radar fighter plane when the enemy had already developed a device to detect it. The results supported our hypothesis that mortality salience increases the tendency to escalate one's level of commitment.

  4. Commitment escalation to a failing family business

    OpenAIRE

    Chirico, Francesco; Salvato, Carlo; Byrne, Barbara; Akhter, Naveed; Arriaga Múzquiz, Juan

    2017-01-01

    The overarching intent of this manuscript is to heighten awareness to the concept of commitment escalation as it bears on a failing family business. Specifically, drawing on the concept of emotional ownership, together with self-justification arguments, we a) identify factors considered to be most forceful in contributing to the presence of commitment escalation and thus, resistance to change in a failing family business (i.e., emotional ownership, feeling of responsibility, investment of cap...

  5. Optimism as modifier of escalation of commitment.

    Science.gov (United States)

    Juliusson, Asgeir

    2006-10-01

    To study whether optimism-pessimism modifies escalation of commitment, 52 undergraduates were told that they had made an unsuccessful investment, then they chose to continue or discontinue this investment. Optimism about future returns was induced in one group by varying the probability of a successful outcome from an initial low to medium, pessimism was induced in another group by varying this probability from an initial high to medium. Supporting the assumption of the manipulation, the results showed that optimistic participants preferred to continue investments whereas pessimistic participants preferred not to. As predicted, when the sunk cost increased, optimism led to escalation of commitment, whereas pessimism led to de-escalation of commitment. These effects were strengthened when probability of a successful outcome was ambiguous.

  6. Neurobiology of escalated aggression and violence

    NARCIS (Netherlands)

    Miczek, Klaus A.; de Almeida, Rosa M. M.; Kravitz, Edward A.; Rissman, Emilie F.; de Boer, Sietse F.; Raine, Adrian

    2007-01-01

    Psychopathological violence in criminals and intense aggression in fruit flies and rodents are studied with novel behavioral, neurobiological, and genetic approaches that characterize the escalation from adaptive aggression to violence. One goal is to delineate the type of aggressive behavior and it

  7. 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).

  8. Nuclear Escalation Ladders in South Asia

    Science.gov (United States)

    2011-04-01

    Ibid., pp. 211-212. 23 Fig. 3. Indian Escalation Ladder - Facing China in the Himalayas Response or Initiative Rung Order Thresholds and Rungs Peace...potential land-warfare ladders in the Himalayas . A. Territorial Boundaries India and Pakistan face each other across a common international... Himalayas from Ladakh in Kashmir south and east for 2,100 miles, interrupted by Nepal and Bhutan, which have their own northern borders with China of 768 and

  9. De-escalating and escalating systemic therapy in triple negative breast cancer.

    Science.gov (United States)

    Carey, Lisa A

    2017-08-01

    Triple negative breast cancer has the highest relapse risk of all the clinical subsets, although the escalation of chemotherapy has benefited this subset substantially over recent years. Systemic options are limited to chemotherapy, which makes meaningful de-escalation or escalation of therapy more challenging but possible. Observational cohorts suggest a less than 10% risk of relapse and minimal if any benefit of chemotherapy in very small (<1 cm), node-negative triple negative disease. In higher risk, particularly node-positive disease, anthracycline/taxane-based regimens remain standard. Neoadjuvant chemotherapy clearly de-escalates surgery, although there are insufficient data to give less than standard chemotherapy on the basis of response to neoadjuvant therapy. Efforts to meaningfully escalate therapy in high-risk disease have included incorporating platinums into Neoadjuvant therapy, with clear benefit in pCR but uncertain impact on relapse and survival at this time. Residual disease after neoadjuvant chemotherapy carries a particularly poor prognosis; a recent randomized trial of 6 months' capecitabine in this setting suggested a survival advantage to this approach in higher risk residual disease. While not validated at this time, future directions are likely to include biologic prognostication with tumor and immune variables, as well as targeted non-cytotoxic approaches leveraging the molecular heterogeneity of triple negative disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. 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.

  11. Tobacco and the Escalating Global Cancer Burden

    Directory of Open Access Journals (Sweden)

    Richard F. Oppeltz

    2011-01-01

    Full Text Available The global burden of cancer is escalating as a result of dramatic increases in the use of tobacco in the developing world. The use of tobacco is linked to the development of a broad variety of cancers, mainly lung cancer, the single most common cancer in the world. Tobacco smoking-attributable deaths extends beyond cancer and include stroke, heart attack and COPD. Widening disparities in cancer-related mortality have shifted towards a more dramatic burden in the developing world. Appropriate interventions must be implemented to reduce tobacco use and prevent global mortality that has escalated to epidemic levels. Tobacco control policies, including public health advertisement campaigns, warning labels, adoption of smoke-free laws, comprehensive bans and tax policies are highly effective measures to control tobacco use. Clinicians and academic institutions have to be actively committed to support tobacco control initiatives. The reduction in cancer related morbidity and mortality should be viewed as a global crisis and definitive results will depend on a multilevel effort to effectively reduce the burden of cancer, particularly in underprivileged regions of the world.

  12. An Investigation of the Relationships between Goals and Software Project Escalation: Insights from Goal Setting and Goal Orientation Theories

    Science.gov (United States)

    Lee, Jong Seok

    2013-01-01

    Escalation of commitment is manifested as a behavior in which an individual resists withdrawing from a failing course of action despite negative feedback, and it is an enduring problem that occurs in a variety of situations, including R&D investment decisions and software project overruns. To date, a variety of theoretical explanations have…

  13. An Investigation of the Relationships between Goals and Software Project Escalation: Insights from Goal Setting and Goal Orientation Theories

    Science.gov (United States)

    Lee, Jong Seok

    2013-01-01

    Escalation of commitment is manifested as a behavior in which an individual resists withdrawing from a failing course of action despite negative feedback, and it is an enduring problem that occurs in a variety of situations, including R&D investment decisions and software project overruns. To date, a variety of theoretical explanations have…

  14. The role of anticipated regret in escalation of commitment.

    Science.gov (United States)

    Wong, Kin Fai Ellick; Kwong, Jessica Y Y

    2007-03-01

    This research tests the general proposition that people are motivated to reduce future regret under escalation situations. This is supported by the findings that (a) escalation of commitment is stronger when the possibility of future regret about withdrawal is high than when this possibility is low (Studies 1a and 1b) and (b) escalation of commitment increases as the net anticipated regret about withdrawal increases (Studies 2a and 2b). Furthermore, the regret effects in the 4 studies were above and beyond the personal responsibility effects on escalation. This research indicates that people in escalation situations are simultaneously influenced by the emotions they expect to experience in the future (e.g., anticipated regret) and by events that have happened in the past (e.g., responsibility for the initiating previous decision).

  15. Saving oil in a hurry

    Energy Technology Data Exchange (ETDEWEB)

    none

    2005-07-01

    During 2004, oil prices reached levels unprecedented in recent years. Though world oil markets remain adequately supplied, high oil prices do reflect increasingly uncertain conditions. Many IEA member countries and non-member countries alike are looking for ways to improve their capability to handle market volatility and possible supply disruptions in the future. This book aims to provide assistance. It provides a new, quantitative assessment of the potential oil savings and costs of rapid oil demand restraint measures for transport. Some measures may make sense under any circumstances; others are primarily useful in emergency situations. All can be implemented on short notice ? if governments are prepared. The book examines potential approaches for rapid uptake of telecommuting, ?ecodriving?, and car-pooling, among other measures. It also provides methodologies and data that policymakers can use to decide which measures would be best adapted to their national circumstances. This ?tool box? may help countries to complement other measures for coping with supply disruptions, such as use of strategic oil stocks.

  16. A New SDH-Based ATM Network Survivability Escalation Mechanism

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    This paper investigates survivability escalation strategies in multi-layers transport networks such as ATM/SDH/WDM networks, and presents oriented-failures and oriented-traffic escalation mechanisms. Furthermore, We present a new survivability Escalation strategy for SDH-Based ATM transport networks, which addresses difficult problem for resources sharing pool(RSP) among different layers restoration mechanisms. In this paper, we also present integer programming (IP) model for the resources sharing pool (RSP) design problem and the node simulation model for escalation Node. The simulation results show that the proposed ESP is very efficient. The proposed model can be easily extended for other types of multi-layer networks, such as WDM-based ATM networks or WDM-based SDH networks.

  17. Soviet declaratory policy regarding the controllability of escalation

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. Escalation and De-escalation of Therapy in COPD: Myths, Realities and Perspectives.

    Science.gov (United States)

    Cazzola, Mario; Rogliani, Paola; Matera, Maria Gabriella

    2015-09-01

    Chronic obstructive pulmonary disease (COPD) guidelines and strategies suggest escalating treatment, mainly depending on the severity of airflow obstruction. However, some de-escalation of therapy in COPD would be appropriate, although we still do not know when we should switch, step-up or step-down treatments in our patients. Unfortunately, trials comparing different strategies of step-up and step-down treatment (e.g. treatment initiation with one single agent and then further step-up if symptoms are not controlled versus initial use of double or triple therapy, possibly with lower doses of the individual components, or the role of N-acetylcysteine in combination therapy for a step-down approach) are still lacking. In general, there is a large and often inappropriate use of the inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) combination. However, the withdrawal of the ICS in COPD patients at low risk of exacerbation can be safe, provided that patients are under regular treatment with long-acting bronchodilators. Maximising the treatment in patients with a degree of clinical instability by including an ICS in the therapeutic regimen is useful to control the disease, but may not be needed during periods of clinical stability. In patients with severe but stable COPD, the withdrawal of the ICS from triple therapy [LABA + long-acting muscarinic antagonist (LAMA) + ICS] is possible, but not when the patient has been hospitalised for an acute exacerbation of COPD. We must still establish how long we should wait before withdrawing the ICS. It is still unclear whether the same is true when only the LABA or the LAMA is withdrawn while continuing treatment with the other bronchodilator and the ICS. In any case, we strongly believe that it is always better to avoid a therapeutic step-up progression when it is not needed rather than being forced subsequently into a step-down approach in which the outcome is always unpredictable.

  19. Looking forward and looking back: integrating completion and sunk-cost effects within an escalation-of-commitment progress decision.

    Science.gov (United States)

    Moon, H

    2001-02-01

    Currently, there are 2 conflicting frameworks with which to understand why decision makers might escalate their commitment to a previously chosen course of action: sunk costs and project completion. The author proposes that sunk costs and need to complete exert simultaneous pressures, both independent and interactive, on a decision maker's level of commitment. The responses of 340 participants were analyzed and supported a complementary relationship between the 2 predictors. In addition, sunk costs demonstrated a curvilinear influence on commitment and an interaction with level of completion that supported a Level of Completion x Sunk Cost moderation model. (A marginal utility model was not supported.) Results are discussed in terms of their relevance toward offering a complementary view of 2 potential antecedents to a decision maker's propensity to escalate his or her commitment to a previously chosen course of action.

  20. 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.

  1. 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.

  2. 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…

  3. Les escales de Likert poden augmentar en sensibilitat?

    Directory of Open Access Journals (Sweden)

    Rafel Bisquerra Alzina

    2015-07-01

    Full Text Available En les investigacions que utilitzen escales tipus Likert s’apliquen principalment escales de 5 punts, sense una fonamentació metodològica que ho justifiqui. La revisió de 3 conegudes revistes permet arribar a aquesta conclusió. Sembla que es fa així per tradició i perquè és difícil posar nom a més de cinc opcions de resposta. En aquest article es posa en qüestió aquesta tradició i s’aporten arguments per proposar altres alternatives. S’analitza la importància de millorar la sensibilitat de les escales augmentant les opcions de resposta; es recomana evitar l’ús de denominacions categòriques, que strictu sensu impedeix el seu ús com a escala d’interval ja que la converteix en nominal (categòrica; s’analitza el rebuig a valors extrems, etc. Com a conseqüència, es recomana la proposta en favor d’escales d’onze punts (de 0 a 10.

  4. How organizational escalation prevention potential affects success of implementation of innovations: electronic medical records in hospitals.

    Science.gov (United States)

    Lambooij, Mattijs S; Koster, Ferry

    2016-05-20

    Escalation of commitment is the tendency that (innovation) projects continue, even if it is clear that they will not be successful and/or become extremely costly. Escalation prevention potential (EPP), the capability of an organization to stop or steer implementation processes that do not meet their expectations, may prevent an organization of losing time and money on unsuccessful projects. EPP consists of a set of checks and balances incorporated in managerial practices that safeguard management against irrational (but very human) decisions and may limit the escalation of implementation projects. We study whether successful implementation of electronic medical records (EMRs) relates to EPP and investigate the organizational factors accounting for this relationship. Structural equation modelling (SEM), using questionnaire data of 427 doctors and 631 nurses who had experience with implementation and use of EMRs in hospitals, was applied to study whether formal governance and organizational culture mediate the relationship between EPP and the perceived added value of EMRs. Doctors and nurses in hospitals with more EPP report more successful implementation of EMR (in terms of perceived added value of the EMR). Formal governance mediates the relation between EPP and implementation success. We found no evidence that open or innovative culture explains the relationship between EPP and implementation success. There is a positive relationship between the level of EPP and perceived added value of EMRs. This relationship is explained by formal governance mechanisms of organizations. This means that management has a set of tangible tools to positively affect the success of innovation processes. However, it also means that management needs to be able to critically reflect on its (previous) actions and decisions and is willing to change plans if elements of EPP signal that the implementation process is hampered.

  5. 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

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

    Directory of Open Access Journals (Sweden)

    REJO MATHEW

    2012-09-01

    Full Text Available 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 provided some sort of respite to the developers but the security feature handling by the developers has not helped much. In this paper we discuss the basics of the privilege escalation attack and the various techniques used to counter and prevent this problem.

  7. 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 ...

  8. Flu, risks, and videotape: escalating fear and avoidance.

    Science.gov (United States)

    Rosoff, Heather; John, Richard S; Prager, Fynnwin

    2012-04-01

    While extensive risk perception research has focused on emotions, cognitions, and behavior at static points in time, less attention has been paid to how these variables might change over time. This study assesses how negative affect, threat beliefs, perceived risk, and intended avoidance behavior change over the course of an escalating biological disaster. A scenario simulation methodology was used that presents respondents with a video simulation of a 15-day series of local news reports to immerse respondents in the developing details of the disaster. Systemic manipulation of the virus's causal origin (terrorist attack, medical lab accident, unknown) and the respondent's proximity to the virus (local vs. opposite coast) allowed us to investigate the dynamics of public response. The unfolding scenario was presented in discrete episodes, allowing responses to be tracked over the episodes. The sample includes 600 respondents equally split by sex and by location, with half in the Washington, DC area, and half in the Los Angeles area. The results showed respondents' reactions to the flu epidemic increased as the disaster escalated. More importantly, there was considerable consistency across respondents' emotional, cognitive, and behavioral responses to the epidemic over the episodes. In addition, the reactions of respondents proximally closer to the epidemic increased more rapidly and with greater intensity than their distant counterparts. Finally, as the flu epidemic escalated, both terrorist and accidental flu releases were perceived as being less risky and were less likely to lead to avoidance behavior compared to the unknown flu release.

  9. Phylogenetic escalation and decline of plant defense strategies.

    Science.gov (United States)

    Agrawal, Anurag A; Fishbein, Mark

    2008-07-22

    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.

  10. Migration, Occupational Mobility, and Regional Escalators in Scotland

    Directory of Open Access Journals (Sweden)

    Maarten van Ham

    2012-01-01

    Full Text Available This paper seeks to unpick the complex relationship between an individual’s migration behaviour, their place of residence, and their occupational performance in the Scottish labour market between 1991 and 2001. We investigate whether Edinburgh has emerged as an occupational escalator region and whether individuals moving there experience more rapid upward occupational mobility than those living and moving elsewhere. Using country of birth, we also control for an individual’s propensity to make long distance moves during earlier periods of their life course. Using data from the Scottish Longitudinal Study, linking 1991 and 2001 individual census records, and logistic regressions, we show that those who migrate over long distances within or to Scotland are most likely to achieve upward occupational mobility. We also found that Edinburgh is by far the most important regional escalator in Scotland; those moving to Edinburgh are the most likely to experience upward occupational mobility from low to high occupational status jobs. This is an important finding as most of the literature on escalator regions focuses on international mega cities.

  11. CONTROL SYSTEM FOR ESCALATOR = SISTEMA DE CONTROLE PARA ESCADA ROLANTE

    Directory of Open Access Journals (Sweden)

    Mauricio Ginez Romero

    2010-01-01

    Full Text Available Many business stablisment utilize escalator that performs it’s function in a regular way of work. There is a big waste of eletric power, as in a good part of it there isn’t a transportation of user. The search for new sources shouldnt’t is the only worry in the context of energetic resource, but also the development of new technologies aimed an optimal use of this recourse. In the conjuncture, this project aims to establish a escalators’ control system, to optimize their use and reduce energy consumption of equipment. The system’s operation is based on the principle that, after a time ta,, a free flow of user, which this time is previously define by a statistician study the escalator reduce its speed, if it has passed a time tb, being tb>ta, the escalator is stopped. If we have the presence of the user, the escalator presents low acceleration, establishing the regular way of work without risks of utilization. The energetic economy happens when the escalator is stopped, or working with reduced speed. The project consists in replace the eletric command of the reversor and with the direct start, by a system’s control proposed. The reduction of the energy comsumption was valued by a statistician study, so trough it we can increase the use of the system and stipulate of the economy zone for the escalators with high and low user’s flow. This system is ecologically correct and contribute for the consumption optimized of electric power. = Muitos estabelecimentos comerciais utilizam escadas rolantes que desempenham sua função em regime normal de funcionamento. Existe um grande desperdício de energia elétrica, já que em boa parte não há transporte de usuário. A busca por novas fontes não deve ser a única preocupação no contexto dos recursos energéticos, mas também o desenvolvimento de novas tecnologias que visam o uso otimizado destes recursos. Nesta conjuntura, este projeto visa implantar um sistema de controle para escadas

  12. Dose escalation studies with caspofungin against Candida glabrata.

    Science.gov (United States)

    Domán, Marianna; Kovács, Renátó; Perlin, David S; Kardos, Gábor; Gesztelyi, Rudolf; Juhász, Béla; Bozó, Aliz; Majoros, László

    2015-09-01

    Echinocandins are recommended as first-line agents against invasive fungal infections caused by Candida glabrata, which still carry a high mortality rate. Dose escalation of echinocandins has been suggested to improve the clinical outcome against C. glabrata. To address this possibility, we performed in vitro and in vivo experiments with caspofungin against four WT C. glabrata clinical isolates, a drug-susceptible ATCC 90030 reference strain and two echinocandin-resistant strains with known FKS mutations. MIC values for the clinical isolates in RPMI 1640 were ≤ 0.03 mg l(-1 ) but increased to 0.125-0.25 mg l(-1 )in RPMI 1640+50% serum. In RPMI 1640+50% serum, the replication of C. glabrata was weaker than in RPMI 1640.Caspofungin in RPMI 1640 at 1 and 4 mg l(-1) showed a fungicidal effect within 7 h against three of the four clinical isolates but was only fungistatic at 16 and 32 mg l(-1) (paradoxically decreased killing activity). In RPMI 1640+50% serum, caspofungin at ≥ 1 mg l(-1) was rapidly fungicidal (within 3.31 h) against three of the four isolates. In a profoundly neutropenic murine model, all caspofungin doses (1, 2, 3, 5 and 20 mg kg(-1) daily) decreased the fungal tissue burdens significantly (P caspofungin dose escalation does not improve efficacy.

  13. IS Project Management and Risk Escalation: Towards A Dynamic Model

    Directory of Open Access Journals (Sweden)

    Angela Y Lin

    2015-03-01

    Full Text Available While the number of substantive investments in IS projects continues to grow, the number of failing projects also continues to increase at an alarming rate. Both the academic and industry literature suggests that inadequate attention to risk and its management continues to be a key factor in project failure. The typical approach taken is to identify and map potential risks, to act as a planning and diagnostic tool, and to prepare a contingency plan has been a factor-based approach. While it remains a valuable tool for mapping anticipated risks the factor-based approach is less effective when viewing project risks as emergent phenomena that un-fold during the course of the project, and require ongoing attention and risk management. In-formed by a case study of a failing university IS development project, this paper focuses on the phenomenon of risk escalation. The case findings suggest that rather than being defined ahead of the project, some project risks may emerge during the project as a consequence of escalation factors that were both antecedent to and a consequence of actual risk management decisions. The article concludes with suggestions as to how project managers can better man-age the emergent rather than static nature of risk phenomena.

  14. Riding the Escalator: How Dangerous is it Really?

    Directory of Open Access Journals (Sweden)

    Louisa H. Schminke

    2013-03-01

    Full Text Available Introduction: About 10,000 escalator-related injuries per year result in emergency departmenttreatment in the United States. Since the 1990s, a steady increase has been reported, but fewstatistics on escalator-related injuries have been published worldwide. We have therefore analyzedescalator accident statistics in admissions to our hospital in Switzerland since 2000.Methods: Using retrospective electronic patient chart analysis, we included in our study patients>16 years treated over an 11-year period. We categorized patients in terms of gender, age andassociated risk factors, and classified accidents according to day, time, location and cause. Resultingtrauma was categorized according to type and location. We divided post-admission treatment intosurgical and conservative, and into treatment as an outpatient, in a short-stay unit, or as a hospitaladmission. Women and men were compared using Fisher’s exact test.Results: We identified 173 patients with 285 discrete injuries. Of these, 87 patients (50% werewomen. Fifty-three (61% of the women and 38 (44% of the men were >60 years old (P = 0.033.Fifty percent of the men (43/86of the men, but only 7% (6/87 of the women showed signs of alcoholintoxication (P < 0.0001. Accidents in women occurred predominantly on Tuesdays (19/87; 22%between 12PM and 6PM (35/87; 40%, and in men on Saturdays (16/86; 19% between 6PM and12AM (29/86; 34%; P = 0.0097. Sixty-two percent (44/71 of the accidents were in public transportfacilities and 30% (21/71 in shopping centers. The majority of injuries in women were to the lowerextremities (49/87; 56%, while most accidents in men were to the head and neck (51/86; 59%; P =0.0052. About half (90; 52% of the patients were treated conservatively. Almost half of all patients(76, 44% required hospital admission. Of those, 45% left the hospital within 24 hours of admission(short stay unit and 55% stayed longer than 24 hours.Conclusion: Escalator accidents can result in severe

  15. The Integrated Web Portal for Escalation with Overdose Control (EWOC).

    Science.gov (United States)

    Wang, Haibin; Tighiouart, Mourad; Huang, Shao-Chi; Berel, Dror; Cook-Wiens, Galen; Bresee, Catherine; Li, Quanlin; Rogatko, André

    2013-01-01

    In this paper, we present the design and implementation of a novel web portal for the cancer phase I clinical trial design method Escalation with Overdose Control (EWOC). The web portal has two major components: a web-based dose finding calculator; and a standalone and downloadable dose finding software which can be installed on Windows operating systems. The web-based dose finding calculator uses industry standards and is a database-driven and distributed computing platform for designing and conducting dose finding in cancer phase I clinical trials utilizing EWOC methodology. The web portal is developed using open source software: PHP, JQuery, R and OpenBUGS. It supports any standard browsers with internet connection. The web portal can be accessed at: http://biostatistics.csmc.edu.

  16. 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.

  17. Do Sell-Side Stock Analysts Exhibit Escalation of Commitment?

    Science.gov (United States)

    Beshears, John; Milkman, Katherine L

    2011-03-01

    This paper presents evidence that when an analyst makes an out-of-consensus forecast of a company's quarterly earnings that turns out to be incorrect, she escalates her commitment to maintaining an out-of-consensus view on the company. Relative to an analyst who was close to the consensus, the out-of-consensus analyst adjusts her forecasts for the current fiscal year's earnings less in the direction of the quarterly earnings surprise. On average, this type of updating behavior reduces forecasting accuracy, so it does not seem to reflect superior private information. Further empirical results suggest that analysts do not have financial incentives to stand by extreme stock calls in the face of contradictory evidence. Managerial and financial market implications are discussed.

  18. Training Tolerance to Delay Using the Escalating Interest Task.

    Science.gov (United States)

    Rung, Jillian M; Young, Michael E

    2014-09-01

    The present study examined the lasting effects of exposure to reinforcement that increased in magnitude as a function of time between responses in a first-person shooter video game preparation of the escalating interest task. When reinforcement density increased as a function of time, it encouraged participants to wait longer between responses (shots of a weapon). Participants exposed to such contingencies waited significantly longer to fire their weapons than participants who were exposed to linear growth, where long inter-response times were not differentially reinforced. Those with experience in conditions where reinforcement density increased as a function of time showed persistently longer wait times when the contingencies changed in the latter portion of the game where the disincentive to fire quickly was removed. The potential utility of such contingencies for training tolerance to delay of reinforcement and the broader implications of training self-control are discussed.

  19. Misonidazole with dexamethasone rescue: an escalating dose toxicity study

    Energy Technology Data Exchange (ETDEWEB)

    Tanasichuk, H.; Urtasun, R.C.; Fulton, D.S.; Raleigh, J.

    1984-09-01

    Neurotoxicity induced by misonidazole (MISO) and desmethylmisonidazole (DMM) has become the dose limiting factor in clinical work. In 1981, the authors reported a preliminary study suggestive that Dexamethasone (DEXA) does have a protective effect against peripheral neuropathies (PN) resulting from toxicity of misonidazole. The authors are presently investigating the use of DEXA, with escalating doses of MISO in an attempt to modify its neurotoxicity. To date, 16 patients have been registered to receive total doses of MISO given in 9 equally divided doses over 3 weeks. DEXA is given 3 days prior to the first dose and continues for the duration of therapy. All patients receive palliative radiation. No toxicity was seen at the total dose of 13.5 gm/M/sub 2/. One grade I PN occurred in the first four patients receiving 15.5 gm/M/sub 2/. Six additional patients were entered at this dose level and no further incidence of PN was observed.

  20. 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…

  1. Inherently irrational? A computational model of escalation of commitment as Bayesian Updating.

    Science.gov (United States)

    Gilroy, Shawn P; Hantula, Donald A

    2016-06-01

    Monte Carlo simulations were performed to analyze the degree to which two-, three- and four-step learning histories of losses and gains correlated with escalation and persistence in extended extinction (continuous loss) conditions. Simulated learning histories were randomly generated at varying lengths and compositions and warranted probabilities were determined using Bayesian Updating methods. Bayesian Updating predicted instances where particular learning sequences were more likely to engender escalation and persistence under extinction conditions. All simulations revealed greater rates of escalation and persistence in the presence of heterogeneous (e.g., both Wins and Losses) lag sequences, with substantially increased rates of escalation when lags comprised predominantly of losses were followed by wins. These methods were then applied to human investment choices in earlier experiments. The Bayesian Updating models corresponded with data obtained from these experiments. These findings suggest that Bayesian Updating can be utilized as a model for understanding how and when individual commitment may escalate and persist despite continued failures.

  2. Escalation research: providing new frontiers for applying behavior analysis to organizational behavior.

    Science.gov (United States)

    Goltz, S 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.

  3. Playing Muller Games in a Hurry

    Directory of Open Access Journals (Sweden)

    John Fearnley

    2010-06-01

    Full Text Available This work studies the following question: can plays in a Muller game be stopped after a finite number of moves and a winner be declared. A criterion to do this is sound if Player 0 wins an infinite-duration Muller game if and only if she wins the finite-duration version. A sound criterion is presented that stops a play after at most 3^n moves, where n is the size of the arena. This improves the bound (n!+1^n obtained by McNaughton and the bound n!+1 derived from a reduction to parity games.

  4. Saving electricity in a hurry - update 2011

    Energy Technology Data Exchange (ETDEWEB)

    Pasquier, Sara Bryan

    2011-06-15

    As demonstrated by the March 2011 earthquake and tsunami-triggered blackouts in Japan, electricity shortfalls can happen anytime and anywhere. Countries can minimise the negative economic, social and environmental impacts of such electricity shortfalls by developing emergency energy-saving strategies before a crisis occurs. This new IEA report highlights preliminary findings and conclusions from electricity shortfalls in Japan, the United States, New Zealand, South Africa and Chile. It draws on recent analysis to: reinforce well-established guidelines on diagnosing electricity shortfalls, identifying energy-saving opportunities and selecting a package of energy-saving measures; and highlight proven practice for implementing emergency energy-saving programmes. This paper will be valuable to government, academic, private-sector and civil-society stakeholders who inform, develop and implement electricity policy in general, and emergency energy-saving programmes in particular.

  5. 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

    2017-03-28

    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.

  6. 77 FR 42353 - Escalate Capital Partners SBIC I, L.P.; Notice Seeking Exemption Under Section 312 of the Small...

    Science.gov (United States)

    2012-07-18

    ... ADMINISTRATION Escalate Capital Partners SBIC I, L.P.; Notice Seeking Exemption Under Section 312 of the Small Business Investment Act, Conflicts of Interest Notice is hereby given that Escalate Capital Partners SBIC I...). Escalate Capital Partners SBIC I, L.P. proposes to make a debt investment in Mavenir Systems, Inc.,...

  7. De-escalation, adequacy of antibiotic therapy and culture positivity in septic patients: an observational study

    Science.gov (United States)

    Moraes, Rafael Barberena; Guillén, Julián Alberto Viteri; Zabaleta, William Javier Castillo; Borges, Flavia Kessler

    2016-01-01

    Objective To evaluate the prevalence of antibiotic de-escalation in patients diagnosed with severe sepsis or septic shock at a public academic tertiary hospital and to evaluate antibiotic adequacy and culture positivity. Methods The prevalence of antibiotic de-escalation, the adequacy of antibiotic treatment and the rates of culture positivity were analyzed in patients with severe sepsis and septic shock between April and December 2013 at an intensive care unit in a tertiary university hospital. Results Among the 224 patients included in the study, de-escalation was appropriate in 66 patients (29.4%) but was implemented in 44 patients (19.6%). Among the patients who underwent de-escalation, half experienced narrowing of the antimicrobial spectrum. The mortality rate was 56.3%, with no differences between the patients with or without de-escalation (56.8% versus 56.1%; p = 0.999) nor in the length of hospital stay. Empirical antibiotic therapy was appropriate in 89% of cases. Microorganisms were isolated from total cultures in 30% of cases and from blood cultures in 26.3% of cases. Conclusion The adequacy rate of empirical antibiotic therapy was high, reflecting an active institutional policy of monitoring epidemiological profiles and institutional protocols on antimicrobial use. However, antibiotic de-escalation could have been implemented in a greater number of patients. De-escalation did not affect mortality rates. PMID:27626951

  8. 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."

  9. Destined to die but not to wage war: how existential threat can contribute to escalation or de-escalation of violent intergroup conflict.

    Science.gov (United States)

    Jonas, Eva; Fritsche, Immo

    2013-10-01

    War means threat to people's lives. Research derived from terror management theory (TMT) illustrates that the awareness of death leads people to defend cultural ingroups and their worldviews to attain a sense of symbolic immortality and thereby buffer existential anxiety. This can result in hostile effects of mortality salience (MS), such as derogation of outgroup members, prejudice, stereotyping, aggression, and racism, which, in turn, can lead to the escalation of violent intergroup conflict and, thus, the escalation of war. Yet, escalation of destructive conflict following MS is not automatic. Instead, research on TMT suggests that MS does not necessarily result in conflict and intolerance but can also foster positive tendencies, such as intergroup fairness or approval of pacifism, depending on how existential threat is perceived, whether the need for symbolic self-transcendence is satisfied, which social norms are salient, and how social situations are interpreted. In the present article, we review current TMT research with the aim of reconciling the seemingly contradictory findings of hostile and peaceful reactions to reminders of death. We present a terror management model of escalation and de-escalation of violent intergroup conflicts, which takes into account the interaction between threat salience and features of the social situation. We also discuss possible intervention strategies to override detrimental consequences of existential threat and argue that war is not the inevitable consequence of threat. PsycINFO Database Record (c) 2013 APA, all rights reserved

  10. Effects of voluntary dose escalation in a placebo-controlled, flexible-dose trial of fesoterodine in subjects with overactive bladder.

    Science.gov (United States)

    Staskin, David; Khullar, Vik; Michel, Martin C; Morrow, Jon D; Sun, Franklin; Guan, Zhonghong; Dmochowski, Roger

    2011-11-01

    To characterize the response to fesoterodine treatment for overactive bladder (OAB) in subjects who did or did not choose to dose escalate in a flexible-dose study. Subjects were randomized to fesoterodine 4  mg or placebo. At week 2, subjects could remain on 4  mg (non-escalators) or choose to increase to 8  mg (escalators) for the remaining 10 weeks (sham escalation for placebo). Subjects completed 3-day bladder diaries at baseline, week 2 and week 12 noting micturitions, urgency episodes, and urgency urinary incontinence (UUI) episodes. Sixty-three per cent of 438 subjects randomized to fesoterodine and 73% of 445 randomized to placebo dose escalated. At baseline, fesoterodine escalators had significantly more micturitions and urgency episodes than fesoterodine non-escalators (P fesoterodine non-escalators versus escalators (P fesoterodine non-escalators and escalators (P > 0.05). The placebo escalator group did not demonstrate a similar response over placebo non-escalators following the dose escalation decision point. A rapid and robust response to fesoterodine 4  mg was demonstrated in non-escalators. Subjects who chose to dose escalate to fesoterodine 8  mg at week 2 showed significant improvement by week 12 versus baseline and week 2 (prior to escalation), as well as versus placebo. Dose escalation to 8  mg fesoterodine provided subjects with efficacy and tolerability similar to those who were satisfied with the 4-mg dose. Copyright © 2011 Wiley Periodicals, Inc.

  11. 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.)

  12. Dengue: an escalating public health problem in Latin America.

    Science.gov (United States)

    Tapia-Conyer, Roberto; Betancourt-Cravioto, Miguel; Méndez-Galván, Jorge

    2012-05-01

    Dengue infection is a significant and escalating public health problem in Latin America. Its re-emergence and subsequent rise in the region over the past 50 years has largely been caused by a combination of a lack of political will, the radical growth of urban populations, migration flow and insufficient financial resources. Its increased incidence has been compounded by climate change, poor sanitation and extreme poverty, which lead to more breeding sites of the mosquito vector Aedes aegypti. In order to control dengue effectively, an integrated approach incorporating vector management and environmental and social solutions is required. To achieve success, these programmes require commitment and responses at both national and community level. The development of a vaccine is a vital tool in the fight against dengue. For successful introduction, those implementing vaccination need to be educated on the value of such a strategy. Effective political leadership, innovative financial mechanisms and co-operation across all disciplines, sectors and national borders are essential to eradication of the disease.

  13. 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

  14. 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.

  15. PtmxGuard: An Improved Method for Android Kernel to Prevent Privilege Escalation Attack

    Directory of Open Access Journals (Sweden)

    Kong Bin

    2017-01-01

    Full Text Available Vulnerabilities in Android kernel give opportunity for attacker to damage the system. Privilege escalation is one of the most dangerous attacks, as it helps attacker to gain root privilege by exploiting kernel vulnerabilities. Mitigation technologies, static detection methods and dynamic defense methods have been suggested to prevent privilege escalation attack, but they still have some disadvantages. In this paper, we propose an improved method named PtmxGuard to enhance Android kernel and defeat privilege escalation attack. We focus on a typical attack pattern that attacker hijacks the control flow of Android kernel to modify process credentials by corrupting critical global function pointers. PtmxGuard enforces Code Pointer Integrity to Android kernel, checks the accuracy and reliability of those pointers when they’re triggered by related system calls, and intercepts the system calls when attack activities are detected. Experiment result demonstrates that PtmxGuard can defense privilege escalation attack effectively.

  16. Efficacy of imatinib dose escalation in Chinese gastrointestinal stromal tumor patients

    Institute of Scientific and Technical Information of China (English)

    Jian Li; Ji-Fang Gong; Jie Li; Jing Gao; Nai-Ping Sun; Lin Shen

    2012-01-01

    AIM:To investigate the efficacy and safety of imatinib dose escalation in Chinese patients with advanced gastrointestinal stromal tumor (GIST).METHODS:Advanced GIST patients previously failing 400 mg imatinib treatment were enrolled in this study.Patients received imatinib with dose escalation to 600mg/d,and further dose escalation to 800 mg/d if imatinib 600 mg/d failed.Progression-free survival,overall survival,clinical efficacy,c-kit/PDGFRA genotype and safety were evaluated.RESULTS:52 patients were enrolled in this study.For the 47 evaluable patients receiving imatinib (600 mg/d),the disease control rate was 40.4%,and the median progression-free survival for all patients was 17 wk (95% CI:3.9-30.1).The median overall survival after dose escalation was 81 wk (95% CI:36.2-125.8).Adverse events,mainly edema,fatigue,granulocytopenia and skin rash were tolerable.However,further dose escalation (800 mg/d) in 14 cases was ineffective,with disease progression and severe adverse events.Among 30 cases examined for gene mutations,patients with exon 9 mutations experienced a better progression-free survival of 47 wk.CONCLUSION:Imatinib dose escalation to 600 mg/d is more appropriate for Chinese patients and may achieve further survival benefit.

  17. BK channel β1 and β4 auxiliary subunits exert opposite influences on escalated ethanol drinking in dependent mice

    Directory of Open Access Journals (Sweden)

    Max eKreifeldt

    2013-12-01

    Full Text Available Large conductance calcium-activated potassium (BK channels play a key role in the control of neuronal activity. Ethanol is a potent activator of BK channel gating, but how this action may impact ethanol drinking still remains poorly understood. Auxiliary β subunits are known to modulate ethanol-induced potentiation of BK currents. In the present study, we investigated whether BK β1 and β4 subunits influence voluntary ethanol consumption using knockout mice. In a first experiment, mice were first subjected to continuous two-bottle choice (2BC and were then switched to intermittent 2BC, which progressively increased ethanol intake as previously described in wildtype mice. BK β1 or β4 subunit deficiency did not affect ethanol self-administration under either schedule of access. In a second experiment, mice were first trained to drink ethanol in a limited-access 2BC paradigm. BK β1 or β4 deletion did not affect baseline consumption. Weeks of 2BC were then alternated with weeks of chronic intermittent ethanol (CIE or air inhalation. As expected, a gradual escalation of ethanol drinking was observed in dependent wildtype mice, while intake remained stable in non-dependent wildtype mice. However, CIE exposure only produced a mild augmentation of ethanol consumption in BK β4 knockout mice. Conversely, ethanol drinking increased after fewer CIE cycles in BK β1 knockout mice than in wildtype mice. In conclusion, BK β1 or β4 did not influence voluntary ethanol drinking in non-dependent mice, regardless of the pattern of access to ethanol. However, deletion of BK β4 attenuated, while deletion of BK β1 accelerated, the escalation of ethanol drinking during withdrawal from CIE. Our data suggest that BK β1 and β4 subunits have an opposite influence on the negative reinforcing properties of ethanol withdrawal. Modulating the expression, distribution or interactions of BK channel auxiliary subunits may therefore represent a novel avenue for the

  18. Terrorist attacks escalate in frequency and fatalities preceding highly lethal attacks.

    Science.gov (United States)

    Martens, Andy; Sainudiin, Raazesh; Sibley, Chris G; Schimel, Jeff; Webber, David

    2014-01-01

    Highly lethal terrorist attacks, which we define as those killing 21 or more people, account for 50% of the total number of people killed in all terrorist attacks combined, yet comprise only 3.5% of terrorist attacks. Given the disproportionate influence of these incidents, uncovering systematic patterns in attacks that precede and anticipate these highly lethal attacks may be of value for understanding attacks that exact a heavy toll on life. Here we examined whether the activity of terrorist groups escalates--both in the number of people killed per attack and in the frequency of attacks--leading up to highly lethal attacks. Analyses of terrorist attacks drawn from a state-of-the-art international terrorism database (The Global Terrorism Database) showed evidence for both types of escalation leading up to highly lethal attacks, though complexities to the patterns emerged as well. These patterns of escalation do not emerge among terrorist groups that never commit a highly lethal attack.

  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. Choosing between stairs and escalators in China: The impact of location, height and pedestrian volume

    Science.gov (United States)

    Zacharias, John; Tang, Boshen

    2015-01-01

    Objective This research examines whether Beijing residents are more or less likely than Montréal residents to avoid stair climbing, by replicating a study in Montréal, Canada that measured the impacts of distance between stairs and escalator, height between floors and pedestrian volume on stair climbing rate. Method 15 stairways, 14 up-escalators and 13 down-escalators were selected in 13 publicly accessible settings in Beijing. Distance between the bottom or top of nearest stair and escalator combinations varied from 2.1 m to 114.1 m with height between floors varying from 3.3 m to 21.7 m. Simultaneous counts were conducted on stair and escalator pairs, for a total of 37,081 counted individuals. Results In the ascent model, pedestrian volume accounted for 16.3% of variance in stair climbing, 16.4% when height was added and 45.1% when distance was added. In the descent model, 40.9% of variance was explained by pedestrian volume, 41.5% when height was added and 45.5% when distance was added. Conclusion Separating stairs and escalator is effective in increasing stair climbing in Beijing, accounting for 29% of the variance in stair climbing, compared with 43% in Montreal. As in the Montreal case, distance has less effect on stair use rate when descending. Overall, 25.4% of Beijingers opted for stairs when ascending compared with 20.3% of Montrealers, and for descending 32.8% and 31.1% respectively. PMID:26844113

  1. Dose escalation for unresectable locally advanced non-small cell lung cancer: end of the line?

    Science.gov (United States)

    Hong, Julian C; Salama, Joseph K

    2016-02-01

    Radiation Therapy Oncology Group (RTOG) 0617 was a randomized trial that investigated both the impact of radiation dose-escalation and the addition of cetuximab on the treatment of non-small cell lung cancer (NSCLC). The results of RTOG 0617 were surprising, with the dose escalation randomization being closed prematurely due to futility stopping rules, and cetuximab ultimately showing no overall survival benefit. Locally advanced unresectable NSCLC has conventionally been treated with concurrent chemoradiation. Though advances in treatment technology have improved the ability to deliver adequate treatment dose, the foundation for radiotherapy (RT) has remained the same since the 1980s. Since then, progressive studies have sought to establish the safety and efficacy of escalating radiation dose to loco-regional disease. Though RTOG 0617 did not produce the anticipated result, much interest remains in dose escalation and establishing an explanation for the findings of this study. Cetuximab was also not found to provide a survival benefit when applied to an unselected population. However, planned retrospective analysis suggests that those patients with high epidermal growth factor receptor (EGFR) expression may benefit, suggesting that cetuximab should be applied in a targeted fashion. We discuss the results of RTOG 0617 and additional findings from post-hoc analysis that suggest that dose escalation may be limited by normal tissue toxicity. We also present ongoing studies that aim to address potential causes for mortality in the dose escalation arm through adaptive or proton therapy, and are also leveraging additional concurrent systemic agents such as tyrosine kinase inhibitors (TKIs) for EGFR-activating mutations or EML4-ALK rearrangements, and poly (ADP-ribose) polymerase (PARP) inhibitors.

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

    Directory of Open Access Journals (Sweden)

    Janet S. Richmond

    2012-04-01

    Full Text Available 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 deescalated 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 deescalation.’’ [West J Emerg Med. 2012;13(1:17–25.

  3. De-escalation empirical antibiotic therapy improved survival for patients with severe aplastic anemia treated with antithymocyte globulin.

    Science.gov (United States)

    Fu, Rong; Chen, Tong; Song, Jia; Wang, Guojin; Li, Lijuan; Ruan, Erbao; Liu, Hui; Wang, Yihao; Wang, Huaquan; Xing, Limin; Wu, Yuhong; Liu, Hong; Qu, Wen; Shao, Zonghong

    2017-02-01

    We aimed to investigate the efficacy and safety of de-escalation empirical therapy for controlling infection in patients with severe aplastic anaemia (SAA) treated with antithymocyte globulin (ATG). Eighty-seven ATG-treated SAA patients who had microbiological culture-confirmed infections from 2006 to 2015 in our center were retrospectively analyzed. The efficacy of de-escalation and non-de-escalation therapy was compared. Among all 87 patients, 63 patients were treated with de-escalation therapy and 24 patients with non-de-escalation therapy. More patients showed response to anti-infection treatment in de-escalation group than in non-de-escalation group both on day 7 (60.32% vs. 25.00%, P = 0.003) and on day 30 (79.37% vs. 58.33%, P = 0.047) since the initial antimicrobial therapy. On day 30, more patients had increased absolute neutrophil count in de-escalation group compared with non-de-escalation group (76.19% vs. 45.83%, P = 0.007), and de-escalation group had lower morality rate (17.46% vs. 37.50%, P = 0.047) and better survival outcome (P = 0.023) on day 90. Twenty-three patients in de-escalation group and 5 patients in non-escalation group received granulocyte transfusions. Granulocyte transfusions helped to control infections in both de-escalation group (P = 0.027) and non-de-escalation group (P = 0.042) on day 7, but did not improve survival on day 90. We concluded that de-escalation antibiotics improved survival in SAA patients after ATG treatment. Early administration of broad-spectrum antibiotics pending microbiological cultures combined with a commitment to change to narrow-spectrum antibiotics should be recommended for controlling infections in SAA patients treated with ATG. Granulocyte transfusions might be an adjunctive therapy in controlling infections.

  4. Inhomogeneous dose escalation increases expected local control for NSCLC patients with lymph node involvement without increased mean lung dose

    DEFF Research Database (Denmark)

    Nielsen, Tine B; Hansen, Olfred; Schytte, Tine;

    2014-01-01

    in mediastinum, and the thorax wall. The dose was escalated using a TCP model implemented into the planning system. The difference in TCP values between the homogeneous and inhomogeneous plans were evaluated using two different TCP models. RESULTS: Dose escalation was possible for all patients. TCP values based...

  5. A Co-operative Inquiry Into Generating, Describing, and Transforming Knowledge About De-escalation Practices in Mental Health Settings

    DEFF Research Database (Denmark)

    Berring, Lene Lauge; Hummelvoll, Jan Kåre; Pedersen, Liselotte

    2016-01-01

    De-escalation is concerned with managing violent behaviour without resorting to coercive measures. Co-operative Inquiry provided the conceptual basis for generating knowledge regarding de-escalation practices in acute mental health care settings. The research included service users and staff...

  6. Some Take the Glass Escalator, Some Hit the Glass Ceiling? Career Consequences of Occupational Sex Segregation.

    Science.gov (United States)

    Hultin, Mia

    2003-01-01

    Analysis of Swedish longitudinal data (1,535 men, 1,584 women) showed that men in female-dominated occupations have substantially better internal promotion opportunities than equally qualified women. In male-dominated occupations, men and women have equal internal promotion chances. Results suggest a "glass escalator" advantage for men…

  7. Deterrence Without Escalation:A Case for the Arctic in 2040

    Science.gov (United States)

    2015-04-08

    and dangerous weather conditions, which make traditional power projection methods less effective. Furthermore, the distances in the Arctic are vast...AIR COMMAND AND STAFF COLLEGE AIR UNIVERSITY Deterrence Without Escalation: A Case for the Arctic in 2040 by Erik Carlson, Maj...1 2. The Arctic in 2040

  8. Temporal Aspects of Moral Disengagement in School Bullying: Crystallization or Escalation?

    Science.gov (United States)

    Obermann, Marie-Louise

    2013-01-01

    This study investigated the stability and change in bullying behavior and their relation to increases and decreases in moral disengagement, specifically exploring whether crystallization and escalation of disengagement occur. Within a 1-year span, two sets of data were collected. A total of 567 sixth to eighth graders participated in both data…

  9. 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

  10. Response Acquisition and Fixed-Ratio Escalation Based on Interresponse Times in Rats

    Science.gov (United States)

    Taylor, Tracy G.; Galuska, Chad M.; Banna, Kelly; Yahyavi-Firouz-Abadi, Noushin; See, Ronald E.

    2010-01-01

    The effectiveness of a fixed-ratio (FR) escalation procedure, developed by Pinkston and Branch (2004) and based on interresponse times (IRTs), was assessed during lever-press acquisition. Forty-nine experimentally naive adult male Long Evans rats were deprived of food for 24 hr prior to an extended acquisition session. Before the start of the…

  11. Army Support of Military Cyberspace Operations: Joint Contexts and Global Escalation Implications

    Science.gov (United States)

    2015-01-01

    updated deterrence strategy incorporating ACD and cyber offence . Richard Kugler posits that U.S. nuclear deterrence worked because it was credible...cyberspace force roles in escalation and deterrence requires a holistic consideration of environmental influences. As Ronald Deibert notes, “Securing

  12. Some Take the Glass Escalator, Some Hit the Glass Ceiling? Career Consequences of Occupational Sex Segregation.

    Science.gov (United States)

    Hultin, Mia

    2003-01-01

    Analysis of Swedish longitudinal data (1,535 men, 1,584 women) showed that men in female-dominated occupations have substantially better internal promotion opportunities than equally qualified women. In male-dominated occupations, men and women have equal internal promotion chances. Results suggest a "glass escalator" advantage for men…

  13. North Korea’s Provocation and Escalation Calculus: Dealing with the Kim Jong-un Regime

    Science.gov (United States)

    2015-08-01

    level” provocations while minimizing risks of potential rapid conflict escalation remains a central dilemma as was demonstrated in the reaction to North...Korean summit because of Seoul’s attempts to “depolitize” the event by keeping it purely at “the artistic, athletic, and cultural ” level. This was

  14. Brain Inflammation in an Infant With Hemimegalencephaly, Escalating Seizures, and Epileptic Encephalopathy

    OpenAIRE

    Kim, Se Hee; Millichap, John J.; Koh, Sookyong

    2016-01-01

    Hemimegalencephaly, a congenital brain malformation typically characterized by enlargement of one hemisphere, is frequently associated with intractable epilepsy. The authors report a case of a 12-month-old girl with hemimegalencephaly who underwent semiurgent hemispherectomy because of rapidly escalating seizures, arrested development, and associated encephalopathy. The brain tissue was examined and evaluated for neuroinflammation. Immunohistochemical analysis of the brain tissue revealed the...

  15. A Dynamical Tool to Study the Cultural Context of Conflict Escalation

    Science.gov (United States)

    2009-07-13

    advancing here is aimedt,. at identifying naturally occurrin se uences in escala . n d ’. . ,., time controlling for cultural conditions which couJd...escalation of provocation by a colleague at work, & om a relatively mild disagreement ("Your colleague criticizes your work") to open confrontation and

  16. Siding and other reactions to a conflict: A theory of escalation toward outsiders

    NARCIS (Netherlands)

    Van de Vliert, E

    1981-01-01

    Siding in a dyadic conflict is important because it precipitates escalation. Nevertheless, little is known about how and why a nonprofessional outsider (P) reacts when a conflict party puts him under pressure to take sides. Coalition and role conflict theories suggest four behavior alternatives (tak

  17. 18 CFR Table 1 to Part 301 - Functionalization and Escalation Codes

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Functionalization and Escalation Codes 1 Table 1 to Part 301 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS FOR FEDERAL POWER MARKETING ADMINISTRATIONS AVERAGE SYSTEM...

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

    Science.gov (United States)

    Bergström, Johan; Dekker, Sidney; Nyce, James M; Amer-Wåhlin, Isis

    2012-06-15

    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. 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. 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.

  19. Impact of antibiotic de-escalation on clinical outcomes in community-acquired pneumococcal pneumonia.

    Science.gov (United States)

    Viasus, Diego; Simonetti, Antonella F; Garcia-Vidal, Carolina; Niubó, Jordi; Dorca, Jordi; Carratalà, Jordi

    2017-02-01

    Although antibiotic de-escalation is regarded as a measure that reduces selection pressure, adverse drug effects and costs, evidence supporting this practice in community-acquired pneumococcal pneumonia (CAPP) is lacking. We carried out a retrospective analysis of prospectively collected data of a cohort of hospitalized adults with CAPP. Pneumococcal aetiology was established in patients with one or more positive cultures for Streptococcus pneumoniae obtained from blood, sterile fluids or sputum, and/or a positive urinary antigen test. De-escalation therapy was considered when the initial antibiotic therapy was narrowed to penicillin, amoxicillin or amoxicillin/clavulanate within the first 72 h after admission. The primary outcomes were 30 day mortality and length of hospital stay (LOS). Adjustment for confounders was performed with multivariate and propensity score analyses. Of 1410 episodes of CAPP, antibiotic de-escalation within the first 72 h after admission was performed in 166 cases. After adjustment, antibiotic de-escalation was not associated with a higher risk of mortality (OR = 0.83, 95% CI = 0.24-2.81), but it was found to be a protective factor for prolonged LOS (above the median) (OR = 0.46, 95% CI = 0.30-0.70). Similar results were found in patients classified into high-risk pneumonia severity index classes (IV-V), those with clinical instability and those with bacteraemia. No significant differences were documented in adverse drug reactions or readmission (Antibiotic de-escalation seems to be safe and effective in reducing the duration of LOS, and did not adversely affect outcomes of patients with CAPP, even those with bacteraemia and severe disease, and those who were clinically unstable. © The Author 2016. 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.

  20. 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

  1. Dose escalation in permanent brachytherapy for prostate cancer: dosimetric and biological considerations

    Energy Technology Data Exchange (ETDEWEB)

    Li, X Allen [Department of Radiation Oncology, University of Maryland, School of Medicine, 22 South Greene Street, Baltimore, MD 21201-1595 (United States); Wang, Jian Z [Department of Radiation Oncology, University of Maryland, School of Medicine, 22 South Greene Street, Baltimore, MD 21201-1595 (United States); Stewart, Robert D [School of Health Sciences, Purdue University, West Lafayette, IN 47907-1338 (United States); Di Biase, Steven J [Department of Radiation Oncology, University of Maryland, School of Medicine, 22 South Greene Street, Baltimore, MD 21201-1595 (United States)

    2003-09-07

    No prospective dose escalation study for prostate brachytherapy (PB) with permanent implants has been reported. In this work, we have performed a dosimetric and biological analysis to explore the implications of dose escalation in PB using {sup 125}I and {sup 103}Pd implants. The concept of equivalent uniform dose (EUD), proposed originally for external-beam radiotherapy (EBRT), is applied to low dose rate brachytherapy. For a given {sup 125}I or {sup 103}Pd PB, the EUD for tumour that corresponds to a dose distribution delivered by EBRT is calculated based on the linear quadratic model. The EUD calculation is based on the dose volume histogram (DVH) obtained retrospectively from representative actual patient data. Tumour control probabilities (TCPs) are also determined in order to compare the relative effectiveness of different dose levels. The EUD for normal tissue is computed using the Lyman model. A commercial inverse treatment planning algorithm is used to investigate the feasibility of escalating the dose to prostate with acceptable dose increases in the rectum and urethra. The dosimetric calculation is performed for five representative patients with different prostate sizes. A series of PB dose levels are considered for each patient using {sup 125}I and {sup 103}Pd seeds. It is found that the PB prescribed doses (minimum peripheral dose) that give an equivalent EBRT dose of 64.8, 70.2, 75.6 and 81 Gy with a fraction size of 1.8 Gy are 129, 139, 150 and 161 Gy for {sup 125}I and 103, 112, 122 and 132 Gy for {sup 103}Pd implants, respectively. Estimates of the EUD and TCP for a series of possible prescribed dose levels (e.g., 145, 160, 170 and 180 Gy for {sup 125}I and 125, 135, 145 and 155 for {sup 103}Pd implants) are tabulated. The EUD calculation was found to depend strongly on DVHs and radiobiological parameters. The dosimetric calculations suggest that the dose to prostate can be escalated without a substantial increase in both rectal and urethral dose

  2. Antipsychotic dose escalation as a trigger for Neuroleptic Malignant Syndrome (NMS: literature review and case series report

    Directory of Open Access Journals (Sweden)

    Langan Julie

    2012-11-01

    Full Text Available Abstract Background “Neuroleptic malignant syndrome” (NMS is a potentially fatal idiosyncratic reaction to any medication which affects the central dopaminergic system. Between 0.5% and 1% of patients exposed to antipsychotics develop the condition. Mortality rates may be as high as 55% and many risk factors have been reported. Although rapid escalation of antipsychotic dose is thought to be an important risk factor, to date it has not been the focus of a published case series or scientifically defined. Description We aimed to identify cases of NMS and review risk factors for its development with a particular focus on rapid dose escalation in the 30 days prior to onset. A review of the literature on rapid dose escalation was undertaken and a pragmatic definition of “rapid dose escalation” was made. NMS cases were defined using DSM-IV criteria and systematically identified within a secondary care mental health service. A ratio of titration rate was calculated for each NMS patient and “rapid escalators” and “non rapid escalators” were compared. 13 cases of NMS were identified. A progressive mean dose increase 15 days prior to the confirmed episode of NMS was observed (241.7 mg/day during days 1–15 to 346.9 mg/day during days 16–30 and the mean ratio of dose escalation for NMS patients was 1.4. Rapid dose escalation was seen in 5/13 cases and non rapid escalators had markedly higher daily cumulative antipsychotic dose compared to rapid escalators. Conclusions Rapid dose escalation occurred in less than half of this case series (n = 5, 38.5%, although there is currently no consensus on the precise definition of rapid dose escalation. Cumulative antipsychotic dose – alongside other known risk factors - may also be important in the development of NMS.

  3. Coping with Violence in Mental Health Care Settings: Patient and Staff Member Perspectives on De-escalation Practices.

    Science.gov (United States)

    Berring, Lene Lauge; Pedersen, Liselotte; Buus, Niels

    2016-10-01

    This multiple case study explored de-escalation processes in threatening and violent situations based on patients and staff members perspectives. Our post hoc analysis indicated that de-escalation included responsive interactions influenced by the perspectives of both patients and staff members. We assembled their perspectives in a mental model consisting of three interdependent stages: (1) memories and hope, (2) safety and creativity and (3) reflective moments. The data indicated that both patients and staff strived for peaceful solutions and that a dynamic and sociological understanding of de-escalation can foster shared problem solving in violent and threatening situations.

  4. Safety and efficacy of flexible-dose fesoterodine in British subjects with overactive bladder: insights into factors associated with dose escalation.

    Science.gov (United States)

    Cardozo, Linda; Hall, Timothy; Ryan, John; Ebel Bitoun, Caty; Kausar, Imran; Darekar, Amanda; Wagg, Adrian

    2012-11-01

    This study evaluated the efficacy and safety of flexible-dose fesoterodine and factors associated with dose escalation in subjects with overactive bladder (OAB). In this 12-week, open-label study, 331 adults with OAB symptoms for ≥3 months, ≥8 micturitions and ≥3 urgency episodes per 24 h and who reported at least "some moderate" bladder-related problems were treated with fesoterodine 4 mg once daily for 4 weeks, with the option to escalate to 8 mg for the remaining 8 weeks based on discussion of efficacy and tolerability with the investigator. Factors influencing dose escalation were identified using stepwise logistic regression. Efficacy was assessed via 3-day bladder diaries and patient-reported outcomes. Of the subjects, 59 % dose escalated at week 4; 93 % of escalators cited insufficient clinical response. The decision to escalate was most often made by the subject (alone or with the investigator). Improvements from baseline were observed in diary and patient-reported outcomes at weeks 4 and 12. Smaller improvements in micturition frequency and worse bladder-related problems at week 4 were significantly associated with increased likelihood of dose escalation; baseline micturition frequency, age, sex, body mass index, antimuscarinic-associated adverse events and OAB symptom duration were not. Non-escalators had greater improvement from baseline to week 4 than escalators; by week 12, improvement was similar among escalators and non-escalators. Fesoterodine was well tolerated. Treatment with flexible-dose fesoterodine improved bladder diary and patient-reported outcomes. Lower clinical response was related to dose escalation; after escalation, response in escalators approached that of non-escalators.

  5. Preventing and De-Escalating Ethical Conflict: A Communication-Training Mediation Model.

    Science.gov (United States)

    Levin, Tomer T; Parker, Patricia A

    2015-01-01

    While ethical conflicts in the provision of healthcare are common, the current third-party mediator model is limited by a lack of expert ethical mediators, who are often not on site when conflict escalates. In order to improve clinical outcomes in situations such as conflicts at the end of life, we suggest that clinicians-physicians, nurses and social workers-be trained to prevent and de-escalate emerging conflicts. This can be achieved using a mediation model framed by a communication-training approach. A case example is presented and the model is discussed. The implication of this preventative/early intervention model for improving clinical outcomes, in particular end-of life conflict, is considered.

  6. The two faces of conscientiousness: duty and achievement striving in escalation of commitment dilemmas.

    Science.gov (United States)

    Moon, H

    2001-06-01

    The author proposes that 2 facets of conscientiousness, duty and achievement striving, affect decision makers in escalation of commitment dilemmas in opposing ways, thus masking the predictive ability of a broad measure of conscientiousness. It is proposed that duty is associated with an other-centered orientation and that achievement striving is associated with a self-centered orientation. Analyses of decisions from 360 respondents showed that duty was associated with a deescalation of commitment, achievement striving was associated with an escalation of commitment, and the broad measure of conscientiousness was unassociated with commitment. The author advocates the utility of understanding potential self-centered versus other-centered aspects of the criterion of interest when conducting personality-based research.

  7. Use of pagers with an alarm escalation system to reduce cardiac monitor alarm signals.

    Science.gov (United States)

    Cvach, Maria M; Frank, Robert J; Doyle, Pete; Stevens, Zeina Khouri

    2014-01-01

    Alarm fatigue desensitizes nurses to alarm signals and presents potential for patient harm. This project describes an innovative method of communicating cardiac monitor alarms to pagers using an alarm escalation algorithm. This innovation was tested on 2 surgical progressive care units over a 6-month period. There was a significant decrease in mean frequency and duration of high-priority monitor alarms and improvement in nurses' perception of alarm response time, using this method of alarm communication.

  8. 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.

  9. Choosing between stairs and escalators in China: The impact of location, height and pedestrian volume

    Directory of Open Access Journals (Sweden)

    John Zacharias

    2015-01-01

    Conclusion: Separating stairs and escalator is effective in increasing stair climbing in Beijing, accounting for 29% of the variance in stair climbing, compared with 43% in Montreal. As in the Montreal case, distance has less effect on stair use rate when descending. Overall, 25.4% of Beijingers opted for stairs when ascending compared with 20.3% of Montrealers, and for descending 32.8% and 31.1% respectively.

  10. Cognitive Targeting: A Coercive Air Power Theory for Conventional Escalation Control Against Nuclear Armed Adversaries

    Science.gov (United States)

    2016-06-01

    COGNITIVE TARGETING: A COERCIVE AIR POWER THEORY FOR CONVENTIONAL ESCALATION CONTROL AGAINST NUCLEAR- ARMED ADVERSARIES BY PAUL A. GOOSSEN, MAJ...process with both critical analysis and with encouragement. Most importantly, I want to express my most sincere appreciation to my family. Their love...regional powers such as North Korea, the post-Cold War geo-political environment characterized by U.S. hegemony is fading away. In the emerging

  11. Dose-Escalated Robotic SBRT for Stage I–II Prostate Cancer

    OpenAIRE

    Meier, Robert

    2015-01-01

    Stereotactic body radiotherapy (SBRT) is the precise external delivery of very high-dose radiotherapy to targets in the body, with treatment completed in one to five fractions. SBRT should be an ideal approach for organ-confined prostate cancer because (I) dose-escalation should yield improved rates of cancer control; (II) the unique radiobiology of prostate cancer favors hypofractionation; and (III) the conformal nature of SBRT minimizes high-dose radiation delivery to immediately adjacent o...

  12. Dose-Escalated Robotic SBRT for Stage I-II Prostate Cancer

    OpenAIRE

    Robert eMeier

    2015-01-01

    Abstract: Stereotactic body radiotherapy (SBRT) is the precise external delivery of very high-dose radiotherapy to targets in the body, with treatment completed in one to five fractions. SBRT should be an ideal approach for organ-confined prostate cancer because (I) dose escalation should yield improved rates of cancer control; (II) the unique radiobiology of prostate cancer favors hypofractionation and (III) the conformal nature of SBRT minimizes high-dose radiation delivery to immediately a...

  13. Strategy Escalation: An emerging paradigm for safe clinical development of T cell gene therapies

    Directory of Open Access Journals (Sweden)

    Junghans Richard

    2010-06-01

    Full Text Available Abstract Gene therapy techniques are being applied to modify T cells with chimeric antigen receptors (CARs for therapeutic ends. The versatility of this platform has spawned multiple options for their application with new permutations in strategies continually being invented, a testimony to the creative energies of many investigators. The field is rapidly expanding with immense potential for impact against diverse cancers. But this rapid expansion, like the Big Bang, comes with a somewhat chaotic evolution of its therapeutic universe that can also be dangerous, as seen by recently publicized deaths. Time-honored methods for new drug testing embodied in Dose Escalation that were suitable for traditional inert agents are now inadequate for these novel "living drugs". In the following, I propose an approach to escalating risk for patient exposures with these new immuno-gene therapy agents, termed Strategy Escalation, that accounts for the molecular and biological features of the modified cells and the methods of their administration. This proposal is offered not as a prescriptive but as a discussion framework that investigators may wish to consider in configuring their intended clinical applications.

  14. Escalating doses of donor lymphocytes for incipient graft rejection following SCT for thalassemia.

    Science.gov (United States)

    Frugnoli, I; Cappelli, B; Chiesa, R; Biral, E; Noè, A; Evangelio, C; Fossati, M; Napolitano, S; Ciceri, F; Roncarolo, M G; Marktel, S

    2010-06-01

    Mixed chimerism (MC) and secondary graft failure are frequent events following SCT for thalassemia. There is limited information regarding the outcome of donor lymphocyte infusion (DLI) to prevent rejection, mainly from case reports describing only successful cases. We describe a series of seven children affected by beta-thalassemia treated with escalating doses of DLI for level 2-3 MC (donor<90%) following myeloablative SCT from a matched family donor. The infusions were safe and no acute or chronic GVHD were documented; five patients experienced neutropenia and thrombocytopenia resolving spontaneously. DLI was successful in converting to full donor chimerism two patients stratified in the low-risk class (Pesaro class II). Conversely, for five high-risk patients, DLI was not effective in preventing secondary graft failure. This limited series suggests that escalating doses of DLI are safe in thalassemia patients post myeloablative therapy but efficacy may be jeopardized by rapidly growing anti-donor alloimmunity in high-risk patients. We suggest giving escalating doses of donor T cells to attempt a graft-versus-thalassemia as soon as level 2-3 MC is detected.

  15. Mucosal healing in inflammatory bowel disease: Maintain orde-escalate therapy

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    In the past decade, thanks to the introduction of biologictherapies, a new therapeutic goal, mucosal healing(MH), has been introduced. MH is the expression of anarrest of disease progression, resulting in minor hospitalizations,surgeries, and prolonged clinical remission.MH may be achieved with several therapeutic strategiesreaching success rates up to 80% for both, ulcerativecolitis (UC) and Crohn's disease (CD). Various scoringsystems for UC and for the transmural CD, have beenproposed to standardize the definition of MH. Severalattempts have been undertaken to de-escalate therapyonce MH is achieved, thus, reducing the risk of adverseevents. In this review, we analysed the available studiesregarding the achievement of MH and the subsequenttreatment de-escalation according to disease typeand administered therapy, together with non-invasivemarkers proposed as predictors for relapse. The availabledata are not encouraging since de-escalation after theachievement of MH is followed by a high number ofclinical relapses reaching up to 50% within one year.Unclear is also another question, in case of combinationtherapies, which drug is more appropriate to stop, inorder to guarantee a durable remission. Predictorsof unfavourable outcome such as disease extension,perianal disease, or early onset disease appear to beinadequate to foresee behaviour of disease. Furtherstudies are warranted to investigate the role of histologichealing for the further course of disease.

  16. Ion Elevators and Escalators in Multilevel Structures for Lossless Ion Manipulations.

    Science.gov (United States)

    Ibrahim, Yehia M; Hamid, Ahmed M; Cox, Jonathan T; Garimella, Sandilya V B; Smith, Richard D

    2017-02-07

    We describe two approaches based upon ion "elevator" and "escalator" components that allow moving ions to different levels in structures for lossless ion manipulations (SLIM). Guided by ion motion simulations, we designed elevator and escalator components based upon ion current measurements providing essentially lossless transmission in multilevel designs. The ion elevator design allowed ions to efficiently bridge a 4 mm gap between levels. The component was integrated in a SLIM and coupled to a QTOF mass spectrometer using an ion funnel interface to evaluate the m/z range transmitted as compared to transmission within a level (e.g., in a linear section). The analysis of singly charged ions of m/z 600-2700 produced similar mass spectra for both elevator and straight (linear motion) components. In the ion escalator design, traveling waves (TW) were utilized to transport ions efficiently between two SLIM levels. Ion current measurements and ion mobility (IM) spectrometry analysis illustrated that ions can be transported between TW-SLIM levels with no significant loss of either ions or IM resolution. These developments provide a path for the development of multilevel designs providing, e.g., much longer IM path lengths, more compact designs, and the implementation of much more complex SLIM devices in which, e.g., different levels may operate at different temperatures or with different gases.

  17. Macroevolutionary patterns of glucosinolate defense and tests of defense-escalation and resource availability hypotheses.

    Science.gov (United States)

    Cacho, N Ivalú; Kliebenstein, Daniel J; Strauss, Sharon Y

    2015-11-01

    We explored macroevolutionary patterns of plant chemical defense in Streptanthus (Brassicaceae), tested for evolutionary escalation of defense, as predicted by Ehrlich and Raven's plant-herbivore coevolutionary arms-race hypothesis, and tested whether species inhabiting low-resource or harsh environments invest more in defense, as predicted by the resource availability hypothesis (RAH). We conducted phylogenetically explicit analyses using glucosinolate profiles, soil nutrient analyses, and microhabitat bareness estimates across 30 species of Streptanthus inhabiting varied environments and soils. We found weak to moderate phylogenetic signal in glucosinolate classes and no signal in total glucosinolate production; a trend toward evolutionary de-escalation in the numbers and diversity of glucosinolates, accompanied by an evolutionary increase in the proportion of aliphatic glucosinolates; some support for the RAH relative to soil macronutrients, but not relative to serpentine soil use; and that the number of glucosinolates increases with microhabitat bareness, which is associated with increased herbivory and drought. Weak phylogenetic signal in chemical defense has been observed in other plant systems. A more holistic approach incorporating other forms of defense might be necessary to confidently reject escalation of defense. That defense increases with microhabitat bareness supports the hypothesis that habitat bareness is an underappreciated selective force on plants in harsh environments.

  18. Terrorist attacks escalate in frequency and fatalities preceding highly lethal attacks.

    Directory of Open Access Journals (Sweden)

    Andy Martens

    Full Text Available Highly lethal terrorist attacks, which we define as those killing 21 or more people, account for 50% of the total number of people killed in all terrorist attacks combined, yet comprise only 3.5% of terrorist attacks. Given the disproportionate influence of these incidents, uncovering systematic patterns in attacks that precede and anticipate these highly lethal attacks may be of value for understanding attacks that exact a heavy toll on life. Here we examined whether the activity of terrorist groups escalates--both in the number of people killed per attack and in the frequency of attacks--leading up to highly lethal attacks. Analyses of terrorist attacks drawn from a state-of-the-art international terrorism database (The Global Terrorism Database showed evidence for both types of escalation leading up to highly lethal attacks, though complexities to the patterns emerged as well. These patterns of escalation do not emerge among terrorist groups that never commit a highly lethal attack.

  19. Impact of de-escalation of beta-lactam antibiotics on the emergence of antibiotic resistance in ICU patients: a retrospective observational study.

    Science.gov (United States)

    De Bus, Liesbet; Denys, Wouter; Catteeuw, Julie; Gadeyne, Bram; Vermeulen, Karel; Boelens, Jerina; Claeys, Geert; De Waele, Jan J; Decruyenaere, Johan; Depuydt, Pieter O

    2016-06-01

    Antibiotic de-escalation is promoted to limit prolonged exposure to broad-spectrum antibiotics, but proof that it prevents the emergence of resistance is lacking. We evaluated determinants of antibiotic de-escalation in an attempt to assess whether the latter is associated with a lower emergence of antimicrobial resistance. Antibiotic treatments, starting with empirical beta-lactam prescriptions, were prospectively documented during 2013 and 2014 in a tertiary intensive care unit (ICU) and categorized as continuation, de-escalation or escalation of the empirical antimicrobial treatment. Determinants of the de-escalation or escalation treatments were identified by multivariate logistic regression; the continuation category was used as the reference group. Using systematically collected diagnostic and surveillance cultures, we estimated the cumulative incidence of antimicrobial resistance following de-escalation or continuation of therapy, with adjustment for ICU discharge and death as competing risks. Of 478 anti-pseudomonal antibiotic prescriptions, 42 (9 %) were classified as escalation of the antimicrobial treatment and 121 (25 %) were classified as de-escalation, mainly through replacement of the originally prescribed antibiotics with those having a narrower spectrum. In multivariate analysis, de-escalation was associated with the identification of etiologic pathogens (p antibiotic course in the ICU in de-escalated versus continued prescriptions was 8 (range 6-10) versus 5 (range 4-7) days, respectively (p resistance to the initial beta-lactam antibiotic on day 14 were 30.6 and 23.5 % for de-escalation and continuation, respectively (p = 0.22). For the selection of multi-drug resistant pathogens, these values were 23.5 (de-escalation) and 18.6 % (continuation) respectively (p = 0.35). The emergence of antibiotic-resistant bacteria after exposure to anti-pseudomonal beta-lactam antibiotics was not lower following de-escalation.

  20. Escalating polypharmacy.

    Science.gov (United States)

    Gorard, D A

    2006-11-01

    New drug treatments, new indications for older drug treatments, lower thresholds for treating risk factors in preventative medicine, and an ageing population acquiring multiple pathologies all contribute to the development of polypharmacy. Longitudinal studies document the rise in prescribed medications, particularly in the elderly. The potential dangers of adverse drug reactions and interactions, poor adherence and confusion associated with ever-increasing polypharmacy are likely to worsen. Strategies to reduce prescribing will obviously decrease the dangers of polypharmacy. These include more considered prescribing when contemplating additions to patients' already lengthy prescription lists, and external reviews of medicine lists by a doctor or pharmacist. Despite such strategies, polypharmacy seems inevitable and considerations must be given to simplifying patients' multiple drug administrations using single-daily-dose regimens, fixed-dose combination pills, calendar-blister packaging and pill organizers.

  1. Action semantics modulate action prediction.

    Science.gov (United States)

    Springer, Anne; Prinz, Wolfgang

    2010-11-01

    Previous studies have demonstrated that action prediction involves an internal action simulation that runs time-locked to the real action. The present study replicates and extends these findings by indicating a real-time simulation process (Graf et al., 2007), which can be differentiated from a similarity-based evaluation of internal action representations. Moreover, results showed that action semantics modulate action prediction accuracy. The semantic effect was specified by the processing of action verbs and concrete nouns (Experiment 1) and, more specifically, by the dynamics described by action verbs (Experiment 2) and the speed described by the verbs (e.g., "to catch" vs. "to grasp" vs. "to stretch"; Experiment 3). These results propose a linkage between action simulation and action semantics as two yet unrelated domains, a view that coincides with a recent notion of a close link between motor processes and the understanding of action language.

  2. 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.

  3. 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.

  4. 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.

  5. Impact of dose escalation and adaptive radiotherapy for cervical cancers on tumour shrinkage—a modelling study

    Science.gov (United States)

    Røthe Arnesen, Marius; Paulsen Hellebust, Taran; Malinen, Eirik

    2017-03-01

    Tumour shrinkage occurs during fractionated radiotherapy and is regulated by radiation induced cellular damage, repopulation of viable cells and clearance of dead cells. In some cases additional tumour shrinkage during external beam therapy may be beneficial, particularly for locally advanced cervical cancer where a small tumour volume may simplify and improve brachytherapy. In the current work, a mathematical tumour model is utilized to investigate how local dose escalation affects tumour shrinkage, focusing on implications for brachytherapy. The iterative two-compartment model is based upon linear-quadratic radiation response, a doubling time for viable cells and a half-time for clearance of dead cells. The model was individually fitted to clinical tumour volume data from fractionated radiotherapy of 25 cervical cancer patients. Three different fractionation patterns for dose escalation, all with an additional dose of 12.2 Gy, were simulated and compared to standard fractionation in terms of tumour shrinkage. An adaptive strategy where dose escalation was initiated after one week of treatment was also considered. For 22 out of 25 patients, a good model fit was achieved to the observed tumour shrinkage. A large degree of inter-patient variation was seen in predicted volume reduction following dose escalation. For the 10 best responding patients, a mean tumour volume reduction of 34  ±  3% (relative to standard treatment) was estimated at the time of brachytherapy. Timing of initiating dose escalation had a larger impact than the number of fractions applied. In conclusion, the model was found useful in evaluating the impact from dose escalation on tumour shrinkage. The results indicate that dose escalation could be conducted from the start of external beam radiotherapy in order to obtain additional tumour shrinkage before brachytherapy.

  6. Successful pregnancy outcome in paroxysmal nocturnal hemoglobinuria (PNH following escalated eculizumab dosing to control breakthrough hemolysis

    Directory of Open Access Journals (Sweden)

    Ruby Sharma

    2015-01-01

    Full Text Available Pregnancy in women with paroxysmal nocturnal hemoglobinuria (PNH is associated with increased maternal and fetal morbidity and mortality. There is limited published experience regarding therapy of PNH during pregnancy. We describe a case of a 30 year old female with hypoplastic myelodysplastic syndrome and PNH. After two years of treatment with eculizumab, she became pregnant. She developed breakthrough hemolysis at 20 weeks gestation. Pharmacokinetic and pharmacodynamic studies demonstrated a subtherapeutic eculizumab level with absence of complement blockade. Escalation of her eculizumab dose successfully controlled hemolysis and restored therapeutic eculizumab level and activity. She delivered a healthy baby at 36 weeks.

  7. Stop the escalators: using the built environment to increase usual daily activity

    OpenAIRE

    Westfall, Jack

    2010-01-01

    John M Westfall, Doug H FernaldDepartment of Family Medicine, University of Colorado Denver, Aurora, CO, USABackground: Obesity is an epidemic in the United States. Two-thirds of the population is overweight and does not get enough exercise. Eastern cities are full of escalators that transport obese Americans to and from the subway. Walking stairs is a moderate activity requiring 3–6 metabolic equivalent tasks (METS) and burning 3.5–7 kcal/min. We determined the caloric ex...

  8. Brain Inflammation in an Infant With Hemimegalencephaly, Escalating Seizures, and Epileptic Encephalopathy.

    Science.gov (United States)

    Kim, Se Hee; Millichap, John J; Koh, Sookyong

    2016-01-01

    Hemimegalencephaly, a congenital brain malformation typically characterized by enlargement of one hemisphere, is frequently associated with intractable epilepsy. The authors report a case of a 12-month-old girl with hemimegalencephaly who underwent semiurgent hemispherectomy because of rapidly escalating seizures, arrested development, and associated encephalopathy. The brain tissue was examined and evaluated for neuroinflammation. Immunohistochemical analysis of the brain tissue revealed the presence of abundant activated CD68-positive microglia and reactive astrogliosis. Detection of active inflammatory changes in the brain of a patient with hemimegalencephaly complicated by intractable epilepsy suggests a potential role of ongoing brain inflammation in seizure exacerbation and epileptic encephalopathy.

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

    Energy Technology Data Exchange (ETDEWEB)

    Bush, K; Holcombe, C; Kapp, D; Buyyounouski, M; Hancock, S; Xing, L; Atwood, T; King, M [Department of Radiation Oncology, Stanford School of Medicine, Stanford, CA (United States)

    2014-06-15

    Purpose: Radiation-therapy dose-escalation beyond 80Gy may improve tumor control rates for patients with localized prostate cancer. Since toxicity remains a concern, treatment planners must achieve dose-escalation while still adhering to dose-constraints for surrounding structures. Patientmatching is a machine-learning technique that identifies prior patients that dosimetrically match DVH parameters of target volumes and critical structures prior to actual treatment planning. We evaluated the feasibility of patient-matching in (1)identifying candidates for safe dose-escalation; and (2)improving DVH parameters for critical structures in actual dose-escalated plans. Methods: We analyzed DVH parameters from 319 historical treatment plans to determine which plans could achieve dose-escalation (8640cGy) without exceeding Zelefsky dose-constraints (rectal and bladder V47Gy<53%, and V75.6Gy<30%, max-point dose to rectum of 8550cGy, max dose to PTV< 9504cGy). We then estimated the percentage of cases that could achieve safe dose-escalation using software that enables patient matching (QuickMatch, Siris Medical, Mountain View, CA). We then replanned a case that had violated DVH constraints with DVH parameters from patient matching, in order to determine whether this previously unacceptable plan could be made eligible with this automated technique. Results: Patient-matching improved the percentage of patients eligible for dose-escalation from 40% to 63% (p=4.7e-4, t-test). Using a commercial optimizer augmented with patient-matching, we demonstrated a case where patient-matching improved the toxicity-profile such that dose-escalation would have been possible; this plan was rapidly achieved using patientmatching software. In this patient, all lower-dose constraints were met with both the denovo and patient-matching plan. In the patient-matching plan, maximum dose to the rectum was 8385cGy, while the denovo plan failed to meet the maximum rectal constraint at 8571c

  10. Toxicity-dependent feasibility bounds for the escalation with overdose control approach in phase I cancer trials.

    Science.gov (United States)

    Wheeler, Graham M; Sweeting, Michael J; Mander, Adrian P

    2017-03-15

    Phase I trials of anti-cancer therapies aim to identify a maximum tolerated dose (MTD), defined as the dose that causes unacceptable toxicity in a target proportion of patients. Both rule-based and model-based methods have been proposed for MTD recommendation. The escalation with overdose control (EWOC) approach is a model-based design where the dose assigned to the next patient is one that, given all available data, has a posterior probability of exceeding the MTD equal to a pre-specified value known as the feasibility bound. The aim is to conservatively dose-escalate and approach the MTD, avoiding severe overdosing early on in a trial. The EWOC approach has been applied in practice with the feasibility bound either fixed or varying throughout a trial, yet some of the methods may recommend incoherent dose-escalation, that is, an increase in dose after observing severe toxicity at the current dose. We present examples where varying feasibility bounds have been used in practice, and propose a toxicity-dependent feasibility bound approach that guarantees coherent dose-escalation and incorporates the desirable features of other EWOC approaches. We show via detailed simulation studies that the toxicity-dependent feasibility bound approach provides improved MTD recommendation properties to the original EWOC approach for both discrete and continuous doses across most dose-toxicity scenarios, with comparable performance to other approaches without recommending incoherent dose escalation. © 2017 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

  11. Daily-diary Evaluated Side Effects of Dose-escalation Radiotherapy of Prostate Cancer Using the Stereotactic Beamcath Technique

    Energy Technology Data Exchange (ETDEWEB)

    Fransson, Per; Bergstroem, Per; Loefroth, Per-Olov; Franzen, Lars; Henriksson, Roger; Widmark, Anders [Umeaa Univ. (Sweden). Dept. of Radiation Sciences

    2003-06-01

    The aim of this study was to evaluate self-assessed late side effects in patients with prostate cancer treated with frameless stereotactic dose-escalation radiotherapy using BeamCath, a new technique that has been developed for accurate positioning of the prostate at treatment set-up, and in which a specially designed urethral catheter containing high-density fiducial markers is used. The method was tested in the first 104 patients in a Scandinavian dose-escalation study with doses up to 76 Gy. Side effects were reported in a daily diary and evaluated at the start of treatment (baseline) and at 1-year follow-up. The patients were compared with those treated with conventional (n=53) and conformal techniques (n=175). Dose-escalation radiotherapy (76 Gy) decreased urinary frequency, urgency and starting problems at 1-year in comparison with baseline. The dose-escalation therapy did not induce any increase in gastrointestinal side effects in comparison with the effect of conformal therapy h70 Gy at the 1-year follow-up, apart from a slight increase in rectal mucus in the 76 Gy group. All groups, except patients receiving the 74 Gy with smaller fields, reported a slight increase in gastrointestinal toxicity at 1-year compared with baseline. Dose-escalation radiotherapy of prostate cancer using the BeamCath technique did not induce any significant increase in late side effects in comparison with conformal technique.

  12. 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.

  13. Chronic CRF1 receptor blockade reduces heroin intake escalation and dependence-induced hyperalgesia.

    Science.gov (United States)

    Park, Paula E; Schlosburg, Joel E; Vendruscolo, Leandro F; Schulteis, Gery; Edwards, Scott; Koob, George F

    2015-03-01

    Opioids represent effective drugs for the relief of pain, yet chronic opioid use often leads to a state of increased sensitivity to pain that is exacerbated during withdrawal. A sensitization of pain-related negative affect has been hypothesized to closely interact with addiction mechanisms. Neuro-adaptive changes occur as a consequence of excessive opioid exposure, including a recruitment of corticotropin-releasing factor (CRF) and norepinephrine (NE) brain stress systems. To better understand the mechanisms underlying the transition to dependence, we determined the effects of functional antagonism within these two systems on hyperalgesia-like behavior during heroin withdrawal utilizing models of both acute and chronic dependence. We found that passive or self-administered heroin produced a significant mechanical hypersensitivity. During acute opioid dependence, systemic administration of the CRF1 receptor antagonist MPZP (20 mg/kg) alleviated withdrawal-induced mechanical hypersensitivity. In contrast, several functional adrenergic system antagonists (clonidine, prazosin, propranolol) failed to alter mechanical hypersensitivity in this state. We then determined the effects of chronic MPZP or clonidine treatment on extended access heroin self-administration and found that MPZP, but not clonidine, attenuated escalation of heroin intake, whereas both drugs alleviated chronic dependence-associated hyperalgesia. These findings suggest that an early potentiation of CRF signaling occurs following opioid exposure that begins to drive both opioid-induced hyperalgesia and eventually intake escalation.

  14. 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.

  15. 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).

  16. Ion Elevators and Escalators in Multilevel Structures for Lossless Ion Manipulations

    Energy Technology Data Exchange (ETDEWEB)

    Ibrahim, Yehia M.; Hamid, Ahmed M.; Cox, Jonathan T.; Garimella, Sandilya V. B.; Smith, Richard D.

    2017-01-19

    We describe two approaches based upon ion ‘elevator’ and ‘escalator’ components that allow moving ions to different levels in structures for lossless ion manipulations (SLIM). Guided by ion motion simulations we designed elevator and escalator components providing essentially lossless transmission in multi-level designs based upon ion current measurements. The ion elevator design allowed ions to efficiently bridge a 4 mm gap between levels. The component was integrated in a SLIM and coupled to a QTOF mass spectrometer using an ion funnel interface to evaluate the m/z range transmitted as compared to transmission within a level (e.g. in a linear section). Mass spectra for singly-charged ions of m/z 600-2700 produced similar mass spectra for both elevator and straight (linear motion) components. In the ion escalator design, traveling waves (TW) were utilized to transport ions efficiently between two SLIM levels. Ion current measurements and ion mobility (IM) spectrometry analysis illustrated that ions can be transported between TW-SLIM levels with no significant loss of either ions or IM resolution. These developments provide a path for the development of multilevel designs providing e.g. much longer IM path lengths, more compact designs, and the implementation of much more complex SLIM devices in which e.g. different levels may operate at different temperatures or with different gases.

  17. Escalation with Overdose Control is More Efficient and Safer than Accelerated Titration for Dose Finding

    Directory of Open Access Journals (Sweden)

    André Rogatko

    2015-07-01

    Full Text Available The standard 3 + 3 or “modified Fibonacci” up-and-down (MF-UD method of dose escalation is by far the most used design in dose-finding cancer trials. However, MF-UD has always shown inferior performance when compared with its competitors regarding number of patients treated at optimal doses. A consequence of using less effective designs is that more patients are treated with doses outside the therapeutic window. In June 2012, the U S Food and Drug Administration (FDA rejected the proposal to use Escalation with Overdose Control (EWOC, an established dose-finding method which has been extensively used in FDA-approved first in human trials and imposed a variation of the MF-UD, known as accelerated titration (AT design. This event motivated us to perform an extensive simulation study comparing the operating characteristics of AT and EWOC. We show that the AT design has poor operating characteristics relative to three versions of EWOC under several practical scenarios. From the clinical investigator’s perspective, lower bias and mean square error make EWOC designs preferable than AT designs without compromising safety. From a patient’s perspective, uniformly higher proportion of patients receiving doses within an optimal range of the true MTD makes EWOC designs preferable than AT designs.

  18. 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.

  19. Terrorist Attacks Escalate in Frequency and Fatalities Preceding Highly Lethal Attacks

    Science.gov (United States)

    Martens, Andy; Sainudiin, Raazesh; Sibley, Chris G.; Schimel, Jeff; Webber, David

    2014-01-01

    Highly lethal terrorist attacks, which we define as those killing 21 or more people, account for 50% of the total number of people killed in all terrorist attacks combined, yet comprise only 3.5% of terrorist attacks. Given the disproportionate influence of these incidents, uncovering systematic patterns in attacks that precede and anticipate these highly lethal attacks may be of value for understanding attacks that exact a heavy toll on life. Here we examined whether the activity of terrorist groups escalates–both in the number of people killed per attack and in the frequency of attacks–leading up to highly lethal attacks. Analyses of terrorist attacks drawn from a state-of-the-art international terrorism database (The Global Terrorism Database) showed evidence for both types of escalation leading up to highly lethal attacks, though complexities to the patterns emerged as well. These patterns of escalation do not emerge among terrorist groups that never commit a highly lethal attack. PMID:24755753

  20. Dose escalation study of rhenium-186 hydroxyethylidene diphosphonate in patients with metastatic prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Klerk, J.M.H. de (Dept. of Nuclear Medicine, Univ. Hospital, Utrecht (Netherlands)); Zonnenberg, B.A. (Oncology Section, Dept. of Internal Medicine, Univ. Hospital, Utrecht (Netherlands)); Schip, A.D. van het (Dept. of Nuclear Medicine, Univ. Hospital, Utrecht (Netherlands)); Dijk, A. van (Center for Hospital Pharmacy, Univ. Hospital, Utrecht (Netherlands)); Han, S.H. (Dept. of Nuclear Medicine, Univ. Hospital, Utrecht (Netherlands)); Quirijnen, J.M.S.P. (Dept. of Nuclear Medicine, Univ. Hospital, Utrecht (Netherlands)); Blijham, G.H. (Oncology Section, Dept. of Internal Medicine, Univ. Hospital, Utrecht (Netherlands)); Rijk, P.P. van (Dept. of Nuclear Medicine, Univ. Hospital, Utrecht (Netherlands))

    1994-10-01

    Rhenium-186 hydroxyethylidene diphosphonate ([sup 186]Re-HEDP) has been used for the palliative treatment of metastatic bone pain. A phase 1 dose escalation study was performed using [sup 186]Re-HEDP. Twenty-four patients with hormone-resistant prostate cancer entered the study. Each patient had at least four bone metastases and adequate haematological function. Groups of at least three consecutive patients were treated with doses starting at 1295 MBq and increasing to 3515 MBq (escalated in increments of 555 MBq). Thrombocytopenia proved to be the dose-limiting toxicity, while leucopenia played a minor role. Early death occurred in one patient (10 days after administration) without clear relationship to the [sup 186]Re-HEDP therapy. Transient neurological dysfunction was seen in two cases. Two patients who received 3515 MBq [sup 186]Re-HEDP showed grade 3 toxicity (thrombocytes 25-50 x 10[sup 9]/l), defined as unacceptable toxicity. After treatment alkaline phosphatase levels showed a transient decrease in all patients (mean: 26% [+-] 10% IU/l; range: 11%-44%). Prostate-specific antigen values showed a decline in eight patients, preceded by a temporary increase in three patients. From this study we conclude that the maximally tolerated dose of [sup 186]Re-HEDP is 2960 MBq. A placebo-controlled comparative study on the efficacy of [sup 186]Re-HEDP has been initiated. (orig.)

  1. [Changes in the cytokine network through escalating SIRS after heart surgery].

    Science.gov (United States)

    Sablotzki, A; Mann, V; Simm, A; Czeslick, E

    2001-09-01

    Changes in the Cytokine Network Through Escalating SIRS After Heart Surgery. Cardiopulmonary bypass is associated with an injury that may cause pathophysiological changes in form of systemic inflammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS). There is a lot of information about the immunologic alterations in patients undergoing cardiopulmonary bypass, but only little is known about the expression of cytokines in patients with severe SIRS or MODS following cardiovascular surgery. In the present study, we investigated the inflammatory response of patients with an escalating SIRS following open heart surgery. Plasma levels of cytokines (IL-1beta, IL-6, IL-8, IL-10, IL-12, IL-18, GM-CSF and TGF-beta) were measured at the first four postoperative days in 12 adult male patients with severe SIRS (SIRS-group), and 15 patients with uncomplicated course (control-group) following myocardial revascularization. All cytokines (except IL-1beta) were significantly elevated in SIRS-patients, the analysis of differences between the survivors and non-survivors within the SIRS-group showed dramatically elevated levels of IL-8 and IL-18 in non-survivors. From the results of our investigation we can conclude that monitoring of immunologic parameters, e.g. IL-8 and/or IL-18 may be helpful for the early detection and prognosis of high-risk patients with severe SIRS and MODS following cardiac surgery.

  2. Action physics

    Science.gov (United States)

    McGinness, Lachlan P.; Savage, C. M.

    2016-09-01

    More than a decade ago, Edwin Taylor issued a "call to action" that presented the case for basing introductory university mechanics teaching around the principle of stationary action [E. F. Taylor, Am. J. Phys. 71, 423-425 (2003)]. We report on our response to that call in the form of an investigation of the teaching and learning of the stationary action formulation of physics in a first-year university course. Our action physics instruction proceeded from the many-paths approach to quantum physics to ray optics, classical mechanics, and relativity. Despite the challenges presented by action physics, students reported it to be accessible, interesting, motivational, and valuable.

  3. Complementary Actions

    Directory of Open Access Journals (Sweden)

    Luisa eSartori

    2015-05-01

    Full Text Available Complementary colors are color pairs which, when combined in the right proportions, produce white or black. Complementary actions refer here to forms of social interaction wherein individuals adapt their joint actions according to a common aim. Notably, complementary actions are incongruent actions. But being incongruent is not sufficient to be complementary (i.e., to complete the action of another person. Successful complementary interactions are founded on the abilities: (i to simulate another person’s movements, (ii to predict another person’s future action/s, (iii to produce an appropriate incongruent response which differ, while interacting, with observed ones, and (iv to complete the social interaction by integrating the predicted effects of one’s own action with those of another person. This definition clearly alludes to the functional importance of complementary actions in the perception–action cycle and prompts us to scrutinize what is taking place behind the scenes. Preliminary data on this topic have been provided by recent cutting-edge studies utilizing different research methods. This mini-review aims to provide an up-to-date overview of the processes and the specific activations underlying complementary actions.

  4. Biological dose escalation and hypofractionation: what is there to be gained and how will it best be done?

    Science.gov (United States)

    Tree, A C; Alexander, E J; Van As, N J; Dearnaley, D P; Khoo, V

    2013-08-01

    The evidence supporting dose escalation for localised prostate cancer is widely accepted, but in tandem with improvements in biochemical control, dose escalation increases side-effects. In a scenario where most patients achieve control of their cancer, quality of life concerns predominate. Here we examine the biological ways in which an effective dose can be escalated without an unacceptable increase in toxicity. Possible avenues include exploiting the unusual radiobiology of prostate cancer by hypofractionation, the use of image guidance, adaptive planning and prostate motion management. We await with anticipation the results of large randomised trials of hypofractionation, moderate and profound, to establish whether we can further improve the balance between cure and quality of life.

  5. 自动扶梯金属结构测试探讨%Discussion on Escalator Metal Structural Test

    Institute of Scientific and Technical Information of China (English)

    陈卫红

    2011-01-01

    结合自动扶梯金属结构的挠度测试标准,通过一个测试实例探讨了自动扶梯金属结构的测试过程;利用桁架有限元模型对自动扶梯结构变形量较大的点进行局部挠度计算,计算结果证明符合客户合同的要求。%Combined with the deflection test standard of escalator metal structure, the escalator metal structural test process is discussed through a test case. The local deflection for the larger points of deformation of the escalator structure is calculated by use of the finite element model of truss, The results meet customer contract requirements.

  6. Escalation to Major Depressive Disorder among adolescents with subthreshold depressive symptoms: evidence of distinct subgroups at risk.

    Science.gov (United States)

    Hill, Ryan M; Pettit, Jeremy W; Lewinsohn, Peter M; Seeley, John R; Klein, Daniel N

    2014-04-01

    The presence of subthreshold depressive symptoms (SubD) in adolescence is associated with high prospective risk of developing Major Depressive Disorder (MDD). Little is known about variables that predict escalation from SubD to MDD. This study used a longitudinal prospective design in a community sample of adolescents to identify combinations of risk factors that predicted escalation from SubD to MDD. Classification tree analysis was used to identify combinations of risk factors that improved the sensitivity and specificity of prediction of MDD onset among 424 adolescents with a lifetime history of SubD. Of the 424, 144 developed MDD during the follow-up period. Evidence for multiple subgroups was found: among adolescents with poor friend support, the highest risk of escalation was among participants with lifetime histories of an anxiety or substance use disorder. Among adolescents with high friend support, those reporting multiple major life events in the past year or with a history of an anxiety disorder were at highest risk of escalation. Study findings may not inform prevention efforts for individuals who first develop SubD during adulthood. This study did not examine the temporal ordering of predictors involved in escalation from SubD to MDD. Adolescents with a history of SubD were at highest risk of escalation to MDD in the presence of poor friend support and an anxiety or substance use disorder, or in the presence of better friend support, multiple major life events, and an anxiety disorder. Findings may inform case identification approaches for adolescent depression prevention programs. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Validation of Treatment Escalation as a Definition of Atopic Eczema Flares

    Science.gov (United States)

    Thomas, Kim S.; Stuart, Beth; O’Leary, Caroline J.; Schmitt, Jochen; Paul, Carle; Williams, Hywel C.; Langan, Sinead

    2015-01-01

    Background 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. Objective 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). Methods 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. Results 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). Conclusion 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. Trial registration Current Controlled Trials ISRCTN71423189 (Study A

  8. Factors associated with dose escalation of fesoterodine for treatment of overactive bladder in people >65 years of age: A post hoc analysis of data from the SOFIA study.

    Science.gov (United States)

    Wagg, Adrian; Darekar, Amanda; Arumi, Daniel; Khullar, Vik; Oelke, Matthias

    2015-06-01

    To investigate factors which may influence dose escalation of antimuscarinics for overactive bladder (OAB) in older patients and how dose escalation affects treatment efficacy. A post hoc analysis of data from the 12-week randomized, placebo controlled phase of the SOFIA study investigating treatment with fesoterodine in older people with OAB. Predictors and outcomes in patients aged ≥65 years with OAB who did or did not choose to escalate from fesoterodine 4 to 8 mg before the first dose-escalation choice point (week 4) and at the end of the study (week 12) were assessed. Variables which significantly increased likelihood of dose escalation were, at baseline, body mass index (OR: 1.06, 95% CI 1.01, 1.12; P = 0.0222), and male gender (OR: 2.06, 95% CI 1.28, 3.32; P = 0.0028) and at week 4, change from baseline in urgency episodes (OR: 1.12, 95% CI 1.05, 1.20; P = 0.0008), patient perception of bladder control (PPBC) (OR: 1.44, 95% CI 1.12, 1.84; P = 0.004). At week 12, dose escalation was associated with slightly reduced treatment outcomes compared to week 4 non-escalators. No baseline disease related factor associated with dose escalation was identified. Magnitude of change in urgency episodes and reduction in PPBC at 4 weeks were associated with dose escalation. These data may be of use to healthcare providers as they allow judgement to be made in individual patients, allowing treatment decisions to be made. At end of treatment, improvements in efficacy and quality of life were achieved in both escalators and non-escalators. © 2014 Wiley Periodicals, Inc.

  9. Can naturopathy provide answers to the escalating health care costs in India?

    Science.gov (United States)

    Tripathy, Jaya Prasad

    2015-01-01

    There are substantial areas of overlap between naturopathy and public health, which include a focus on health rather than disease, a preventive approach, and an emphasis on health promotion and health education. Public health can look to naturopathy for answers to the emergence of chronic disease through natural therapies, many of which can take the role of primordial and primary prevention of several diseases. Some selected naturopathic therapies include nutrition, hydrotherapy, fasting therapy, yoga, behavioral therapy, and health promotion. We must reorient our focus on prevention and wellness to make a true impact on escalating health care costs. With the National Health Policy in India emphasizing the need for integrating the Indian Systems of Medicines with modern medicine, now is the right time for naturopathy and public health to come together to provide a holistic health care system. PMID:26151012

  10. Can naturopathy provide answers to the escalating health care costs in India?

    Directory of Open Access Journals (Sweden)

    Jaya Prasad Tripathy

    2015-04-01

    Full Text Available There are substantial areas of overlap between naturopathy and public health, which include a focus on health rather than disease, a preventive approach, and an emphasis on health promotion and health education. Public health can look to naturopathy for answers to the emergence of chronic disease through natural therapies, many of which can take the role of primordial and primary prevention of several diseases. Some selected naturopathic therapies include nutrition, hydrotherapy, fasting therapy, yoga, behavioral therapy, and health promotion. We must reorient our focus on prevention and wellness to make a true impact on escalating health care costs. With the National Health Policy in India emphasizing the need for integrating the Indian Systems of Medicines with modern medicine, now is the right time for naturopathy and public health to come together to provide a holistic health care system.

  11. 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

  12. The snowball effect: friendship moderates escalations in depressed affect among avoidant and excluded children.

    Science.gov (United States)

    Bukowski, William M; Laursen, Brett; Hoza, Betsy

    2010-11-01

    A three-wave longitudinal study conducted with preadolescent boys and girls (N = 231 at Time 1 [T1]) was used to assess the hypotheses that aspects of social withdrawal would be predictors of a "snowball" cascade of depressed affect, and that friendship experiences would moderate these effects. Consistent with these hypotheses, multilevel modeling showed that measures of avoidance and exclusion at T1 were associated with concurrent levels of depressed affect and were antecedent to escalating trajectories of depressed affect over time. These accelerating growth curves fit a snowball cascade model. The analyses also showed the protective effects of friendship. Specifically, the snowball effect was limited to avoidant and excluded children who were friendless. Depressed affect did not increase among avoidant and excluded children who were friended.

  13. The butterfly plant arms-race escalated by gene and genome duplications.

    Science.gov (United States)

    Edger, Patrick P; Heidel-Fischer, Hanna M; Bekaert, Michaël; Rota, Jadranka; Glöckner, Gernot; Platts, Adrian E; Heckel, David G; Der, Joshua P; Wafula, Eric K; Tang, Michelle; Hofberger, Johannes A; Smithson, Ann; Hall, Jocelyn C; Blanchette, Matthieu; Bureau, Thomas E; Wright, Stephen I; dePamphilis, Claude W; Eric Schranz, M; Barker, Michael S; Conant, Gavin C; Wahlberg, Niklas; Vogel, Heiko; Pires, J Chris; Wheat, Christopher W

    2015-07-07

    Coevolutionary interactions are thought to have spurred the evolution of key innovations and driven the diversification of much of life on Earth. However, the genetic and evolutionary basis of the innovations that facilitate such interactions remains poorly understood. We examined the coevolutionary interactions between plants (Brassicales) and butterflies (Pieridae), and uncovered evidence for an escalating evolutionary arms-race. Although gradual changes in trait complexity appear to have been facilitated by allelic turnover, key innovations are associated with gene and genome duplications. Furthermore, we show that the origins of both chemical defenses and of molecular counter adaptations were associated with shifts in diversification rates during the arms-race. These findings provide an important connection between the origins of biodiversity, coevolution, and the role of gene and genome duplications as a substrate for novel traits.

  14. Escalation, timing and severity of insurgent and terrorist events: Toward a unified theory of future threats

    CERN Document Server

    Johnson, Neil F

    2011-01-01

    I present a unified discussion of several recently published results concerning the escalation, timing and severity of violent events in human conflicts and global terrorism, and set them in the wider context of real-world and cyber-based collective violence and illicit activity. I point out how the borders distinguishing between such activities are becoming increasingly blurred in practice -- from insurgency, terrorism, criminal gangs and cyberwars, through to the 2011 Arab Spring uprisings and London riots. I review the robust empirical patterns that have been found, and summarize a minimal mechanistic model which can explain these patterns. I also explain why this mechanistic approach, which is inspired by non-equilibrium statistical physics, fits naturally within the framework of recent ideas within the social science literature concerning analytical sociology. In passing, I flag the fundamental flaws in each of the recent critiques which have surfaced concerning the robustness of these results and the re...

  15. Vaginal dose de-escalation in image guided adaptive brachytherapy for locally advanced cervical cancer.

    Science.gov (United States)

    Mohamed, Sandy; Lindegaard, Jacob Christian; de Leeuw, Astrid A C; Jürgenliemk-Schulz, Ina; Kirchheiner, Kathrin; Kirisits, Christian; Pötter, Richard; Tanderup, Kari

    2016-09-01

    Vaginal stenosis is a major problem following radiotherapy in cervical cancer. We investigated a new dose planning strategy for vaginal dose de-escalation (VDD). Fifty consecutive locally advanced cervical cancer patients without lower or middle vaginal involvement at diagnosis from 3 institutions were analysed. External beam radiotherapy was combined with MRI-guided brachytherapy. VDD was obtained by decreasing dwell times in ovoid/ring and increasing dwell times in tandem/needles. The aim was to maintain the target dose (D90 of HR-CTV⩾85Gy EQD2) while reducing the dose to the surface of the vagina to vaginal loading (ovoid/ring) was reduced from 51% to 33% of the total loading with VDD, which significantly reduced the dose to the vaginal dose points (pvaginal point was reduced by a mean of 4±4Gy EQD2 (pvaginal stenosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Standardization of lyophilization medium for Streptococcus thermophilus subjected to viability escalation on freeze drying

    Directory of Open Access Journals (Sweden)

    Rohit Sharma

    2014-09-01

    Full Text Available The objective of the present study is to develop a lyophilization medium for Streptococcus thermophilus (NCIM 2904 as the industrial exploitation of this bacterium totally depends upon preservation and lyophilization protocols. Protective effect of 18 compounds were observed individually and in combinations with different sugars, sugar alcohols, polymers, protein concentrates and buffers. Among all the protectants tested, ammonium citrate (1% w/w, K2HPO4 (1% w/w and KH2PO4 (1% w/w provided lowest protection to these bacterial cells while 10% (w/w sodium caseinate, whey protein concentrate, sweet whey powder, and skim milk showed significant results in viability escalation. Survival in carbon sources like lactose, sucrose and maltodextrine was also favored maximally. Combination of sodium caseinate 10%, skim milk 5%, sucrose 5%, lactose 5% and mono sodium glutamate 1% in distilled water in ratio of 1:5 with S. thermophilus showed survival percentage of 96%.

  17. 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.

  18. Radiation Therapy Dose Escalation for Glioblastoma Multiforme in the Era of Temozolomide

    Energy Technology Data Exchange (ETDEWEB)

    Badiyan, Shahed N.; Markovina, Stephanie; Simpson, Joseph R.; Robinson, Clifford G.; DeWees, Todd [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Tran, David D.; Linette, Gerry [Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri (United States); Jalalizadeh, Rohan [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Dacey, Ralph; Rich, Keith M.; Chicoine, Michael R.; Dowling, Joshua L.; Leuthardt, Eric C.; Zipfel, Gregory J.; Kim, Albert H. [Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri (United States); Huang, Jiayi, E-mail: jhuang@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

    2014-11-15

    Purpose: To review clinical outcomes of moderate dose escalation using high-dose radiation therapy (HDRT) in the setting of concurrent temozolomide (TMZ) in patients with newly diagnosed glioblastoma multiforme (GBM), compared with standard-dose radiation therapy (SDRT). Methods and Materials: Adult patients aged <70 years with biopsy-proven GBM were treated with SDRT (60 Gy at 2 Gy per fraction) or with HDRT (>60 Gy) and TMZ from 2000 to 2012. Biological equivalent dose at 2-Gy fractions was calculated for the HDRT assuming an α/β ratio of 5.6 for GBM. Results: Eighty-one patients received SDRT, and 128 patients received HDRT with a median (range) biological equivalent dose at 2-Gy fractions of 64 Gy (61-76 Gy). Overall median follow-up time was 1.10 years, and for living patients it was 2.97 years. Actuarial 5-year overall survival (OS) and progression-free survival (PFS) rates for patients that received HDRT versus SDRT were 12.4% versus 13.2% (P=.71), and 5.6% versus 4.1% (P=.54), respectively. Age (P=.001) and gross total/near-total resection (GTR/NTR) (P=.001) were significantly associated with PFS on multivariate analysis. Younger age (P<.0001), GTR/NTR (P<.0001), and Karnofsky performance status ≥80 (P=.001) were associated with improved OS. On subset analyses, HDRT failed to improve PFS or OS for those aged <50 years or those who had GTR/NTR. Conclusion: Moderate radiation therapy dose escalation above 60 Gy with concurrent TMZ does not seem to improve clinical outcomes for patients with GBM.

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

    Energy Technology Data Exchange (ETDEWEB)

    Morganti, Alessio G.; Picardi, Vincenzo; Ippolito, Edy; Massaccesi, Mariangela; Macchia, Gabriella; Deodato, Francesco (Radiotherapy Unit, Dept. of Oncology, ' John Paul II' Center for High Technology Research and Education in Biomedical Sciences, Catholic Univ., Campobasso (Italy)), E-mail: gmacchia@rm.unicatt.it; Caravatta, Luciana; Tambaro, Rosa; Mignogna, Samantha (Palliative Therapies Unit, Dept. of Oncology, ' John Paul II' Center for High Technology Research and Education in Biomedical Sciences, Catholic Univ., Campobasso (Italy)); Cellini, Numa; Valentini, Vincenzo; Mattiucci, Gian Carlo (Dept. of Radiotherapy, Policlinico Universitario ' A. Gemelli' , Catholic Univ., Rome (Italy)); Di Lullo, Liberato (Dept. of Oncology, ' F. Veneziale' General Hospital, Isernia (Italy)); Giglio, Gianfranco (Dept. of Oncology, ' A. Cardarelli' General Hospital Campobasso (Italy)); Caprino, Paola; Sofo, Luigi (Surgery Unit, Dept. of Oncology, ' John Paul II' Center for High Technology Research and Education in Biomedical Sciences, Catholic Univ., Campobasso (Italy)); Ingrosso, Marcello (Endoscopy Unit, Dept. of Oncology, ' John Paul II' Center for High Technology Research and Education in Biomedical Sciences, Catholic Univ., Campobasso (Italy))

    2010-05-15

    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/m2. 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/m2) in patients with resected pancreatic carcinoma.

  20. Caspofungin dose escalation for invasive candidiasis due to resistant Candida albicans.

    Science.gov (United States)

    Wiederhold, Nathan P; Najvar, Laura K; Bocanegra, Rosie A; Kirkpatrick, William R; Patterson, Thomas F

    2011-07-01

    Previous in vivo studies have reported caspofungin dose escalation to be effective against Candida glabrata with reduced susceptibility. We hypothesized that higher doses of caspofungin would be effective against invasive candidiasis caused by the more virulent species Candida albicans, including isolates resistant to this echinocandin. Immunocompetent mice were inoculated with one of three C. albicans isolates, including one susceptible and two resistant isolates with different FKS1 hot spot 1 point mutations. Mice received daily caspofungin treatment for 7 days and were then followed off therapy for 2 weeks to assess survival. Kidney tissue and blood were collected, and fungal burden and serum (1 → 3)-β-D-glucan were measured. Significant differences in virulence were observed among the three C. albicans isolates, which translated into differences in responses to caspofungin. The most virulent of the resistant isolates studied (isolate 43001; Fks1p F641S) did not respond to caspofungin doses of up to 10 mg/kg of body weight, as there were no differences in survival (survival range, 0 to 12% with treatment), tissue burden, or (1 → 3)-β-D-glucan concentration compared to those for untreated controls. Higher doses of caspofungin did improve survival against the second resistant isolate (53264; Fks1p S645P) that demonstrated reduced virulence (5 and 10 mg/kg; 80% survival). In contrast, caspofungin doses as low as 1 mg/kg improved survival (85 to 95%) and reduced tissue burden and (1 → 3)-β-D-glucan concentration against the susceptible isolate (ATCC 90028). These data suggest that caspofungin dose escalation for invasive candidiasis may not be consistently effective against resistant C. albicans isolates, and this may be associated with the virulence of the strain.

  1. Strategy for stochastic dose-rate induced enhanced elimination of malignant tumour without dose escalation.

    Science.gov (United States)

    Paul, Subhadip; Roy, Prasun Kumar

    2016-09-01

    The efficacy of radiation therapy, a primary modality of cancer treatment, depends in general upon the total radiation dose administered to the tumour during the course of therapy. Nevertheless, the delivered radiation also irradiates normal tissues and dose escalation procedure often increases the elimination of normal tissue as well. In this article, we have developed theoretical frameworks under the premise of linear-quadratic-linear (LQL) model using stochastic differential equation and Jensen's inequality for exploring the possibility of attending to the two therapeutic performance objectives in contraposition-increasing the elimination of prostate tumour cells and enhancing the relative sparing of normal tissue in fractionated radiation therapy, within a prescribed limit of total radiation dose. Our study predicts that stochastic temporal modulation in radiation dose-rate appreciably enhances prostate tumour cell elimination, without needing dose escalation in radiation therapy. However, constant higher dose-rate can also enhance the elimination of tumour cells. In this context, we have shown that the sparing of normal tissue with stochastic dose-rate is considerably more than the sparing of normal tissue with the equivalent constant higher dose-rate. Further, by contrasting the stochastic dose-rate effects under LQL and linear-quadratic (LQ) models, we have also shown that the LQ model over-estimates stochastic dose-rate effect in tumour and under-estimates the stochastic dose-rate effect in normal tissue. Our study indicates the possibility of utilizing stochastic modulation of radiation dose-rate for designing enhanced radiation therapy protocol for cancer.

  2. Methylphenidate as a reinforcer for rats: contingent delivery and intake escalation.

    Science.gov (United States)

    Marusich, Julie A; Beckmann, Joshua S; Gipson, Cassandra D; Bardo, Michael T

    2010-06-01

    Methylphenidate (MPH) is one of the most widely prescribed drugs for treating attention-deficit hyperactivity disorder. Previous research suggested that MPH is a reinforcer for rats, but not all of the manipulations to show that lever pressing is controlled by the contingency to obtain MPH have been examined. In Experiment 1, responding for MPH on a progressive ratio (PR) schedule was assessed. Rats self-administered varying doses of MPH (0.056-1.0 mg/kg/infusion) on a PR schedule of reinforcement, and self-administered more MPH than saline, with maximal responding occurring at a unit dose of 0.56 mg/kg/infusion. Experiment 2 examined if there were differences in responding between contingent and noncontingent MPH (0.56 mg/kg/infusion) on a fixed ratio schedule of reinforcement. Results showed that rats responded for contingent MPH, and that responding was not maintained when MPH was delivered noncontingently. Experiment 3 examined self-administration of MPH (0.1 or 0.3 mg/kg/infusion) during long access (6 hr) compared to short access sessions (1 hr). Results showed that rats given long access to MPH showed an escalation of intake across sessions, with this escalation being more pronounced at the lower unit dose (0.1 mg/kg/infusion); in contrast, rats given short access to MPH did not show an increase in MPH self-administration across sessions at either MPH dose tested. Taken together, these results indicate that MPH is an effective intravenous reinforcer for rats and that, similar to other stimulants such as cocaine, amphetamine and methamphetamine, MPH is subject to abuse as reflected by dysregulated intake across repeated long access sessions.

  3. Dose escalation in patients receiving whole-brain radiotherapy for brain metastases from colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Heisterkamp, Christine; Rades, Dirk [Dept. of Radiation Oncology, Univ. Hospital Schleswig-Holstein, Luebeck (Germany); Haatanen, Tiina [Dept. of Radiation Oncology, Univ. Hospital Hamburg-Eppendorf, Hamburg (Germany); Schild, Steven E. [Dept. of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States)

    2010-02-15

    Background and Purpose: Whole-brain radiotherapy (WBRT) alone is the most common treatment for brain metastases from colorectal cancer, as most patients are not candidates for more aggressive therapies such as resection or radiosurgery. The standard WBRT regimen, 30 Gy in ten fractions (10 x 3 Gy), has generally resulted in poor outcomes. This study investigated whether an escalation of the WBRT dose improves these results. Patients and Methods: Data from 53 patients receiving WBRT alone for brain metastases from colorectal cancer were retrospectively analyzed. 10 x 3 Gy (n = 35) was compared to higher doses (40 Gy/20 fractions or 45 Gy/15 fractions; n = 18) for overall survival (OS) and local control (LC). Additional factors evaluated for prognostic importance included age, gender, performance status, number of metastases, and extracerebral metastases. Results: The OS rates at 6 months were 17% after 10 x 3 Gy and 50% after 20 x 2 Gy/15 x 3 Gy (p = 0.014). On multivariate analysis, improved OS was significantly associated with higher WBRT dose (p = 0.047), Karnofsky Performance Score (KPS) {>=} 70 (p = 0.034), less than four brain metastases (p = 0.036), and lack of extracerebral metastases (p = 0.010). The LC rates at 6 months were 17% after 10 x 3 Gy and 50% after higher doses (p = 0.018). On multivariate analysis of LC, higher WBRT dose was significant (p = 0.028). A trend was observed for KPS {>=} 70 (p = 0.08) and less than four brain metastases (p = 0.06). Conclusion: These data suggest that patients with brain metastases from colorectal cancer treated with WBRT alone appeared to benefit from escalation of the radiation dose beyond 10 x 3 Gy in terms of improved OS and LC. (orig.)

  4. The Role of Age on Dose Limiting Toxicities (DLTs) in Phase I Dose-escalation Trials

    Science.gov (United States)

    Schwandt, A; Harris, P. J.; Hunsberger, S.; Deleporte, A.; Smith, G. L.; Vulih, D.; Anderson, B. D.; Ivy, S. P.

    2016-01-01

    Purpose Elderly oncology patients are not enrolled in early phase trials in proportion to the numbers of geriatric patients with cancer. There may be concern that elderly patients will not tolerate investigational agents as well as younger patients resulting in a disproportionate number of dose-limiting toxicities (DLTs). Recent single-institution studies provide conflicting data on the relationship between age and DLT. Experimental Design We retrospectively reviewed data about patients treated on single-agent, dose-escalation, phase I clinical trials sponsored by the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute. Patients’ dose levels were described as percentage of maximum tolerated dose (%MTD), the highest dose level at which <33% of patients had a DLT, or recommended phase II dose (RP2D). Mixed-effect logistic regression models were used to analyze relationships between the probability of a DLT and age and other explanatory variables. Results Increasing dose, increasing age, and worsening performance status (PS) were significantly related to an increased probability of a DLT in this model (p<0.05). There was no association between dose level administered and age (p=0.57). Conclusions This analysis of phase I dose-escalation trials involving over 500 patients older than 70 years of age, is the largest reported. As age and dose level increased and PS worsened, the probability of a DLT increased. While increasing age was associated with occurrence of DLT, this risk remained within accepted thresholds of risk for phase I trials. There was no evidence of age bias on enrollment of patients on low or high dose levels. PMID:25028396

  5. Words of Violence: “Fear Speech,” or How Violent Conflict Escalation Relates to the Freedom of Expression

    NARCIS (Netherlands)

    Buyse, Antoine

    2014-01-01

    The limits of the freedom of expression are a perennial discussion in human rights discourse. This article focuses on identifying yardsticks to establish the boundaries of freedom of expression in cases where violence is a risk. It does so by using insights from the social sciences on the escalation

  6. 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

    , at escalating doses from 0.0004 to 20 mg/kg, with extension of therapy until disease progression for responding or stable patients receiving 0.09 mg/kg or higher doses. RESULTS: A total of 35 patients were enrolled. The most common adverse events were fatigue, pyrexia, headache, and nausea. Adverse events were...

  7. Words of Violence: “Fear Speech,” or How Violent Conflict Escalation Relates to the Freedom of Expression

    NARCIS (Netherlands)

    Buyse, Antoine

    2014-01-01

    The limits of the freedom of expression are a perennial discussion in human rights discourse. This article focuses on identifying yardsticks to establish the boundaries of freedom of expression in cases where violence is a risk. It does so by using insights from the social sciences on the escalation

  8. Listen to the patient. It frightens me. It's personal. Hurry.

    Science.gov (United States)

    Humphreys, G F

    2000-07-15

    What follows are the perceptions of two individuals--a patient and a highly respected medical oncologist who did not participate in the care of this patient but read the patient's essay. We encourage readers to share their thoughts about these essays in correspondence.

  9. How to Gamble If You're In a Hurry

    CERN Document Server

    Ekhad, Shalosh B; Zeilberger, Doron

    2011-01-01

    The beautiful theory of statistical gambling, started by Dubins and Savage (for subfair games) and continued by Kelly and Breiman (for superfair games) has mostly been studied under the unrealistic assumption that we live in a continuous world, that money is indefinitely divisible, and that our life is indefinitely long. Here we study these fascinating problems from a purely discrete, finitistic, and computational, viewpoint, using Both Symbol-Crunching and Number-Crunching (and simulation just for checking purposes).

  10. Host-parasite arms race in mutation modifications: indefinite escalation despite a heavy load?

    Science.gov (United States)

    Haraguchi, Y; Sasaki, A

    1996-11-21

    If constantly changing genotypes are favorable in host and parasite coevolution, an indefinite escalation of mutation rates would result despite heavy mutational loads. We theoretically study this possibility by examining the mutation modifier dynamics of host and parasite that engage in genotype-specific epidemiological interaction. In the first model, we study the evolutionarily stable (ESS) mutation rate or switching rate if two alleles in a single locus are subjected to frequency-dependent selection favoring the rarer of the two. Mutation modifier locus is either tightly linked or unlinked to the selected locus. Sufficiently strong frequency-dependent selection may cause cycles in allele frequencies and a modifier with higher mutation rate enjoys the long-term advantage by randomizing the genotype of their offspring. Through the repeated events of invasion and replacement of mutation modifiers, the mutation rate continues to increase until the allele frequencies are stabilized. If some fraction of mutations are deleterious, there is no longer a pure ESS mutation rate: the evolutionarily stable population then consists of multiple strains concerning mutation modifier, typically one with a very high mutation rate and the other with a very low rate, stably coexisting and fighting off invasion by any other modifiers. These results are almost independent of the linkage between the selected and the modifier loci. In the second model, we consider the joint evolution of host and parasite mutation modifiers, assuming that a specific pair of host and parasite genotype densities change following the Nicholson-Bailey type model. If there is no cost of deleterious mutations, mutation rates of both species are escalated indefinitely by modifier evolution until they completely suppress the fluctuation of genotype densities. However, a small cost of deleterious mutation is enough to collapse this coevolutionary equilibrium of inflated mutations. Typical coevolutionary outcome

  11. Avoidance orientation and the escalation of negative communication in intimate relationships.

    Science.gov (United States)

    Kuster, Monika; Bernecker, Katharina; Backes, Sabine; Brandstätter, Veronika; Nussbeck, Fridtjof W; Bradbury, Thomas N; Martin, Mike; Sutter-Stickel, Dorothee; Bodenmann, Guy

    2015-08-01

    Avoidance goals heighten the salience of negative social experiences, and in intimate relationships such an orientation may contribute to communication difficulties and the perpetuation of avoidance. We therefore hypothesized that individuals with stronger avoidance goals would be particularly prone to engage in escalating levels of negative communication with their intimate partner, and we tested this prediction by conducting sequential analyses on videotaped observational data (28,470 observations) collected from 365 heterosexual couples engaging in a relationship-related conflict. While less avoidance-oriented spouses showed a decline in their likelihood of negative communication over the course of the 8-min conflict discussion, the likelihood that more avoidance-oriented spouses would display negative communication behaviors remained at a high level. The likelihood of negative communication even increased when avoidance-oriented spouses were confronted with negative communication behavior of their partners. The effects of avoidance orientation were independent of relationship satisfaction and neuroticism. These findings demonstrate that avoidance goals underlie individuals' heightened reactivity to the partner's negative behavior, while also clarifying 1 possible reason why some individuals engage in communication behaviors that may prove maladaptive to their relationship. (c) 2015 APA, all rights reserved.

  12. Real Option Method and Escalation of Commitment in the Evaluation of Investment Projects

    Directory of Open Access Journals (Sweden)

    Mehrdad Karami

    2011-01-01

    Full Text Available Problem statement: This study applies an experimental method to find out whether using the real option method along with the discounted cash flow techniques can reduce the decision-makers’ Escalation of Commitment (EC hereafter or their desire to keep up their commitment to a failed project. Approach: The real option method used for the evaluation of long-term projects also measures the flexibility value which may be produced during the implementation of the project. Results: The results indicate that those who use the real option method show lower EC to a failed project than those who merely use the net present value method. Conclusion/Recommendations: The major conclusion might be that using the real option method in capital budgeting can affect the users’ behavior and decisions and lead to better decision-making in the long-term projects. In view of the fact that longterm investment projects are costly and time-consuming, a greater need is felt for better methods of evaluating such projects and, in consequence, researchers should also consider the other affective aspects of using real method options on the users' behavior and decisions.

  13. Dose-Escalated Robotic SBRT for Stage I-II Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Robert eMeier

    2015-04-01

    Full Text Available Abstract: Stereotactic body radiotherapy (SBRT is the precise external delivery of very high-dose radiotherapy to targets in the body, with treatment completed in one to five fractions. SBRT should be an ideal approach for organ-confined prostate cancer because (I dose escalation should yield improved rates of cancer control; (II the unique radiobiology of prostate cancer favors hypofractionation and (III the conformal nature of SBRT minimizes high-dose radiation delivery to immediately adjacent organs, potentially reducing complications. This approach is also more convenient for patients, and is cheaper than intensity modulated radiotherapy (IMRT. Several external beam platforms are capable of delivering SBRT for early-stage prostate cancer, although most of the mature reported series have employed a robotic non-coplanar platform (i.e., CyberKnife. Several large studies report 5-year biochemical relapse rates which compare favorably to IMRT. Rates of late GU toxicity are similar to those seen with IMRT, and rates of late rectal toxicity may be less than with IMRT and low dose rate (LDR brachytherapy. Patient-reported quality of life (QOL outcomes appear similar to IMRT in the urinary domain. Bowel QOL may be less adversely affected by SBRT than with other radiation modalities. After five years of follow-up, SBRT delivered on a robotic platform is yielding outcomes at least as favorable as IMRT, and may be considered appropriate therapy for stage I-II prostate cancer.

  14. 自动扶梯的历史%The History of the Escalator

    Institute of Scientific and Technical Information of China (English)

    David A.Cooper; 马英俊

    2000-01-01

    1859年,纳森·艾母兹发明了自动扶梯的第1个专利.这在当时是很超前的,因为第1台电动机是在19世纪70的年终逐出来的.在之后的80年代,西伯格、列诺、哈利、惠勒、道奇发展了自动扶梯这一事业.西伯格将elevatus(上升)和scale(梯级)合二为一创造出来自动扶梯(escalator)这一名词.那时,Otis公司是自司生产经营有冲突且是唯一有资格使用大写E开头拼写Escalator的公司.1911年,伦敦地铁安装了其第1台自动扶梯.自动扶梯迷人的历史从1859年发明以来延续至今.

  15. Biological equivalent dose studies for dose escalation in the stereotactic synchrotron radiation therapy clinical trials

    Energy Technology Data Exchange (ETDEWEB)

    Prezado, Y.; Fois, G.; Edouard, M.; Nemoz, C.; Renier, M.; Requardt, H.; Esteve, F.; Adam, JF.; Elleaume, H.; Bravin, A., E-mail: prezado@esrf.fr [ID17 Biomedical Beamline, European Synchrotron Radiation Facility (ESRF), 6 rue Jules Horowitz, BP 220, 38043 Grenoble Cedex (France)

    2009-03-15

    Synchrotron radiation is an innovative tool for the treatment of brain tumors. In the stereotactic synchrotron radiation therapy (SSRT) technique a radiation dose enhancement specific to the tumor is obtained. The tumor is loaded with a high atomic number (Z) element and it is irradiated in stereotactic conditions from several entrance angles. The aim of this work was to assess dosimetric properties of the SSRT for preparing clinical trials at the European Synchrotron Radiation Facility (ESRF). To estimate the possible risks, the doses received by the tumor and healthy tissues in the future clinical conditions have been calculated by using Monte Carlo simulations (PENELOPE code). The dose enhancement factors have been determined for different iodine concentrations in the tumor, several tumor positions, tumor sizes, and different beam sizes. A scheme for the dose escalation in the various phases of the clinical trials has been proposed. The biological equivalent doses and the normalized total doses received by the skull have been calculated in order to assure that the tolerance values are not reached.

  16. Incorporating a Patient Dichotomous Characteristic in Cancer Phase I Clinical Trials Using Escalation with Overdose Control

    Directory of Open Access Journals (Sweden)

    Mourad Tighiouart

    2012-01-01

    Full Text Available We describe a design for cancer phase I clinical trials that takes into account patients heterogeneity thought to be related to treatment susceptibility. The goal is to estimate the maximum tolerated dose (MTD given patient’s specific dichotomous covariate value. The design is Bayesian adaptive and is an extension of escalation with overdose control (EWOC. We will assess the performance of this method by comparing the following designs via extensive simulations: (1 design using a covariate; patients are accrued to the trial sequentially and the dose given to a patient depends on his/her baseline covariate value, (2 design ignoring the covariate; patients are accrued to the trial sequentially and the dose given to a patient does not depend on his/her baseline covariate value, and (3 design using separate trials; in each group, patients are accrued to the trial sequentially and EWOC is implemented in each group. These designs are compared with respect to safety of the trial and efficiency of the estimates of the MTDs via extensive simulations. We found that ignoring a significant baseline binary covariate in the model results in a substantial number of patients being overdosed. On the other hand, accounting for a nonsignificant covariate in the model has practically no effect on the safety of the trial and efficiency of the estimates of the MTDs.

  17. Importance of appropriate initial antibiotic therapy and de-escalation in the treatment of nosocomial pneumonia

    Directory of Open Access Journals (Sweden)

    J. Rello

    2007-08-01

    Full Text Available Inappropriate initial antibiotic therapy in nosocomial pneumonia is associated with higher mortality, longer hospital stays and increased healthcare costs. The key pathogens associated with these adverse outcomes include Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus and Acinetobacter baumannii. Due to the increasing rates of resistance, a new paradigm is needed for treating nosocomial infections in the intensive care unit (ICU. Optimal initial therapy consists of a broad-spectrum antibiotic started in a timely manner and administered at the correct dose and via the correct route. Because pathogen aetiology and resistance patterns vary from one ICU to another, recommendations for initial therapy should be tailored to each institution. Selection of the broad-spectrum antibiotic should be based on the patient's risk factors (including comorbidities, duration of ventilation and recent antibiotic exposure, suspected pathogen and up-to-date local resistance patterns. After 48–72 h, the patient should be reassessed and antibiotic therapy de-escalated based on the microbiological results and the clinical response.

  18. The influence of toxicity constraints in models of chemotherapeutic protocol escalation

    KAUST Repository

    Boston, E. A. J.

    2011-04-06

    The prospect of exploiting mathematical and computational models to gain insight into the influence of scheduling on cancer chemotherapeutic effectiveness is increasingly being considered. However, the question of whether such models are robust to the inclusion of additional tumour biology is relatively unexplored. In this paper, we consider a common strategy for improving protocol scheduling that has foundations in mathematical modelling, namely the concept of dose densification, whereby rest phases between drug administrations are reduced. To maintain a manageable scope in our studies, we focus on a single cell cycle phase-specific agent with uncomplicated pharmacokinetics, as motivated by 5-Fluorouracil-based adjuvant treatments of liver micrometastases. In particular, we explore predictions of the effectiveness of dose densification and other escalations of the protocol scheduling when the influence of toxicity constraints, cell cycle phase specificity and the evolution of drug resistance are all represented within the modelling. For our specific focus, we observe that the cell cycle and toxicity should not simply be neglected in modelling studies. Our explorations also reveal the prediction that dose densification is often, but not universally, effective. Furthermore, adjustments in the duration of drug administrations are predicted to be important, especially when dose densification in isolation does not yield improvements in protocol outcomes. © The author 2011. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

  19. Dose-Escalated Robotic SBRT for Stage I-II Prostate Cancer.

    Science.gov (United States)

    Meier, Robert

    2015-01-01

    Stereotactic body radiotherapy (SBRT) is the precise external delivery of very high-dose radiotherapy to targets in the body, with treatment completed in one to five fractions. SBRT should be an ideal approach for organ-confined prostate cancer because (I) dose-escalation should yield improved rates of cancer control; (II) the unique radiobiology of prostate cancer favors hypofractionation; and (III) the conformal nature of SBRT minimizes high-dose radiation delivery to immediately adjacent organs, potentially reducing complications. This approach is also more convenient for patients, and is cheaper than intensity-modulated radiotherapy (IMRT). Several external beam platforms are capable of delivering SBRT for early-stage prostate cancer, although most of the mature reported series have employed a robotic non-coplanar platform (i.e., CyberKnife). Several large studies report 5-year biochemical relapse rates which compare favorably to IMRT. Rates of late GU toxicity are similar to those seen with IMRT, and rates of late rectal toxicity may be less than with IMRT and low-dose rate brachytherapy. Patient-reported quality of life (QOL) outcomes appear similar to IMRT in the urinary domain. Bowel QOL may be less adversely affected by SBRT than with other radiation modalities. After 5 years of follow-up, SBRT delivered on a robotic platform is yielding outcomes at least as favorable as IMRT, and may be considered appropriate therapy for stage I-II prostate cancer.

  20. Active measures for reducing the global climatic impacts of escalating CO 2 concentrations

    Science.gov (United States)

    Penner, S. S.; Schneider, A. M.; Kennedy, E. M.

    The buildup of CO 2 by fossil-fuel burning and associated climatic changes have become the subject of intensive investigations. Although the time scale on which significant climatic changes (e.g. mean temperature changes of several degrees, appreciable changes in global and regional rainfalls and winds, etc.) are expected to occur is long, it has been noted that the magnitude of the energy system is so vast that modifications in the primary resource mix should preferably be initiated within a decade or sooner. The notion that the most economical energy source will be replaced globally in response to longterm climate model predictions is probably false. Before policy matters of this type can be discussed reasonably, careful assessments must be made of alternative global measures that do not require curtailments of fossil-fuel applications. This study on active measures for reducing climate changes caused by escalating CO 2 concentrations deals with potentially important areas of research. We find: (a) reductions in the solar input to the Earth by reflecting sunlight directly are prohibitively costly; (b) desired changes in Earth albedo through judicious introduction of small particles can probably be accomplished at acceptable cost through the use of modified combustors on high-flying aircraft.

  1. Anticipatory 50 kHz ultrasonic vocalizations are associated with escalated alcohol intake in dependent rats.

    Science.gov (United States)

    Buck, Cara L; Malavar, Jordan C; George, Olivier; Koob, George F; Vendruscolo, Leandro F

    2014-09-01

    Rats emit 50kHz ultrasonic vocalizations (USVs) in situations of increased motivation, such as during the anticipation of palatable food or drugs of abuse. Whether the same holds true for the anticipation of alcohol intake remains unknown. Alcohol drinking in a nondependent state is thought to be mediated by its rewarding effects (positive reinforcement), whereas drinking in the dependent state is motivated by alcohol's stress-relieving effects (negative reinforcement). Here, we measured context-elicited 50kHz USVs in alcohol-dependent (alcohol vapor-exposed) and nondependent rats immediately before operant alcohol self-administration sessions. Dependent rats showed escalated levels of alcohol intake compared with nondependent rats. Overall, dependent and nondependent rats showed similar levels of anticipatory 50kHz USVs. However, the number of anticipatory USVs was positively correlated with alcohol intake in dependent rats but not nondependent rats. Additionally, dependent rats with higher alcohol intake displayed increased anticipatory 50kHz USVs compared with rats that had lower alcohol intake, whereas no difference was observed between rats with high and low alcohol intake in the nondependent group. Increased 50kHz USVs were specific for the anticipation of alcohol self-administration and did not generalize to a novel environment. These findings suggest that anticipatory 50kHz USVs may be an indicator of context-elicited negative reinforcement learning.

  2. Hydrogeologic assessment of escalating groundwater exploitation in the Indus Basin, Pakistan

    Science.gov (United States)

    Khan, S.; Rana, T.; Gabriel, H. F.; Ullah, Muhammad K.

    2008-12-01

    Groundwater development has contributed significantly to food security and reduction in poverty in Pakistan. Due to rapid population growth there has been a dramatic increase in the intensity of groundwater exploitation leading to declining water tables and deteriorating groundwater quality. In such prevailing conditions, the hydrogeological appraisal of escalating groundwater exploitation has become of paramount importance. Keeping this in view, a surface water-groundwater quantity and quality model was developed to assess future groundwater trends in the Rechna Doab (RD), a sub-catchment of the Indus River Basin. Scenario analysis shows that if dry conditions persist, there will be an overall decline in groundwater levels of around 10 m for the whole of RD during the next 25 years. The lower parts of RD with limited surface water supplies will undergo the highest decline in groundwater levels (10 to 20 m), which will make groundwater pumping very expensive for farmers. There is a high risk of groundwater salinization due to vertical upconing and lateral movement of highly saline groundwater into the fresh shallow aquifers in the upper parts of RD. If groundwater pumping is allowed to increase at the current rate, there will be an overall decline in groundwater salinity for the lower and middle parts of RD because of enhanced river leakage.

  3. 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

  4. Reward devaluation and heroin escalation is associated with differential expression of CRF signaling genes.

    Science.gov (United States)

    McFalls, Ashley J; Imperio, Caesar G; Bixler, Georgina; Freeman, Willard M; Grigson, Patricia Sue; Vrana, Kent E

    2016-05-01

    One of the most damaging aspects of drug addiction is the degree to which natural rewards (family, friends, employment) are devalued in favor of seeking, obtaining and taking drugs. We have utilized an animal model of reward devaluation and heroin self-administration to explore the role of the coricotropin releasing factor (CRF) pathway. Given access to a saccharin cue followed by the opportunity to self-administer heroin, animals will parse into distinct phenotypes that suppress their saccharin intake (in favor of escalating heroin self-administration) or vice versa. We find that large saccharin suppressors (large heroin takers) demonstrate increased mRNA expression for elements of the CRF signaling pathway (CRF, CRF receptors and CRF binding protein) within the hippocampus, medial prefrontal cortex and the ventral tegmental area. Moreover, there were no gene expression changes of these components in the nucleus accumbens. Use of bisulfite conversion sequencing suggests that changes in CRF binding protein and CRF receptor gene expression may be mediated by differential promoter methylation.

  5. Beyond the mucus escalator: Complex ciliary hydrodynamics in disease and function

    Science.gov (United States)

    Nawroth, Janna; Guo, Hanliang; John, Dabiri; Kanso, Eva; McFall-Ngai, Margaret

    2015-11-01

    Cilia are microscopic, hair-like structures lining external and internal body surfaces where they interact with fluids. The main function of motile cilia is often described as that of a ``mucus escalator'', i.e., a homogeneous ciliary carpet moving along layer of mucus along the surface to transport food, germ cells, debris, or pathogens. Accordingly, the performance of ciliary systems is usually measured in terms of a single metric, transport velocity, or its presumed proxy, ciliary beat frequency. We challenge this simple view through the observation that both healthy and diseased biological systems exhibit a variety of cilia morphologies, beat patterns, and arrangements, resulting in complex flow patterns and transport phenomena that cannot be reduced to a single parameter. Here we present two case studies. In one system, the ciliated surface creates two distinct flow regimes for first trapping and then sheltering potential symbiont bacteria for further biochemical screening. In the other system, chronic disease induces a misalignment of ciliary beat, leading to a pathological transition from uniform mucus transport to a pattern of stagnation and circulation. These studies suggest that (a), we need to develop a wider range of metrics for describing ciliary transport in biological and clinical contexts, and (b), engineered ciliated systems exploiting a variety of design parameters could provide novel ways of manipulating fluids at the microscale.

  6. Action Emulation

    NARCIS (Netherlands)

    D.J.N. van Eijck (Jan); J. Ruan; T. Sadzik

    2012-01-01

    textabstractThe effects of public announcements, private communications, deceptive messages to groups, and so on, can all be captured by a general mechanism of updating multi-agent models with update action models, now in widespread use. There is a natural extension of the definition of

  7. China's Actions

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    @@ China's National Development and Reform Commission publicized the country's policies and actions for addressing climate change in a report released on November 26,2009.The report highlighted China's efforts in cutting greenhouse gas emissions in 2009 by: (1)Rigorously checking the blind expansion of its energy-and pollution-intensive industries.

  8. 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.)

  9. Words of Violence: “Fear Speech,” or How Violent Conflict Escalation Relates to the Freedom of Expression

    OpenAIRE

    Buyse, Antoine

    2014-01-01

    The limits of the freedom of expression are a perennial discussion in human rights discourse. This article focuses on identifying yardsticks to establish the boundaries of freedom of expression in cases where violence is a risk. It does so by using insights from the social sciences on the escalation of violent conflict. By emphasizing the interaction between violence and discourse, and its effect on antagonisms between groups, it offers an interdisciplinary perspective on an ongoing legal deb...

  10. 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.

  11. Rituximab and escalated chemotherapy in elderly patients with aggressive diffuse large-cell lymphoma: a controlled clinical trial.

    Science.gov (United States)

    Avilés, Agustin; Nambo, María Jesus; Castañeda, Claudia; Cleto, Sergio; Neri, Natividad; Murillo, Edgar; Huerta-Guzmán, Judith; Contreras, Margarita

    2007-04-01

    The treatment of elderly patients with aggressive malignant lymphoma has not been defined. The addition of rituximab to conventional chemotherapy has been reported to improve the outcome, but most patients have good prognostic factors (performance status < 2, no severe associated diseases, low or low-intermediate clinical risk). Thus, we developed a combined regimen, including escalated doses of anthracycline and rituximab. The endpoint was to improve event-free survival (EFS) and overall survival. Two hundred and four (204) patients were randomly assigned to receive an escalated chemotherapy regimen (CEOP) with escalated dose of epirubicin, compared to the same regimen and addition of rituximab. All patients had poor prognostic factors: high- or high-intermediate clinical risk, poor performance status, bulky disease, and more than 2 with extranodal involvement. In an intent-to-treat analysis, all patients were evaluable for efficacy and toxicity. The complete response rates were similar in both arms: 74% in chemotherapy and 78% in the rituximab + chemotherapy program. EFS and overall survival were similar: 77% and 84%, respectively, in combined chemotherapy and 75% and 81% in the rituximab-chemotherapy regimen. Toxicity was mild and well tolerated. In elderly patients with diffuse large-cell lymphoma and poor prognostic factors, rituximab did not improve their outcome.

  12. 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.

  13. Strategies of dose escalation in the treatment of locally advanced non-small cell lung cancer: image guidance and beyond

    Directory of Open Access Journals (Sweden)

    Alexander eChi

    2014-06-01

    Full Text Available Radiation dose in the setting of chemo-radiation for locally advanced non-small cell lung cancer (NSCLC has been historically limited by the risk of normal tissue toxicity and this has been hypothesized to correlate with the poor results in regard to local tumor recurrences. Dose escalation, as a means to improve local control, with concurrent chemotherapy has been shown to be feasible with three-dimensional conformal radiotherapy in early phase studies with good clinical outcome. However, the potential superiority of moderate dose escalation to 74 Gy has not been shown in phase III randomized studies. In this review, the limitations in target volume definition in previous studies; and the factors that may be critical to safe dose escalation in the treatment of locally advanced NSCLC, such as respiratory motion management, image guidance, intensity modulation, FDG-PET incorporation in the treatment planning process, and adaptive radiotherapy, are discussed. These factors, along with novel treatment approaches that have emerged in recent years, are proposed to warrant further investigation in future trials in a more comprehensive and integrated fashion.

  14. Strategic Stability Reconsidered: Prospects for Escalation and Nuclear War in the Middle East

    Energy Technology Data Exchange (ETDEWEB)

    Russell, J.A.

    2009-07-01

    for survival'. The paper first draws upon Thomas Schelling's ideas to assess the regional strategic framework, and finds systemic uncertainties which suggest that escalation by various parties - state and non-state actors - is a possible outcome. Both near-term and long-term scenarios are considered. The near-term nuclear use scenarios are all predicated on the assumption that nuclear use will occur within the context of escalation to or within war. As dangerous as these circumstances are, longer-term scenarios for nuclear use will also be proposed, which, like the alarming near-term scenarios, flow from the same unstable regional dynamics. The Middle East's unstable dynamics occur within a global environment characterized by a general sense of insecurity about various nuclear issues. Reflecting this situation, the Bulletin of Atomic Scientists recently moved its 'Doomsday Clock' from seven- to five minutes to midnight - the most advanced setting since 1981. Citing Iran's nuclear ambitions, North Korea's test of a nuclear weapon, the failure to secure nuclear materials, a controversial U.S. nuclear doctrine that some argue suggests an expanded role for nuclear weapons, and the continued presence of 26,000 nuclear weapons in the United States and Russia, the Bulletin expressed new concerns about global strategic stability. These developments occurred against a backdrop of the collapse of the 2005 Nonproliferation Treaty Review conference due, among other things, to disinterest in the global community in supporting the spread of nonproliferation norms. (author)

  15. 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 treatment target in most people with 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/.

  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. Short-term Disulfiram to Reverse Latent HIV Infection: A Phase 2 Dose Escalation Study

    Science.gov (United States)

    Elliott, Julian H.; McMahon, James H.; Chang, Christina C.; Lee, Sulggi A.; Hartogensis, Wendy; Bumpus, Namandje; Savic, Rada; Roney, Janine; Hoh, Rebecca; Solomon, Ajantha; Piatak, Michael; Gorelick, Robert J.; Lifson, Jeff; Bacchetti, Peter; Deeks, Steven G.; Lewin, Sharon R.

    2016-01-01

    Background Disulfiram activates HIV transcription in a primary T-cell model of HIV latency and in a pilot clinical study increased plasma HIV RNA in individuals with adequate diulfiram exposure. Methods We conducted a prospective dose escalation study in order to optimise disulfiram exposure. Thirty people with HIV on suppressive antiretroviral therapy (ART) were enrolled, allocated sequentially to one of three dosing cohorts and received disulfiram daily for three days at a dose of 500mg, 1000mg or 2000mg. The primary endpoint was cell-associated unspliced (CA-US) HIV RNA in CD4+ T-cells. The study is registered with ClinicalTrials.gov, number NCT01944371. Findings The estimated fold increases in CA-US HIV RNA during and post-disulfiram for each cohort were: 500mg: 1·7 (95% confidence interval 1·3 – 2·2) and 2·1 (1·5 – 2·9); 1000mg: 1·9 (1·6 – 2·4) and 2·5 (1·9 – 3·3); and 2000mg: 1·6 (1·2 – 2·1) and 2·1 (1·5 – 3·1) respectively (p<0·003 for all). Disulfiram was well tolerated at all doses. Interpretation Short-term administration of disulfiram resulted in increases in CA-US HIV RNA at all doses, consistent with activating HIV latency. Disulfiram may be suited for future studies of combination and prolonged therapy to activate latent HIV. PMID:26614966

  18. Correcting the Science Record: Direct Stratospheric Injection vs. Asian Monsoon and the Solar Escalator

    Science.gov (United States)

    Fromm, M. D.; Nedoluha, G. E.; Kablick, G. P.

    2012-12-01

    Two entries in the literature in 2012 make provocative but unsupportable claims regarding pollutant pathways from the Earth to the stratosphere. One claims the 13 June 2011 Nabro volcano (Eritrea) emitted gases and particles into the troposphere, and these constituents reached the stratosphere in great abundance via the Asian Monsoon circulation [Bourassa et al., 2012]. The other claims that smoke from the Black Saturday fire storms (Australia) was emitted into the troposphere, and was lofted ~15 km into the stratosphere by solar-induced diabatic heating [de Laat et al., 2012]. In both cases the stratospheric plumes attributed to these events spread around the globe and lasted for months. We will show that in both cases the postulated pathways are incorrect; the correct pathway is a direct convective injection by volcanic eruption and pyrocumulonimbus (pyroCb), respectively. We will present satellite data that will unambiguously reveal multiple, distinct stratospheric volcano-convection columns from Nabro connected to height-resolved volcanic SO2 and sulfate particles. In the case of Black Saturday we will characterize the pyroCb columns with ground-based radar and satellite imagery. The young pyroCb plume in the stratosphere will be characterized with a synergistic analysis of several NASA A-Train passive and active remote sensors. We will discuss the implications of our findings with respect to how satellite-based data are best used for tracking and characterizing point source injection plumes in the stratosphere. Bourassa et al. (2012), Large Volcanic Aerosol Load in the Stratosphere Linked to Asian Monsoon Transport, Science, 337, 78, DOI: 10:1126/Science.1219371 de Laat, et al. (2012), A solar escalator: Observational evidence of the self-lifting of smoke and aerosols by absorption of solar radiation in the February 2009 Australian Black Saturday plume, J. Geophys. Res., 117, D04204, doi:10.1029/2011JD017016.

  19. 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.)

  20. Younger age of escalation of cardiovascular risk factors in Asian Indian subjects

    Directory of Open Access Journals (Sweden)

    Gupta Shaon

    2009-07-01

    Full Text Available Abstract Background Cardiovascular risk factors start early, track through the young age and manifest in middle age in most societies. We conducted epidemiological studies to determine prevalence and age-specific trends in cardiovascular risk factors among adolescent and young urban Asian Indians. Methods Population based epidemiological studies to identify cardiovascular risk factors were performed in North India in 1999–2002. We evaluated major risk factors-smoking or tobacco use, obesity, truncal obesity, hypertension, dysglycemia and dyslipidemia using pre-specified definitions in 2051 subjects (male 1009, female 1042 aged 15–39 years of age. Age-stratified analyses were performed and significance of trends determined using regression analyses for numerical variables and Χ2 test for trend for categorical variables. Logistic regression was used to identify univariate and multivariate odds ratios (OR for correlation of age and risk factors. Results In males and females respectively, smoking or tobacco use was observed in 200 (11.8% and 18 (1.4%, overweight or obesity (body mass index, BMI ≥ 25 kg/m2 in 12.4% and 14.3%, high waist-hip ratio, WHR (males > 0.9, females > 0.8 in 15% and 32.3%, hypertension in 5.6% and 3.1%, high LDL cholesterol (≥ 130 mg/dl in 9.4% and 8.9%, low HDL cholesterol ( Conclusion Low prevalence of multiple cardiovascular risk factors (smoking, hypertension, dyslipidemias, diabetes and metabolic syndrome in adolescents and rapid escalation of these risk factors by age of 30–39 years is noted in urban Asian Indians. Interventions should focus on these individuals.

  1. Escalation, retreat, and female indifference as alternative outcomes of sexually antagonistic coevolution.

    Science.gov (United States)

    Rowe, Locke; Cameron, Erin; Day, Troy

    2005-05-01

    Verbal and quantitative genetic models of sexually antagonistic coevolution suggest that coevolutionary arms races should be common. Sexual selection favors exaggeration of male persistence traits that are costly to females, and females, in turn, are selected to resist these traits. The heightened resistance by females is thought to then favor further exaggeration in the male trait, leading to an escalating coevolutionary arms race between persistence and resistance traits. Much of this theory, however, is based on an (implicit) assumption that there are tight constraints on how female resistance can evolve. We develop a theory that identifies and relaxes these constraints, allowing female resistance to evolve in a fashion that better reflects known empirical patterns in the evolution of female preference functions (the resistance trait). Our results suggest that evolutionary arms races that lead to the exaggeration of persistence and resistance will be much less common than formerly predicted. Females sometimes evolve indifference to male traits rather than resistance and can even evolve to discriminate against these traits. These alternative outcomes depend on the existence of genetic variance in the components of the female sensory system underlying female resistance and on the strength of natural selection acting on these components. Female indifference tends to evolve when natural selection on the sensory system is weak, and under these conditions, sexually antagonistic coevolution tends not to reduce female fitness significantly at equilibrium. When natural selection on the female sensory system is strong, however, then arms races are more likely, and female fitness is then sometimes significantly depressed at equilibrium. Sexually antagonistic coevolution is thus likely to have strong deleterious effects on population fitness only when female sensory traits are under strong natural selection to perform functions in addition to those involved with mating

  2. Controlling cost escalation of healthcare: making universal health coverage sustainable in China.

    Science.gov (United States)

    Tang, Shenglan; Tao, Jingjing; Bekedam, Henk

    2012-01-01

    An increasingly number of low- and middle-income countries have developed and implemented a national policy towards universal coverage of healthcare for their citizens over the past decade. Among them is China which has expanded its population coverage by health insurance from around 29.7% in 2003 to over 90% at the end of 2010. While both central and local governments in China have significantly increased financial inputs into the two newly established health insurance schemes: new cooperative medical scheme (NCMS) for the rural population, and urban resident basic health insurance (URBMI), the cost of healthcare in China has also been rising rapidly at the annual rate of 17.0%% over the period of the past two decades years. The total health expenditure increased from 74.7 billion Chinese yuan in 1990 to 1998 billion Chinese yuan in 2010, while average health expenditure per capital reached the level of 1490.1 Chinese yuan per person in 2010, rising from 65.4 Chinese yuan per person in 1990. The repaid increased population coverage by government supported health insurance schemes has stimulated a rising use of healthcare, and thus given rise to more pressure on cost control in China.There are many effective measures of supply-side and demand-side cost control in healthcare available. Over the past three decades China had introduced many measures to control demand for health care, via a series of co-payment mechanisms. The paper introduces and discusses new initiatives and measures employed to control cost escalation of healthcare in China, including alternative provider payment methods, reforming drug procurement systems, and strengthening the application of standard clinical paths in treating patients at hospitals, and analyses the impacts of these initiatives and measures. The paper finally proposes ways forward to make universal health coverage in China more sustainable.

  3. Releasing stimuli and aggression in crickets: octopamine promotes escalation and maintenance but not initiation

    Directory of Open Access Journals (Sweden)

    Jan eRillich

    2015-04-01

    Full Text Available Biogenic amines have widespread effects on numerous behaviors, but their natural functions are often unclear. We investigated the role of octopamine (OA, the invertebrate analogue of noradrenaline, on initiation and maintenance of aggression in male crickets of different social status. The key-releasing stimulus for aggression is antennal fencing between males, a behavior occurring naturally on initial contact. We show that mechanical antennal stimulation (AS alone is sufficient to initiate an aggressive response (mandible threat display. The efficacy of AS was augmented in winners of a previous fight, but unaffected in losers. The efficacy of AS was not, however, influenced by OA receptor (OAR agonists or antagonists, regardless of social status. Additional experiments indicate that the efficacy of AS is also not influenced by dopamine (DA or serotonin (5HT. In addition to initiating an aggressive response, prior AS enhanced aggression exhibited in subsequent fights, whereby AS with a male antenna was now necessary, indicating a role for male contact pheromones. This priming effect of male-AS on subsequent aggression was dependent on OA since it was blocked by OAR-antagonists, and enhanced by OAR-agonists. Together our data reveal that neither OA, DA nor 5HT are required for initiating aggression in crickets, nor do these amines influence the efficacy of the natural releasing stimulus to initiate aggression. OA’s natural function is restricted to promoting escalation and maintenance of aggression once initiated, and this can be invoked by numerous experiences, including prior contact with a male antenna as shown here.

  4. Decision Regret in Men Undergoing Dose-Escalated Radiation Therapy for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Steer, Anna N. [Department of Radiation Oncology, North Coast Cancer Institute, Coffs Harbour (Australia); Aherne, Noel J., E-mail: noel.aherne@ncahs.health.nsw.gov.au [Department of Radiation Oncology, North Coast Cancer Institute, Coffs Harbour (Australia); Rural Clinical School Faculty of Medicine, University of New South Wales, Coffs Harbour (Australia); Gorzynska, Karen; Hoffman, Matthew; Last, Andrew; Hill, Jacques [Department of Radiation Oncology, North Coast Cancer Institute, Coffs Harbour (Australia); Shakespeare, Thomas P. [Department of Radiation Oncology, North Coast Cancer Institute, Coffs Harbour (Australia); Rural Clinical School Faculty of Medicine, University of New South Wales, Coffs Harbour (Australia)

    2013-07-15

    Purpose: Decision regret (DR) is a negative emotion associated with medical treatment decisions, and it is an important patient-centered outcome after therapy for localized prostate cancer. DR has been found to occur in up to 53% of patients treated for localized prostate cancer, and it may vary depending on treatment modality. DR after modern dose-escalated radiation therapy (DE-RT) has not been investigated previously, to our knowledge. Our primary aim was to evaluate DR in a cohort of patients treated with DE-RT. Methods and Materials: We surveyed 257 consecutive patients with localized prostate cancer who had previously received DE-RT, by means of a validated questionnaire. Results: There were 220 responses (85.6% response rate). Image-guided intensity modulated radiation therapy was given in 85.0% of patients and 3-dimensional conformal radiation therapy in 15.0%. Doses received included 73.8 Gy (34.5% patients), 74 Gy (53.6%), and 76 Gy (10.9%). Neoadjuvant androgen deprivation (AD) was given in 51.8% of patients and both neoadjuvant and adjuvant AD in 34.5%. The median follow-up time was 23 months (range, 12-67 months). In all, 3.8% of patients expressed DR for their choice of treatment. When asked whether they would choose DE-RT or AD again, only 0.5% probably or definitely would not choose DE-RT again, compared with 8.4% for AD (P<.01). Conclusion: Few patients treated with modern DE-RT express DR, with regret appearing to be lower than in previously published reports of patients treated with radical prostatectomy or older radiation therapy techniques. Patients experienced more regret with the AD component of treatment than with the radiation therapy component, with implications for informed consent. Further research should investigate regret associated with individual components of modern therapy, including AD, radiation therapy and surgery.

  5. Restriction of Convertible Bonds on Commitment Escalation%可转换债券对恶性增资的制约作用

    Institute of Scientific and Technical Information of China (English)

    唐洋; 胡张丽

    2012-01-01

    总结了已有的关于恶性增资形成机理及控制机制的研究成果,并且分析了股权融资及债券融资对恶性增资的治理作用。本文认为股权融资及债权融资都难以有效地控制恶性增资,而可转债作为一种特殊的融资方式,其特有的双重属性能够有效地制约恶性增资行为。具体来说,特别向下修正条款不仅不能制约恶性增资,反而会刺激恶性增资;回售条款能够在一定程度上制约恶性增资;赎回条款对恶性增资毫无治理作用。%The paper summarizes the findings about formation mechanism and control mechanism of commitment escalation,and analyzes the governance effect of equity financing and debt financing on commitment escalation.It thinks that equity financing and debt financing are difficult to control commitment escalation.However,dual properties of convertible bonds can help to restrict commitment escalation.Concretely speaking,the Downward Modification Provision can't restrict commitment escalation;on the contrary,it will stimulate commitment escalation.The Put Provision can restrict commitment escalation to some extent.The Call Provision has no governance effect on commitment escalation.

  6. Action Learning: Avoiding Conflict or Enabling Action

    Science.gov (United States)

    Corley, Aileen; Thorne, Ann

    2006-01-01

    Action learning is based on the premise that action and learning are inextricably entwined and it is this potential, to enable action, which has contributed to the growth of action learning within education and management development programmes. However has this growth in action learning lead to an evolution or a dilution of Revan's classical…

  7. Dose-escalation study for the targeting of CD44v(+) cancer stem cells by sulfasalazine in patients with advanced gastric cancer (EPOC1205).

    Science.gov (United States)

    Shitara, Kohei; Doi, Toshihiko; Nagano, Osamu; Imamura, Chiyo K; Ozeki, Takeshi; Ishii, Yuya; Tsuchihashi, Kenji; Takahashi, Shunji; Nakajima, Takako E; Hironaka, Shuichi; Fukutani, Miki; Hasegawa, Hiromi; Nomura, Shogo; Sato, Akihiro; Einaga, Yasuaki; Kuwata, Takeshi; Saya, Hideyuki; Ohtsu, Atsushi

    2017-03-01

    Cancer stem cells (CSCs) have enhanced mechanisms of protection from oxidative stress. A variant form of CD44 (CD44v), a major CSC marker, was shown to interact with xCT, a subunit of cystine-glutamate transporter, which maintains high levels of intracellular reduced glutathione (GSH) which defend the cell against oxidative stress. Sulfasalazine (SSZ) is an inhibitor of xCT and was shown to suppress the survival of CD44v-positive stem-like cancer cells both in vitro and in vivo. To find the dose of SSZ which can safely reduce the population of CD44v-positive cells in tumors, a dose-escalation study in patients with advanced gastric cancer was conducted. SSZ was given four times daily by oral administration with 2 weeks as one cycle. Tumor biopsies were obtained before and after 14 days of administration of SSZ to evaluate expression of CD44v and the intratumoral level of GSH. Eleven patients were enrolled and received a dosage from 8 to 12 g/day. Safety was confirmed up to a dosage of 12 g/day, which was considered the maximum tolerated dose. Among the eight patients with CD44v-positive cells in their pretreatment biopsy samples, the CD44v-positive cancer cell population appeared to be reduced in the posttreatment biopsy tissues of four patients. Intratumoral GSH levels were also decreased in two patients, suggesting biological effectiveness of SSZ at 8 g/day or greater. This is the first study of SSZ as an xCT inhibitor for targeting CSCs. Reduction of the levels of CD44v-positive cells and GSH was observed in some patients, consistent with the mode of action of SSZ in CSCs.

  8. A planning study of radiotherapy dose escalation of PET-active tumour volumes in non-small cell lung cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Sloth Moeller, Ditte; Hoffmann, Lone (Dept. of Medical Physics, Aarhus Univ. Hospital, Aarhus (Denmark)), e-mail: dittmoel@rm.dk; Khalil, Azza Ahmed; Marquard Knap, Marianne (Dept. of Oncology, Aarhus Univ. Hospital, Aarhus (Denmark)); Muren, Ludvig Paul (Dept. of Medical Physics, Aarhus Univ. Hospital, Aarhus (Denmark); Dept. of Oncology, Aarhus Univ. Hospital, Aarhus (Denmark))

    2011-08-15

    Background. Patients with non-small cell lung cancer (NSCLC) have poor prognosis partly because of high local failure rates. Escalating the dose to the tumour may decrease the local failure rates and thereby, improve overall survival, but the risk of complications will limit the possibility to dose-escalate a broad range of patients. Escalating only PET-active areas of the tumour may increase the potential for reaching high doses for a variety of tumour sizes and locations. Material and methods. Ten patients were randomly chosen for a dose escalation planning study. A planning target volume (PTV) was defined on the mid-ventilation scan of a four-dimensional computed tomography (4D-CT) scan and a boost planning target volume (PTV-boost) was defined based on a positron emission tomography computed tomography (PET-CT) scan. Treatment plans were created aiming to reach the highest achievable of 74 Gy, 78 Gy or 82 Gy in 2 Gy per fraction prescribed to the PTV-boost without compromising normal tissue constraints and with the PTV prescribed in all cases a biological equivalent dose in 2 Gy fractions of 66 Gy. Results. Nine of ten patients could be escalated to the highest dose level (82 Gy), while one patient was limited by the oesophagus dose constraint and could only reach 74 Gy. Four patients could be dose-escalated above 82 Gy without compromising normal tissue constraints. Conclusion. Dose-escalating only the PET-active areas of lung tumours to doses of 82 Gy while respecting normal tissue constraints is feasible, also in a series of unselected patients including cases with relatively large tumours

  9. Is Androgen Deprivation Therapy Necessary in All Intermediate-Risk Prostate Cancer Patients Treated in the Dose Escalation Era?

    Energy Technology Data Exchange (ETDEWEB)

    Castle, Katherine O., E-mail: kocastle@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hoffman, Karen E.; Levy, Lawrence B.; Lee, Andrew K.; Choi, Seungtaek; Nguyen, Quynh N.; Frank, Steven J.; Pugh, Thomas J.; McGuire, Sean E.; Kuban, Deborah A. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-03-01

    Purpose: The benefit of adding androgen deprivation therapy (ADT) to dose-escalated radiation therapy (RT) for men with intermediate-risk prostate cancer is unclear; therefore, we assessed the impact of adding ADT to dose-escalated RT on freedom from failure (FFF). Methods: Three groups of men treated with intensity modulated RT or 3-dimensional conformal RT (75.6-78 Gy) from 1993-2008 for prostate cancer were categorized as (1) 326 intermediate-risk patients treated with RT alone, (2) 218 intermediate-risk patients treated with RT and ≤6 months of ADT, and (3) 274 low-risk patients treated with definitive RT. Median follow-up was 58 months. Recursive partitioning analysis based on FFF using Gleason score (GS), T stage, and pretreatment PSA concentration was applied to the intermediate-risk patients treated with RT alone. The Kaplan-Meier method was used to estimate 5-year FFF. Results: Based on recursive partitioning analysis, intermediate-risk patients treated with RT alone were divided into 3 prognostic groups: (1) 188 favorable patients: GS 6, ≤T2b or GS 3+4, ≤T1c; (2) 71 marginal patients: GS 3+4, T2a-b; and (3) 68 unfavorable patients: GS 4+3 or T2c disease. Hazard ratios (HR) for recurrence in each group were 1.0, 2.1, and 4.6, respectively. When intermediate-risk patients treated with RT alone were compared to intermediate-risk patients treated with RT and ADT, the greatest benefit from ADT was seen for the unfavorable intermediate-risk patients (FFF, 74% vs 94%, respectively; P=.005). Favorable intermediate-risk patients had no significant benefit from the addition of ADT to RT (FFF, 94% vs 95%, respectively; P=.85), and FFF for favorable intermediate-risk patients treated with RT alone approached that of low-risk patients treated with RT alone (98%). Conclusions: Patients with favorable intermediate-risk prostate cancer did not benefit from the addition of ADT to dose-escalated RT, and their FFF was nearly as good as patients with low-risk disease

  10. Safety, Tolerability, and Preliminary Activity of LB-100, an Inhibitor of Protein Phosphatase 2A, in Patients with Relapsed Solid Tumors: An Open-Label, Dose Escalation, First-in-Human, Phase I Trial.

    Science.gov (United States)

    Chung, Vincent; Mansfield, Aaron S; Braiteh, Fadi; Richards, Donald; Durivage, Henry; Ungerleider, Richard S; Johnson, Francis; Kovach, John S

    2017-07-01

    Purpose: To determine the MTD and to assess the safety, tolerability, and potential activity of LB-100, a first-in-class small-molecule inhibitor of protein phosphatase 2A (PP2A) in adult patients with progressive solid tumors.Experimental Design: LB-100 was administered intravenously daily for 3 days in 21-day cycles in a 3 + 3 dose escalation design.Results: There were 29 patient entries over 7 dose escalations. One patient stopped treatment after one dose because of an acute infection and was reenrolled after recovery; each course was analyzed as a separate patient entry. Two patients had dose-limiting toxicity (reversible increases in serum creatinine or calculated serum creatinine clearance) at the 3.1 mg/m(2) level. Probable or possible study drug-related grade 3 adverse events occurred in 6 (20.7%) patients [anemia (n = 2), decreased creatinine clearance, dyspnea, hyponatremia, and lymphopenia]. Ten (50%) of 20 response-evaluable patients had stable disease for four or more cycles. One patient with pancreatic adenocarcinoma had a partial response noted after 10 cycles, which was maintained for five additional cycles. The other patients achieving stable disease had one of the following: fibrosarcoma, chondrosarcoma, thymoma, atypical carcinoid of lung, or ovarian, testicular, breast (n = 2), and prostate cancer. The recommended phase II dose of LB-100 is 2.33 mg/m(2) daily for 3 days every 3 weeks.Conclusions: The safety, tolerability, preliminary evidence of antitumor activity, and novel mechanism of action of LB-100 support its continued development alone and in combination with other therapies. Clin Cancer Res; 23(13); 3277-84. ©2016 AACR. ©2016 American Association for Cancer Research.

  11. Learning and performance outcomes of mental health staff training in de-escalation techniques for the management of violence and aggression.

    Science.gov (United States)

    Price, Owen; Baker, John; Bee, Penny; Lovell, Karina

    2015-06-01

    De-escalation techniques are a recommended non-physical intervention for the management of violence and aggression in mental health. Although taught as part of mandatory training for all National Health Service (NHS) mental health staff, there remains a lack of clarity around training effectiveness. To conduct a systematic review of the learning, performance and clinical safety outcomes of de-escalation techniques training. The review process involved a systematic literature search of 20 electronic databases, eligibility screening of results, data extraction, quality appraisal and data synthesis. A total of 38 relevant studies were identified. The strongest impact of training appears to be on de-escalation-related knowledge, confidence to manage aggression and deescalation performance (although limited to artificial training scenarios). No strong conclusions could be drawn about the impact of training on assaults, injuries, containment and organisational outcomes owing to the low quality of evidence and conflicting results. It is assumed that de-escalation techniques training will improve staff's ability to de-escalate violent and aggressive behaviour and improve safety in practice. There is currently limited evidence that this training has these effects. © The Royal College of Psychiatrists 2015.

  12. Prospective evaluation of a hydrogel spacer for rectal separation in dose-escalated intensity-modulated radiotherapy for clinically localized prostate cancer

    Directory of Open Access Journals (Sweden)

    Eckert Franziska

    2013-01-01

    Full Text Available Abstract Background As dose-escalation in prostate cancer radiotherapy improves cure rates, a major concern is rectal toxicity. We prospectively assessed an innovative approach of hydrogel injection between prostate and rectum to reduce the radiation dose to the rectum and thus side effects in dose-escalated prostate radiotherapy. Methods Acute toxicity and planning parameters were prospectively evaluated in patients with T1-2 N0 M0 prostate cancer receiving dose-escalated radiotherapy after injection of a hydrogel spacer. Before and after hydrogel injection, we performed MRI scans for anatomical assessment of rectal separation. Radiotherapy was planned and administered to 78 Gy in 39 fractions. Results From eleven patients scheduled for spacer injection the procedure could be performed in ten. In one patient hydrodissection of the Denonvillier space was not possible. Radiation treatment planning showed low rectal doses despite dose-escalation to the target. In accordance with this, acute rectal toxicity was mild without grade 2 events and there was complete resolution within four to twelve weeks. Conclusions This prospective study suggests that hydrogel injection is feasible and may prevent rectal toxicity in dose-escalated radiotherapy of prostate cancer. Further evaluation is necessary including the definition of patients who might benefit from this approach. Trial registration: German Clinical Trials Register DRKS00003273.

  13. O conhecimento tático declarativo e processual em jogadores de futebol de diferentes escalões

    Directory of Open Access Journals (Sweden)

    Diogo Schüler Giacomini

    2011-03-01

    Full Text Available A qualidade na prestação esportiva, nos jogos esportivos coletivos, relaciona-se com as capacidades cognitivas, especificamente com o conhecimento. Esse estudo verificou a associação entre o conhecimento tático processual convergente e divergente, assim como as associações entre o conhecimento tático processual e declarativo. Participaram do estudo 221 jogadores de futebol de campo, do sexo masculino, do escalão sub-14, sub-15 e sub-17. O conhecimento tático processual foi avaliado através da aplicação do teste KORA-OO no parâmetro “oferecer-se” e “orientar-se”. O conhecimento tático declarativo foi avaliado através de cenas-situação do futebol. Os resultados indicaram uma alta associação entre o conhecimento tático processual, convergente e divergente, geral e especifico por escalão, além de uma baixa associação entre o conhecimento tático declarativo e processual (convergente e divergente. Esses dados suportam a idéia de que os conhecimentos progridem serialmente do declarativo ao processual.

  14. Stair descending exercise using a novel automatic escalator: effects on muscle performance and health-related parameters.

    Science.gov (United States)

    Paschalis, Vassilis; Theodorou, Anastasios A; Panayiotou, George; Kyparos, Antonios; Patikas, Dimitrios; Grivas, Gerasimos V; Nikolaidis, Michalis G; Vrabas, Ioannis S

    2013-01-01

    A novel automatic escalator was designed, constructed and used in the present investigation. The aim of the present investigation was to compare the effect of two repeated sessions of stair descending versus stair ascending exercise on muscle performance and health-related parameters in young healthy men. Twenty males participated and were randomly divided into two equal-sized groups: a stair descending group (muscle-damaging group) and a stair ascending group (non-muscle-damaging group). Each group performed two sessions of stair descending or stair ascending exercise on the automatic escalator while a three week period was elapsed between the two exercise sessions. Indices of muscle function, insulin sensitivity, blood lipid profile and redox status were assessed before and immediately after, as well as at day 2 and day 4 after both exercise sessions. It was found that the first bout of stair descending exercise caused muscle damage, induced insulin resistance and oxidative stress as well as affected positively blood lipid profile. However, after the second bout of stair descending exercise the alterations in all parameters were diminished or abolished. On the other hand, the stair ascending exercise induced only minor effects on muscle function and health-related parameters after both exercise bouts. The results of the present investigation indicate that stair descending exercise seems to be a promising way of exercise that can provoke positive effects on blood lipid profile and antioxidant status.

  15. Parents' and older siblings' smoking during childhood: changing influences on smoking acquisition and escalation over the course of adolescence.

    Science.gov (United States)

    Bricker, Jonathan B; Peterson, Arthur V; Andersen, M Robyn; Sarason, Irwin G; Rajan, K Bharat; Leroux, Brian G

    2007-09-01

    This study investigated prospectively the change in the influence of parents' and older siblings' smoking at the start of the childhood and adolescent smoking acquisition period (i.e., 3rd grade, or age 8) on the initiation and escalation of smoking over the course of adolescence. In a sample of 5,520 individuals in 3rd grade, we measured parents' and older siblings' smoking. Individuals' smoking data were provided at four grade intervals over the course of adolescence. The influence of parents' smoking, measured at 3rd grade, was stable and significant for the transition to trying smoking and increased over the course of adolescence for the transition from monthly to daily smoking (p = .001). In contrast, we found no evidence that influence of older siblings' smoking, measured at 3rd grade, changed (p>.05) across the grade intervals for any adolescent smoking transition. The results suggest that the influence of parents' smoking on smoking initiation is stable and enduring whereas it increases substantially for smoking escalation occurring over the course of adolescence.

  16. Impact of obesity on outcomes after definitive dose-escalated intensity-modulated radiotherapy for localized prostate cancer.

    Science.gov (United States)

    Wang, Lora S; Murphy, Colin T; Ruth, Karen; Zaorsky, Nicholas G; Smaldone, Marc C; Sobczak, Mark L; Kutikov, Alexander; Viterbo, Rosalia; Horwitz, Eric M

    2015-09-01

    Previous publications have demonstrated conflicting results regarding body mass index (BMI) and prostate cancer (CaP) outcomes after definitive radiotherapy (RT) before the dose escalation era. The goal of the current study was to determine whether increasing BMI was associated with outcomes in men with localized CaP who were treated with dose-escalated RT. The authors identified patients with localized (T1b-T4N0M0) CaP who were treated with definitive intensity-modulated RT and image-guided RT from 2001 through 2010. BMI was analyzed as a continuous variable. Adjusting for confounders, multivariable competing risk and Cox proportional hazards regression models were used to assess the association between BMI and the risk of biochemical failure (BF), distant metastases (DM), cause-specific mortality (CSM), and overall mortality. Of the 1442 patients identified, approximately 20% had a BMI prostate-specific antigen level (P = .018). On multivariable analysis, increasing BMI was associated with an increased risk of BF (hazard ratio [HR], 1.03; 95% confidence interval [95% CI], 1.00-1.07 [P = .042]), DM (HR, 1.07; 95% CI, 1.02-1.11 [P = .004]), CSM (HR, 1.15; 95% CI, 1.07-1.23 [PCancer Society.

  17. Steepness of the radiation dose-response curve for dose-per-fraction escalation keeping the number of fractions fixed.

    Science.gov (United States)

    Bentzen, Søren M

    2005-01-01

    Clinically, there is growing interest in strategies for intensifying radiation therapy by escalating the dose per fraction. This paper considers the steepness of the dose-response curve in this case. The steepness of a radiation dose-response curve is most conveniently quantified by the normalized dose-response gradient, gamma. Under the assumption of a linear-quadratic dose-effect model, a simple analytical relationship is derived between the gamma-value for a dose-response curve generated by varying the total dose while keeping the number of fractions constant, i.e. escalating the dose per fraction, and the gamma-value for a dose-response curve generated by varying the total dose while keeping the dose per fraction constant. This formulation is compared with clinical dose-response data from the literature and shown to be in good agreement with the observations. Some implications of this formulation for non-uniform dose distributions delivered using 3D conformal radiotherapy or intensity modulated radiotherapy (IMRT) are briefly discussed.

  18. Optimizing Collimator Margins for Isotoxically Dose-Escalated Conformal Radiation Therapy of Non-Small Cell Lung 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); Oxford Cancer Centre, Oxford University Hospitals, Oxford (United Kingdom); Panettieri, Vanessa [William Buckland Radiotherapy Centre, Alfred Hospital, Commercial Road, Melbourne (Australia); Panakis, Niki; Bates, Nicholas [Oxford Cancer Centre, Oxford University Hospitals, Oxford (United Kingdom); Lester, Jason F. [Velindre Cancer Centre, Velindre Road, Whitchurch, Cardiff (United Kingdom); Jain, Pooja [Clatterbridge Cancer Centre, Clatterbridge Road, Wirral (United Kingdom); Landau, David B. [Department of Radiotherapy, Guy' s and St. Thomas' NHS Foundation Trust, London (United Kingdom); Nahum, Alan E.; Mayles, W. Philip M. [Clatterbridge Cancer Centre, Clatterbridge Road, Wirral (United Kingdom); Fenwick, John D. [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom); Oxford Cancer Centre, Oxford University Hospitals, Oxford (United Kingdom)

    2014-04-01

    Purpose: Isotoxic dose escalation schedules such as IDEAL-CRT [isotoxic dose escalation and acceleration in lung cancer chemoradiation therapy] (ISRCTN12155469) individualize doses prescribed to lung tumors, generating a fixed modeled risk of radiation pneumonitis. Because the beam penumbra is broadened in lung, the choice of collimator margin is an important element of the optimization of isotoxic conformal radiation therapy for lung cancer. Methods and Materials: Twelve patients with stage I-III non-small cell lung cancer (NSCLC) were replanned retrospectively using a range of collimator margins. For each plan, the prescribed dose was calculated according to the IDEAL-CRT isotoxic prescription method, and the absolute dose (D{sub 99}) delivered to 99% of the planning target volume (PTV) was determined. Results: Reducing the multileaf collimator margin from the widely used 7 mm to a value of 2 mm produced gains of 2.1 to 15.6 Gy in absolute PTV D{sub 99}, with a mean gain ± 1 standard error of the mean of 6.2 ± 1.1 Gy (2-sided P<.001). Conclusions: For NSCLC patients treated with conformal radiation therapy and an isotoxic dose prescription, absolute doses in the PTV may be increased by using smaller collimator margins, reductions in relative coverage being offset by increases in prescribed dose.

  19. A Phase I trial of dose escalation of topotecan combined with whole brain radiotherapy for brain metastasis in lung cancer

    Institute of Scientific and Technical Information of China (English)

    Xiaohui Ge; Wenyan Zhao; Xiaocang Ren; Yongqiang Wang; Zhigang Li; Yanqi Li; Yuee Liu; Qiang Lin

    2012-01-01

    Objective: The aim of this study was to define the maximum-tolerated dose (MTD) and observe the toxicity of escalating topotecan combined whole brain radiotherapy for brain metastasis in lung cancer. Methods: Patients with brain metastasis of lung cancer received conventional fractionation radiotherapy, with 5 daily fractions of 2 Gy per week, the total radiation dose was 40 Gy, while the larger lesions were boosted to 50-60 Gy. The initial dose of topotecan was 1.0 mg/m2. Escalation dose was 0.25 mg/m2. 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: Eighteen patients were recruited. Two cases of grade 3 leucopenia/neutropenia was observed as DLT at the level of topotecan 2.0 mg/m2. MTD of topotecan was defined as 1.75 mg/m2.The major side effects were leucopenia/neutropenia, nausea and vomiting. Conclusion: Topotecan combined with whole brain radiotherapy for brain metastasis in lung cancer is well tolerated. Maximum-tolerated dose of topotecan is 1.75 mg/m2, once a week of a total of four.

  20. Cardiovascular pleiotropic actions of DPP-4 inhibitors: a step at the cutting edge in understanding their additional therapeutic potentials.

    Science.gov (United States)

    Balakumar, Pitchai; Dhanaraj, Sokkalingam A

    2013-09-01

    Dipeptidyl peptidase 4 (DPP-4) is a serine protease enzyme expressed widely in many tissues, including the cardiovascular system. The incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from the small intestine into the vasculature during a meal, and these incretins have a potential to release insulin from pancreatic beta cells of islets of Langerhans, affording a glucose-lowering action. However, both incretins are hurriedly degraded by the DPP-4. Inhibitors of DPP-4, therefore, enhance the bioavailability of GLP-1 and GIP, and thus have been approved for better glycemic management in patients afflicted with type 2 diabetes mellitus (T2DM). Five different DPP-4 inhibitors, often called as 'gliptins', namely sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin have been approved hitherto for clinical use. These drugs are used along with diet and exercise to lower blood sugar in diabetic subjects. T2DM is intricately related with an increased risk of cardiovascular disease. Growing body of evidence suggests that gliptins, in addition to their persuasive anti-diabetic action, have a beneficial pleiotropic action on the heart and vessels. In view of the fact of cardiovascular disease susceptibility of patients afflicted with T2DM, gliptins might offer additional therapeutic benefits in treating diabetic cardiovascular complications. Exploring further the cardiovascular pleiotropic potentials of gliptins might open a panorama in impeccably employing these agents for the dual management of T2DM and T2DM-associated perilous cardiovascular complications. This review will shed lights on the newly identified beneficial pleiotropic actions of gliptins on the cardiovascular system.

  1. Improving the Safety and Protective Automatic Actions of the CMS Electromagnetic Calorimeter Detector Control System

    CERN Document Server

    Jimenez Estupinan, Raul

    2017-01-01

    The CMS ECAL Detector Control System (DCS) features several monitoring mechanisms able to react and perform automatic actions based on pre-defined action matrices. The DCS is capable of early detection of anomalies inside the ECAL and on its off-detector support systems, triggering automatic actions to mitigate the impact of these events and preventing them from escalating to the safety system. The treatment of such events by the DCS allows for a faster recovery process, better understanding of the development of issues, and in most cases, actions with higher granularity than the safety system. This paper presents the details of the DCS automatic action mechanisms, as well as their evolution based on several years of CMS ECAL operations.

  2. A phase I dose-escalation study of MSC1992371A, an oral inhibitor of aurora and other kinases, in advanced hematologic malignancies.

    Science.gov (United States)

    Graux, Carlos; Sonet, Anne; Maertens, Johan; Duyster, Justus; Greiner, Jochen; Chalandon, Yves; Martinelli, Giovanni; Hess, Dagmar; Heim, Dominik; Giles, Francis J; Kelly, Kevin R; Gianella-Borradori, Athos; Longerey, Blandine; Asatiani, Ekaterine; Rejeb, Narmyn; Ottmann, Oliver G

    2013-09-01

    A phase I dose-escalation study of MSC1992371A, an oral aurora kinase inhibitor, was carried out in patients with hematologic malignancies. Patients received escalating doses either on days 1-3 and 8-10 (n=36) or on days 1-6 (n=39) of a 21-day cycle. The maximum tolerated doses were 37 and 28 mg/m(2)/day, respectively. Dose-limiting toxicities included severe neutropenia with infection and sepsis, mucositis/stomatitis, and diarrhea. Complete responses occurred in 3 patients. Four disease-specific expansion cohorts then received the dose and schedule dictated by the escalation phase but the study was prematurely discontinued due to hematologic and gastrointestinal toxicity at clinically effective doses. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Finite Element Caiculation of the Escalator Truss%自动扶梯桁架结构的有限元分析

    Institute of Scientific and Technical Information of China (English)

    丁建新; 高静丹

    2011-01-01

    介绍了自动扶梯桁架有限元分析的应用,借助通用有限元软件对自动扶梯进行静载分析,研究自动扶梯在满载时的力学特性,得到自动扶梯满载时的挠度、安全系数等各种计算结果。%The finite element application of escalator truss is introduced and the dead weight of escalator truss is analyzed with software. The escalator mechanical characteristic is researched when it is under full load, The results of deflection, safety factor are obtained.

  4. Effect of health-promoting posters placed on the platforms of two train stations in Copenhagen, Denmark, on the choice between taking the stairs or the escalators

    DEFF Research Database (Denmark)

    Iversen, Mette Kathrine; Händel, M N; Nydal Jensen, Eva;

    2007-01-01

    OBJECTIVE: The purpose of this study was to determine whether posters placed on the platforms of two train stations in Copenhagen, promoting use of the stairs, would encourage people to use the stairs rather than the adjacent escalator. An additional purpose was to see if the effect of the interv......OBJECTIVE: The purpose of this study was to determine whether posters placed on the platforms of two train stations in Copenhagen, promoting use of the stairs, would encourage people to use the stairs rather than the adjacent escalator. An additional purpose was to see if the effect...... of the intervention was maintained for a week after the poster was removed. MEASUREMENTS: The number of people using stairs and escalators at Copenhagen Central Station and Østerport Train Station in Copenhagen was recorded before and during posters promoting stair use were placed on the platforms, and a week after...

  5. 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

  6. Design and Analysis on Dalian Metro Station Escalators%大连地铁车站自动扶梯设计分析

    Institute of Scientific and Technical Information of China (English)

    孙晓亮

    2014-01-01

    Taking Dalian metro project as an example, the paper introduces the system design of metro station escalators. Focusing on three aspects of safety, comfort and performance, it makes a detailed analysis on the main design content of the escalators.%结合大连地铁项目,对地铁车站自动扶梯的设计进行了介绍,并针对安全性、乘坐舒适性和使用性能3个方面对自动扶梯的主要设计内容进行了详细的分析。

  7. Fatigue Design of Step Pin of the Escalator Chain%自动扶梯梯级链销轴的疲劳设计

    Institute of Scientific and Technical Information of China (English)

    王胜; 叶斌

    2012-01-01

    The normal type and structure of the escalator chain are introduced. Taking one type of the public transportation escalator as object, optimization design and three - dimensional modeling of step pin are carried out, the fatigue test of the design is carried out, and unlimited lifetime can he reached.%介绍梯级链常用型式和结构,选取公共交通型重载自动扶梯链为对象,对其梯级销轴进行三维建模和优化设计,并对设计进行疲劳测试,达到无限疲劳寿命.

  8. Uncertainty "escalation" and use of machine learning to forecast residual and data model uncertainties

    Science.gov (United States)

    Solomatine, Dimitri

    2016-04-01

    some variant of the Monte Carlo simulation when values of parameters or inputs are sampled from the assumed distributions and the model is run multiple times to generate multiple outputs. This is the most widely used approach. The data generated by Monte Carlo analysis can be used to build a machine learning model which will be able to make predictions of model uncertainty for the future his method is named MLUE (Machine Learning for Uncertainty Estimation) and is covered in [4,5] With this in mind, one may consider the following framework based on the stepwise "building up" (or "escalation") of the model uncertainty: • first consider the residual uncertainty of an optimal model M (X, p*) • then add and consider the model uncertainty due the parameters uncertainty (p) • then add and consider the model uncertainty due the data (mainly, input) uncertainty (X) • then add and consider the structural uncertainty of the model M (X, p). The paper presents the details of this framework and examples if its application in hydrological forecasting. This study is partly supported by the FP7 European Project WeSenseIt Citizen Water Observatory (www.http://wesenseit.eu/). References [1] Koenker, R., and G. Bassett (1978). Regression quantiles. Econometrica, 46(1), 33- 50, doi:10.2307/1913643. [2] D.L. Shrestha, D.P. Solomatine (2006). Machine learning approaches for estimation of prediction interval for the model output. Neural Networks J., 19(2), 225-235. [3] D.P. Solomatine, D.L. Shrestha (2009). A novel method to estimate model uncertainty using machine learning techniques. Water Resources Res. 45, W00B11. [4] D. L. Shrestha, N. Kayastha, and D. P. Solomatine. A novel approach to parameter uncertainty analysis of hydrological models using neural networks. Hydrol. Earth Syst. Sci., 13, 1235-1248, 2009. [5] F. Pianosi and L. Raso (2012). Dynamic modeling of predictive uncertainty by regression on absolute errors. WRR, 48, W03516. [6] Shrestha, D.L., Kayastha, N., Solomatine

  9. SU-E-T-183: Feasibility of Extreme Dose Escalation for Glioblastoma Multiforme Using 4π Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, D; Rwigema, J; Yu, V; Kaprealian, T; Kupelian, P; Selch, M; Low, D; Sheng, K [Department of Radiation Oncology, UCLA, Los Angeles, CA (United States)

    2014-06-01

    Purpose: GBM recurrence primarily occurs inside or near the high-dose radiation field of original tumor site requiring greater than 100 Gy to significantly improve local control. We utilize 4π non-coplanar radiotherapy to test the feasibility of planning target volume (PTV) margin expansions or extreme dose escalations without incurring additional radiation toxicities. Methods: 11 GBM patients treated with VMAT to a prescription dose of 59.4 Gy or 60 Gy were replanned with 4π. Original VMAT plans were created with 2 to 4 coplanar or non-coplanar arcs using 3 mm hi-res MLC. The 4π optimization, using 5 mm MLC, selected and inverse optimized 30 beams from a candidate pool of 1162 beams evenly distributed through 4π steradians. 4π plans were first compared to clinical plans using the same prescription dose. Two more studies were then performed to respectively escalate the GTV and PTV doses to 100 Gy, followed by a fourth plan expanding the PTV by 5 mm and maintaining the prescription dose. Results: The standard 4π plan significantly reduced (p<0.01) max and mean doses to critical structures by a range of 47.0–98.4% and 61.0–99.2%, respectively. The high dose PTV/high dose GTV/expanded PTV studies showed a reduction (p<0.05) or unchanged* (p>0.05) maximum dose of 72.1%/86.7%/77.1% (chiasm), 7.2%*/27.7%*/30.7% (brainstem), 39.8%*/84.2%/51.9%* (spinal cord), 69.0%/87.0%/66.9% (L eye), 76.2%/88.1%/84.1% (R eye), 95.0%/98.6%/97.5% (L lens), 93.9%/98.8%/97.6% (R lens), 74.3%/88.5%/72.4% (L optical nerve), 80.4%/91.3%/75.7% (R optical nerve), 64.8%/84.2%/44.9%* (L cochlea), and 85.2%/93.0%/78.0% (R cochlea), respectively. V30 and V36 for both brain and (brain - PTV) were reduced for all cases except the high dose PTV plan. PTV dose coverage increased for all 4π plans. Conclusion: Extreme dose escalation or further margin expansion is achievable using 4π, maintaining or reducing OAR doses. This study indicates that clinical trials employing 4π delivery using

  10. Phase I Trial of Pelvic Nodal Dose Escalation With Hypofractionated IMRT for High-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Adkison, Jarrod B.; McHaffie, Derek R.; Bentzen, Soren M.; Patel, Rakesh R.; Khuntia, Deepak [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, Madison, WI (United States); Petereit, Daniel G. [Department of Radiation Oncology, John T. Vucurevich Regional Cancer Care Institute, Rapid City Regional Hospital, Rapid City, SD (United States); Hong, Theodore S.; Tome, Wolfgang [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, Madison, WI (United States); Ritter, Mark A., E-mail: ritter@humonc.wisc.edu [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, Madison, WI (United States)

    2012-01-01

    Purpose: Toxicity concerns have limited pelvic nodal prescriptions to doses that may be suboptimal for controlling microscopic disease. In a prospective trial, we tested whether image-guided intensity-modulated radiation therapy (IMRT) can safely deliver escalated nodal doses while treating the prostate with hypofractionated radiotherapy in 5 Vulgar-Fraction-One-Half weeks. Methods and Materials: Pelvic nodal and prostatic image-guided IMRT was delivered to 53 National Comprehensive Cancer Network (NCCN) high-risk patients to a nodal dose of 56 Gy in 2-Gy fractions with concomitant treatment of the prostate to 70 Gy in 28 fractions of 2.5 Gy, and 50 of 53 patients received androgen deprivation for a median duration of 12 months. Results: The median follow-up time was 25.4 months (range, 4.2-57.2). No early Grade 3 Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events v.3.0 genitourinary (GU) or gastrointestinal (GI) toxicities were seen. The cumulative actuarial incidence of Grade 2 early GU toxicity (primarily alpha blocker initiation) was 38%. The rate was 32% for Grade 2 early GI toxicity. None of the dose-volume descriptors correlated with GU toxicity, and only the volume of bowel receiving {>=}30 Gy correlated with early GI toxicity (p = 0.029). Maximum late Grades 1, 2, and 3 GU toxicities were seen in 30%, 25%, and 2% of patients, respectively. Maximum late Grades 1 and 2 GI toxicities were seen in 30% and 8% (rectal bleeding requiring cautery) of patients, respectively. The estimated 3-year biochemical control (nadir + 2) was 81.2 {+-} 6.6%. No patient manifested pelvic nodal failure, whereas 2 experienced paraaortic nodal failure outside the field. The six other clinical failures were distant only. Conclusions: Pelvic IMRT nodal dose escalation to 56 Gy was delivered concurrently with 70 Gy of hypofractionated prostate radiotherapy in a convenient, resource-efficient, and well-tolerated 28-fraction schedule. Pelvic nodal dose

  11. Dose Escalation of Total Marrow Irradiation With Concurrent Chemotherapy in Patients With Advanced Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Jeffrey Y.C., E-mail: jwong@coh.org [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Forman, Stephen; Somlo, George [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Rosenthal, Joseph [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Department of Pediatrics, City of Hope National Medical Center, Duarte, California (United States); Liu An; Schultheiss, Timothy; Radany, Eric [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Palmer, Joycelynne [Department of Biostatistics, City of Hope National Medical Center, Duarte, California (United States); Stein, Anthony [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States)

    2013-01-01

    Purpose: We have demonstrated that toxicities are acceptable with total marrow irradiation (TMI) at 16 Gy without chemotherapy or TMI at 12 Gy and the reduced intensity regimen of fludarabine/melphalan in patients undergoing hematopoietic cell transplantation (HCT). This article reports results of a study of TMI combined with higher intensity chemotherapy regimens in 2 phase I trials in patients with advanced acute myelogenous leukemia or acute lymphoblastic leukemia (AML/ALL) who would do poorly on standard intent-to-cure HCT regimens. Methods and Materials: Trial 1 consisted of TMI on Days -10 to -6, etoposide (VP16) on Day -5 (60 mg/kg), and cyclophosphamide (CY) on Day -3 (100 mg/kg). TMI dose was 12 (n=3 patients), 13.5 (n=3 patients), and 15 (n=6 patients) Gy at 1.5 Gy twice daily. Trial 2 consisted of busulfan (BU) on Days -12 to -8 (800 {mu}M min), TMI on Days -8 to -4, and VP16 on Day -3 (30 mg/kg). TMI dose was 12 (n=18) and 13.5 (n=2) Gy at 1.5 Gy twice daily. Results: Trial 1 had 12 patients with a median age of 33 years. Six patients had induction failures (IF), and 6 had first relapses (1RL), 9 with leukemia blast involvement of bone marrow ranging from 10%-98%, 5 with circulating blasts (24%-85%), and 2 with chloromas. No dose-limiting toxicities were observed. Eleven patients achieved complete remission at Day 30. With a median follow-up of 14.75 months, 5 patients remained in complete remission from 13.5-37.7 months. Trial 2 had 20 patients with a median age of 41 years. Thirteen patients had IF, and 5 had 1RL, 2 in second relapse, 19 with marrow blasts (3%-100%) and 13 with peripheral blasts (6%-63%). Grade 4 dose-limiting toxicities were seen at 13.5 Gy (stomatitis and hepatotoxicity). Stomatitis was the most frequent toxicity in both trials. Conclusions: TMI dose escalation to 15 Gy is possible when combined with CY/VP16 and is associated with acceptable toxicities and encouraging outcomes. TMI dose escalation is not possible with BU/VP16 due to

  12. Harmful Algal Blooms in Asia: an insidious and escalating water pollution phenomenon with effects on ecological and human health

    Directory of Open Access Journals (Sweden)

    Patricia M Glibert

    2014-02-01

    Full Text Available Harmful Algal Blooms (HABs, those proliferations of algae that causeenvironmental, economic, or human health problems, are increasing in frequency,duration, and geographic extent due to nutrient pollution. The scale of the HABproblem in Asia has escalated in recent decades in parallel with the increase in useof agricultural fertilizer, the development of aquaculture, and a growing population.Three examples, all from China but illustrative of the diversity of events and theirecological, economic, and human health effects throughout Asia, are highlightedhere. These examples include inland (Lake Tai or Taihu as well as offshore (EastChina Sea and Yellow Sea waters. The future outlook for controlling these bloomsis bleak. The effects of advancing industrialized agriculture and a continually growingpopulation will continue to result in more nutrient pollution and more HABs—-and more effects - in the foreseeable future.

  13. Escalation of methamphetamine-related crime and fatalities in the Dresden region, Germany, between 2005 and 2011.

    Science.gov (United States)

    Pietsch, J; Paulick, T; Schulz, K; Flössel, U; Engel, A; Schmitter, S; Schmidt, U

    2013-12-10

    Methamphetamine (MA), a central nervous system stimulating recreational drug, is a worldwide problem related to crime as well as forensic and health aspects. The data, exemplarily presented in this study for the Dresden region, Saxony, Germany, demonstrate the escalation of MA-related crime and fatalities between 2005 and 2011. Easy availability and an attractive price of MA in the Czech Republic are responsible for both the increase of the occurrence of MA in relation to the entire drug crime as well as the increase of the occurrence of MA-positive cases of driving under influence (DUI). Higher percentage of very pure MA on the Saxon drug market since 2010 seems to be the reason for the fatalities directly caused by MA in 2010 and 2011.

  14. The Tripartite Model of Neuroticism and the suppression of depression and anxiety within an escalation of commitment dilemma.

    Science.gov (United States)

    Moon, Henry; Hollenbeck, John R; Humphrey, Stephen E; Maue, Brian

    2003-06-01

    We found evidence of a mutual suppression effect between anxiety and depression on an individual's level of commitment within escalation dilemmas. On the one hand, our results demonstrate a positive relationship between anxiety and level of commitment; on the other, our results demonstrate a negative relationship between depression and level of commitment. Based on the opposing relationships between anxiety and depression and commitment, the broad factor of neuroticism does not demonstrate any relationship with level of commitment, and the significant effects of anxiety and depression on commitment is contingent upon partialling the effect of the other facet of neuroticism. Thus, we contend that applied psychologists, who have focused on neuroticism as a broad construct, should consider the large body of work among clinical psychologists, who argue that anxiety and depression have unique variance associated with them. We conclude by addressing organizational implications of measuring the broad trait of neuroticism more narrowly.

  15. Pelvic nodal dose escalation with prostate hypofractionation using conformal avoidance defined (H-CAD) intensity modulated radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Theodore S.; Tome, Wolfgang A.; Jaradat, Hazim; Raisbeck, Bridget M.; Ritter, Mark A. [Univ. of Wisconsin Medical School, Madison, WI (United States). Dept. of Human Oncology

    2006-09-15

    The management of prostate cancer patients with a significant risk of pelvic lymph node involvement is controversial. Both whole pelvis radiotherapy and dose escalation to the prostate have been linked to improved outcome in such patients, but it is unclear whether conventional whole pelvis doses of only 45-50 Gy are optimal for ultimate nodal control. The purpose of this study is to examine the dosimetric and clinical feasibility of combining prostate dose escalation via hypofractionation with conformal avoidance-based IMRT (H-CAD) dose escalation to the pelvic lymph nodes. One conformal avoidance and one conventional plan were generated for each of eight patients. Conformal avoidance-based IMRT plans were generated that specifically excluded bowel, rectum, and bladder. The prostate and lower seminal vesicles (PTV 70) were planned to receive 70 Gy in 2.5 Gy/fraction while the pelvic lymph nodes (PTV 56) were to concurrently receive 56 Gy in 2 Gy/fraction. The volume of small bowel receiving >45 Gy was restricted to 300 ml or less. These conformal avoidance plans were delivered using helical tomotherapy or LINAC-based IMRT with daily imaging localization. All patients received neoadjuvant and concurrent androgen deprivation with a planned total of two years. The conventional, sequential plans created for comparison purposes for all patients consisted of a conventional 4-field pelvic box prescribed to 50.4 Gy (1.8 Gy/fraction) followed by an IMRT boost to the prostate of 25.2 Gy (1.8 Gy/fraction) yielding a final prostate dose of 75.6 Gy. For all plans, the prescription dose was to cover the target structure. Equivalent uniform dose (EUD) analyses were performed on all targets and dose-volume histograms (DVH) were displayed in terms of both physical and normalized total dose (NTD), i.e. dose in 2 Gy fraction equivalents. H-CAD IMRT plans were created for and delivered to all eight patients. Analysis of the H-CAD plans demonstrates prescription dose coverage of >95

  16. The role of motivation, responsibility, and integrative complexity in crisis escalation: comparative studies of war and peace crises.

    Science.gov (United States)

    Winter, David G

    2007-05-01

    Drawing on D. G. Winter's (1993) comparison of 1914 and the Cuban Missile Crisis, the author identified 8 paired crises (1 escalating to war, 1 peacefully resolved). Documents (diplomatic messages, speeches, official media commentary) from each crisis were scored for power, affiliation, and achievement motivation; text measures of responsibility and activity inhibition; and integrative complexity. Aggregated effect-size results show that war crises had significantly higher levels of power motivation and responsibility, whereas peace crises showed trends toward higher integrative complexity and achievement motivation. Follow-up analyses suggested that these results are robust with respect to both sides in a crisis, type of material scored, and historical time. The power motive results extend previous findings, but the responsibility results suggest that responsibility plays a paradoxical role in war. Future research directions are sketched, and the role of psychological content analysis in monitoring the danger of war is discussed.

  17. Dose-Escalated Hypofractionated Intensity-Modulated Radiotherapy in High-Risk Carcinoma of the Prostate: Outcome and Late Toxicity

    Directory of Open Access Journals (Sweden)

    David Thomson

    2012-01-01

    Results. Median followup was 84 months. Five-year overall survival (OS was 83% and biochemical progression-free survival (bPFS was 50% for 57 Gy. Five-year OS was 75% and bPFS 58% for 60 Gy. At 7 years, toxicity by RTOG criteria was acceptable with no grade 3 or above toxicity. Compared with baseline, there was no significant change in urinary symptoms at 2 or 7 years. Bowel symptoms were stable between 2 and 7 years. All patients continued to have significant sexual dysfunction. Conclusion. In high-risk prostate cancer, dose-escalated hypofractionated radiotherapy using IMRT results in encouraging outcomes and acceptable late toxicity.

  18. A Phase I Clinical and Pharmacology Study Using Amifostine as a Radioprotector in Dose-escalated Whole Liver Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Mary, E-mail: maryfeng@umich.edu [Department of Radiation Oncology, School of Medicine, University of Michigan, Ann Arbor, Michigan (United States); Smith, David E. [Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan (United States); Normolle, Daniel P. [Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Knol, James A. [Department of Surgery, School of Medicine, University of Michigan, Ann Arbor, Michigan (United States); Pan, Charlie C.; Ben-Josef, Edgar [Department of Radiation Oncology, School of Medicine, University of Michigan, Ann Arbor, Michigan (United States); Lu Zheng; Feng, Meihua R.; Chen Jun [Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan (United States); Ensminger, William [Department of Internal Medicine, School of Medicine, University of Michigan, Ann Arbor, Michigan (United States); Lawrence, Theodore S. [Department of Radiation Oncology, School of Medicine, University of Michigan, Ann Arbor, Michigan (United States)

    2012-08-01

    Purpose: Diffuse intrahepatic tumors are difficult to control. Whole-liver radiotherapy has been limited by toxicity, most notably radiation-induced liver disease. Amifostine is a prodrug free-radical scavenger that selectively protects normal tissues and, in a preclinical model of intrahepatic cancer, systemic amifostine reduced normal liver radiation damage without compromising tumor effect. We hypothesized that amifostine would permit escalation of whole-liver radiation dose to potentially control microscopic disease. We also aimed to characterize the pharmacokinetics of amifostine and its active metabolite WR-1065 to optimize timing of radiotherapy. Methods and Materials: We conducted a radiation dose-escalation trial for patients with diffuse, intrahepatic cancer treated with whole-liver radiation and intravenous amifostine. Radiation dose was assigned using the time-to-event continual reassessment method. A companion pharmacokinetic study was performed. Results: Twenty-three patients were treated, with a maximum dose of 40 Gy. Using a logistical regression model, compared with our previously treated patients, amifostine increased liver tolerance by 3.3 {+-} 1.1 Gy (p = 0.007) (approximately 10%) with similar response rates. Peak concentrations of WR-1065 were 25 {mu}M with an elimination half-life of 1.5 h; these levels are consistent with radioprotective effects of amifostine in patients. Conclusion: These findings demonstrate for the first time that amifostine is a normal liver radioprotector. They further suggest that it may be useful to combine amifostine with fractionated or stereotactic body radiation therapy for patients with focal intrahepatic cancer.

  19. Escalating dose pretreatment induces pharmacodynamic and not pharmacokinetic tolerance to a subsequent high-dose methamphetamine binge.

    Science.gov (United States)

    O'Neil, Meghan L; Kuczenski, Ronald; Segal, David S; Cho, Arthur K; Lacan, Goran; Melega, William P

    2006-11-01

    A major feature of human methamphetamine (METH) abuse is the gradual dose escalation that precedes high-dose exposure. The period of escalating doses (EDs) is likely associated with development of tolerance to aspects of METH's pharmacologic and toxic effects but the relative contributions of pharmacokinetic and pharmacodynamic factors have not been well defined. In our prior studies in rats, we showed that pretreatment with an ED-METH regimen (0.1-4.0 mg/kg over 14 days) attenuated the toxicity of a subsequently administered high-dose METH binge (4 x 6 mg/kg at 2 h interval) that itself produced behavioral stereotypy, increases in core temperature, and decreases in DA system phenotypic markers in caudate-putamen (CP). Using those ED-METH and binge protocols in the present studies, pharmacokinetic and pharmacodynamic parameters that may have contributed to the apparent neuroprotection afforded by ED-METH were assessed. The ED-METH regimen itself reduced [(3)H]WIN35,428 (WIN) binding to the dopamine transporter (DAT) by 15% in CP, but did not affect DA content. During the METH binge, ED-METH pretreated animals showed attenuated increases in core temperature while concurrent microdialysis studies in CP showed a reduced DA response despite unaltered extracellular levels of METH. At 1 h after the binge, concentrations of METH and its metabolite amphetamine in brain and plasma were unaffected by the ED-METH. The results show that ED-METH pretreatment produces reductions in DAT binding and the DA response during a subsequent METH binge by altering pharmacodynamic and not pharmacokinetic parameters.

  20. 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.

  1. Safety and immunogenicity of the PRAME cancer immunotherapeutic in metastatic melanoma: results of a phase I dose escalation study

    Science.gov (United States)

    Gutzmer, R; Rivoltini, L; Levchenko, E; Testori, A; Utikal, J; Ascierto, P A; Demidov, L; Grob, J J; Ridolfi, R; Schadendorf, D; Queirolo, P; Santoro, A; Loquai, C; Dreno, B; Hauschild, A; Schultz, E; Lesimple, T P; Vanhoutte, N; Salaun, B; Gillet, M; Jarnjak, S; De Sousa Alves, P M; Louahed, J; Brichard, V G; Lehmann, F F

    2016-01-01

    Purpose The PRAME tumour antigen is expressed in several tumour types but in few normal adult tissues. A dose-escalation phase I/II study (NCT01149343) assessed the safety, immunogenicity and clinical activity of the PRAME immunotherapeutic (recombinant PRAME protein (recPRAME) with the AS15 immunostimulant) in patients with advanced melanoma. Here, we report the phase I dose-escalation study segment. Patients and methods Patients with stage IV PRAME-positive melanoma were enrolled to 3 consecutive cohorts to receive up to 24 intramuscular injections of the PRAME immunotherapeutic. The RecPRAME dose was 20, 100 or 500 µg in cohorts 1, 2 and 3, respectively, with a fixed dose of AS15. Adverse events (AEs), including predefined dose-limiting toxicity (DLT) and the anti-PRAME humoral response (ELISA), were coprimary end points. Cellular immune responses were evaluated using in vitro assays. Results 66 patients were treated (20, 24 and 22 in the respective cohorts). AEs considered by the investigator to be causally related were mostly grade 1 or 2 injection site symptoms, fatigue, chills, fever and headache. Two DLTs (grade 3 brain oedema and proteinuria) were recorded in two patients in two cohorts (cohorts 2 and 3). All patients had detectable anti-PRAME antibodies after four immunisations. Percentages of patients with predefined PRAME-specific-CD4+T-cell responses after four immunisations were similar in each cohort. No CD8+ T-cell responses were detected. Conclusions The PRAME immunotherapeutic had an acceptable safety profile and induced similar anti-PRAME-specific humoral and cellular immune responses in all cohorts. As per protocol, the phase II study segment was initiated to further evaluate the 500 µg PRAME immunotherapeutic dose. Trial registration number NCT01149343, Results. PMID:27843625

  2. Genetic mapping of escalated aggression in wild-derived mouse strain MSM/Ms: association with serotonin-related genes

    Directory of Open Access Journals (Sweden)

    Aki eTakahashi

    2014-06-01

    Full Text Available The Japanese wild-derived mouse strain MSM/Ms (MSM retains a wide range of traits related to behavioral wildness, including high levels of emotionality and avoidance of humans. In this study, we observed that MSM showed a markedly higher level of aggression than the standard laboratory strain C57BL/6J. Whereas almost all MSM males showed high frequencies of attack bites and pursuit in the resident-intruder test, only a few C57BL/6J males showed aggressive behaviors, with these behaviors observed at only a low frequency. Sexually mature MSM males in their home cages killed their littermates, or sometimes female pair-mates. To study the genetic and neurobiological mechanisms that underlie the escalated aggression observed in MSM mice, we analyzed reciprocal F1 crosses and five consomic strains of MSM (Chr 4, 13, 15, X and Y against the background of C57BL/6J. We identified two chromosomes, Chr 4 and Chr 15, which were involved in the heightened aggression observed in MSM. These chromosomes had different effects on aggression: whereas MSM Chr 15 increased agitation and initiation of aggressive events, MSM Chr 4 induced a maladaptive level of aggressive behavior. Expression analysis of mRNAs of serotonin receptors, serotonin transporter and Tph2, an enzyme involved in serotonin synthesis in seven brain areas, indicated several differences among MSM, C57BL/6J, and their consomic strains. We found that Tph2 expression in the midbrain was increased in the Chr 4 consomic strain, as well as in MSM, and that there was a strong positive genetic correlation between aggressive behavior and Tph2 expression at the mRNA level. Therefore, it is possible that increased expression of the Tph2 gene is related to escalated aggression observed in MSM.

  3. Stereotactic Body Radiation Therapy for Prostate Cancer: Review of Experience of a Multicenter Phase I/II Dose Escalation Study

    Directory of Open Access Journals (Sweden)

    D. Nathan W. Kim

    2014-11-01

    Full Text Available Introduction: Stereotactic body radiation therapy (SBRT is an area of active investigation for treatment of prostate cancer. In our phase I dose escalation study maximum tolerated dose was not reached, and subsequently phase II study has been completed. The purpose of this article is to review our experiences of dose escalated SBRT for localized prostate cancer. Methods and Materials: Patients enrolled to phase I/II study from 2006-2011 were reviewed. Prescription dose groups were 45, 47.5 and 50 Gray (Gy in 5 fractions over 2.5 weeks. Toxicity and quality of life questionnaire data were collected and analyzed. Descriptive statistics were obtained in the form of means, medians, and ranges for the continuous variables, and frequencies and percentages for the categoric variables. Results: 91 patients were enrolled from five institutions. Median follow up for PSA evaluation was 42 months. PSA control remains at 99%. While the maximum tolerated dose was not reached in the phase I study, excess high grade rectal toxicity (10.6% was noted in the phase II study. The 13 patients treated to 50 Gy in the phase I study that did not have high grade rectal toxicity, in retrospect met these parameters and have not had further events on longer follow up. Conclusion: PSA control rate, even for patients with intermediate risk, is thus far excellent at these dose levels. This study provides a platform for exploration of SBRT based clinical trials aimed at optimizing outcome for intermediate and high risk patients. High grade toxicities specifically related to the rectum were observed in a small but meaningful minority at the highest dose level. Dose constraints based on physiologic parameters have been defined to mitigate this risk, and strategies to minimize rectal exposure to such doses are being explored.

  4. Ketamine augmentation for outpatients with treatment-resistant depression: Preliminary evidence for two-step intravenous dose escalation.

    Science.gov (United States)

    Cusin, Cristina; Ionescu, Dawn Flosnik; Pavone, Kara Jean; Akeju, Oluwaseun; Cassano, Paolo; Taylor, Norman; Eikermann, Matthias; Durham, Kelley; Swee, Michaela Ballentyne; Chang, Trina; Dording, Christina; Soskin, David; Kelley, John; Mischoulon, David; Brown, Emery Neal; Fava, Maurizio

    2017-01-01

    Preliminary evidence supports the safety and efficacy of subanesthetic ketamine as an experimental antidepressant, although its effects are often not sustained beyond one week. Studies are lacking that have examined the sustained effects of escalating ketamine doses as augmentation in outpatients with treatment-resistant depression. Therefore, the aims of this study were twofold: (1) to assess the safety and antidepressant efficacy of two-step, repeated-dose ketamine augmentation and (2) to assess the duration of ketamine's antidepressant efficacy as augmentation to ongoing antidepressant pharmacotherapy for 3 months after the final infusion. Fourteen patients with treatment-resistant depression were eligible to receive augmentation with six open-label intravenous ketamine infusions over 3 weeks. For the first three infusions, ketamine was administered at a dose of 0.5 mg/kg over 45 minutes; the dose was increased to 0.75 mg/kg over 45 minutes for the subsequent three infusions. The primary outcome measure was response (as measured on Hamilton Depression Rating Scale-28 items). After the completion of three ketamine infusions, 7.1% (1/14) responded; after all six ketamine infusions, 41.7% (5/12) completers responded and 16.7% (2/12) remitted. Intent-to-treat response and remission rates at the end of the final infusion were 35.7% (5/14) and 14.3% (2/14), respectively. However, all but one responder relapsed within 2 weeks after the final infusion. Repeated, escalating doses of intravenous ketamine augmentation were preliminarily found to be feasible, efficacious and well tolerated. Interaction with concomitant medications and elevated level of treatment resistance are possible factors for non-response.

  5. 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.

  6. Feasibility of PET-CT based hypofractionated accelerated dose escalation in oropharyngeal cancers: Final dosimetric results of the VORTIGERN study. (Secondary endpoint of UK NCRI portfolio: MREC No: 08/H0907/127, UKCRN ID 7341

    Directory of Open Access Journals (Sweden)

    Sanjoy Chatterjee

    2015-01-01

    Conclusion: Hypofractionated, slightly accelerated dose escalation in oropharyngeal cancers is likely to be safe and the chance of trismus is not any higher than when standard dose radiotherapy is used. Active measures to reduce dose to the MA achieves acceptable dose volume parameters even at escalated doses.

  7. Exploring the Feasibility of Dose Escalation Positron Emission Tomography-Positive Disease with Intensity-Modulated Radiation Therapy and the Effects on Normal Tissue Structures for Thoracic Malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Turner, Lehendrick M., E-mail: lehendrickt@yahoo.com [University of Texas M. D. Anderson Cancer Center School of Health Professions, Medical Dosimetry Program, Houston, TX (United States); Howard, Joshua A.; Dehghanpour, Pouya; Barrett, Renee D. [University of Texas M. D. Anderson Cancer Center School of Health Professions, Medical Dosimetry Program, Houston, TX (United States); Rebueno, Neal; Palmer, Matthew [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Vedam, Sastry [Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Klopp, Ann; Komaki, Ritsuko; Welsh, James W. [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)

    2011-01-01

    The pattern of failure is one of the major causes of mortality among thoracic patients. Studies have shown a correlation between local control and dose. Intensity-modulated radiation therapy (IMRT) has resulted in conformal dose distributions while limiting dose to normal tissue. However, thoracic malignancies treated with IMRT to highly conformal doses up to 70 Gy still have been found to fail. Thus, the need for dose escalation through simultaneous integrated boost (SIB) may prove effective in minimizing reoccurrences. For our study, 28 thoracic IMRT plans were reoptimized via dose escalation to the gross tumor volume (GTV) and planning target volume (PTV) of 79.2 Gy and 68.4 Gy, respectively. Reoccurrences in surrounding regions of microscopic disease are rare therefore, dose-escalating regional nodes (outside GTV) were not included. Hence, the need to edit GTV margins was acceptable for our retrospective study. A median dose escalation of approximately 15 Gy (64.8-79.2 Gy) via IMRT using SIB was deemed achievable with minimal percent differences received by critical structures compared with the original treatment plan. The target's mean doses were significantly increased based on p-value analysis, while the normal tissue structures were not significantly changed.

  8. Isotoxic dose escalation in the treatment of lung cancer by means of heterogeneous dose distributions in the presence of respiratory motion

    DEFF Research Database (Denmark)

    Baker, Mariwan; Nielsen, Morten; Hansen, Olfred;

    2011-01-01

    To test, in the presence of intrafractional respiration movement, a margin recipe valid for a homogeneous and conformal dose distribution and to test whether the use of smaller margins combined with heterogeneous dose distributions allows an isotoxic dose escalation when respiratory motion is con...

  9. Extended schedule, escalated dose temozolomide versus dacarbazine in stage IV melanoma: final results of a randomised phase III study (EORTC 18032)

    NARCIS (Netherlands)

    Patel, P.M.; Suciu, S.; Mortier, L.; Kruit, W.H.; Robert, C.; Schadendorf, D.; Trefzer, U.; Punt, C.J.A.; Dummer, R.; Davidson, N.; Becker, J.; Conry, R.; Thompson, J.A.; Hwu, W.J.; Engelen, K. van; Agarwala, S.S.; Keilholz, U.; Eggermont, A.M.M.; Spatz, A.

    2011-01-01

    PURPOSE: To compare the efficacy of an extended schedule escalated dose of temozolomide versus standard dose dacarbazine in a large population of patients with stage IV melanoma. PATIENTS AND METHODS: A total of 859 patients were randomised to receive oral temozolomide at 150 mg/m(2)/day for seven c

  10. Adaptation requirements due to anatomical changes in free-breathing and deep-inspiration breath-hold for standard and dose-escalated radiotherapy of lung cancer patients

    DEFF Research Database (Denmark)

    Sibolt, Patrik; Ottosson, Wiviann; Sjöström, David;

    2015-01-01

    Background. Radiotherapy of lung cancer patients is subject to uncertainties related to heterogeneities, anatomical changes and breathing motion. Use of deep-inspiration breath-hold (DIBH) can reduce the treated volume, potentially enabling dose-escalated (DE) treatments. This study was designed...

  11. 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; Jensen, Lars Henrik; Sorensen, Morten;

    2011-01-01

    ) 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...

  12. Implicit Emotion Regulation: Protecting the Self Against Escalating Affective States%内隐情绪调节:一种有效的自我保护

    Institute of Scientific and Technical Information of China (English)

    任俊; 朱琼嫦

    2015-01-01

    Implicit emotion regulation is an important form of emotion regulation. It is a process aimed at modifying the quality, intensity, or duration of an emotional response without the need for conscious supervision or explicit intentions. The underlying psychological mechanism of implicit emotion regulation is automatic counter-regulation, which produces balance in affective processing and thus protects the self against escalating affective and motivational states. Experimental studies of counter-regulation typically comprise of two successive steps, which are (1) inducing a particular emotion (positive vs. negative), (2) establishing an implicit counter-regulation process. Implicit emotion regulation mainly activates the anterior cingulate cortex, ventrolateral prefrontal cortex and ventral medial prefrontal cortex. The main forms of implicit emotion regulation are implicit cognitive reappraisal, affect labeling and habitual practice. The efficiency of implicit emotion regulation is also affected by individual differences (e.g., action vs. state orientation, psychopathology), and by the intensity of emotional experience (automatic counter-regulation is stronger for intense emotions).%内隐情绪调节是情绪调节的一种重要形式, 它是指个体在没有意识监控和意图的情况下改变了自身情绪反应的品质、强度和持续时间等的一种情绪活动过程.内隐情绪调节的内部机制是自动反向调节, 它能让个体的情绪保持平衡状态, 具有自我保护作用; 其实验研究过程一般分为诱导特定情绪、引发内隐调节过程两个步骤.内隐情绪调节涉及的脑区主要有前扣带回皮层、腹外侧前额叶皮层和腹内侧前额叶皮层.内隐情绪调节的形式包括内隐认知重评和情绪标签等, 这些调节方式本身可能受个体差异、情绪体验强度等多种因素的影响.

  13. 根据效率曲线及负载特点合理配置扶梯主机%Configuration of Escalator Machine Based on Efficiency Curve and Load Pattern

    Institute of Scientific and Technical Information of China (English)

    陈正

    2014-01-01

    叙述了扶梯的负载特点、扶梯主机效率曲线的应用、扶梯主机损耗和效率的影响因素、电机和减速箱的类型及其在扶梯中的应用特点,给扶梯主机的合理配置和节能应用提供了实用性的参考建议。%Describe escalator load pattern characters, escalator machine efficiency curve, escalator machine power loss and efficiency impact factors, analyze motor and gearbox type and respective application purpose for escalator, recommend practical reference comment for escalator machine reasonable configuration and energy-saving application.

  14. 轨道交通站内自动扶梯通行能力分析%Analysis of passenger capacity of escalator at metro station

    Institute of Scientific and Technical Information of China (English)

    孟宪强; 廖明军; 王凯英

    2012-01-01

    For the planning and configuration of escalator at metro station, the characteristics and the process of passengers who use escalator are surveyed; the passing behavior of passengers under different congestion and the factors that influence the capacity of escalators are analyzed. A computation model of the capacity of escalators is built based on the physical and operational characteristics of escalator, and two kinds of passing behavior are assumed; one is all the passengers standing still on the escalator, the other is half passengers standing and half passengers walking, and the passenger distribution coefficients on escalator under the two conditions are also assumed. The passenger flow on escalators of Shanghai metro stations during the rush hour is surveyed, and the observed capacity of passenger flow is got by using statistical method, and then the observed data is compared with the data that are provided by the manufacturers. The result shows that the capacity of escalator provided by the manufacturer and the metro des-gin code are greater than the observed data. Thus the recommended capacity of escalator with width of 1 m and the operating speed of 0.5 m/s is 5 200 persons/(h · m).%为规划和配置轨道交通站的自动扶梯,对轨道交通站内乘客使用自动扶梯的方式和过程进行观测,分析乘客在不同拥挤情况下通过自动扶梯的行为以及影响自动扶梯通行能力的因素;基于自动扶梯的物理和工作特性,假定乘客站立、一半站立和一半行走两种通过行为,以及乘客在自动扶梯上的分布系数,构建自动扶梯通行能力计算模型.在上海地铁站内,调查高峰期自动扶梯的流量,运用统计方法得到实际观测的自动扶梯通行能力,并将其与厂家提供的通行能力数据进行比较.结果表明,厂家和规范数据稍偏大.推荐设计速度为0.5 m/s,宽为1 m的自动扶梯的通行能力为5 200人/(h·m).

  15. Lack of benefit for the addition of androgen deprivation therapy to dose-escalated radiotherapy in the treatment of intermediate- and high-risk prostate cancer.

    LENUS (Irish Health Repository)

    Krauss, Daniel

    2012-02-01

    PURPOSE: Assessment of androgen deprivation therapy (ADT) benefits for prostate cancer treated with dose-escalated radiotherapy (RT). METHODS AND MATERIALS: From 1991 to 2004, 1,044 patients with intermediate- (n = 782) or high-risk (n = 262) prostate cancer were treated with dose-escalated RT at William Beaumont Hospital. Patients received external-beam RT (EBRT) alone, brachytherapy (high or low dose rate), or high dose rate brachytherapy plus pelvic EBRT. Intermediate-risk patients had Gleason score 7, prostate-specific antigen (PSA) 10.0-19.9 ng\\/mL, or Stage T2b-T2c. High-risk patients had Gleason score 8-10, PSA >\\/=20, or Stage T3. Patients were additionally divided specifically by Gleason score, presence of palpable disease, and PSA level to further define subgroups benefitting from ADT. RESULTS: Median follow-up was 5 years; 420 patients received ADT + dose-escalated RT, and 624 received dose-escalated RT alone. For all patients, no advantages in any clinical endpoints at 8 years were associated with ADT administration. No differences in any endpoints were associated with ADT administration based on intermediate- vs. high-risk group or RT modality when analyzed separately. Patients with palpable disease plus Gleason >\\/=8 demonstrated improved clinical failure rates and a trend toward improved survival with ADT. Intermediate-risk patients treated with brachytherapy alone had improved biochemical control when ADT was given. CONCLUSION: Benefits of ADT in the setting of dose-escalated RT remain poorly defined. This question must continue to be addressed in prospective study.

  16. Concept Design of the Double-spiral Escalator%关于双螺旋形自动扶梯的概念设计

    Institute of Scientific and Technical Information of China (English)

    田慧勇; 李玉翔

    2012-01-01

    在对三菱电机公司的螺旋形自动扶梯分析的基础上,指出了人们对螺旋形自动扶梯的功能和结构的认识误区;建议以新的空间观念、结构理念和机械手段来解决现有的螺旋形自动扶梯的设计和制造的理想度,基于Triz理论分析并提出了螺旋形自动扶梯的功能核心和技术难点。同时指出现有设计理念中螺旋形自动扶梯各个系统之间的问题,如空间结构、动力学模型、机构设置等,都是源于人们一直固守的链式传动机制。%According to the analysis of the spiral escalator made by Mitsubishi Electric Corporation, this paper points out the misunderstanding to the function and the construction of the spiral escalator and the current design concept for the spiral escalator such as its space construction, dynamic model and mechanism setting etc. originating from the chain transmission theory, and puts forward the core function and the technical difficulties of the spiral escalator design based on Triz theoretical analysis. It also suggests how to get the ideal of the spiral escalator design and the manufacture with the new space idea, the new structure concept and the new mechanical means.

  17. HIV infection and tuberculosis in South Africa: an urgent need to escalate the public health response.

    Science.gov (United States)

    Abdool Karim, Salim S; Churchyard, Gavin J; Karim, Quarraisha Abdool; Lawn, Stephen D

    2009-09-12

    One of the greatest challenges facing post-apartheid South Africa is the control of the concomitant HIV and tuberculosis epidemics. HIV continues to spread relentlessly, and tuberculosis has been declared a national emergency. In 2007, South Africa, with 0.7% of the world's population, had 17% of the global burden of HIV infection, and one of the world's worst tuberculosis epidemics, compounded by rising drug resistance and HIV co-infection. Until recently, the South African Government's response to these diseases has been marked by denial, lack of political will, and poor implementation of policies and programmes. Nonetheless, there have been notable achievements in disease management, including substantial improvements in access to condoms, expansion of tuberculosis control efforts, and scale-up of free antiretroviral therapy (ART). Care for acutely ill AIDS patients and long-term provision of ART are two issues that dominate medical practice and the health-care system. Decisive action is needed to implement evidence-based priorities for the control of the HIV and tuberculosis epidemics. By use of the framework of the Strategic Plans for South Africa for tuberculosis and HIV/AIDS, we provide prioritised four-step approaches for tuberculosis control, HIV prevention, and HIV treatment. Strong leadership, political will, social mobilisation, adequate human and financial resources, and sustainable development of health-care services are needed for successful implementation of these approaches.

  18. 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

  19. Acute toxicity evaluation of proliferol: a dose-escalating, placebo-controlled study in rats.

    Science.gov (United States)

    Dagenais, Simon; Mayer, John; Wooley, James R; Haldeman, Scott; Hite, Mark

    2007-01-01

    Proliferol is an investigational new drug containing lidocaine hydrochloride 0.25%, dextrose 12.5%, glycerin 12.5%, and phenol 1.0% in aqueous solution. Despite extensive human experience with similar drugs administered by intraligamentous injection for chronic musculoskeletal disorders, little is known concerning preclinical toxicity. The purpose of this study was to assess the acute toxicity of intramuscular Proliferol in 96 (48 male, 48 female) Charles River strain rats, which were randomly assigned to low- (1x), medium- (5x), or high- (10x) dose Proliferol (derived from a human dose of 20 ml on a volume per bodyweight basis), or high-dose saline placebo. Observations included clinical observations, biochemistry, hematology, urinalysis, and full histopathology after 24 h or 14 days. There were no signs of ill health or reaction to treatment, and gait and body temperature were within normal limits. Biochemistry findings at 24 h included elevated aspartate aminotransferase, alanine aminotransferase, and haptoglobin; at 14 days all values were within normal ranges. Urinalysis findings at 24 h included increased urobilinogen and blood in all dose groups compared with placebo. Urine concentrations of phenol and lidocaine were greatest at 2 h and absent at 24 h. Histopathology findings included localized acute inflammatory soft tissue changes at the injection sites at 24 h and skeletal muscle regeneration at 14 days, which were consistent with the anticipated mechanism of action of Proliferol. There was no evidence of systemic toxicity from intramuscular injection of Proliferol in rats at up to 10x the human dose.

  20. Impulsive action and motivation

    NARCIS (Netherlands)

    Frijda, N.H.

    2010-01-01

    This paper explores the way in which emotions are causal determinants of action. It argues that emotional events, as appraised by the individual, elicit changes in motive states (called states of action readiness), which in turn may (or may not) cause action. Actions can be elicited automatically,

  1. Action Research: Rethinking Lewin.

    Science.gov (United States)

    Dickens, Linda; Watkins, Karen

    1999-01-01

    Explores both historical and contemporary definitions of action research. Describes the process and goals of action research in the tradition of Lewin. Presents a case study of an action-research project involving two teams in a high-technology corporation that depicts the process in action. (Author/CCM)

  2. Limits of dose escalation in lung cancer: a dose-volume histogram analysis comparing coplanar and non-coplanar techniques

    Energy Technology Data Exchange (ETDEWEB)

    Derycke, S.; Van Duyse, B.; Schelfhout, J.; De Neve, W.

    1995-12-01

    To evaluate the feasibility of dose escalation in radiotherapy of inoperable lung cancer, a dose-volume histogram analysis was performed comparing standard coplanar (2D) with non-coplanar (3D) beam arrangements on a non-selected group of 20 patients planned by Sherouse`s GRATISTM 3D-planning system. Serial CT-scanning was performed and 2 Target Volumes (Tvs) were defined. Gross Tumor Volume (GTV) defined a high-dose Target Volume (TV-1). GTV plus location of node stations with > 10% probability of invasion (Minet et al.) defined an intermediate-dose Target Volume (TV-2). However, nodal regions which are incompatible with cure were excluded from TV-2. These are ATS-regions 1, 8, 9 and 14 all left and right as well as heterolateral regions. For 3D-planning, Beam`s Eye View selected (by an experienced planner) beam arrangements were optimised using Superdot, a method of target dose-gradient annihilation developed by Sherouse. A second 3D-planning was performed using 4 beam incidences with maximal angular separation. The linac`s isocenter for the optimal arrangement was located at the geometrical center of gravity of a tetraheder, the tetraheder`s comers being the consecutive positions of the virtual source. This ideal beam arrangement was approximated as close as possible, taking into account technical limitations (patient-couch-gantry collisions). Criteria for tolerance were met if no points inside the spinal cord exceeded 50 Gy and if at least 50% of the lung volume received less than 20Gy. If dose regions below 50 Gy were judged acceptable at TV-2, 2D- as well as 3D-plans allow safe escalation to 80 Gy at TV-1. When TV-2 needed to be encompassed by isodose surfaces exceeding 50Gy, 3D-plans were necessary to limit dose at the spinal cord below tolerance. For large TVs dose is limited by lung tolerance for 3D-plans. An analysis (including NTCP-TCP as cost functions) of rival 3D-plans is being performed.

  3. Trigeminal Neuralgia Treated With Stereotactic Radiosurgery: The Effect of Dose Escalation on Pain Control and Treatment Outcomes.

    Science.gov (United States)

    Kotecha, Rupesh; Kotecha, Ritesh; Modugula, Sujith; Murphy, Erin S; Jones, Mark; Kotecha, Rajesh; Reddy, Chandana A; Suh, John H; Barnett, Gene H; Neyman, Gennady; Machado, Andre; Nagel, Sean; Chao, Samuel T

    2016-09-01

    To analyze the effect of dose escalation on treatment outcome in patients undergoing stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN). A retrospective review was performed of 870 patients who underwent SRS for a diagnosis of TN from 2 institutions. Patients were typically treated using a single 4-mm isocenter placed at the trigeminal nerve dorsal root entry zone. Patients were divided into groups based on treatment doses: ≤82 Gy (352 patients), 83 to 86 Gy (85 patients), and ≥90 Gy (433 patients). Pain response was classified using a categorical scoring system, with fair or poor pain control representing treatment failure. Treatment-related facial numbness was classified using the Barrow Neurological Institute scale. Log-rank tests were performed to test differences in time to pain failure or development of facial numbness for patients treated with different doses. Median age at first pain onset was 63 years, median age at time of SRS was 71 years, and median follow-up was 36.5 months from the time of SRS. A majority of patients (827, 95%) were clinically diagnosed with typical TN. The 4-year rate of excellent to good pain relief was 87% (95% confidence interval 84%-90%). The 4-year rate of pain response was 79%, 82%, and 92% in patients treated to ≤82 Gy, 83 to 86 Gy, and ≥90 Gy, respectively. Patients treated to doses ≤82 Gy had an increased risk of pain failure after SRS, compared with patients treated to ≥90 Gy (hazard ratio 2.0, P=.0007). Rates of treatment-related facial numbness were similar among patients treated to doses ≥83 Gy. Nine patients (1%) were diagnosed with anesthesia dolorosa. Dose escalation for TN to doses >82 Gy is associated with an improvement in response to treatment and duration of pain relief. Patients treated at these doses, however, should be counseled about the increased risk of treatment-related facial numbness. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Third parties, violence, and conflict resolution: the role of group size and collective action in the microregulation of violence.

    Science.gov (United States)

    Levine, Mark; Taylor, Paul J; Best, Rachel

    2011-03-01

    Although researchers know much about the causes of aggression, they know surprisingly little about how aggression leads to violence or how violence is controlled. To explore the microregulation of violence, we conducted a systematic behavioral analysis of footage from closed-circuit television surveillance of public spaces. Using 42 incidents involving 312 people, we compared aggressive incidents that ended in violence with those that did not. Behaviors of antagonists and third parties were coded as either escalating or conciliatory acts. Results showed that third parties were more likely to take conciliatory actions than to escalate violence and that this tendency increased as group size increased. This analysis revealed a pattern of third-party behaviors that prevent aggression from becoming violent and showed that conciliatory behaviors are more successful when carried out by multiple third parties than when carried out by one person. We conclude by emphasizing the importance of collective third-party dynamics in understanding conflict resolution.

  5. Hybrid Action Systems

    DEFF Research Database (Denmark)

    Rönnkö, M.; Ravn, Anders Peter; Sere, K.

    2003-01-01

    In this paper we investigate the use of action systems with differential actions in the specifcation of hybrid systems. As the main contribution we generalize the definition of a differential action, allowing the use of arbitrary relations over model variables and their time-derivatives in modell......In this paper we investigate the use of action systems with differential actions in the specifcation of hybrid systems. As the main contribution we generalize the definition of a differential action, allowing the use of arbitrary relations over model variables and their time...... parallel composition. Moreover, as the strength of the action system formalism is the support for stepwise development by refinement, we investigate refinement involving a differential action. We show that, due to the predicate transformer semantics, standard action refinement techniques apply also...... to the differential action, thus, allowing stepwise development of hybrid systems Udgivelsesdato: JAN 1...

  6. Changing the future of obesity: science, policy, and action.

    Science.gov (United States)

    Gortmaker, Steven L; Swinburn, Boyd A; Levy, David; Carter, Rob; Mabry, Patricia L; Finegood, Diane T; Huang, Terry; Marsh, Tim; Moodie, Marjory L

    2011-08-27

    The global obesity epidemic has been escalating for four decades, yet sustained prevention efforts have barely begun. An emerging science that uses quantitative models has provided key insights into the dynamics of this epidemic, and enabled researchers to combine evidence and to calculate the effect of behaviours, interventions, and policies at several levels--from individual to population. Forecasts suggest that high rates of obesity will affect future population health and economics. Energy gap models have quantified the association of changes in energy intake and expenditure with weight change, and have documented the effect of higher intake on obesity prevalence. Empirical evidence that shows interventions are effective is limited but expanding. We identify several cost-effective policies that governments should prioritise for implementation. Systems science provides a framework for organising the complexity of forces driving the obesity epidemic and has important implications for policy makers. Many parties (such as governments, international organisations, the private sector, and civil society) need to contribute complementary actions in a coordinated approach. Priority actions include policies to improve the food and built environments, cross-cutting actions (such as leadership, healthy public policies, and monitoring), and much greater funding for prevention programmes. Increased investment in population obesity monitoring would improve the accuracy of forecasts and evaluations. The integration of actions within existing systems into both health and non-health sectors (trade, agriculture, transport, urban planning, and development) can greatly increase the influence and sustainability of policies. We call for a sustained worldwide effort to monitor, prevent, and control obesity.

  7. Hybrid Action Systems

    DEFF Research Database (Denmark)

    Ronkko, Mauno; Ravn, Anders P.

    1997-01-01

    a differential action, which allows differential equations as primitive actions. The extension allows us to model hybrid systems with both continuous and discrete behaviour. The main result of this paper is an extension of such a hybrid action system with parallel composition. The extension does not change...... the original meaning of the parallel composition, and therefore also the ordinary action systems can be composed in parallel with the hybrid action systems....

  8. A Unified Electronic Tool for CPR and Emergency Treatment Escalation Plans Improves Communication and Early Collaborative Decision Making for Acute Hospital Admissions.

    Science.gov (United States)

    Johnson, Mae; Whyte, Martin; Loveridge, Robert; Yorke, Richard; Naleem, Shairana

    2017-01-01

    The National Confidential Enquiry into Patient Outcomes and Death (NCEPOD) report 'Time to Intervene' (2012) stated that in a substantial number of cases, resuscitation is attempted when it was thought a 'do not attempt cardiopulmonary resuscitation' (DNACPR) decision should have been in place. Early decisions about CPR status and advance planning about limits of care now form part of national recommendations by the UK Resuscitation Council (2016). Treatment escalation plans (TEP) document what level of treatment intervention would be appropriate if a patient were to become acutely unwell and were not previously formally in place at King's College Hospital. A unifying paper based form was successfully piloted in the Acute Medical Unit, introducing the TEP and bringing together decision making around both treatment escalation and CPR status. Subsequently an electronic order-set for CPR status and treatment escalation was launched in April 2015 which led to a highly visible CPR and escalation status banner on the main screen at the top of the patient's electronic record. Ultimately due to further iterations in the electronic process by December 2016, all escalation decisions for acutely admitted patients now have high quality supporting, explanatory documentation with 100% having TEPs in place. There is now widespread multidisciplinary engagement in the process of defining limits of care for acutely admitted medical patients within the first 14 hours of admission and a strategy for rolling this process out across all the divisions of the hospital through our Deteriorating Patient Group (DPG). The collaborative design with acute medical, palliative and intensive care teams and the high visibility provided by the electronic process in the Electronic Patient Record (EPR) has enhanced communication with these teams, patients, nursing staff and the multidisciplinary team by ensuring clarity through a universally understood process about escalation and CPR. Clarity and

  9. Gut hormone release and appetite regulation in healthy non-obese participants following oligofructose intake. A dose-escalation study.

    Science.gov (United States)

    Pedersen, Camilla; Lefevre, Solenne; Peters, Véronique; Patterson, Michael; Ghatei, Mohammad A; Morgan, Linda M; Frost, Gary S

    2013-07-01

    Prevention of weight gain in adults is a major public health target. Animal experiments have consistently demonstrated a relationship between fermentable carbohydrate intake, such as oligofructose, anorectic gut hormones, and appetite suppression and body weight control. This study was designed to determine the dose of oligofructose which would augment the release of anorectic gut hormones and reduce appetite consistently in non-obese humans. Twelve non-obese participants were recruited for a 5-week dose-escalation study. Following a 9-14-day run-in, participants increased their daily oligofructose intake every week from 15, 25, 35, 45, to 55 g daily. Subjective appetite and side effects were monitored daily. Three-day food diaries were completed every week. Appetite study sessions explored the acute effects of 0, 15, 35, and 55 g oligofructose on appetite-related hormones, glycaemia, subjective appetite, and energy intake. In the home environment, oligofructose suppressed hunger, but did not affect energy intake. Oligofructose dose-dependently increased peptide YY, decreased pancreatic polypeptide and tended to decrease ghrelin, but did not significantly affect appetite profile, energy intake, glucose, insulin, or glucagon-like peptide 1 concentrations during appetite study sessions. In conclusion, oligofructose supplementation at ≥ 35 g/day increased peptide YY and suppressed pancreatic polypeptide and hunger; however, energy intake did not change significantly.

  10. Imatinib dose escalation versus sunitinib as a second line treatment in KIT exon 11 mutated GIST: a retrospective analysis.

    Science.gov (United States)

    Vincenzi, Bruno; Nannini, Margherita; Fumagalli, Elena; Bronte, Giuseppe; Frezza, Anna Maria; De Lisi, Delia; Spalato Ceruso, Mariella; Santini, Daniele; Badalamenti, Giuseppe; Pantaleo, Maria Abbondanza; Russo, Antonio; Dei Tos, Angelo Paolo; Casali, Paolo; Tonini, Giuseppe

    2016-10-25

    We retrospectively reviewed data from 123 patients (KIT exon 11 mutated) who received sunitinib or dose-escalated imatinib as second line.All patients progressed on imatinib (400 mg/die) and received a second line treatment with imatinib (800 mg/die) or sunitinib (50 mg/die 4 weeks on/2 off or 37.5 mg/day). Deletion versus other KIT 11 mutation was recorded, correlated with clinical benefits.64% received imatinib, 36% sunitinib. KIT exon 11 mutation was available in 94 patients. With a median follow-up of 61 months, median time to progression (TTP) in patients receiving sunitinib and imatinib was 10 (95% CI 9.7-10.9) and 5 months (95% CI 3.6-6.7) respectively (P = 0.012). No difference was found in overall survival (OS) (P = 0.883). In imatinib arm, KIT exon 11 deletions was associated with a shorter TTP (7 vs 17 months; P = 0.02), with a trend in OS (54 vs 71 months P = 0.063). No difference was found in patients treated with sunitinib (P = 0.370).A second line with sunitinib was associated with an improved TTP in KIT exon 11 mutated patients progressing on imatinib 400 mg/die. Deletions in exon 11 seemed to be correlated with worse outcome in patients receiving imatinib-based second line.

  11. Validation of the French version of the Acceptability E-scale (AES) for mental E-health systems.

    Science.gov (United States)

    Micoulaud-Franchi, Jean-Arthur; Sauteraud, Alain; Olive, Jérôme; Sagaspe, Patricia; Bioulac, Stéphanie; Philip, Pierre

    2016-03-30

    Despite the increasing use of E-health systems for mental-health organizations, there is a lack of psychometric tools to evaluate their acceptability by patients with mental disorders. Thus, this study aimed to translate and validate a French version of the Acceptability E-scale (AES), a 6-item self-reported questionnaire that evaluates the extent to which patients find E-health systems acceptable. A forward-backward translation of the AES was performed. The psychometric properties of the French AES version, with construct validity, internal structural validity and external validity (Pearson's coefficient between AES scores and depression symptoms on the Beck Depression Inventory II) were analyzed. In a sample of 178 patients (mean age=46.51 years, SD=12.91 years), the validation process revealed satisfactory psychometric properties: factor analysis revealed two factors: "Satisfaction" (3 items) and "Usability" (3 items) and Cronbach's alpha was 0.7. No significant relation was found between AES scores and depression symptoms. The French version of the AES revealed a two-factor scale that differs from the original version. In line with the importance of acceptability in mental health and with a view to E-health systems for patients with mental disorders, the use of the AES in psychiatry may provide important information on acceptability (i.e., satisfaction and usability).

  12. Project Plans, Constraints to Growth and the Impact of Cost Escalation through The Middle East and North Africa (MENA) Prism

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-07-01

    MENA national oil companies (NOCs) are targeting ambitious energy expansion, with mid-term plans for a 5.8 million b/d net boost to crude capacity, 1.9 million b/d more NGLs and 400 Bcm/year more gas, alongside significant refining and LNG additions. Nevertheless, a review of historical project delivery sounds a note of caution over timing - with a number of countries prone to delays and others, outright deferrals, even if market leaders, Saudi Arabia and Qatar, remain more resolutely on course. Cost escalation since 2002 has compounded the regional tendency towards delays, although the impact on project delivery has been moderated by a willingness to increase budgets where project economics remain sound. That leaves political factors as the principal constraint to regional expansion, complicated in part by increasing pluralism in political participation and valid concerns about the management of resources for long-term sustainability, rather than near-term profit. With most constraints to development expected to remain at the political level, there is a clear case for consumers to be more explicit about future needs. There is also a need to engage with growing constituencies in some states favouring a 'go slow' approach to hydrocarbon development where policymakers have made the case for considered expansion.

  13. Dose-Escalated Stereotactic Body Radiation Therapy for Prostate Cancer: Quality of Life Comparison of Two Prospective Trials

    Directory of Open Access Journals (Sweden)

    Harvey Charles Quon

    2016-08-01

    Full Text Available IntroductionThe optimal prostate stereotactic body radiation therapy (SBRT dose-fractionation scheme is controversial. This study compares long-term quality of life (QOL from two prospective trials of prostate SBRT to investigate the effect of increasing dose (NCT01578902 and NCT01146340.Material and MethodsPatients with localized prostate cancer received SBRT 35 or 40 Gy delivered in 5 fractions, once per week. QOL was measured using the Expanded Prostate Cancer Index Composite (EPIC at baseline and every 6 months. Fisher’s exact test and generalized estimating equations were used to analyze proportions of patients with clinically significant change and longitudinal changes in QOL.Results114 patients were included, 84 treated to 35 Gy and 30 treated to 40 Gy. Median QOL follow-up was 56 months (interquartile range [IQR] 46-60 and 38 months (IQR 32-42, respectively. The proportion of patients reporting clinically significant declines in average urinary, bowel, and sexual scores were not significantly different between dose levels, and were 20.5 vs. 24.1% (p=0.60, 26.8 vs. 41.4% (p=0.16, and 42.9 vs. 38.5% (p=0.82, respectively. Similarly, longitudinal analysis did not identify significant differences in QOL between treatment groups.ConclusionDose-escalated prostate SBRT from 35 to 40 Gy in 5 fractions was not associated with significant decline in long-term QOL.

  14. Acute and late toxicity in prostate cancer patients treated by dose escalated intensity modulated radiation therapy and organ tracking

    Directory of Open Access Journals (Sweden)

    Behrensmeier Frank

    2008-10-01

    Full Text Available Abstract Background To report acute and late toxicity in prostate cancer patients treated by dose escalated intensity-modulated radiation therapy (IMRT and organ tracking. Methods From 06/2004 to 12/2005 39 men were treated by 80 Gy IMRT along with organ tracking. Median age was 69 years, risk of recurrence was low 18%, intermediate 21% and high in 61% patients. Hormone therapy (HT was received by 74% of patients. Toxicity was scored according to the CTC scale version 3.0. Median follow-up (FU was 29 months. Results Acute and maximal late grade 2 gastrointestinal (GI toxicity was 3% and 8%, late grade 2 GI toxicity dropped to 0% at the end of FU. No acute or late grade 3 GI toxicity was observed. Grade 2 and 3 pre-treatment genitourinary (GU morbidity (PGUM was 20% and 5%. Acute and maximal late grade 2 GU toxicity was 56% and 28% and late grade 2 GU toxicity decreased to 15% of patients at the end of FU. Acute and maximal late grade 3 GU toxicity was 8% and 3%, respectively. Decreased late ≥ grade 2 GU toxicity free survival was associated with higher age (P = .025, absence of HT (P = .016 and higher PGUM (P Discussion GI toxicity rates after IMRT and organ tracking are excellent, GU toxicity rates are strongly related to PGUM.

  15. DAPs: Deep Action Proposals for Action Understanding

    KAUST Repository

    Escorcia, Victor

    2016-09-17

    Object proposals have contributed significantly to recent advances in object understanding in images. Inspired by the success of this approach, we introduce Deep Action Proposals (DAPs), an effective and efficient algorithm for generating temporal action proposals from long videos. We show how to take advantage of the vast capacity of deep learning models and memory cells to retrieve from untrimmed videos temporal segments, which are likely to contain actions. A comprehensive evaluation indicates that our approach outperforms previous work on a large scale action benchmark, runs at 134 FPS making it practical for large-scale scenarios, and exhibits an appealing ability to generalize, i.e. to retrieve good quality temporal proposals of actions unseen in training.

  16. All in action

    CERN Document Server

    Annila, Arto

    2010-01-01

    The principle of least action provides a holistic worldview in which nature in its entirety and every detail is pictured in terms of actions. Each and every action is ultimately composed of one or multiples of the most elementary action which corresponds to the Planck's constant. Elements of space are closed actions, known as fermions, whereas elements of time are open actions, known as bosons. The actions span energy landscape, the Universe which evolves irreversibly according to the 2nd law of thermodynamics by diminishing density differences in least time. During the step-by-step evolution densely-curled actions unfold by opening up and expelling one or multiple elementary actions to their surrounding sparser space. The manifold's varieties process from one symmetry group to another until the equivalence to their dual, i.e., the surrounding density has been attained. The scale-free physical portrayal of nature does not recognize any fundamental difference between fundamental particles and fundamental force...

  17. Collective action control by goals and plans: applying a self-regulation perspective to group performance.

    Science.gov (United States)

    Wieber, Frank; Thürmer, J Lukas; Gollwitzer, Peter M

    2012-01-01

    In celebration of the 125th anniversary of The American Journal of Psychology, this article discusses a seminal publication by Marjorie Shaw (1932) on small group performance in the rational solution of complex problems. We then propose an approach for the effective regulation of group goal striving based on the collective action control perspective. From this perspective, group performance might be hindered by a collective intention-behavior gap: Groups fail to act on their intentions despite being strongly committed to the collective goal, knowing what the necessary actions are, and being capable of performing them. To reduce this gap, we suggest specific if-then plans (implementation intentions) in which groups specify when, where, and how to act toward their collective goal as an easily applicable self-regulation strategy to automate collective action control. Studies in which implementation intentions improved group performance in hidden profile, escalation of commitment, and cooperation task paradigms are reported and discussed.

  18. Study of FEA Static Analysis Application on the Calculation of Escalator Truss%扶梯桁架静应力计算分析应用研究

    Institute of Scientific and Technical Information of China (English)

    梁剑

    2014-01-01

    Through the study of FEA software application on calculation of truss analysis,which can solve successfully the requirement of customer about the safety factor of steel structure with the load of escalator standard (EN115). Finally it provide the escalator product to match the requirement of customer.%通过应用有限元分析软件对扶梯桁架进行计算分析,以扶梯标准EN115的载荷要求进行分析计算,成功解决客户对于钢结构安全系数的要求,从而设计出满足客户需求的扶梯产品。

  19. Implementation and Design of an Escalator Cabinet Test Bench%自动扶梯控制柜检测台的设计与实现

    Institute of Scientific and Technical Information of China (English)

    陈洁

    2014-01-01

    According to GB16899-2011 Manufacturing and Installing Safety Specifications of Escalators and Au-tomatic Sidewalks, this paper analyzed the configuration of escalator cabinet system, came up with the adjust-ment, tested scheme, provided the electricity circuit theory and the method to produce velocity pulse and listed the materials.%根据GB16899-2011《自动扶梯和自动人行道的制造与安装安全规范》的要求,分析了扶梯控制系统的组成结构,提出了一种检测自动扶梯控制柜功能的方案,给出了电路原理、产生速度脉冲的方法,并列出了材料清单。

  20. POTENTIAL APPLICATIONS OF IMAGE-GUIDED RADIOTHERAPY FOR RADIATION DOSE ESCALATION IN PATIENTS WITH EARLY STAGE HIGH-RISK PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    Nam Phong Nguyen

    2015-02-01

    Full Text Available Patients with early stage high-risk prostate cancer (PSA >20, Gleason score >7 are at high risk of recurrence following prostate cancer irradiation. Radiation dose escalation to the prostate may improve biochemical free survival for these patients. However, high rectal and bladder dose with conventional three-dimensional conformal radiotherapy (3D-CRT may lead to excessive gastrointestinal and genitourinary toxicity. Image-guided radiotherapy (IGRT, by virtue of combining the steep dose gradient of intensity-modulated radiotherapy (IMRT and daily pretreatment imaging, may allow for radiation dose escalation and decreased treatment morbidity. Reduced treatment time is feasible with hypofractionated IGRT and it may improve patient quality of life.

  1. Feasibility of safe ultra-high (EQD{sub 2}>100 Gy) dose escalation on dominant intra-prostatic lesions (DILs) by Helical Tomotheraphy

    Energy Technology Data Exchange (ETDEWEB)

    Maggio, Angelo; Fiorino, Claudio; Mangili, Paola; Cattaneo, Giovanni Mauro; Del Maschio, Alessandro; Calandrino, Riccardo (Medical Physics, San Raffaele Scientific Inst., Milano (Italy)), e-mail: fiorino.claudio@hsr.it; Muzio, Nadia Di; Cozzarini, Cesare (Radiotherapy, San Raffaele Scientific Inst., Milano (Italy)); Cobelli, Francesco de (Radiology, San Raffaele Scientific Inst., Milano (Italy)); Rancati, Tiziana (Programma Prostata, National Inst. of Cancer, Milano (Italy))

    2011-01-15

    Purpose. To verify the possibility of using Helical Tomotherapy to safely escalate dose to single or multiple highly radioresistant dominant intra-prostatic lesions (DILs) as assessed by functional magnetic resonance imaging (MRI). Material. In seven intermediate/high risk patients, T2WI, T1WI and DWI MRI imaging showed evidence of one DIL in four patients and two DILs in three patients in the peripheral zone of the prostate. The planning strategy was to deliver median doses of 80, 90, 100 and 120 Gy to PTVDIL while delivering 71.4 Gy/28 fractions (EQD{sub 2}=75 Gy) to the remaining portion of PTV. A higher priority was assigned to rectal constraints relative to DIL coverage. Rectal NTCP calculations were performed using the most recently available model data. Results. The median dose to DIL could safely be escalated to at least 100 Gy (EQD{sub 2,{alpha}/{beta}=10}=113 Gy) without violating safe constraints for the organs at risk. Typical rectal NTCP values were around or below 1-3% for G3 toxicity and 5-7% for G2-G3 toxicity. For the 100 Gy DIL dose boost strategy, mean D95% of DIL and PTVDIL were 98.8 Gy and 86.7 Gy, respectively. The constraints for bladder, urethra and femoral heads were always respected. Conclusions. IGRT by Helical Tomotherapy may permit the safe escalation of EQD{sub 2,{alpha}/{eta}=10} to at least 113 Gy to DILs without significantly increasing rectal NTCP compared to plans without dose escalation. A Phase I-II clinical study is warranted

  2. Acute side effects after dose-escalation treatment of prostate cancer using the new urethral catheter BeamCath{sup R} technique

    Energy Technology Data Exchange (ETDEWEB)

    Fransson, Per; Loefroth, P.O.; Franzen, L.; Henriksson, Roger; Bergstroem, P.; Widmark, A. [Umeaa Univ. (Sweden). Dept. of Oncology

    2001-11-01

    Acute side effects after dose-escalated radiotherapy for prostate cancer with different treatment techniques were evaluated, using a daily diary recorded by the patients. Dose escalation was performed using the urethral catheter BeamCath{sup R} (registered trade mark name) technique. Side effects were evaluated in 267 patients by means of a daily diary during the treatment and at 3-months' follow-up. The patients' evaluations were compared with those of patients treated with conventional or conformal techniques. Looser stools were reported in the conventional (placebo) and 76 Gy groups at 3-months' follow-up compared with at week 1. No other obvious increase in rectal or bladder morbidity was seen in the 76 Gy group. The catheter did not increase the urinary frequency in comparison to the other groups. The reported urgency and starting problems at the beginning of treatment seemed to improve in all groups at 3-months' follow-up. External beam radiotherapy dose escalation using the BeamCath{sup R} technique did not result in a dose-dependent increase in acute side effects.

  3. 'Take the stairs instead of the escalator': effect of environmental prompts on community stair use and implications for a national 'Small Steps' campaign.

    Science.gov (United States)

    Dolan, M S; Weiss, L A; Lewis, R A; Pietrobelli, A; Heo, M; Faith, M S

    2006-02-01

    The US government initiated a national health campaign targeting 100 'small step' lifestyle changes to combat obesity. Small Step #67 advocates stair instead of escalator usage in public settings. The aim of this study is to evaluate the effects of motivational signs prompting stair use over escalator use on pedestrians' stair usage in commuter settings. Eight studies, testing the effects of motivational prompts on stair vs. escalator usage in public settings, were reviewed. Participant and study attributes were descriptively coded. Effect size was calculated as the change in percent units of stair users during the intervention phases vs. the baseline phase. The average study included approximately 45,000 observations that were recorded across an average of 15 weeks of intervention. The mean +/- SD change in percent units of stair users was 2.8% +/- 2.4% (P stairs/building, baseline stair use, and total intervention weeks predicted change in stair use, although the effects were clinically miniscule. In a hypothetical city intervention, we projected that a 2.8% increase in stair usage would result in a weight loss and/or weight gain prevention of 300 g/person/year among new stair users. In sum, point-of-decision motivational signs may help communities attain Small Step #67. However, the singular impact of this community intervention on correcting energy imbalance may be minimal, having slight impact itself on reducing the national obesity prevalence.

  4. Recovery Action Mapping Tool

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Recovery Action Mapping Tool is a web map that allows users to visually interact with and query actions that were developed to recover species listed under the...

  5. Various Actions for Pregeometry

    Science.gov (United States)

    Terazawa, H.

    1991-08-01

    Various actions for pregeometry are presented and compared. The ``space-field identity'' which equates the n-beins to the derivatives of fundamental scalars is derived from a simple action but seems to be too restrictive to be practical.

  6. Action Rules Mining

    CERN Document Server

    Dardzinska, Agnieszka

    2013-01-01

    We are surrounded by data, numerical, categorical and otherwise, which must to be analyzed and processed to convert it into information that instructs, answers or aids understanding and decision making. Data analysts in many disciplines such as business, education or medicine, are frequently asked to analyze new data sets which are often composed of numerous tables possessing different properties. They try to find completely new correlations between attributes and show new possibilities for users.   Action rules mining discusses some of data mining and knowledge discovery principles and then describe representative concepts, methods and algorithms connected with action. The author introduces the formal definition of action rule, notion of a simple association action rule and a representative action rule, the cost of association action rule, and gives a strategy how to construct simple association action rules of a lowest cost. A new approach for generating action rules from datasets with numerical attributes...

  7. On Action Theory Change

    OpenAIRE

    Varzinczak, Ivan José

    2014-01-01

    As historically acknowledged in the Reasoning about Actions and Change community, intuitiveness of a logical domain description cannot be fully automated. Moreover, like any other logical theory, action theories may also evolve, and thus knowledge engineers need revision methods to help in accommodating new incoming information about the behavior of actions in an adequate manner. The present work is about changing action domain descriptions in multimodal logic. Its contribution is threefold: ...

  8. Action Theory Evolution

    OpenAIRE

    Varzinczak, Ivan

    2008-01-01

    Like any other logical theory, domain descriptions in reasoning about actions may evolve, and thus need revision methods to adequately accommodate new information about the behavior of actions. The present work is about changing action domain descriptions in propositional dynamic logic. Its contribution is threefold: first we revisit the semantics of action theory contraction that has been done in previous work, giving more robust operators that express minimal change based on a notion of dis...

  9. Action and Interactiv research

    DEFF Research Database (Denmark)

    Nielsen, Kurt Aagaard; Svensson, Lennart

    The text is written as a first version of editors introduction to a book about action research/interactive research in Nordic countries. You can read abouttrends and contradictions in the history of action research.The authors question the trends and demands a more explicit critical approach...... to actual action research/interactive research....

  10. Action Research for Democracy

    DEFF Research Database (Denmark)

    , to innovation policies combining Action Research with gender science. In the second part of the book epistemological and ontological dimensions of Action Research are discussed addressing questions of validity criteria related to Action Research, the transformation of knowledge institutions and the specific...

  11. Conservation Action Handbook.

    Science.gov (United States)

    National Rifle Association, Washington, DC.

    Conservation problems are identified, with some suggestions for action. General areas covered are: Wildlife Conservation, Soil Conservation, Clean Water, Air Pollution Action, and Outdoor Recreation Action. Appendices list private organizations or agencies concerned with natural resource use and/or management, congressional committees considering…

  12. Putting Action in Perspective

    Science.gov (United States)

    Lozano, Sandra C.; Hard, Bridgette Martin; Tversky, Barbara

    2007-01-01

    Embodied approaches to cognition propose that our own actions influence our understanding of the world. Do other people's actions also have this influence? The present studies show that perceiving another person's actions changes the way people think about objects in a scene. In Study 1, participants viewed a photograph and answered a question…

  13. 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, C.M.L. (Carla); F.A.L.M. Eskens (Ferry); M.J.A. de Jonge (Maja); I. Desar; 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

  14. 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, C.M.L. (Carla); F.A.L.M. Eskens (Ferry); M.J.A. de Jonge (Maja); I. Desar; 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 paclitaxe

  15. Phase I trial of dose-escalating metronomic temozolomide plus bevacizumab and bortezomib for patients with recurrent glioblastoma.

    Science.gov (United States)

    McCracken, D Jay; Celano, Emma C; Voloschin, Alfredo D; Read, William L; Olson, Jeffrey J

    2016-10-01

    The average survival time for patients with recurrent glioblastoma is between 5 and 9 months. Phase I and II trials have shown a modest survival benefit with combination temozolomide and other chemotherapeutics. We conducted a phase I trial of dose-escalating temozolomide with bevacizumab and the proteasome inhibitor bortezomib for patients with recurrent disease. Three groups of three patients were scheduled to receive daily doses of temozolomide at 25, 50, and 75 mg/m(2). Fixed doses of bortezomib and bevacizumab were given at standard intervals. Patients were monitored for dose-limiting toxicities (DLT) to determine the maximum-tolerated dose (MTD) of temozolomide with this regimen. No DLT were seen in the first two groups (25 and 50 mg/m(2) temozolomide). One patient in the 75 mg/m(2) group experienced a grade 4 elevation of ALT and three more patients were accrued for a total of six patients at that dose level. No other DLT occurred, thus making 75 mg/m(2) the MTD. Progression-free survival was 3.27 months for all patients and mean overall survival was 20.75 months. The MTD of temozolomide was 75 mg/m(2) in combination with bevacizumab and bortezomib for recurrent glioblastoma. Only one patient experienced a severe (Grade 4) elevation of ALT. This study will provide the framework for further studies to elicit effectiveness and better determine a safety profile for this drug combination.

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

    Energy Technology Data Exchange (ETDEWEB)

    Safdieh, Joseph; Schwartz, David; Weiner, Joseph; Weiss, Jeffrey P.; Madeb, Isaac; Rotman, Marvin; Schreiber, David [Dept.of Veteran Affairs, New York Harbor Healthcare System, Brooklyn (United States); Rineer, Justin [University of Florida Health Cancer Center, Orlando (United States)

    2014-09-15

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

  17. Dosimetric Feasibility of Dose Escalation Using SBRT Boost for Stage III Non-Small Cell Lung Cancer

    Science.gov (United States)

    Hepel, Jaroslaw T.; Peter, Justin; Hiatt, Jessica R.; Patel, Salil; Osibanjo, Oluwademilade; Safran, Howard; Curran, Bruce; DiPetrillo, Thomas

    2012-01-01

    Purpose: Standard chemoradiation therapy for stage III non-small cell lung cancer (NSCLCa) results in suboptimal outcomes with a high rate of local failure and poor overall survival. We hypothesize that dose escalation using stereotactic body radiotherapy (SBRT) boost could improve upon these results. We present here a study evaluating the dosimetric feasibility of such an approach. Methods: Anonymized CT data sets from five randomly selected patients with stage III NSCLCa undergoing definitive chemoradiation therapy in our department with disease volumes appropriate for SBRT boost were selected. Three-dimensional conformal radiation therapy (3D-CRT) plans to 50.4 Gy in 28 fractions were generated follow by SBRT plans to two dose levels, 16 Gy in two fractions and 28 Gy in two fractions. SBRT plans and total composite (3D-CRT and SBRT) were optimized and evaluated for target coverage and dose to critical structures; lung, esophagus, cord, and heart. Results: All five plans met predetermined target coverage and normal tissue dose constraints. PTV V95 was equal to or greater than 95% in all cases. The cumulative lung V20 and V5 of the combined 3D-CRT and SBRT plans were less than or equal to 30 and 55%, respectively. The 5 cc esophageal dose was less than 12 Gy for all low and high dose SBRT plans. The cumulative dose to the esophagus was also acceptable with less than 10% of the esophagus receiving doses in excess of 50 Gy. The cumulative spinal cord dose was less than 33 Gy and heart V25 was less than 5%. Conclusion: The combination of chemoradiation to 50.4 Gy followed by SBRT boost to gross disease at the primary tumor and involved regional lymph nodes is feasible with respect to normal tissue dose constraints in this dosimetric pilot study. A phase I/II trial to evaluate the clinical safety and efficacy of this approach is being undertaken. PMID:23057009

  18. Rats markedly escalate their intake and show a persistent susceptibility to reinstatement only when cocaine is injected rapidly.

    Science.gov (United States)

    Wakabayashi, Ken T; Weiss, Mark J; Pickup, Kristen N; Robinson, Terry E

    2010-08-25

    When drugs enter the brain rapidly, liability for addiction is increased, but why this is the case is not well understood. Here we examined the influence of varying the speed of intravenous cocaine delivery on self-administration behavior in rats given limited or extended opportunity to take drug. The speed of cocaine delivery had no effect on self-administration behavior when rats were given only 1 h each day to take cocaine. When given sixfold more time to take cocaine, rats that received cocaine rapidly (5-45 s) increased their total intake eightfold. However, rats that received cocaine more slowly (>90 s) did not avail themselves of the opportunity to take much more drug: they increased their intake only twofold. Furthermore, when tested 45 d after the last self-administration session, a drug-priming injection reinstated drug-seeking behavior only in rats that in the past had cocaine injected rapidly (5 s), and this was associated with a persistent suppression in the ability of cocaine to induce immediate early gene expression. Cocaine may be potentially more addictive when it reaches the brain rapidly because (1) this promotes a marked escalation in intake and (2) it renders individuals more susceptible to relapse long after the discontinuation of drug use. This is presumably because the rapid uptake of drug to the brain preferentially promotes persistent changes in brain systems that regulate motivation for drug, and continuing exposure to large amounts of drug produces a vicious cycle of additional maladaptive changes in brain and behavior.

  19. SU-E-T-500: Dose Escalation Strategy for Lung Cancer Patients Using a Biologically- Guided Target Definition

    Energy Technology Data Exchange (ETDEWEB)

    Shusharina, N; Khan, F; Choi, N; Sharp, G [Massachusetts General Hospital, Boston, MA (United States)

    2014-06-01

    Purpose: Dose escalation strategy for lung cancer patients can lead to late symptoms such as pneumonitis and cardiac injury. We propose a strategy to increase radiation dose for improving local tumor control while simultaneously striving to minimize the injury of organs at risk (OAR). Our strategy is based on defining a small, biologically-guided target volume for receiving additional radiation dose. Methods: 106 patients with lung cancer treated with radiotherapy were selected for patients diagnosed with stage II and III disease. Previous research has shown that 50% of the maximum SUV threshold in FDG-PET imaging is appropriate for delineation of the most aggressive part of a tumor. After PET- and CT-derived targets were contoured, an IMRT treatment plan was designed to deliver 60 Gy to the GTV as delineated on a 4D CT (Plan 1). A second plan was designed with additional dose of 18 Gy to the PET-derived volume (Plan 2). A composite plan was generated by the addition of Plan 1 and Plan 2. Results: Plan 1 was compared to the composite plan and increases in OAR dose were assessed. For seven patients on average, lung V5 was increased by 1.4% and V20 by 4.2% for ipsilateral lung and by 13.5% and 7% for contralateral lung. For total lung, V5 and V20 were increased by 4.5% and 4.8% respectively. Mean lung dose was increased by 9.7% for the total lung. The maximum dose to the spinal cord increased by 16% on average. For the heart, V20 increased by 4.2% and V40 by 5.2%. Conclusion: It seems feasible that an additional 18 Gy of radiation dose can be delivered to FDG PET-derived subvolume of the CT-based GTV of the primary tumor without significant increase in total dose to the critical organs such as lungs, spinal cord and heart.

  20. Phase I Trial of Escalating-dose Cisplatin with 5-fluorouracil and Concurrent Radiotherapy in Chinese Patients with Esophageal Cancer

    Directory of Open Access Journals (Sweden)

    Zhao,Yan-Nan

    2008-02-01

    Full Text Available We defined the maximum-tolerated dose (MTD of chemoradiotherapy (cisplatin (CDDP with 5-fluorouracil (5-FU and concurrent chemoradiotherapy for Chinese patients with esophageal cancer. Twenty-one previously untreated patients with primary esophageal cancer were entered into this study. Escalating doses of CDDP with 5-FU were administered in a modified Fibonacci sequence, with concurrent conventional fractionation radiotherapy (CFR of 60 Gy or 50 Gy. The starting doses were CDDP 37.5 mg/m2 on day 1, and 5-FU 500 mg/m2 on days 1-5, respectively. The regimen was repeated 4 times every 28 days. If no dose-limiting toxicity (DLT was observed, the next dose level was applied. The procedures were repeated until DLT appeared. The MTD was declared to be 1 dose level below the level at which DLT appeared. DLT was grade 3 radiation-induced esophagitis at a dose level of CDDP 60 mg/m2 with 5-FU 700 mg/m2 and concurrent 60 Gy CFR. MTD was defined as CDDP 52.5 mg/m2 with 5-FU 700 mg/m2 and concurrent 50 Gy CFR. The MTD of CDDP with 5-FU and in concurrent chemoradiotherapy for Chinese patients with esophageal cancer is CDDP 52.5 mg/m2 on day 1 and 5FU 700 mg/m2 on days 1-5, repeated 4 times every 28 days, and concurrent 50 Gy CFR. Further evaluation of this regimen in a prospective phase II trial is ongoing.

  1. Effects of Intracoronary Infusion of Escalating Doses of Cardiac Stem Cells in Rats With Acute Myocardial Infarction.

    Science.gov (United States)

    Tang, Xian-Liang; Rokosh, Gregg; Sanganalmath, Santosh K; Tokita, Yukichi; Keith, Matthew C L; Shirk, Gregg; Stowers, Heather; Hunt, Gregory N; Wu, Wenjian; Dawn, Buddhadeb; Bolli, Roberto

    2015-07-01

    Although c-kit(pos) cardiac stem cells (CSCs) preserve left ventricular (LV) function and structure after myocardial infarction, CSC doses have been chosen arbitrarily, and the dose-effect relationship is unknown. Rats underwent a 90-minute coronary occlusion followed by 35 days of reperfusion. Vehicle or CSCs at 5 escalating doses (0.3×10(6), 0.75×10(6), 1.5×10(6), 3.0×10(6), and 6.0×10(6) cells/heart) were given intracoronarily 4 h after reperfusion. The lowest dose (0.3×10(6)) had no effect on LV function and morphology, whereas 0.75, 1.5, and 3.0×10(6) significantly improved regional and global LV function (echocardiography and hemodynamic studies). These 3 doses had similar effects on echocardiographic parameters (infarct wall thickening fraction, LV end-systolic and end-diastolic volumes, LV ejection fraction) and hemodynamic variables (LV end-diastolic pressure, LV dP/dtmax, preload adjusted maximal power, end-systolic elastance, preload recruitable stroke work) and produced similar reductions in apoptosis, scar size, infarct wall thinning, and LV expansion index and similar increases in viable myocardium in the risk region (morphometry). Infusion of 6.0×10(6) CSCs markedly increased postprocedural mortality. Green fluorescent protein and 5-bromo-2'-deoxyuridine staining indicated that persistence of donor cells and formation of new myocytes were negligible with all doses. Surprisingly, in this rat model of acute myocardial infarction, the dose-response relationship for intracoronary CSCs is flat. A minimal dose between 0.3 and 0.75×10(6) is necessary for efficacy; above this threshold, a 4-fold increase in cell number does not produce greater improvement in LV function or structure. Further increases in cell dose are harmful. © 2015 American Heart Association, Inc.

  2. Phase I trial of escalating-dose cisplatin with 5-fluorouracil and concurrent radiotherapy in Chinese patients with esophageal cancer.

    Science.gov (United States)

    Lin, Qiang; Gao, Xian-Shu; Qiao, Xue-Ying; Zhou, Zhi-Guo; Zhang, Ping; Chen, Kun; Zhao, Yan-Nan; Asaumi, Junichi

    2008-02-01

    We defined the maximum-tolerated dose (MTD) of chemoradiotherapy (cisplatin (CDDP) with 5-fluorouracil (5-FU) and concurrent chemoradiotherapy) for Chinese patients with esophageal cancer. Twenty-one previously untreated patients with primary esophageal cancer were entered into this study. Escalating doses of CDDP with 5-FU were administered in a modified Fibonacci sequence, with concurrent conventional fractionation radiotherapy (CFR) of 60 Gy or 50 Gy. The starting doses were CDDP 37.5 mg/m2 on day 1, and 5-FU 500 mg/m2 on days 1-5, respectively. The regimen was repeated 4 times every 28 days. If no dose-limiting toxicity (DLT) was observed, the next dose level was applied. The procedures were repeated until DLT appeared. The MTD was declared to be 1 dose level below the level at which DLT appeared. DLT was grade 3 radiation-induced esophagitis at a dose level of CDDP 60 mg/m2 with 5-FU 700 mg/m2 and concurrent 60 Gy CFR. MTD was defined as CDDP 52.5 mg/m2 with 5-FU 700 mg/m2 and concurrent 50 Gy CFR. The MTD of CDDP with 5-FU and in concurrent chemoradiotherapy for Chinese patients with esophageal cancer is CDDP 52.5 mg/m2 on day 1 and 5FU 700 mg/m2 on days 1-5, repeated 4 times every 28 days, and concurrent 50 Gy CFR. Further evaluation of this regimen in a prospective phase II trial is ongoing.

  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. Gestion de crise et aide internationale après le séisme du 12 janvier à Port-au-Prince Haïti, toujours dans l’urgence ! (Témoignage Crisis Management and International Aid after Earthquake of January 12 in Port-au-Prince Haiti, always in a Hurry! (Testimony

    Directory of Open Access Journals (Sweden)

    Jean-Philippe Pierre

    2012-01-01

    Full Text Available Dans le cadre de l’intervention qui a été déclenchée pour venir en aide aux sinistrés du tremblement de terre en Haïti le 12 janvier dernier, la France a envoyé des moyens importants. Le déploiement de ces moyens comme celui de ceux envoyés par le reste de la communauté internationale s’est déroulé sur un territoire ravagé. En plus des difficultés liées aux destructions, il a été relativement difficile d’avoir une vision globale de la situation. L’absence quasi totale de moyens de communication sur place et l’interprétation faite par certains médias internationaux, d’évènements anodins ont également contribué à compliquer cette situation.  Aujourd’hui, on énumère les actions et les projets mais qu’en est-il de la situation sur le terrain ?As part of the intervention was triggered to help victims of earthquake in Haiti on January 12 this year, France sent substantial resources. The deployment of these resources such as those sent by the rest of the international community took place on a ravaged territory. In addition to difficulties related to destruction, it was relatively difficult to obtain an overview of the situation. The almost total absence of means of communication on site and the interpretation made by some international media, benign events also helped to complicate the situation. Today, it lists the actions and projects, but what about the situation on the ground?

  6. The collective action problem in primate territory economics.

    Science.gov (United States)

    Willems, Erik P; Hellriegel, Barbara; van Schaik, Carel P

    2013-05-22

    Group-living animals often do not maintain territories, but instead have highly overlapping ranges, even though in principle these are economically defendable. We investigate whether this absence of range defence reflects a collective action problem, since a territory can be considered a public good. In a comparative analysis comprising 135 primate species, we find a positive association between range overlap and group size, controlling for economic defendability and phylogenetic non-independence. We subsequently demonstrate that groups with multiple adults of both sexes suffer levels of range overlap twice as high as groups with only a single adult representative of either sex, consistent with the presence of a collective action problem. Finally, we reveal that this collective action problem can be overcome through philopatry of the larger sex. These results suggest that a social complication of group living is a stronger determinant of between-group relations among social animals than ecological factors, but also that collective defence is still achieved where the dominant sex is philopatric and effective defence is critical to reproductive success and survival. In addition, our findings support the idea that human-like warfare, defined as escalated collective territorial conflict, has an evolutionary basis reflected by cases of convergent evolution among non-human primates.

  7. Understanding affirmative action.

    Science.gov (United States)

    Crosby, Faye J; Iyer, Aarti; Sincharoen, Sirinda

    2006-01-01

    Affirmative action is a controversial and often poorly understood policy. It is also a policy that has been widely studied by social scientists. In this review, we outline how affirmative action operates in employment and education settings and consider the major points of controversy. In addition, we detail the contributions of psychologists and other social scientists in helping to demonstrate why affirmative action is needed; how it can have unintended negative consequences; and how affirmative action programs can be most successful. We also review how psychologists have examined variations in people's attitudes toward affirmative action, in part as a means for testing different theories of social behavior.

  8. Differential Equations as Actions

    DEFF Research Database (Denmark)

    Ronkko, Mauno; Ravn, Anders P.

    1997-01-01

    We extend a conventional action system with a primitive action consisting of a differential equation and an evolution invariant. The semantics is given by a predicate transformer. The weakest liberal precondition is chosen, because it is not always desirable that steps corresponding to differential...... actions shall terminate. It is shown that the proposed differential action has a semantics which corresponds to a discrete approximation when the discrete step size goes to zero. The extension gives action systems the power to model real-time clocks and continuous evolutions within hybrid systems....

  9. Action Theory Evolution

    CERN Document Server

    Varzinczak, Ivan

    2008-01-01

    Like any other logical theory, domain descriptions in reasoning about actions may evolve, and thus need revision methods to adequately accommodate new information about the behavior of actions. The present work is about changing action domain descriptions in propositional dynamic logic. Its contribution is threefold: first we revisit the semantics of action theory contraction that has been done in previous work, giving more robust operators that express minimal change based on a notion of distance between Kripke-models. Second we give algorithms for syntactical action theory contraction and establish their correctness w.r.t. our semantics. Finally we state postulates for action theory contraction and assess the behavior of our operators w.r.t. them. Moreover, we also address the revision counterpart of action theory change, showing that it benefits from our semantics for contraction.

  10. All in Action

    Directory of Open Access Journals (Sweden)

    Arto Annila

    2010-11-01

    Full Text Available The principle of least action provides a holistic worldview in which Nature in its entirety and every detail is described in terms of actions. Each and every action is ultimately composed of one or multiple of the most elementary actions which relates to Planck’s constant. Elements of space are closed actions, known as fermions, whereas elements of time are open actions, known as bosons. The actions span an energy landscape, the Universe, which evolves irreversibly according to the 2nd law of thermodynamics by diminishing energy density differences in least time. During evolution densely-curled actions unfold step-by-step when opening up and expelling one or multiple elementary actions to their surrounding sparser space. The energy landscape will process from one symmetry group to another until the equivalence to its dual, i.e., the surrounding density has been attained. The scale-free physical portrayal of nature in terms of actions does not recognize any fundamental difference between fundamental particles and fundamental forces. Instead a plethora of particles and a diaspora of forces are perceived merely as diverse manifestations of a natural selection for various mechanisms and ways to decrease free energy in the least time.

  11. Antisymmetric string actions

    Science.gov (United States)

    Aragone, C.

    1986-12-01

    An action is presented for the free bosonic string on external flat space in terms of an antisymmetric second-rank string background tensor which is classically equivalent to the Nambu-Goto action. Both action and field equations are entirely described in terms of 2D world-sheet forms, without any reference to a 2D metric tensor background. The analysis of its canonical formulation shows how the quadratic Virasoro constraints are generated in this case and what their connection with the Bianchi identities are. Since in the orthonormal gauge the reduced action coincides with the standard one, it has the same critical dimension D = 26. The existence of an interaction term of a purely geometric structure stemming in the extrinsic curvature is pointed out. Its action and the new string field equations are then derived. This polynomial antisymmetric string action is uniformly generalized in order to describe d Apartado 80659, Caracas 1080A, Venezuela.

  12. Hypofractionated Dose Escalated 3D Conformal Radiotherapy for Prostate Cancer: Outcomes from a Mono-Institutional Phase II Study.

    Science.gov (United States)

    Tramacere, Francesco; Arcangeli, Stefano; Pignatelli, Antonietta; Castagna, Roberta; Portaluri, Maurizio

    2015-05-01

    (bNED) was 83% for all patients. Our study confirms that 3D conformal radiotherapy (3DCRT) remains a safe and effective method to deliver a dose-escalated hypofractionated regimen for PCa patients in all risk classes with acceptable toxicity rates and optimal biochemical control. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  13. Precision Hypofractionated Radiation Therapy in Poor Performing Patients With Non-Small Cell Lung Cancer: Phase 1 Dose Escalation Trial

    Energy Technology Data Exchange (ETDEWEB)

    Westover, Kenneth D. [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Loo, Billy W. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Gerber, David E. [Division of Hematology-Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Iyengar, Puneeth; Choy, Hak [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Diehn, Maximilian [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Hughes, Randy; Schiller, Joan; Dowell, Jonathan [Division of Hematology-Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Wardak, Zabi [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Sher, David [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); Christie, Alana; Xie, Xian-Jin [Department of Clinical Science, Southwestern Medical Center, Dallas, Texas (United States); Corona, Irma [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Sharma, Akanksha [School of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Wadsworth, Margaret E. [Radiation Oncology of Mississippi, Jackson, Mississippi (United States); Timmerman, Robert, E-mail: Robert.Timmerman@utsouthwestern.edu [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States)

    2015-09-01

    Purpose: Treatment regimens for locally advanced non-small cell lung cancer (NSCLC) give suboptimal clinical outcomes. Technological advancements such as radiation therapy, the backbone of most treatment regimens, may enable more potent and effective therapies. The objective of this study was to escalate radiation therapy to a tumoricidal hypofractionated dose without exceeding the maximally tolerated dose (MTD) in patients with locally advanced NSCLC. Methods and Materials: Patients with stage II to IV or recurrent NSCLC and Eastern Cooperative Oncology Group performance status of 2 or greater and not candidates for surgical resection, stereotactic radiation, or concurrent chemoradiation were eligible. Highly conformal radiation therapy was given to treat intrathoracic disease in 15 fractions to a total of 50, 55, or 60 Gy. Results: Fifty-five patients were enrolled: 15 at the 50-Gy, 21 at the 55-Gy, and 19 at the 60-Gy dose levels. A 90-day follow-up was completed in each group without exceeding the MTD. With a median follow-up of 12.5 months, there were 93 grade ≥3 adverse events (AEs), including 39 deaths, although most AEs were considered related to factors other than radiation therapy. One patient from the 55- and 60-Gy dose groups developed grade ≥3 esophagitis, and 5, 4, and 4 patients in the respective dose groups experienced grade ≥3 dyspnea, but only 2 of these AEs were considered likely related to therapy. There was no association between fraction size and toxicity (P=.24). The median overall survival was 6 months with no significant differences between dose levels (P=.59). Conclusions: Precision hypofractionated radiation therapy consisting of 60 Gy in 15 fractions for locally advanced NSCLC is generally well tolerated. This treatment regimen could provide patients with poor performance status a potent alternative to chemoradiation. This study has implications for the cost effectiveness of lung cancer therapy. Additional studies of long

  14. Dose escalation of the hypoxic cell sensitizer etanidazole combined with ifosfamide, carboplatin, etoposide, and autologous hematopoietic stem cell support.

    Science.gov (United States)

    Elias, A D; Wheeler, C; Ayash, L J; Schwartz, G; Ibrahim, J; Mills, L; McCauley, M; Coleman, N; Warren, D; Schnipper, L; Antman, K H; Teicher, B A; Frei, E

    1998-06-01

    Multiple mechanisms of drug resistance contribute to treatment failure. Although high-dose therapy attempts to overwhelm these defenses pharmacologically, this approach is only successful in a fraction of treated patients. Many drug resistance mechanisms are shared between malignant and normal cells, but the expression of various drug resistance mechanisms associated with hypoxia is largely confined to tumor tissue. Thus, reversal of this mechanism is likely to provide a therapeutic advantage to the host. This study was designed to define the dose-limiting toxicities and maximum tolerated dose of etanidazole when it is given concurrently with high-dose ifosfamide, carboplatin, and etoposide (ICE), with hematopoietic stem cell support. The maximum tolerated doses of high-dose ICE were administered concurrently with dose escalations of etanidazole, a hypoxic cell sensitizer. All agents were given by 96-h continuous i.v. infusion beginning on day -7. Mesna uroprotection was provided. Autologous marrow and cytokine mobilized peripheral blood progenitor cells were reinfused on day 0. Granulocyte colony-stimulating factor was administered following reinfusion until the granulocytes recovered to > 1000/microliter. Fifty-five adults with advanced malignancies were enrolled in cohorts of five to nine patients. Four dose levels of etanidazole between 3 and 5.5 g/m2/day (12, 16, 20, and 22 g/m2 total doses) and two doses of carboplatin (1600 and 1800 mg/m2 total doses) were evaluated. Seven patients died of organ toxicity (13%); two each from veno-occlusive disease of liver and sepsis; and one each from sudden death, renal failure, and refractory thrombocytopenic hemorrhage. Five deaths occurred at the top dose level. One additional patient suffered a witnessed cardiorespiratory arrest from ventricular fibrillation and was resuscitated. Dose-dependent and largely reversible peripheral neuropathy was observed consisting of two syndromes: severe cramping myalgic/neuralgic pain

  15. Pharmacodynamics of dose-escalated 'front-loading' polymyxin B regimens against polymyxin-resistant mcr-1-harbouring Escherichia coli.

    Science.gov (United States)

    Smith, Nicholas M; Bulman, Zackery P; Sieron, Arthur O; Bulitta, Jürgen B; Holden, Patricia N; Nation, Roger L; Li, Jian; Wright, Gerard D; Tsuji, Brian T

    2017-08-01

    Gram-negative bacteria harbouring the mcr-1 plasmid are resistant to the 'last-line' polymyxins and have been reported worldwide. Our objective was to define the impact of increasing the initial polymyxin B dose intensity against an mcr-1 -harbouring strain to delineate the impact of plasmid-mediated polymyxin resistance on the dynamics of bacterial killing and resistance. A hollow fibre infection model (HFIM) was used to simulate polymyxin B regimens against an mcr-1 -harbouring Escherichia coli (MIC 8 mg/L) over 10 days. Four escalating polymyxin B 'front-loading' regimens (3.33, 6.66, 13.3 or 26.6 mg/kg for one dose followed by 1.43 mg/kg every 12 h starting 12 h later) simulating human pharmacokinetics were utilized in the HFIM. A mechanism-based, mathematical model was developed using S-ADAPT to characterize bacterial killing. The 3.33 mg/kg 'front-loading' regimen resulted in regrowth mirroring the growth control. The 6.66, 13.3 and 26.6 mg/kg 'front-loading' regimens resulted in maximal bacterial reductions of 1.91, 3.79 and 6.14 log 10 cfu/mL, respectively. Irrespective of the early polymyxin B exposure (24 h AUC), population analysis profiles showed similar growth of polymyxin B-resistant subpopulations. The HFIM data were well described by the mechanism-based model integrating three subpopulations (susceptible, intermediate and resistant). Compared with the susceptible subpopulation of mcr-1 -harbouring E. coli , the resistant subpopulation had an approximately 10-fold lower rate of killing due to polymyxin B treatment. Manipulating initial dose intensity of polymyxin B was not able to overcome plasmid-mediated resistance due to mcr-1 in E. coli . This reinforces the need to develop new combinatorial strategies to combat these highly resistant Gram-negative bacteria.

  16. Vorinostat and Concurrent Stereotactic Radiosurgery for Non-Small Cell Lung Cancer Brain Metastases: A Phase 1 Dose Escalation Trial.

    Science.gov (United States)

    Choi, Clara Y H; Wakelee, Heather A; Neal, Joel W; Pinder-Schenck, Mary C; Yu, Hsiang-Hsuan Michael; Chang, Steven D; Adler, John R; Modlin, Leslie A; Harsh, Griffith R; Soltys, Scott G

    2017-09-01

    To determine the maximum tolerated dose (MTD) of vorinostat, a histone deacetylase inhibitor, given concurrently with stereotactic radiosurgery (SRS) to treat non-small cell lung cancer (NSCLC) brain metastases. Secondary objectives were to determine toxicity, local failure, distant intracranial failure, and overall survival rates. In this multicenter study, patients with 1 to 4 NSCLC brain metastases, each ≤2 cm, were enrolled in a phase 1, 3 + 3 dose escalation trial. Vorinostat dose levels were 200, 300, and 400 mg orally once daily for 14 days. Single-fraction SRS was delivered on day 3. A dose-limiting toxicity (DLT) was defined as any Common Terminology Criteria for Adverse Events version 3.0 grade 3 to 5 acute nonhematologic adverse event related to vorinostat or SRS occurring within 30 days. From 2009 to 2014, 17 patients were enrolled and 12 patients completed study treatment. Because no DLTs were observed, the MTD was established as 400 mg. Acute adverse events were reported by 10 patients (59%). Five patients discontinued vorinostat early and withdrew from the study. The most common reasons for withdrawal were dyspnea (n=2), nausea (n=1), and fatigue (n=2). With a median follow-up of 12 months (range, 1-64 months), Kaplan-Meier overall survival was 13 months. There were no local failures. One patient (8%) at the 400-mg dose level with a 2.0-cm metastasis developed histologically confirmed grade 4 radiation necrosis 2 months after SRS. The MTD of vorinostat with concurrent SRS was established as 400 mg. Although no DLTs were observed, 5 patients withdrew before completing the treatment course, a result that emphasizes the need for supportive care during vorinostat administration. There were no local failures. A larger, randomized trial may evaluate both the tolerability and potential local control benefit of vorinostat concurrent with SRS for brain metastases. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Action in Introductory Physics

    CERN Document Server

    McGinness, Lachlan P

    2015-01-01

    We have investigated the teaching and learning of the stationary action formulation of classical physics in a first-year university class. Instruction proceeded from the many-paths approach to quantum physics through to ray optics, classical mechanics, and relativity. Student learning and misconceptions were studied with quantitative and qualitative techniques. In particular, an action concept inventory was developed through a process of expert consultation and student feedback. Students reported action physics to be accessible, interesting and valuable.

  18. Talk and Action

    DEFF Research Database (Denmark)

    Christensen, Lars Thøger; Morsing, Mette; Thyssen, Ole

    The aim of this paper is to analyze the relationship between organizational talk and action. Focusing in particular on the temporal dimension of this relationship, that is, the potential for talk to become action over time, we put forward ideal types of organizational strategies for possible talk......-action relationships. While we illustrate our theoretical points with examples from both corporate and political contexts, we draw especially on the field of corporate social responsibility (as an extreme case) where expectations of consistency between talk and actions are most explicitly pronounced....

  19. Action principles in nature

    Science.gov (United States)

    Barrow, John D.; Tipler, Frank J.

    1988-01-01

    Physical theories have their most fundamental expression as action integrals. This suggests that the total action of the universe is the most fundamental physical quantity, and hence finite. In this article it is argued that finite universal action implies that the universe is spatially closed. Further, the possible spatial topologies, the types of matter that can dominate the early universe dynamics, and the form of any quadratic additions to the lagrangian of general relativity are constrained. Initial and final cosmological curvature singularities are required to avoid a universal action singularity.

  20. Action principles in nature

    Energy Technology Data Exchange (ETDEWEB)

    Barrow, J.D.; Tipler, F.J.

    1988-01-07

    Physical theories have their most fundamental expression as action integrals. This suggests that the total action of the Universe is the most fundamental physical quantity, and hence finite. In this article it is argued that finite universal action implies that the Universe is spatially closed. Further, the possible spatial topologies, the types of matter that can dominate the early universe dynamics, and the form of any quadratic additions to the lagrangian of general relativity are constrained. Initial and final cosmological curvature singularities are required to avoid a universal action singularity.

  1. Perception, Action, and Consciousness

    DEFF Research Database (Denmark)

    What is the relationship between perception and action, between an organism and its environment, in explaining consciousness? These are issues at the heart of philosophy of mind and the cognitive sciences. This book explores the relationship between perception and action from a variety of interdi......What is the relationship between perception and action, between an organism and its environment, in explaining consciousness? These are issues at the heart of philosophy of mind and the cognitive sciences. This book explores the relationship between perception and action from a variety...

  2. CHAOTIC GROUP ACTIONS

    Institute of Scientific and Technical Information of China (English)

    ShiEnhui; ZhouLizhen; ZhouYoucheng

    2003-01-01

    It is proved that there is no chaotic group actions on any topological space with free arc.In this paper the chaotic actions of the group like G×F,where F is a finite group,are studied.In particular,under a suitable assumption ,if F is a cyclic group,then the topological space which admits a chaotic action of Z×F must admit a chatotic homeomorphism.A topological space which admits a chaotic group action but admits no chaotic horneomorphism is constructed.

  3. Intensity modulated radiation therapy with simultaneous integrated boost based dose escalation on neoadjuvant chemoradiation therapy for locally advanced distal esophageal adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Ming Zeng; Fernando N Aguila; Taral Patel; Mark Knapp; XueQiang Zhu; XiLin Chen; Phillip D Price

    2016-01-01

    AIM:To evaluate impact of radiation therapy dose escalation through intensity modulated radiation therapy with simultaneous integrated boost(IMRT-SIB).METHODS:We retrospectively reviewed the patients who underwent four-dimensional-based IMRT-SIBbased neoadjuvant chemoradiation protocol.During the concurrent chemoradiation therapy,radiation therapy was through IMRT-SIB delivered in 28 consecutive daily fractions with total radiation doses of 56 Gy to tumor and 5040 Gy dose-painted to clinical tumor volume,with a regimen at the discretion of the treating medical oncologist.This was followed by surgical tumor resection.We analyzed pathological completion response(p CR) rates its relationship with overall survival and event-freesurvival.RESULTS:Seventeen patients underwent dose escalation with the IMRT-SIB protocol between 2007 and 2014 and their records were available for analysis.Among the IMRT-SIB-treated patients,the toxicity appeared mild,the most common side effects were grade 1-3 esophagitis(46%) and pneumonitis(11.7%).There were no cardiac events.The Ro resection rate was 94%(n = 16),the p CR rate was 47%(n = 8),and the postoperative morbidity was zero.There was one mediastinal failure found,one patient had local failure at the anastomosis site,and the majority of failures were distant in the lung or bone.The 3-year diseasefree survival and overall survival rates were 41%(n = 7) and 53%(n = 9),respectively.CONCLUSION:The dose escalation through IMRT-SIB in the chemoradiation regimen seems responsible for down-staging the distal esophageal with well-tolerated complications.

  4. Weekly paclitaxel in escalating doses in a patient with anthracycline-resistant, triple-negative, metastatic breast cancer with severe liver dysfunction

    Directory of Open Access Journals (Sweden)

    Ajay Gupta

    2012-01-01

    Full Text Available Liver dysfunction in a patient with anthracycline-resistant breast cancer and liver metastases with poor performance status (PS represents a serious situation. Taxanes are the drugs of choice, but once the transaminase enzyme levels are raised more than 10-times the upper limit of normal (>10 ULN, paclitaxel administration is contraindicated. We present the report of one such case who had a gratifying response to escalating doses of weekly paclitaxel thus suggesting that even patients with severe liver dysfunction can derive benefits from such a strategy. The patient, a 54-year-old lady with breast cancer metastatic to the liver and bones and previous receipt of anthracycline-based therapy, presented to us with a PS of 3. Her liver functions (LFT were: serum bilirubin 2.2 mg% (0.3-1.1 mg%, aspartate aminotransferase 375 IU/L (0-25 IU/L, alanine aminotransferase 369 IU/L (0-35 IU/L and alkaline phosphatase 363 IU/L (38-126 IU/L. She was started on weekly paclitaxel 20 mg/m 2 and zoledronate. After the first dose, the LFTs rose marginally but the skin lesions stabilized. Dose was subsequently escalated to 40 mg/m 2 . At the end of the 10th week, her PS improved to 1 and the disease showed a partial response. LFTs improved markedly. However, 5 days after the administration of the 13 th dose, the disease progressed and paclitaxel had to be discontinued. It is possible to derive maximum palliative benefit with escalating doses of weekly paclitaxel even in patients whose liver functions are deranged with transaminase levels (>10 ULN and in whom conventional administration of paclitaxel is contraindicated.

  5. Dose escalation for patients with decreasing PSA during radiotherapy for elevated PSA after radical prostatectomy improves biochemical progression-free survival. Results of a retrospective study

    Energy Technology Data Exchange (ETDEWEB)

    Siegmann, Alessandra; Faehndrich, Julia; Lohm, Gunnar; Hinkelbein, Wolfgang [Charite Universitaetsmedizin, Berlin (Germany). Dept. of Radiation Oncology; Bottke, Dirk; Bartkowiak, Detlef; Wiegel, Thomas [University Hospital Ulm (Germany). Dept. of Radiation Oncology; Miller, Kurt [Charite Universitaetsmedizin, Berlin (Germany). Dept. of Urology

    2011-08-15

    The optimal dose for salvage radiotherapy (SRT) after radical prostatectomy (RP) is still not defined. It should be at least 66 Gy. In the present study, the suitability of PSA regression as a selection criterion for an SRT dose escalation to 70.2 Gy was examined. Between 1997 and 2007, 301 prostate cancer patients received SRT after RP at the Charite - University Medicine Berlin, Campus Benjamin Franklin. None of the patients had antihormone therapy prior to SRT. A total of 234 patients received 66.6 Gy. From 2002 on, 67 patients with a PSA decrease during SRT were irradiated with 70.2 Gy. The influence of this selection and dose escalation on freedom from biochemical progression (bNED) was analyzed. The median follow-up of the whole group was 30 months, the median pre-SRT PSA was 0.28 ng/ml. Of the patients, 27% (82/301) developed biochemical progression, 31% from the 66.6 Gy cohort (73/292) and 13% from the 70.2 Gy cohort (9/67) (p = 0.01). The calculated 2-years bNED was 74% for the whole group, 88% vs. 71% after 70.2 Gy and 66.6 Gy, respectively (p = 0.01). In a multivariate analysis, the total dose (p = 0.017), the re-achievement of an undetectable PSA after SRT (p = 0.005), and the infiltration of the seminal vesicles (p = 0.049) were independent parameters of bNED. Our analysis suggests that patient selection during SRT for a dose escalation to 70.2 Gy can improve the freedom from biochemical progression in patients with SRT after RP. (orig.)

  6. FOLFIRI and regorafenib combination therapy with dose escalation of irinotecan as fourth-line treatment for patients with metastatic colon cancer according to UGT1A1 genotyping

    Directory of Open Access Journals (Sweden)

    Lu CY

    2014-11-01

    Full Text Available Chien-Yu Lu,1,2 Yung-Sung Yeh,3–5 Ching-Wen Huang,5,6, Cheng-Jen Ma,4,5 Fang-Jung Yu,1,2 Jaw-Yuan Wang4–10 1Division of Gastroenterology, Department of Internal Medicine, 2Department of Internal Medicine, Faculty of Medicine, College of Medicine, 3Department of Emergency Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, 4Graduate Institute of Clinical Medicine, College of Medicine, 5Division of Gastroenterology and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, 6Graduate Institute of Medicine, College of Medicine, 7Cancer Center, Kaohsiung Medical University Hospital, 8Department of Genomic Medicine, 9Department of Surgery, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 10Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan Abstract: Here we report a case of metastatic colon cancer treated with 5-fluorouracil, leucovorin, and escalated doses of irinotecan (FOLFIRI combined with regorafenib in the fourth-line setting after uridine diphosphate glucuronosyltransferase (UGT1A1 genotyping analysis. A 66-year-old male was initially diagnosed with Union Internationale Contre le Cancer stage III descending colon cancer and underwent curative surgery. He received postoperative adjuvant chemotherapy; however, liver metastasis developed and a partial hepatectomy was performed thereafter. Unfortunately, pulmonary metastases and recurrent liver tumors were found despite a series of systemic treatments with multiple combinations of cytotoxic and biologic agents. Recently, a novel multikinase inhibitor, regorafenib, was approved for the treatment of metastatic colorectal cancer refractory to other therapeutic modalities. As further treatment, we combined regorafenib with FOLFIRI, which included dose escalations of irinotecan, after UGT1A1 genotyping analysis. The therapeutic results were promising, with the improvement in liver and pulmonary metastases being

  7. 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

  8. Action Learning in China

    Science.gov (United States)

    Marquardt, Michael J.

    2015-01-01

    Action learning was introduced into China less than 20 years ago, but has rapidly become a valuable tool for organizations seeking to solve problems, develop their leaders, and become learning organizations. This article provides an historical overview of action learning in China, its cultural underpinnings, and five case studies. It concludes…

  9. An Action Environment

    DEFF Research Database (Denmark)

    van den Brand, Mark; Iversen, Jørgen; Mosses, Peter David

    2004-01-01

    constructs underlying Core ML. The paper also describes the Action Environment, a new environment supporting use and validation of ASDF descriptions. The Action Environment has been implemented on top of the ASF+SDF Meta-Environment, exploiting recent advances in techniques for integration of different...

  10. Validity in Action Research.

    Science.gov (United States)

    Watkins, Karen E.

    Emerging criteria are reported for judging the trustworthiness of action research studies as compared to the criteria established for judging the trustworthiness of other forms of naturalistic inquiry set forth by Y. S. Lincoln and E. Guba (1985). Differing conceptions of the nature of action research are delineated, and their accompanying…

  11. On action theory change

    CSIR Research Space (South Africa)

    Varzinczak, IJ

    2010-02-01

    Full Text Available revisit the semantics of action theory contraction proposed in previous work, giving more robust operators that express minimal change based on a notion of distance between Kripke-models. Second we give algorithms for syntactical action theory contraction...

  12. Action Learning and Leadership.

    Science.gov (United States)

    Marquardt, Michael J.

    2000-01-01

    Today's leaders perform the following roles: systems thinker, change agent, innovator, servant, polychronic coordinator, teacher-mentor, and visionary. The elements of action learning (real problems, teams, reflective inquiry, commitment to action, focus on learning) contribute to the development of these critical skills. (Author/SK)

  13. Critical Utopian Action Research

    DEFF Research Database (Denmark)

    Nielsen, Birger Steen; Nielsen, Kurt Aagaard

    2016-01-01

    The specific concept of critical utopian action research is presented and discussed, as to its origin, use and potentials. The inspiration from Robert Jungk and his future creating workshops is elaborated.......The specific concept of critical utopian action research is presented and discussed, as to its origin, use and potentials. The inspiration from Robert Jungk and his future creating workshops is elaborated....

  14. Action Learning in China

    Science.gov (United States)

    Marquardt, Michael J.

    2015-01-01

    Action learning was introduced into China less than 20 years ago, but has rapidly become a valuable tool for organizations seeking to solve problems, develop their leaders, and become learning organizations. This article provides an historical overview of action learning in China, its cultural underpinnings, and five case studies. It concludes…

  15. Renormalized action improvements

    Energy Technology Data Exchange (ETDEWEB)

    Zachos, C.

    1984-01-01

    Finite lattice spacing artifacts are suppressed on the renormalized actions. The renormalized action trajectories of SU(N) lattice gauge theories are considered from the standpoint of the Migdal-Kadanoff approximation. The minor renormalized trajectories which involve representations invariant under the center are discussed and quantified. 17 references.

  16. Creativity as action

    DEFF Research Database (Denmark)

    Glaveanu, Vlad Petre; Lubart, Todd; Bonnardel, Nathalie

    2013-01-01

    The present paper outlines an action theory of creativity and substantiates this approach by investigating creative expression in five different domains. We propose an action framework for the analysis of creative acts built on the assumption that creativity is a relational, inter......-subjective phenomenon. This framework, drawing extensively from the work of Dewey (1934) on art as experience, is used to derive a coding frame for the analysis of interview material. The article reports findings from the analysis of 60 interviews with recognized French creators in five creative domains: art, design......, science, scriptwriting, and music. Results point to complex models of action and inter-action specific for each domain and also to interesting patterns of similarity and differences between domains. These findings highlight the fact that creative action takes place not “inside” individual creators but “in...

  17. "Adulterated" Androstenedione: What FDA's Action against Andro Means for Industry

    Directory of Open Access Journals (Sweden)

    Collins Richard D

    2004-05-01

    Full Text Available Abstract On March 11, 2004, the Food and Drug Administration (FDA pronounced that dietary supplement products containing androstenedione were adulterated new dietary ingredients under the Dietary Supplement Health and Education Act of 1994 (DSHEA. The FDA issued a press release, held a news conference, and sent warning letters to 23 companies that had manufactured, marketed or distributed the products containing androstenedione. In its warning letters, FDA threatened possible enforcement actions for noncompliance. The authors have looked at the warning letters, statutes, regulations, and media reports to analyze the legal grounds and standards upon which FDA acted against androstenedione and question the appropriateness of the action taken. They have also looked at the negative impact that FDA's lack of communication and cooperation with Industry is having upon the fitness nutrition industry and the marketing of dietary supplements containing new dietary ingredients. The authors also suggest what might be done to ameliorate this escalating problem including more cooperation between FDA and Industry and more research into the benefits and use of supplement products.

  18. Action spectra again?

    Science.gov (United States)

    Coohill, T P

    1991-11-01

    Action spectroscopy has a long history and is of central importance to photobiological studies. Action spectra were among the first assays to point to chlorophyll as the molecule most responsible for plant growth and to DNA as the genetic material. It is useful to construct action spectra early in the investigation of new areas of photobiological research in an attempt to determine the wavelength limits of the radiation region causing the studied response. But due to the severe absorption of ultraviolet (UV) radiation by biological samples, UV action spectra were first limited to small cells (bacteria and fungi). Advances in techniques (e.g. single cell culture) and analysis allowed accurate action spectra to be reported even for mammalian cells. But precise analytical action spectra are often difficult to obtain when large, pigmented, or groups of cells are investigated. Here some action spectra are limited in interpretation and merely supply a wavelength vs effect curve. When polychromatic sources are employed, the interpretation of action spectra is even more complex and formidable. But such polychromatic action spectra can be more directly related to ambient responses. Since precise action spectra usually require the completion of a relatively large number of careful experiments using somewhat sophisticated equipment over a range of at least six wavelengths, they are often not pursued. But they remain central to the elucidation of the effect being studied. The worldwide community has agreed that stratospheric ozone is depleting, with the possibility of a consequent rise in the amount of UV-B (290-320 nm) reaching the earth's surface. It is therefore essential that new action spectra be completed for UV-B effects on a large variety of responses of human, animal, and aquatic plant systems. Combining these action spectra with the known amounts of UV-B reaching the biosphere can give rise to solar UV effectiveness spectra that, in turn, can give rise to estimates

  19. Continuous intracerebroventricular infusion of the competitive NMDA receptor antagonist, LY235959, facilitates escalation of cocaine self-administration and increases break point for cocaine in Sprague-Dawley rats.

    Science.gov (United States)

    Allen, Richard M; Uban, Kristina A; Atwood, Elizabeth M; Albeck, David S; Yamamoto, Dorothy J

    2007-11-01

    Although escalation of consumption is an important characteristic of cocaine dependence, the neurobiological mechanisms that mediate this phenomenon have not been fully described. In this study, we used male, Sprague-Dawley rats to measure the effects of acute and continuous intracerebroventricular (ICV) administration of the competitive NMDA receptor antagonist, LY235959, on cocaine self-administration behavior under various schedules of reinforcement and access conditions. Single ICV infusions of LY235959 (0.03-0.3 microg/5 microl) produced dose-dependent and statistically significant decreases in the number of cocaine infusions earned under a progressive ratio schedule of reinforcement. In a second experiment, vehicle or LY235959 (0.2-0.3 microg/day) was continuously administered ICV to rats via surgically-implanted subcutaneous osmotic minipump/intracranial cannula assemblies. Both vehicle- and LY235959-treated rats significantly escalated cocaine self-administration over the 10 long access sessions; however, rats treated with LY235959 escalated cocaine self-administration faster and to a greater degree than vehicle-treated rats. There was a statistically significant increase in cocaine infusions earned under the PR schedule in LY235959-treated rats, but not vehicle-treated rats, after 10 long access cocaine self-administration sessions. These data support the hypothesis that escalation of cocaine consumption is mediated by hypo-glutamatergic tone in the central nervous system and this facilitation of escalation is associated with an increase in motivation to respond for cocaine.

  20. A prospective study of differences in duodenum compared to remaining small bowel motion between radiation treatments: Implications for radiation dose escalation in carcinoma of the pancreas

    Directory of Open Access Journals (Sweden)

    Wahab Sasha H

    2006-09-01

    Full Text Available Abstract Purpose As a foundation for a dose escalation trial, we sought to characterize duodenal and non-duodenal small bowel organ motion between fractions of pancreatic radiation therapy. Patients and methods Nine patients (4 women, 5 men undergoing radiation therapy were enrolled in this prospective study. The patients had up to four weekly CT scans performed during their course of radiation therapy. Pancreas, duodenum and non-duodenal small bowel were then contoured for each CT scan. On the initial scan, a four-field plan was generated to fully cover the pancreas. This plan was registered to each subsequent CT scan. Dose-volume histogram (DVH analyses were performed for the duodenum, non-duodenal small bowel, large bowel, and pancreas. Results With significant individual variation, the volume of duodenum receiving at least 80% of the prescribed dose was consistently greater than the remaining small bowel. In the patient with the largest inter-fraction variation, the fractional volume of non-duodenal small bowel irradiated to at least the 80% isodose line ranged from 1% to 20%. In the patient with the largest inter-fraction variation, the fractional volume of duodenum irradiated to at least the 80% isodose line ranged from 30% to 100%. Conclusion The volume of small bowel irradiated during four-field pancreatic radiation therapy changes substantially between fractions. This suggests dose escalation may be possible. However, dose limits to the duodenum should be stricter than for other segments of small bowel.

  1. Ventilator-associated pneumonia: the influence of bacterial resistance, prescription errors, and de-escalation of antimicrobial therapy on mortality rates

    Directory of Open Access Journals (Sweden)

    Ana Carolina Souza-Oliveira

    Full Text Available Abstract Ventilator-associated pneumonia is the most prevalent nosocomial infection in intensive care units and is associated with high mortality rates (14–70%. Aim This study evaluated factors influencing mortality of patients with Ventilator-associated pneumonia (VAP, including bacterial resistance, prescription errors, and de-escalation of antibiotic therapy. Methods This retrospective study included 120 cases of Ventilator-associated pneumonia admitted to the adult adult intensive care unit of the Federal University of Uberlândia. The chi-square test was used to compare qualitative variables. Student's t-test was used for quantitative variables and multiple logistic regression analysis to identify independent predictors of mortality. Findings De-escalation of antibiotic therapy and resistant bacteria did not influence mortality. Mortality was 4 times and 3 times higher, respectively, in patients who received an inappropriate antibiotic loading dose and in patients whose antibiotic dose was not adjusted for renal function. Multiple logistic regression analysis revealed the incorrect adjustment for renal function was the only independent factor associated with increased mortality. Conclusion Prescription errors influenced mortality of patients with Ventilator-associated pneumonia, underscoring the challenge of proper Ventilator-associated pneumonia treatment, which requires continuous reevaluation to ensure that clinical response to therapy meets expectations.

  2. Talk and Action

    DEFF Research Database (Denmark)

    Christensen, Lars Thøger; Morsing, Mette; Thyssen, Ole

    of organizational talk and their associated activities, the paper discusses the different ways time shape the relationship between talk and action. Acknowledging that talk gives rise to different expectations over time, we put forward ideal types of organizational strategies for possible talk-action relationships....... While we illustrate our theoretical points with examples from both corporate and political contexts, we draw especially on the field of corporate social responsibility (as an extreme case) where expectations of consistency between talk and actions are most explicitly pronounced....

  3. Actions for Curved Branes

    CERN Document Server

    Abou-Zeid, M

    2000-01-01

    The nondeterminantal forms of the Born-Infeld and related brane actions in which the gauge fields couple to both an induced metric and an intrinsic metric are generalised by letting either or both metrics be dynamical. The resulting actions describe ` brane world' and cosmological scenarios in which the gauge fields are confined to the brane, while gravity propagates in both the world-volume and the bulk. In particular, for actions involving a nonsymmetric ` metric', nonsymmetric gravity propagates on the worldvolume. For 3-branes with a symmetric metric, conformal (Weyl) gravity propagates on the worldvolume and has conformally invariant couplings to the gauge fields.

  4. Violence as Situational Action

    Directory of Open Access Journals (Sweden)

    Kyle H. Treiber

    2009-05-01

    Full Text Available Violence comes in many forms and occurs in many different circumstances for many different reasons. Is it really possible to develop a single theory that can explain all these disparate acts? In this paper, we argue it is. We make the case that acts of violence are essentially moral actions and therefore can, and should, be analysed and explained as such. We maintain that all acts of violence can be explained within the general framework of a theory of moral action. We present just such a theory – Situational Action Theory – and demonstrate how it can be applied to the explanation and study of violence.

  5. Reasoning about Unreliable Actions

    CERN Document Server

    White, Graham

    2012-01-01

    We analyse the philosopher Davidson's semantics of actions, using a strongly typed logic with contexts given by sets of partial equations between the outcomes of actions. This provides a perspicuous and elegant treatment of reasoning about action, analogous to Reiter's work on artificial intelligence. We define a sequent calculus for this logic, prove cut elimination, and give a semantics based on fibrations over partial cartesian categories: we give a structure theory for such fibrations. The existence of lax comma objects is necessary for the proof of cut elimination, and we give conditions on the domain fibration of a partial cartesian category for such comma objects to exist.

  6. Action Investment Energy Games

    DEFF Research Database (Denmark)

    Larsen, Kim Guldstrand; Laursen, Simon; Srba, Jiri

    2012-01-01

    We introduce the formalism of action investment energy games where we study the trade-off between investments limited by given budgets and resource constrained (energy) behavior of the underlying system. More specifically, we consider energy games extended with costs of enabling actions and fixed...... budgets for each player. We ask the question whether for any Player 2 investment there exists a Player 1 investment such that Player 1 wins the resulting energy game. We study the action investment energy game for energy intervals with both upper and lower bounds, and with a lower bound only, and give...... a complexity results overview for the problem of deciding the winner in the game....

  7. Spacelike brane actions.

    Science.gov (United States)

    Hashimoto, Koji; Ho, Pei-Ming; Wang, John E

    2003-04-11

    We derive effective actions for "spacelike branes" (S-branes) and find a solution describing the formation of fundamental strings in the rolling tachyon background. The S-brane action is a Dirac-Born-Infeld action for Euclidean world volumes defined in the context of time-dependent tachyon condensation of non-BPS (Bogomol'nyi-Prasad-Sommerfield) branes. It includes gauge fields and, in particular, a scalar field associated with translation along the time direction. We show that the BIon spike solutions constructed in this system correspond to the production of a confined electric flux tube (a fundamental string) at late time of the rolling tachyon.

  8. Perception, Action, and Consciousness

    DEFF Research Database (Denmark)

    What is the relationship between perception and action, between an organism and its environment, in explaining consciousness? These are issues at the heart of philosophy of mind and the cognitive sciences. This book explores the relationship between perception and action from a variety of interdi......What is the relationship between perception and action, between an organism and its environment, in explaining consciousness? These are issues at the heart of philosophy of mind and the cognitive sciences. This book explores the relationship between perception and action from a variety...... of interdisciplinary perspectives, ranging from theoretical discussion of concepts to findings from recent scientific studies. It incorporates contributions from leading philosophers, psychologists, neuroscientists, and an artificial intelligence theorist. The contributions take a range of positions with respect...

  9. Call to Action

    African Journals Online (AJOL)

    in countries throughout Africa. Countries should take immediate action to decentralise postabortion care, .... used to provide care, specific activities (includ- ing management of .... a dynamic strategy for addressing unsafe abor- tions in diverse ...

  10. NSP Action Plans

    Data.gov (United States)

    Department of Housing and Urban Development — NSP Action Plans, also known as Substantial Amendments, contain a description of a grantee’s intended use for NSP funds. The plans contain information on the...

  11. Affirmative Action's Contradictory Consequences.

    Science.gov (United States)

    Heilman, Madeline E.

    1996-01-01

    Addresses affirmative action's success at creating a more equal workplace. Explores some potential psychological costs of this policy--costs that paradoxically may undermine its objectives--and their implications for achieving the goal of workplace equality. (GR)

  12. Benzidine Dyes Action Plan

    Science.gov (United States)

    This Action Plan addresses the use of benzidine-based dyes and benzidine congener-based dyes, both metalized and non-metalized, in products that would result in consumer exposure, such as for use to color textiles.

  13. Normative Action Research

    DEFF Research Database (Denmark)

    Baboroglu, Oguz; Ravn, Ib

    1992-01-01

    /organizational research, the futures perspective implies that knowledge of the social/organizational world must be based upon images of desirable futures, so-called "futures theories", not causal descriptions of a problematic present. Futures theories identify ends and means for individual and organizational development......This paper presents an argument for an enrichment of action research methodology. To the current state of action research, we add a constructivist epistemological argument, as well as a crucial inspiration from some futures-oriented planning approaches. Within the domain of social....... They are generated jointly by the stakeholders of a system and the involved action researchers and are tested every time that the prescriptions for action contained in them are followed by a system's stakeholders....

  14. Normative Action Research

    DEFF Research Database (Denmark)

    Baboroglu, Oguz; Ravn, Ib

    1992-01-01

    /organizational research, the futures perspective implies that knowledge of the social/organizational world must be based upon images of desirable futures, so-called "futures theories", not causal descriptions of a problematic present. Futures theories identify ends and means for individual and organizational development......This paper presents an argument for an enrichment of action research methodology. To the current state of action research, we add a constructivist epistemological argument, as well as a crucial inspiration from some futures-oriented planning approaches. Within the domain of social....... They are generated jointly by the stakeholders of a system and the involved action researchers and are tested every time that the prescriptions for action contained in them are followed by a system's stakeholders....

  15. Introducere in Action Learning

    DEFF Research Database (Denmark)

    Clausen, Søren Witzel

    In these years action learning has become an increasing aspect of qualifying in service training of teachers in Western European countries. In this article the model of action learning which has been developed by teachers at VIA University College and introduced to the teachers at the SCAN...... in service program will be described and the interaction and the learning aspects in the model will be analyzed....

  16. Institutional Logics in Action

    DEFF Research Database (Denmark)

    Lounsbury, Michael; Boxenbaum, Eva

    2013-01-01

    This double volume presents state-of-the-art research and thinking on the dynamics of actors and institutional logics. In the introduction, we briefly sketch the roots and branches of institutional logics scholarship before turning to the new buds of research on the topic of how actors engage ins...... prolific stream of research on institutional logics by deepening our insight into the active use of institutional logics in organizational action and interaction, including the institutional effects of such (inter)actions....

  17. Color Blind Affirmative Action

    OpenAIRE

    2003-01-01

    This paper presents a conceptual framework for understanding the consequences of the widespread adoption of race-neutral alternatives' to conventional racial affirmative action policies in college admissions. A simple model of applicant competition with endogenous effort is utilized to show that, in comparison to color-conscious affirmative action, these color-blind alternatives can significantly lower the efficiency of the student selection process in equilibrium. We examine data on matricul...

  18. [Addictions and action systems].

    Science.gov (United States)

    Loonis, E; Apter, M J

    2000-01-01

    Generalizing from some previous analyses of addiction, and introducing the concept of an action system which governs all actions which are focussed on what Brown (1988) calls "hedonic management", we argue that addictions of every kind involve an action system that displays high salience, low variety and low vicariance. Addictions also involve what Apter (1982) calls the "paratelic state". A study was carried out comparing 31 drug addicts with 29 control subjects in terms of action system variables. To measure these variables, we constructed a new instrument, the Activity-System Drawing Test, and also used the Telic Dominance Scale to measure frequency of paratelic states. Dysphoria was measured by means of the BATE (anxiety), IDA-13 (depression), SEI (self-esteem), and TAS-20 (alexithymia) instruments. Strongly significant differences were found between groups for both action system variables and dysphoria, and there were also strong correlations between both groups of variables. This supports the idea that addictions emerge from systemic properties of the action system.

  19. Topological Lattice Actions

    CERN Document Server

    Bietenholz, W; Pepe, M; Wiese, U -J

    2010-01-01

    We consider lattice field theories with topological actions, which are invariant against small deformations of the fields. Some of these actions have infinite barriers separating different topological sectors. Topological actions do not have the correct classical continuum limit and they cannot be treated using perturbation theory, but they still yield the correct quantum continuum limit. To show this, we present analytic studies of the 1-d O(2) and O(3) model, as well as Monte Carlo simulations of the 2-d O(3) model using topological lattice actions. Some topological actions obey and others violate a lattice Schwarz inequality between the action and the topological charge $Q$. Irrespective of this, in the 2-d O(3) model the topological susceptibility $\\chi_t = \\l/V$ is logarithmically divergent in the continuum limit. Still, at non-zero distance the correlator of the topological charge density has a finite continuum limit which is consistent with analytic predictions. Our study shows explicitly that some cla...

  20. 关于扶梯防逆转保护装置的设置及检验的探讨%About setting of anti-reversal protection device of escalator and inspection

    Institute of Scientific and Technical Information of China (English)

    海曼

    2009-01-01

    According to explanation of setting of anti-reversal protection device of escalator in relative specifications, the paper discusses about methods and working principles of setting of anti-reversal protection device of escalator, it also concludes method and requirements of anti-re-versal protection device, so as to make sure common running of escalator.%根据相关规范关于扶梯设置防逆转保护装置的解释,对防逆转保护装置的设置方法及工作原理作了探讨,并总结了防逆转保护装置的检验方法及要求,以确保扶梯的正常运作.

  1. Decrease of D2 receptor binding but increase in D2-stimulated G-protein activation, dopamine transporter binding and behavioural sensitization in brains of mice treated with a chronic escalating dose 'binge' cocaine administration paradigm.

    Science.gov (United States)

    Bailey, A; Metaxas, A; Yoo, J H; McGee, T; Kitchen, I

    2008-08-01

    Understanding the neurobiology of the transition from initial drug use to excessive drug use has been a challenge in drug addiction. We examined the effect of chronic 'binge' escalating dose cocaine administration, which mimics human compulsive drug use, on behavioural responses and the dopaminergic system of mice and compared it with a chronic steady dose (3 x 15 mg/kg/day) 'binge' cocaine administration paradigm. Male C57BL/6J mice were injected with saline or cocaine in an escalating dose paradigm for 14 days. Locomotor and stereotypy activity were measured and quantitative autoradiographic mapping of D(1) and D(2) receptors, dopamine transporters and D(2)-stimulated [(35)S]GTPgammaS binding was performed in the brains of mice treated with this escalating and steady dose paradigm. An initial sensitization to the locomotor effects of cocaine followed by a dose-dependent increase in the duration of the locomotor effect of cocaine was observed in the escalating but not the steady dose paradigm. Sensitization to the stereotypy effect of cocaine and an increase in cocaine-induced stereotypy score was observed from 3 x 20 to 3 x 25 mg/kg/day cocaine. There was a significant decrease in D(2) receptor density, but an increase in D(2)-stimulated G-protein activity and dopamine transporter density in the striatum of cocaine-treated mice, which was not observed in our steady dose paradigm. Our results document that chronic 'binge' escalating dose cocaine treatment triggers profound behavioural and neurochemical changes in the dopaminergic system, which might underlie the transition from drug use to compulsive drug use associated with addiction, which is a process of escalation.

  2. What's an Asthma Action Plan?

    Science.gov (United States)

    ... to 2-Year-Old What's an Asthma Action Plan? KidsHealth > For Parents > What's an Asthma Action Plan? ... normal everyday activities without having asthma symptoms. Action Plans Are Unique Each person's experience with asthma is ...

  3. 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

  4. Introducing Actions into Qualitative Simulation

    Science.gov (United States)

    1988-08-01

    include the effects of actions to form action-augmented envisionments . The action-augmented envisionment incorporates both the effects of an agent’s...procedure generation than any previous representation . This paper defines action- augmented envisionments and an algorithm for directly computing...Moving actions into the physics . The next section introduces a new representation, the action-augmented envisionment (or .fie), which inte- grates the

  5. Head-to-head comparison of aggressive conventional therapy and three biological treatments and comparison of two de-escalation strategies in patients who respond to treatment: study protocol for a multicenter, randomized, open-label, blinded-assessor, phase 4 study.

    Science.gov (United States)

    Glinatsi, Daniel; Heiberg, Marte S; Rudin, Anna; Nordström, Dan; Haavardsholm, Espen A; Gudbjornsson, Bjorn; Østergaard, Mikkel; Uhlig, Till; Grondal, Gerdur; Hørslev-Petersen, Kim; van Vollenhoven, Ronald; Hetland, Merete L

    2017-04-04

    New targeted therapies and improved treatment strategies have dramatically improved the outcomes of patients with rheumatoid arthritis (RA). However, it is unknown whether different early aggressive interventions can induce stable remission or a low-active disease state that can be maintained with conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy, and whether they differ in efficacy and safety. The Nordic Rheumatic Diseases Strategy Trials And Registries (NORD-STAR) study will assess and compare (1) the proportion of patients who achieve remission in a head-to-head comparison between csDMARD plus glucocorticoid therapy and three different biological DMARD (bDMARD) therapies with different modes of action and (2) two de-escalation strategies in patients who respond to first-line therapy. In a pragmatic, 80-160-week, multicenter, randomized, open-label, assessor-blinded, phase 4 study, 800 patients with early RA (symptom duration less than 24 months) are randomized 1:1:1:1 to one of four different treatment arms: (1) aggressive csDMARD therapy with methotrexate + sulphasalazine + hydroxychloroquine + i.a. glucocorticoids (arm 1A) or methotrexate + prednisolone p.o. (arm 1B), (2) methotrexate + certolizumab-pegol, (3) methotrexate + abatacept, or (4) methotrexate + tocilizumab. The primary clinical endpoint is the proportion of patients reaching Clinical Disease Activity Index (CDAI) remission at week 24. Patients in stable remission over 24 consecutive weeks enter part 2 of the study earliest after 48 weeks. Patients not achieving sustained CDAI remission over 24 consecutive weeks, exit the study after 80 weeks. In part 2, patients are re-randomized to two different de-escalation strategies, either immediate or delayed (after 24 weeks) tapering, followed by cessation of study medication. All patients remain on stable doses of methotrexate. The primary clinical endpoint in part 2 is the proportion of patients

  6. Classifying Facial Actions

    Science.gov (United States)

    Donato, Gianluca; Bartlett, Marian Stewart; Hager, Joseph C.; Ekman, Paul; Sejnowski, Terrence J.

    2010-01-01

    The Facial Action Coding System (FACS) [23] is an objective method for quantifying facial movement in terms of component actions. This system is widely used in behavioral investigations of emotion, cognitive processes, and social interaction. The coding is presently performed by highly trained human experts. This paper explores and compares techniques for automatically recognizing facial actions in sequences of images. These techniques include analysis of facial motion through estimation of optical flow; holistic spatial analysis, such as principal component analysis, independent component analysis, local feature analysis, and linear discriminant analysis; and methods based on the outputs of local filters, such as Gabor wavelet representations and local principal components. Performance of these systems is compared to naive and expert human subjects. Best performances were obtained using the Gabor wavelet representation and the independent component representation, both of which achieved 96 percent accuracy for classifying 12 facial actions of the upper and lower face. The results provide converging evidence for the importance of using local filters, high spatial frequencies, and statistical independence for classifying facial actions. PMID:21188284

  7. Rethinking therapeutic action.

    Science.gov (United States)

    Gabbard, Glen O; Westen, Drew

    2003-08-01

    Like other core psychoanalytic constructs, the theory of therapeutic action is currently in flux, as theorists of differing persuasions propose different mechanisms. In this article, the authors attempt to integrate developments within and without psychoanalysis to provide a working model of the multifaceted processes involved in producing change in psychoanalysis and psychoanalytic psychotherapy. A theory of therapeutic action must describe both what changes (the aims of treatment) and what strategies are likely to be useful in facilitating those changes (technique). The authors believe that single-mechanism theories of therapeutic action, no matter how complex, are unlikely to prove useful at this point because of the variety of targets of change and the variety of methods useful in effecting change in those targets (such as techniques aimed at altering different kinds of conscious and unconscious processes). Interventions that facilitate change may be classified into one of three categories: those that foster insight, those that make use of various mutative aspects of the treatment relationship and a variety of secondary strategies that can be of tremendous importance. They propose that, in all forms of psychoanalytic treatment, we would be more accurate to speak of the therapeutic actions, rather than action.

  8. Immigration Enforcement Actions - Annual Report

    Data.gov (United States)

    Department of Homeland Security — Each year, the Department of Homeland Security (DHS) undertakes immigration enforcement actions involving hundreds of thousands of foreign nationals. These actions...

  9. Hurry-up and hatch: selective filial cannibalism of slower developing eggs.

    Science.gov (United States)

    Klug, Hope; Lindström, Kai

    2008-04-23

    Filial cannibalism (the consumption of one's own offspring) is thought to represent an adaptive strategy in many animals. However, little is known about the details of which offspring are consumed when a parent cannibalizes. Here, we examined patterns of within-brood filial cannibalism in the sand goby (Pomatoschistus minutus). Males spawned sequentially with two females, and we asked whether males cannibalized selectively with regard to egg size or the order in which eggs were received. Males preferentially consumed the larger eggs of the second female they spawned with. Because larger eggs took longer to hatch, and because female 2's eggs were up to 1 day behind those of female 1, such preferential cannibalism might allow males to decrease the time spent caring for the current brood and re-enter the mating pool sooner. More work is needed to understand the fitness consequences of such selective cannibalism.

  10. Clearing a Hurried Path: Study on Education Programs for Migrant Workers in Six Asian Countries.

    Science.gov (United States)

    Villalba, Noel C.

    Against the backdrop of the Asian economic crisis, this study examined the range of education programs for migrant workers in six Asian countries. Surveys were returned from 145 migrant worker support organizations in three host countries--Hong Kong, South Korea, and Japan--and three sending countries--the Philippines, Indonesia, and India. The…

  11. Hurry All to Sea: Union Naval, Strategy to Counter Confederate Commerce Raiding

    Science.gov (United States)

    1992-06-01

    support a conflict that used a vast new array of warfare technologies. The South, on the other hand, was agriculturally oriented and depended on...San Jacinto reported from the Island of Guadeloupe : . Our consul at this place tells me he has information from a reliable source that the Alabama

  12. Human Actions Made Tangible

    DEFF Research Database (Denmark)

    Buur, Jacob; Caglio, Agnese; Jensen, Lars Christian

    2014-01-01

    projects, it remains a challenge to investigate in detail how people interact with all of their body. Analysis of full-body movement is time consuming, notation techniques are rare, and findings are difficult to share between members of a design team. In this paper we propose tangible video analysis......, a method developed to engage people from different backgrounds in collaboratively analysing videos with the help of physical objects. We will present one of these tools, Action Scrabble, for analysing temporal organisation of human actions. We work with a case of skilled forklift truck driving....... By backtracking our design research experiments, we will unfold how and why the tangible tool succeeds in engaging designers with varied analysis experience to collaboratively focus on human action structures – and even find video analysis fun!...

  13. Theater and action research

    DEFF Research Database (Denmark)

    Tofteng, Ditte Maria Børglum; Husted, Mia

    2011-01-01

    difficulties reaching the public agenda or influencing structures of power. In this article we follow the creation of a play and of scenes that address the life, sufferings, and wishes of unemployed people. The skills of actors, writers, and producers are worked into a critical utopian action research project...... and used to highlight and enlarge both critique and dreams in life outside the labor market. The article also discusses some of the reactions the plays received and the formation of knowledge linked to these processes.......Action research on marginalization and exclusion often seeks to examine relations between recognition, respect, and inclusion, but addressing these topics is difficult. Theatre-based action research opens up a new way to communicate and make visible knowledge and experiences from below that have...

  14. Sustainability and Entrepreneurial Action

    DEFF Research Database (Denmark)

    Korsgaard, Steffen T.; Anderson, Alistair

    Abstract Objectives - This paper explores how entrepreneurial action can lead to environmental sustainability. It builds on the assumption that the creation of sustainble practices is one of the most important challenges facing the global society, and that entrepreneurial action is a vital...... instrument in the pursuit of sustainability.  Prior Work - Extant literature identifies two main approaches to sustainable entrepreneurship. (i) traditional exploitation of environmentally relevant opportunities and (ii) institutional entrepreneurship creating opportunities. We identify a novel form......: resource oriented sustainable entrepreneurial action.  Approach - The paper uses a case study approach to build deeper theoretical knowledge of environmentally sustainable entrepreneurship.  Results - The paper identifies and analyses a distinct form of sustainable entrepreneurship -  resource oriented...

  15. THE ACTION RESEARCH METHOD

    Directory of Open Access Journals (Sweden)

    Petre GEORGIEVSKI

    1999-05-01

    Full Text Available The effort in this work to elaborate an action research method as a central research problem considering the recent contemporary sociological and educa­tional literature. The author begins with the statement that the method is a complex notion, composed of three main components: approach to the research problem, data gathering procedures and data analysis procedures. This point of view is further applied and elaborated in the author's text, emphasizing the action research characteristics: interruption with the positive tradition in social research and the divided of the objective and subjective, application of the qualitative data. The sub­stantial difference between the action research in regard with the other kinds of research, is not only in getting to new knowledge's, but also in problem solving or a change in the situation in a concrete social context.

  16. Knowledge into Action

    DEFF Research Database (Denmark)

    Larsen, Lars Thorup

    between health knowledge and individual action. The book investigates what political rationality characterizes this new ambition in public health policies to put knowledge into action in the hands of individual citizens and how these policies adapt to the continuous experience that citizens often do...... not listen. Based on a Foucauldian framework, the genealogy demonstrates the new governmentality in Danish and American public health policy, which depends upon a specific politics of truth. Not only does public health policy build on a large amount of scientific knowledge. It also demands a change...... in the production and circulation of health knowledge, which attempts to replace the usual 'ifs, buts and maybes' of medical science with an action-minded public health knowledge just telling people what to do....

  17. Multimodal responsive action

    DEFF Research Database (Denmark)

    Oshima, Sae

    While a first pair part projects a limited set of second pair parts to be provided next, responders select different types and formats for second pair parts to assemble activities (Schegloff 2007). Accordingly, various ways of shaping responses have been extensively studied (e.g. Pomerantz 1984......; Raymond 2003; Schegloff and Lerner 2009), including those with multimodal actions (e.g. Olsher 2004; Fasulo & Monzoni 2009). Some responsive actions can also be completed with bodily behavior alone, such as: when an agreement display is achieved by using only nonvocal actions (Jarmon 1996), when...... both verbal and body-behavioral elements. This paper explores one such situation in professional-client interaction, during the event of evaluating a service outcome in a haircutting session. In general, a haircutting session is brought to its closure through the service-assessment sequence, in which...

  18. Controversies on affirmative action

    Directory of Open Access Journals (Sweden)

    Milan Mesić

    2005-09-01

    Full Text Available Affirmative action was launched by American presidents J.F. Kennedy and L.B. Johnson, yet by ironic historical accident it attained its greatest expansion and most radical form during R. Nixon’s conservative administration. Affirmative action was originally a government programme aimed at improving the social position of Afro-Americans, mostly in the sphere of employment and education, as a kind of compensation for racial discrimination, and also other forms of social injustice suffered by minority and underprivileged groups. Its goal was to increase the proportion of Afro-Americans, and later members of other minorities, as well as women, in higher education institutions and in various types of employment. It was supported by many social researchers and activists. Law courts, namely their verdicts and explanations in the case of precedents, had an especially important role in the debate on affirmative action. Political conservatives attacked various affirmative action programmes (especially preferential enrolment quotas for minority students, basing their criticism on the American constitutional principles on equal rights for every citizen. Market conservatives, furthermore, claimed that the government’s policy of racial preference brought into question the very basis of the capital system (competition and at the same time was not in the interest of the Afro-American working class. Namely, the social strata that profited most was the relatively affluent segment of the Afro-American community, which only increased economic and social differences within the latter. Recently the debate on affirmative action in the US has not been limited only to two opposing sides (liberals and conservatives. More and more scientists and other participants have recognised the negative aspects and also the failures of affirmative action, while at the same time refuting conservative opinions and goals.

  19. Improvisation in Action

    DEFF Research Database (Denmark)

    Bansler, Jørgen P.; Havn, Erling C.

    2003-01-01

    The paper discusses the role of extemporaneous action and bricolage in designing and implementing information systems in organizations. We report a longitudinal field study of design and implementation of a Web-based groupware application in a multinational corporation. We adopt a sensemaking...... perspective to analyze the dynamics of this process and show that improvisational action and bricolage (making do with the materials at hand) played a vital role in the development of the application. Finally, we suggest that this case study provides an occasion to reconsider how we conceptualize information...

  20. Class Actions in Denmark

    DEFF Research Database (Denmark)

    Werlauff, Erik

    2009-01-01

    The article deals with the relatively new Danish Act on Class Action (Danish: gruppesøgsmål) which was suggested by The Permanent Council on Civil procedure (Retsplejerådet) of which the article's author is a member. The operability of the new provisions is illustrated through some wellknown Dani...... cases: Hafnia case (investment prospectus), and Danish Eternit (roof elements) where the existence of Danish provisions on class actions might have made a difference, and the article also deals with the delicate questions of opt-in and opt-out....

  1. Characterizations of proper actions

    Science.gov (United States)

    Biller, Harald

    2004-03-01

    Three kinds of proper actions of increasing strength are defined. We prove that the three definitions specialize to the definitions by Bourbaki, by Palais and by Baum, Connes and Higson in their respective settings. The third of these, which thus turns out to be the strongest, originally only concerns actions of second countable locally compact groups on metrizable spaces. In this situation, it is shown to coincide with the other two definitions if the total space locally has the Lindelöf property and the orbit space is regular.

  2. Action Programming Languages

    CERN Document Server

    Thielscher, Michael

    2008-01-01

    Artificial systems that think and behave intelligently are one of the most exciting and challenging goals of Artificial Intelligence. Action Programming is the art and science of devising high-level control strategies for autonomous systems which employ a mental model of their environment and which reason about their actions as a means to achieve their goals. Applications of this programming paradigm include autonomous software agents, mobile robots with high-level reasoning capabilities, and General Game Playing. These lecture notes give an in-depth introduction to the current state-of-the-ar

  3. Hypoxia imaging with [18F]-FMISO-PET for guided dose escalation with intensity-modulated radiotherapy in head-and-neck cancers

    Energy Technology Data Exchange (ETDEWEB)

    Henriques de Figueiredo, B. [Institut Bergonie, Department of Radiotherapy, Bordeaux (France); INCIA UMR-CNRS 5287, Bordeaux (France); Zacharatou, C. [Institut Bergonie, Department of Radiotherapy, Bordeaux (France); Galland-Girodet, S.; Benech, J. [Hospital Haut-Leveque, Department of Radiotherapy, CHRU Bordeaux (France); Clermont-Gallerande, H. de [Hospital Pellegrin, Department of Nuclear Medicine, CHRU Bordeaux (France); Lamare, F. [INCIA UMR-CNRS 5287, Bordeaux (France); Hospital Haut-Leveque, Department of Radiotherapy, CHRU Bordeaux (France); Hatt, M. [LaTIM INSERM U1101, Brest (France); Digue, L. [Hospital Saint-Andre, Department of Clinical Oncology, CHRU Bordeaux (France); Mones del Pujol, E. de [Department of Oto-rhino-laryngology, CHRU Bordeaux (France); Fernandez, P. [INCIA UMR-CNRS 5287, Bordeaux (France); Hospital Pellegrin, Department of Nuclear Medicine, CHRU Bordeaux (France); University Bordeaux 2, Bordeaux (France)

    2014-09-23

    Positron emission tomography (PET) with [{sup 18}F]-fluoromisonidazole ([{sup 18}F]-FMISO) provides a non-invasive assessment of hypoxia. The aim of this study is to assess the feasibility of a dose escalation with volumetric modulated arc therapy (VMAT) guided by [{sup 18}F]-FMISO-PET for head-and-neck cancers (HNC). Ten patients with inoperable stages III-IV HNC underwent [{sup 18}F]-FMISO-PET before radiotherapy. Hypoxic target volumes (HTV) were segmented automatically by using the fuzzy locally adaptive Bayesian method. Retrospectively, two VMAT plans were generated delivering 70 Gy to the gross tumour volume (GTV) defined on computed tomography simulation or 79.8 Gy to the HTV. A dosimetric comparison was performed, based on calculations of tumour control probability (TCP), normal tissue complication probability (NTCP) for the parotid glands and uncomplicated tumour control probability (UTCP). The mean hypoxic fraction, defined as the ratio between the HTV and the GTV, was 0.18. The mean average dose for both parotids was 22.7 Gy and 25.5 Gy without and with dose escalation respectively. FMISO-guided dose escalation led to a mean increase of TCP, NTCP for both parotids and UTCP by 18.1, 4.6 and 8 % respectively. A dose escalation up to 79.8 Gy guided by [{sup 18}F]-FMISO-PET with VMAT seems feasible with improvement of TCP and without excessive increase of NTCP for parotids. (orig.) [German] Die Positronenemissionstomographie (PET) mit [{sup 18}F]-Fluoromisonidazol ([{sup 18}F]-FMISO) ermoeglicht eine nichtinvasive Beurteilung der Hypoxie. Ziel dieser Studie ist es, die Durchfuehrbarkeit einer [{sup 18}F]-FMISO-PET-gefuehrten Dosissteigerung bei volumetrisch modulierter Arc-Therapie (VMAT) von Kopf-Hals-Tumoren (KHT) zu bewerten. Zehn Patienten mit inoperablen KHT der Stadien III-IV erhielten vor der Strahlentherapie eine [{sup 18}F]-FMISO-PET. Hypoxische Zielvolumina (HV) wurden automatisch mit Hilfe des FLAB(Fuzzy Locally Adaptive Bayesian

  4. Um sistema de processamento escalável de consultas analíticas sobre data warehouses criptografados e armazenados na nuvem

    Directory of Open Access Journals (Sweden)

    Claudivan Cruz Lopes

    2017-06-01

    Full Text Available Sistemas de processamento de consultas para bancos de dados criptografados têm sido propostos como uma solução para proteger a confidencialidade de dados armazenados em servidores não confiáveis, tais como provedores de computação em nuvem, e para reduzir o impacto da criptografia no desempenho de consultas sobre dados criptografados. Pouca atenção, no entanto, tem sido dedicada em determinar como a escalabilidade provida pela computação em nuvem pode ser usada para melhorar o desempenho de consultas analíticas sobre Data Warehouses (DW criptografados. Nesse sentido, este artigo descreve um sistema de processamento escalável de consultas analíticas sobre DW criptografados armazenados na nuvem, em que são especificados os componentes arquiteturais que dão suporte a esta escalabilidade.

  5. The Wing Beat of the Butterfly. The Causality of Asymmetric Cultural Encounters and Escalation in Babel (2006 and Valley of Wolves – Iraq/ Kurtlar Vadisi – Irak (2006

    Directory of Open Access Journals (Sweden)

    Veronika Bernard

    2011-10-01

    Full Text Available The term ‘asymmetric conflict’ describes a war-like situation in which the opponents involved do not have equal access to decisive logistic resources. The author of this article states that cultural en­coun­ters can also be of asymmetric quality: in situations of provoked or accidental (intercultural mis­understandings, in hierarchical situations and in cases of emergency. She further states that the mo­vies Babel (2006 and Valley of Wolves – Iraq (2006 can be seen as cinematic adaptations of such cases putting the focus on the causality of asymmetric cultural encounters and escalation. The ar­tic­le deals with the major cinematic tools applied in visualizing this causality in the two films.

  6. 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

    , dyspnoea, and nausea. One serious AE, a lung embolus in a patient with non-small cell lung cancer treated with 10 mg kg(-1) weekly, was deemed possibly related to TB-403. No dose-limiting toxicities were observed, and a maximum-tolerated dose was not reached. The PK parameters were dose linear...... and the terminal half-life values ranged from 9 to 14 days. Six patients exhibited stable disease for at least 8 weeks. Two patients, (oesophageal squamous cell carcinoma and pancreatic adenocarcinoma) both treated with 5 mg kg(-1) weekly, remained stable for 12 months. CONCLUSION: TB-403 treatment in this patient......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...

  7. 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

  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. Short-term Androgen-Deprivation Therapy Improves Prostate Cancer-Specific Mortality in Intermediate-Risk Prostate Cancer Patients Undergoing Dose-Escalated External Beam Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Zumsteg, Zachary S.; Spratt, Daniel E.; Pei, Xin; Yamada, Yoshiya; Kalikstein, Abraham [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Kuk, Deborah; Zhang, Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Zelefsky, Michael J., E-mail: zelefskm@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2013-03-15

    Purpose: We investigated the benefit of short-term androgen-deprivation therapy (ADT) in patients with intermediate-risk prostate cancer (PC) receiving dose-escalated external beam radiation therapy. Methods and Materials: The present retrospective study comprised 710 intermediate-risk PC patients receiving external beam radiation therapy with doses of ≥81 Gy at a single institution from 1992 to 2005, including 357 patients receiving neoadjuvant and concurrent ADT. Prostate-specific antigen recurrence-free survival (PSA-RFS) and distant metastasis (DM) were compared using the Kaplan-Meier method and Cox proportional hazards models. PC-specific mortality (PCSM) was assessed using competing-risks analysis. Results: The median follow-up was 7.9 years. Despite being more likely to have higher PSA levels, Gleason score 4 + 3 = 7, multiple National Comprehensive Cancer Network intermediate-risk factors, and older age (P≤.001 for all comparisons), patients receiving ADT had improved PSA-RFS (hazard ratio [HR], 0.598; 95% confidence interval [CI], 0.435-0.841; P=.003), DM (HR, 0.424; 95% CI, 0.219-0.819; P=.011), and PCSM (HR, 0.380; 95% CI, 0.157-0.921; P=.032) on univariate analysis. Using multivariate analysis, ADT was an even stronger predictor of improved PSA-RFS (adjusted HR [AHR], 0.516; 95% CI, 0.360-0.739; P<.001), DM (AHR, 0.347; 95% CI, 0.176-0.685; P=.002), and PCSM (AHR, 0.297; 95% CI, 0.128-0.685; P=.004). Gleason score 4 + 3 = 7 and ≥50% positive biopsy cores were other independent predictors of PCSM. Conclusions: Short-term ADT improves PSA-RFS, DM, and PCSM in patients with intermediate-risk PC undergoing dose-escalated external beam radiation therapy.

  10. Percentage of Cancer Volume in Biopsy Cores Is Prognostic for Prostate Cancer Death and Overall Survival in Patients Treated With Dose-Escalated External Beam Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Vance, Sean M.; Stenmark, Matthew H.; Blas, Kevin; Halverson, Schulyer [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Hamstra, Daniel A., E-mail: dhamm@umich.edu [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Feng, Felix Y. [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Department of Radiation Oncology, Veterans Affairs Medical Center, Ann Arbor, Michigan (United States)

    2012-07-01

    Purpose: To investigate the prognostic utility of the percentage of cancer volume (PCV) in needle biopsy specimens for prostate cancer patients treated with dose-escalated external beam radiotherapy. Methods and Materials: The outcomes were analyzed for 599 men treated for localized prostate cancer with external beam radiotherapy to a minimal planning target volume dose of 75 Gy (range, 75-79.2). We assessed the effect of PCV and the pretreatment and treatment-related factors on the freedom from biochemical failure, freedom from metastasis, cause-specific survival, and overall survival. Results: The median number of biopsy cores was 7 (interquartile range, 6-12), median PCV was 10% (interquartile range, 2.5-25%), and median follow-up was 62 months. The PCV correlated with the National Comprehensive Cancer Network risk group and individual risk features, including T stage, prostate-specific antigen level, Gleason score, and percentage of positive biopsy cores. On log-rank analysis, the PCV stratified by quartile was prognostic for all endpoints, including overall survival. In addition, the PCV was a stronger prognostic factor than the percentage of positive biopsy cores when the two metrics were analyzed together. On multivariate analysis, the PCV predicted a worse outcome for all endpoints, including freedom from biochemical failure, (hazard ratio, 1.9; p = .0035), freedom from metastasis (hazard ratio, 1.7, p = .09), cause-specific survival (hazard ratio, 3.9, p = .014), and overall survival (hazard ratio, 1.8, p = .02). Conclusions: For patients treated with dose-escalated external beam radiotherapy, the volume of cancer in the biopsy specimen adds prognostic value for clinically relevant endpoints, particularly in intermediate- and high-risk patients. Although the PCV determination is more arduous than the percentage of positive biopsy cores, it provides superior risk stratification.

  11. 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.

  12. Escalation of i.v. cocaine intake in peri-adolescent vs. adult rats selectively bred for high (HiS) vs. low (LoS) saccharin intake.

    Science.gov (United States)

    Holtz, Nathan A; Carroll, Marilyn E

    2013-05-01

    Adolescence marks a period of increased vulnerability to the development of substance use disorders. High sweet preference is a genetically mediated behavioral trait that also predicts vulnerability to substances of abuse. Previous research has shown that while adolescent rats selectively bred for high (HiS) saccharin intake acquire cocaine self-administration at the same rate as adult HiS rats, adolescent rats bred for low saccharin intake (LoS) acquire cocaine self-administration faster than adult LoS rats. This study was conducted to investigate the interaction of the addiction vulnerability factors of peri-adolescence and saccharin preference on cocaine intake using an animal model of escalation of cocaine consumption over 6-h/day sessions. Peri-adolescent and adult HiS and LoS female rats self-administered i.v. cocaine (0.4 mg/kg/inf) during short-access (2-h/day) sessions for 2 days. Next, a long-access (6-h/day) period (LgA) commenced and lasted 16 days. Following LgA, session length was returned to 2-h/day for a second short access phase. LoS peri-adolescent rats escalated cocaine intake over the LgA period and consumed more drug than LoS adult rats; however, peri-adolescent and adult HiS rats consumed similar amounts of cocaine during this period. Additionally, adult HiS rats self-administered more cocaine than adult LoS rats during the LgA period, while there was no phenotypic difference between the rat lines during peri-adolescence for the LgA period. During the first short-access phase, peri-adolescent rats self-administered more cocaine than adult rats. These results emphasize the importance of adolescent drug abuse prevention by illustrating that phenotypic protection from addiction may not be expressed until adulthood.

  13. De-escalation treatment protocols for human papillomavirus-associated oropharyngeal squamous cell carcinoma: a systematic review and meta-analysis of current clinical trials.

    Science.gov (United States)

    Masterson, Liam; Moualed, Daniel; Liu, Zi Wei; Howard, James E F; Dwivedi, Raghav C; Tysome, James R; Benson, Richard; Sterling, Jane C; Sudhoff, Holger; Jani, Piyush; Goon, Peter K C

    2014-10-01

    Iatrogenic complications associated with current treatment protocols for oropharyngeal squamous cell carcinoma are noted to cause high rates of acute and chronic morbidity. The aims of this study are to provide an overview of the current de-escalation trials for human papillomavirus positive (HPV+) oropharyngeal carcinoma and to evaluate the evidence supporting improved response to treatment of patients within this viral cohort. This study reviewed all completed or in progress randomised controlled trials (RCTs) assessing clinical interventions for human papillomavirus-associated locally advanced oropharyngeal squamous cell carcinoma. We utilised a validated 'risk of bias' tool to assess study quality. We identified nine RCTs that met the full inclusion criteria for this review (all of which are currently on-going and will report from 2015 onwards). Five RCTs performed a post hoc analysis by HPV status, which allowed meta-analysis of 1130 patients. The data reveal a significant difference in overall survival (hazard ratio (HR) 0.49 [95% confidence interval (CI) 0.35-0.69]), loco-regional failure (HR 0.43 [95% CI 0.17-1.11]) and disease specific survival (0.41 [95% 0.3-0.56]) in favour of the HPV+ category. In considering de-escalation treatment protocols, nine studies are currently ongoing. Our meta-analysis provides strong evidence for an improved prognosis in the viral associated cohort when treated by platinum based chemotherapy in combination with radiotherapy or primary radiotherapy. So far, one trial (with moderate to high risk of bias) suggests a reduced survival outcome for the HPV+ population when using the epidermal growth factor receptor (EGFR) inhibitor cetuximab.

  14. Dosimetric feasibility of ablative dose escalated focal monotherapy with MRI-guided high-dose-rate (HDR) brachytherapy for prostate cancer.

    Science.gov (United States)

    Hosni, Ali; Carlone, Marco; Rink, Alexandra; Ménard, Cynthia; Chung, Peter; Berlin, Alejandro

    2017-01-01

    To determine the dosimetric feasibility of dose-escalated MRI-guided high-dose-rate brachytherapy (HDR-BT) focal monotherapy for prostate cancer (PCa). In all patients, GTV was defined with mpMRI, and deformably registered onto post-catheter insertion planning MRI. PTV included the GTV plus 9mm craniocaudal and 5mm in every other direction. In discovery-cohort, plans were obtained for each PTV independently aiming to deliver ⩾16.5Gy/fraction (two fraction schedule) while respecting predefined organs-at-risk (OAR) constraints or halted when achieved equivalent single-dose plan (24Gy). Dosimetric results of original and focal HDR-BT plans were evaluated to develop a planning protocol for the validation-cohort. In discovery-cohort (20-patients, 32-GTVs): PTV D95% ⩾16.5Gy could not be reached in a single plan (3%) and was accomplished (range 16.5-23.8Gy) in 15 GTVs (47%). Single-dose schedule was feasible in 16 (50%) plans. In the validation-cohort (10-patients, 10-GTVs, two separate implants each): plans met acceptable and ideal criteria in 100% and 43-100% respectively. Migration to single-dose treatment schedule was feasible in 7 implants (35%), without relaxing OAR's constraints or increasing the dose (D100% and D35%) to mpMRI-normal prostate (p>0.05). Focal ablative dose-escalated radiation is feasible with the proposed protocol. Prospective studies are warranted to determine the clinical outcomes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Dose escalation in large anterior skull-base tumors by means of IMRT. First experience with the Novalis {sup registered} system

    Energy Technology Data Exchange (ETDEWEB)

    Ernst-Stecken, A.; Sauer, R.; Grabenbauer, G. [Dept. of Radiation Therapy and Novalis Shaped Beam Surgery Center, Univ. Hospital of Erlangen-Nuremberg, Erlangen (Germany); Lambrecht, U.; Mueller, R. [Dept. of Radiation Therapy and Novalis Shaped Beam Surgery Center, Univ. Hospital of Erlangen-Nuremberg, Erlangen (Germany); Div. of Medical Physics, Dept. of Radiation Therapy, Univ. Hospital of Erlangen-Nuremberg, Erlangen (Germany); Ganslandt, O. [Dept. of Neurosurgery, Univ. of Erlangen-Nuremberg, Erlangen (Germany)

    2006-03-15

    Purpose: to evaluate the feasibility and tolerance of dose escalation with stereotactic intensity-modulated radiotherapy (sIMRT) for skull-base tumors. Patients and Methods: between 01/2003 and 12/2004, twelve patients were treated. Nine were exclusively treated at the Novalis {sup registered} site with one planning target volume (PTV) field boost, three were administered boost IMRT treatment (two with each one PTV-shrinking field, one with single PTV) after conventional three-dimensional conformal radiotherapy. This resulted in 23 PTVs with a median volume of 93.63 cm{sup 3} (range, 88.58-125.88 cm{sup 3}). Dose calculation was done by the pencil-beam algorithm. Median total doses of 66.6, 77.4, and 63.9 Gy were prescribed for sIMRT alone, sIMRT after 3-D conformal irradiation of the nasopharynx and cervical lymph nodes with 59.4 Gy, and for reirradiation, respectively. Results: 95% isodose PTV coverage was reached in 86.5% (range, 80-93%). Homogeneity (D{sub max}/D{sup ref}) was 1.11, 1.09, and 1.08. Median total doses to 50% of chiasm, right and left optic nerve were 16.21, 16.82 and 10.23 Gy. 11/12 patients are locally controlled with a median follow-up of 11 months (range, 3-23 months), one has died of pulmonary embolism after cerebrospinal dissemination of retinal adenocarcinoma. Conclusion: SIMRT enables dose escalation to tumors located close to critical organs. Inverse planning for micro-multileaf collimator stereotactic irradiation is practicable in the daily routine irradiation program. SIMRT needs special verification and still, the following parameters have to be standardized: IMRT dose specification, dose maxima, length of radiation delivery time. (orig.)

  16. China’s Actions

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    China’s National Development and Reform Commission publicized the country’s policies and actions for addressing climate change in a report released on November 26,2009.The report highlighted China’s efforts in cutting greenhouse gas emissions in 2009 by

  17. CANEGROWERS Action Research Toolkit

    NARCIS (Netherlands)

    Mostert, R.H.; Brouwer, J.H.

    2015-01-01

    This toolkit contains a selection of tools to conduct action research, organized around four phases: Identify problems and possibilities; Analyze problems and possibilities; Search for solutions; and Reflection tools. The toolkit is customized for staff of Canegrowers in South Africa, who used the t

  18. Hope for Environmental Action

    Science.gov (United States)

    Fleischer, Barbara J.; DeMoor, Emily

    2015-01-01

    Environmental consciousness-raising programs tend to emphasize the magnitude of imminent ecological disasters, if humans continue on their current trajectory. While these environmental literacy programs also call for action to avoid cataclysmic ecological changes, psychological research on "learned helplessness" suggests that information…

  19. Sustainability as Moral Action

    Science.gov (United States)

    Dunn, Merrily S.; Hart-Steffes, Jeanne S.

    2012-01-01

    When one considers sustainability as a moral action, there are equally complex realities at hand--climate change, resource depletion, water and land rights. One author describes this broad sense of sustainability as "the connection of specific social and environmental problems to the functioning of human and ecological systems" (Jenkins, 2011).…

  20. Reconnecting Actions and Consequences

    DEFF Research Database (Denmark)

    Petersen, Marianne Graves; Ludvigsen, Martin; Krogh, Peter

    2009-01-01

    In this paper we present a brief critique of the current approach to the design of pervasive computing artifacts; claiming that this in itself promotes solutions that prevent end-users from accessing and understanding the consequences of their actions in terms of energy sustainability, specifical...

  1. Duality symmetric actions

    CERN Document Server

    Schwarz, J H; Schwarz, John H.; Sen, Ashoke

    1994-01-01

    It is frequently useful to construct dual descriptions of theories containing antisymmetric tensor fields by introducing a new potential whose curl gives the dual field strength, thereby interchanging field equations with Bianchi identities. We describe a general procedure for constructing actions containing both potentials at the same time, such that the dual relationship of the field strengths arises as an equation of motion. The price for doing this is the sacrifice of manifest Lorentz invariance or general coordinate invariance, though both symmetries can be realized nonetheless. There are various examples of global symmetries that have been realized as symmetries of field equations but not actions. These can be elevated to symmetries of the action by our method. The main example that we focus on is the low-energy effective action description of the heterotic string theory compactified on a six-torus to four dimensions. We show that the SL(2,R) symmetry, whose SL(2,Z) subgroup has been conjectured to be a...

  2. The Shape of Action

    Science.gov (United States)

    Hard, Bridgette Martin; Recchia, Gabriel; Tversky, Barbara

    2011-01-01

    How do people understand the everyday, yet intricate, behaviors that unfold around them? In the present research, we explored this by presenting viewers with self-paced slideshows of everyday activities and recording looking times, subjective segmentation (breakpoints) into action units, and slide-to-slide physical change. A detailed comparison of…

  3. Angels in Action

    Science.gov (United States)

    Stylianou, Xanthippi Cynthia

    2009-01-01

    In this article, the author discusses the importance of the placement of action lines to show the direction of movement. The author shows some visuals of angels and discusses in details the texture of the wings, the hair and the clothing.

  4. Affirmative Action Fallout

    Science.gov (United States)

    Roach, Ronald

    2005-01-01

    Race-conscious affirmative action in higher education survived a close challenge in 2003 when the U.S. Supreme Court ruled that race was a valid academic admission criteria in the "Grutter v. Bollinger" case. Two years later, a number of "pipeline" programs to help under-represented minorities gain admission to and complete graduate school have…

  5. Affirmative Action for Men?

    Science.gov (United States)

    Malveaux, Julianne

    2005-01-01

    If colleges are willing to consider "social engineering" and affirmative action to ensure the inclusion of White men, are they willing to do so for African Americans and other people of color? Will the Center for Individual Rights ride to the rescue of the White women who may be unfairly nudged out of positions for which they are "qualified" in…

  6. Being observed magnifies action

    NARCIS (Netherlands)

    Steinmetz, J.|info:eu-repo/dai/nl/411851675; Xu, Q.; Fishbach, A.; Zhang, Y.

    2016-01-01

    We test the hypothesis that people, when observed, perceive their actions as more substantial because they add the audience’s perspective to their own perspective. We find that participants who were observed while eating (Study 1) or learned they were observed after eating (Study 2) recalled eating

  7. Classroom Assessment in Action

    Science.gov (United States)

    Shermis, Mark D.; DiVesta, Francis J.

    2011-01-01

    "Classroom Assessment in Action" clarifies the multi-faceted roles of measurement and assessment and their applications in a classroom setting. Comprehensive in scope, Shermis and Di Vesta explain basic measurement concepts and show students how to interpret the results of standardized tests. From these basic concepts, the authors then…

  8. Cognitive framing in action.

    Science.gov (United States)

    Huhn, John M; Potts, Cory Adam; Rosenbaum, David A

    2016-06-01

    Cognitive framing effects have been widely reported in higher-level decision-making and have been ascribed to rules of thumb for quick thinking. No such demonstrations have been reported for physical action, as far as we know, but they would be expected if cognition for physical action is fundamentally similar to cognition for higher-level decision-making. To test for such effects, we asked participants to reach for a horizontally-oriented pipe to move it from one height to another while turning the pipe 180° to bring one end (the "business end") to a target on the left or right. From a physical perspective, participants could have always rotated the pipe in the same angular direction no matter which end was the business end; a given participant could have always turned the pipe clockwise or counter-clockwise. Instead, our participants turned the business end counter-clockwise for left targets and clockwise for right targets. Thus, the way the identical physical task was framed altered the way it was performed. This finding is consistent with the hypothesis that cognition for physical action is fundamentally similar to cognition for higher-level decision-making. A tantalizing possibility is that higher-level decision heuristics have roots in the control of physical action, a hypothesis that accords with embodied views of cognition.

  9. Collective Action under Globalization

    DEFF Research Database (Denmark)

    Scheuer, Steen

    Collective action in the form of industrial conflict has declined dramatically since the high tide in the 1970s in Europe. This article argues that this decline is the result of significant changes in both economic and institutional factors, influencing the calculations of employees and of their ...

  10. Classroom Assessment in Action

    Science.gov (United States)

    Shermis, Mark D.; DiVesta, Francis J.

    2011-01-01

    "Classroom Assessment in Action" clarifies the multi-faceted roles of measurement and assessment and their applications in a classroom setting. Comprehensive in scope, Shermis and Di Vesta explain basic measurement concepts and show students how to interpret the results of standardized tests. From these basic concepts, the authors then…

  11. Sensemaking from Actions

    NARCIS (Netherlands)

    J. van Rekom (Johan); C.B.M. van Riel (Cees); B. Wierenga (Berend)

    2000-01-01

    textabstractThis study presents a method to establish empirically what drives organization members in their day-to-day behavior. The method starts from the sense employees make of their own actions. The approach consists of two steps: qualitative laddering interviews to determine the most central me

  12. CANEGROWERS Action Research Toolkit

    NARCIS (Netherlands)

    Mostert, R.H.; Brouwer, J.H.

    2015-01-01

    This toolkit contains a selection of tools to conduct action research, organized around four phases: Identify problems and possibilities; Analyze problems and possibilities; Search for solutions; and Reflection tools. The toolkit is customized for staff of Canegrowers in South Africa, who used the

  13. The Body in Action

    DEFF Research Database (Denmark)

    Grünbaum, Thor

    2008-01-01

    This article is about how to describe an agent's awareness of her bodily movements when she is aware of executing an action for a reason. Against current orthodoxy, I want to defend the claim that the agent's experience of moving has an epistemic place in the agent's awareness of her own intentio...

  14. Reconnecting Actions and Consequences

    DEFF Research Database (Denmark)

    Ludvigsen, Martin; Krogh, Peter; Petersen, Marianne Graves

    2009-01-01

    In this paper we present a brief critique of the current approach to the design of pervasive computing artifacts; claiming that this in itself promotes solutions that prevent end-users from accessing and understanding the consequences of their actions in terms of energy sustainability, specifically...

  15. Justifying Action Research

    Science.gov (United States)

    Helskog, Guro Hansen

    2014-01-01

    In this paper I use a general philosophy of science perspective in looking at the problem of justifying action research. First I try to clarify the concept of justification, by contrasting it with the concept of validity, which seems to be used almost as a synonym in some parts of the literature. I discuss the need for taking a stand in relation…

  16. The Constitution in Action

    Science.gov (United States)

    Potter, Lee Ann

    2007-01-01

    In this article, the author describes the experiences middle school students on a field trip to the new Constitution in Action Learning Lab in the Boeing Learning Center at the National Archives can expect. There, middle school students take on the roles of archivists and researchers collecting and analyzing primary sources from the holdings of…

  17. Learning Action Models: Qualitative Approach

    NARCIS (Netherlands)

    Bolander, T.; Gierasimczuk, N.; van der Hoek, W.; Holliday, W.H.; Wang, W.-F.

    2015-01-01

    In dynamic epistemic logic, actions are described using action models. In this paper we introduce a framework for studying learnability of action models from observations. We present first results concerning propositional action models. First we check two basic learnability criteria: finite

  18. 自动扶梯安装工艺及其智能成图软件开发与应用%Development and Application of Escalator Installation Technology Intelligent Mapping Software

    Institute of Scientific and Technical Information of China (English)

    李成洋

    2015-01-01

    为了保证城市轨道交通自动扶梯的正确安装,提高设计质量和效率,研究了自动扶梯与相关专业接口工艺,总结自动扶梯安装工艺图出图要素,并利用模块化、流程化的3层软件框架,开发了1套自动扶梯安装工艺图智能绘制软件,实现了城市轨道交通自动扶梯工艺设计的简易化、标准化、智能化。%In order to ensure correct installation of escalators, improve the design quality and efficiency, the paper studies the escalator and related interface, and summarize the escalator installation process diagram and drawing elements. By using the 3 layer software framework of modular and worklfow process, it makes the development of 1 set of escalator installation process diagram intelligent drawing software.

  19. Clinical-grade manufacturing of autologous mature mRNA-electroporated dendritic cells and safety testing in acute myeloid leukemia patients in a phase I dose-escalation clinical trial.

    NARCIS (Netherlands)

    Driessche, A. Van; Velde, A.L. Van de; Nijs, G.; Braeckman, T.; Stein, B.; Vries, I.J.M. de; Berneman, Z.N.; Tendeloo, V.F. Van

    2009-01-01

    BACKGROUND AIMS: RNA-electroporated dendritic cell (DC)-based vaccines are rapidly gaining interest as therapeutic cancer vaccines. We report on a phase I dose-escalation trial using clinical-grade manufactured mature RNA-electroporated DC in acute myeloid leukemia (AML) patients. METHODS: CD14(+)

  20. Big Data and Data Analytics: An Action Platform for the Science of Prediction

    Directory of Open Access Journals (Sweden)

    Sahith Rampelli

    2014-07-01

    Full Text Available Analytics is the detection and communication of meaningful motive in data. Analytics plays a key role in areas rich with recorded information. The role of data is escalating tenaciously in the present day. Analysis of the data is the process of inspecting, removing the obsolete information and transforming the data into useful information. Data analytics approach is pragmatic in nature. Data Analytics uses multiple approaches and techniques, like use of mathematical approach and data analytics is used in multiple domains namely business, technology, automobile and many more. This paper focuses on how data plays a key role in the field of analytics. It deals with the implementation of data analytics in different domains. Data analytics:An action platform for the science of prediction.

  1. Antimicrobial resistance: addressing the global threat through greater awareness and transformative action.

    Science.gov (United States)

    Keown, Oliver P; Warburton, Will; Davies, Sally C; Darzi, Ara

    2014-09-01

    Antimicrobial therapies have played an unquestionably important role in advancing modern medical and surgical care, treating animals, reducing the global burden of communicable disease, and prolonging human life expectancy. These transformational benefits are threatened because of the rapidly advancing phenomenon of antimicrobial resistance. As a result of complex factors across many sectors and international actors, the global impact of antimicrobial resistance is an escalating economic and health crisis. This article draws on the collective expertise and summit report of the Antimicrobial Resistance Working Group from the 2013 World Innovation Summit for Health, in Doha, Qatar. It defines a framework of principles and tasks for key policy makers to raise international awareness of antimicrobial resistance and lead transformative action through policy-driven improvements in sanitation, antimicrobial conservation, agricultural practices, and research and development.

  2. Partial Actions and Power Sets

    Directory of Open Access Journals (Sweden)

    Jesús Ávila

    2013-01-01

    Full Text Available We consider a partial action (X,α with enveloping action (T,β. In this work we extend α to a partial action on the ring (P(X,Δ,∩ and find its enveloping action (E,β. Finally, we introduce the concept of partial action of finite type to investigate the relationship between (E,β and (P(T,β.

  3. Action Research for Sustainability

    DEFF Research Database (Denmark)

    Egmose, Jonas

    to provide local citizens with a greater say in the future of urban sustainability research, this book shows how action research can make important methodological contributions to processes of social learning between citizens and scientists by enabling free spaces in peoples everyday life and within academia...... by analysing processes of social learning. The book addresses the need to move towards sustainability at societal level as a democratic challenge questioning the way we live on planet earth. By conceptualising sustain-ability as an immanent and emergent ability of ecological and social life, continuously...... to renew itself without eroding its own foundation of existence, it argues that since sustainability cannot be invented but only supported (or eroded) by science, we need to reframe science in the role of sustaining sustain-ability. Through analyses of a three year action research programme, aiming...

  4. Knowledge into Action

    DEFF Research Database (Denmark)

    Larsen, Lars Thorup

    In the 1970s, most Western nations began to shift the emphasis of health care provision from treatment to prevention. While originally motivated by the rise of lifestyle diseases, the emergence of the new public health policy mainly involves a new way to understand and structure the relationship...... between health knowledge and individual action. The book investigates what political rationality characterizes this new ambition in public health policies to put knowledge into action in the hands of individual citizens and how these policies adapt to the continuous experience that citizens often do...... not listen. Based on a Foucauldian framework, the genealogy demonstrates the new governmentality in Danish and American public health policy, which depends upon a specific politics of truth. Not only does public health policy build on a large amount of scientific knowledge. It also demands a change...

  5. From Knowledge to Action

    DEFF Research Database (Denmark)

    Hjelmar, Ulf; Møller, Anne Mette

    2016-01-01

    of a greater process of bringing knowledge to action, encompassing the social and organisational contexts of research utilisation. The article concludes by stating that knowledge portals have the potential to be effective instruments in knowledge-to-action processes. The two main challenges, however......In recent years, focus has been on the utilisation of research-based knowledge and evidence in social work policy and practice in order to make it more effective. A part of this process has been the launch of knowledge portals to make use of knowledge from research. In this article, we investigate...... how knowledge portals about vulnerable children and youth present knowledge and evidence, and how they try to work as ?knowledge brokers? or intermediaries of evidence. We argue that knowledge portals are not merely channels for dissemination of knowledge. Knowledge portals could be considered as part...

  6. Mathematics in Action

    DEFF Research Database (Denmark)

    December 2004-November 2007 Denmark, Hungary, Lithuania, the Netherlands, Norway, Slovenia and Spain have cooperated in the project Mathematics in Action (MiA). The MiA project is supported by the Grundtvig action in the Socrates program of the European Commission. The aim of the project...... education.  Chapter 3 enlightens some relevant theory for MiA on what it means to be numerate, on learning in practice and on adult education, on transfer of knowledge and on six steps in problem solving. Here you will also find the MiA research questions on adults' learning, on teaching and on the role......A research questions and discusses implications for professional development for teachers in adult mathematics education....

  7. INFORM'ACTION

    CERN Multimedia

    STAFF ASSOCIATION

    2010-01-01

    INFORM’ACTION Commission ! It’s all in the title ! At a time when one of the keywords is COMMUNICATE, the Staff Association has a duty to take it seriously. This is why, among other reasons, the youngest of the Staff Association internal commissions was created in 20005. As its name indicates, this commission is responsible for INFORMING, TRAINING (FORMER) and organizing ACTIONs. INFORMING : The members of this commission endeavour to work using all imaginable and known channels of information: articles, emails, alerts, posters, web site, organizing meetings, distributing flyers, banners, videos, etc. In 2009 a new web site (http://cern.ch/association) was put on line.   Since then this site has been continually updated to provide information regarding the latest news in the social domain (Pension Fund, CHIS, 5YR), and also special offers for our members, club news, and social and cultural activities. In 2009 and 2010, the Staff Association notice boards were ...

  8. Action Type Deontic Logic

    DEFF Research Database (Denmark)

    Bentzen, Martin Mose

    2014-01-01

    A new deontic logic, Action Type Deontic Logic, is presented. To motivate this logic, a number of benchmark cases are shown, representing inferences a deontic logic should validate. Some of the benchmark cases are singled out for further comments and some formal approaches to deontic reasoning ar...... the benchmarks. Finally, possibilities for further research are indicated. In the appendix, decidability of the satisfiability of formulas is proved via a technique known from monadic First Order Logic....

  9. Students in Action Initiative

    OpenAIRE

    Ryan, Theresa; Mottiar, Ziene; Quinn, Bernadette; Gorman, Catherine; Griffin, Kevin; Craggs, Ruth; Quinn, Deirdre

    2015-01-01

    The Students in Action Project in the School of Hospitality Management and Tourism was established in 2012 as a way of engaging students and working with stakeholders in a destination. The overall aim of the project was to immerse students in an active collaborative learning environment within the destination to identify ways in which tourism could be enhanced. In the 2014/2015 academic year the project involved over 300 students from a variety of programmes and modules working with local sta...

  10. Empirical microeconomics action functionals

    Science.gov (United States)

    Baaquie, Belal E.; Du, Xin; Tanputraman, Winson

    2015-06-01

    A statistical generalization of microeconomics has been made in Baaquie (2013), where the market price of every traded commodity, at each instant of time, is considered to be an independent random variable. The dynamics of commodity market prices is modeled by an action functional-and the focus of this paper is to empirically determine the action functionals for different commodities. The correlation functions of the model are defined using a Feynman path integral. The model is calibrated using the unequal time correlation of the market commodity prices as well as their cubic and quartic moments using a perturbation expansion. The consistency of the perturbation expansion is verified by a numerical evaluation of the path integral. Nine commodities drawn from the energy, metal and grain sectors are studied and their market behavior is described by the model to an accuracy of over 90% using only six parameters. The paper empirically establishes the existence of the action functional for commodity prices that was postulated to exist in Baaquie (2013).

  11. Archetypes as action patterns.

    Science.gov (United States)

    Hogenson, George B

    2009-06-01

    The discovery of mirror neurons by researchers at the University of Parma promises to radically alter our understanding of fundamental cognitive and affective states. This paper explores the relationship of mirror neurons to Jung's theory of archetypes and proposes that archetypes may be viewed as elementary action patterns. The paper begins with a review of a proposed interpretation of the fainting spells of S. Freud in his relationship with Jung as an example of an action pattern that also defines an archetypal image. The challenge that mirror neurons present to traditional views in analytical psychology and psychoanalysis, however, is that they operate without recourse to a cognitive processing element. This is a position that is gaining increasing acceptance in other fields as well. The paper therefore reviews the most recent claims made by the Boston Process of Change Study Group as well as conclusions drawn from dynamic systems views of development and theoretical robotics to underline the conclusion that unconscious agency is not a requirement for coherent action. It concludes with the suggestion that this entire body of research may lead to the conclusion that the dynamic unconscious is an unnecessary hypothesis in psychoanalysis and analytical psychology.

  12. Finding minimal action sequences with a simple evaluation of actions

    Directory of Open Access Journals (Sweden)

    Ashvin eShah

    2014-11-01

    Full Text Available Animals are able to discover the minimal number of actions that achieves an outcome (the minimal action sequence. In most accounts of this, actions are associated with a measure of behavior that is higher for actions that lead to the outcome with a shorter action sequence, and learning mechanisms find the actions associated with the highest measure. In this sense, previous accounts focus on more than the simple binary signal of ``was the outcome achieved?''; they focus on ``how well was the outcome achieved?'' However, such mechanisms may not govern all types of behavioral development. In particular, in the process of action discovery (Redgrave and Gurney, 2006, actions are reinforced if they simply lead to a salient outcome because biological reinforcement signals occur too quickly to evaluate the consequences of an action beyond an indication of the outcome's occurrence. Thus, action discovery mechanisms focus on the simple evaluation of ``was the outcome achieved?'' and not ``how well was the outcome achieved?'' Notwithstanding this impoverishment of information, can the process of action discovery find the minimal action sequence? We address this question by implementing computational mechanisms, referred to in this paper as no-cost learning rules, in which each action that leads to the outcome is associated with the same measure of behavior. No-cost rules focus on ``was the outcome achieved?'' and are consistent with action discovery. No-cost rules discover the minimal action sequence in simulated tasks and execute it for a substantial amount of time. Extensive training, however, results in extraneous actions, suggesting that a separate process (which has been proposed in action discovery must attenuate learning if no-cost rules participate in behavioral development. We describe how no-cost rules develop behavior, what happens when attenuation is disrupted, and relate the new mechanisms to wider computational and biological context.

  13. Learning Actions Models: Qualitative Approach

    DEFF Research Database (Denmark)

    Bolander, Thomas; Gierasimczuk, Nina

    2015-01-01

    —they are identifiable in the limit.We then move on to a particular learning method, which proceeds via restriction of a space of events within a learning-specific action model. This way of learning closely resembles the well-known update method from dynamic epistemic logic. We introduce several different learning......In dynamic epistemic logic, actions are described using action models. In this paper we introduce a framework for studying learnability of action models from observations. We present first results concerning propositional action models. First we check two basic learnability criteria: finite...... identifiability (conclusively inferring the appropriate action model in finite time) and identifiability in the limit (inconclusive convergence to the right action model). We show that deterministic actions are finitely identifiable, while non-deterministic actions require more learning power...

  14. What good are actions? Accelerating learning using learned action priors

    CSIR Research Space (South Africa)

    Rosman, Benjamin S

    2012-11-01

    Full Text Available The computational complexity of learning in sequential decision problems grows exponentially with the number of actions available to the agent at each state. We present a method for accelerating this process by learning action priors that express...

  15. Dissociable regulation of instrumental action within mouse prefrontal cortex.

    Science.gov (United States)

    Gourley, Shannon L; Lee, Anni S; Howell, Jessica L; Pittenger, Christopher; Taylor, Jane R

    2010-11-01

    Evaluation of the behavioral 'costs', such as effort expenditure relative to the benefits of obtaining reward, is a major determinant of goal-directed action. Neuroimaging evidence suggests that the human medial orbitofrontal cortex (mOFC) is involved in this calculation and thereby guides goal-directed and choice behavior, but this region's functional significance in rodents is unknown despite extensive work characterizing the role of the lateral OFC in cue-related response inhibition processes. We first tested mice with mOFC lesions in an instrumental reversal task lacking discrete cues signaling reinforcement; here, animals were required to shift responding based on the location of the reinforced aperture within the chamber. Mice with mOFC lesions acquired the reversal but failed to inhibit responding on the previously reinforced aperture, while mice with prelimbic prefrontal cortex lesions were unaffected. When tested on a progressive ratio schedule of reinforcement, mice with prelimbic cortical lesions were unable to maintain responding, resulting in declining response levels. Mice with mOFC lesions, by contrast, escalated responding. Neither lesion affected sensitivity to satiety-specific outcome devaluation or non-reinforcement (i.e. extinction), and neither had effects when placed after animals were trained on a progressive ratio response schedule. Lesions of the ventral hippocampus, which projects to the mOFC, resulted in similar response patterns, while lateral OFC and dorsal hippocampus lesions resulted in response acquisition, though not inhibition, deficits in an instrumental reversal. Our findings thus selectively implicate the rodent mOFC in braking reinforced goal-directed action when reinforcement requires the acquisition of novel response contingencies.

  16. Rethinking actions: implementation and association.

    Science.gov (United States)

    Quandt, Lorna C; Chatterjee, Anjan

    2015-01-01

    Action processing allows us to move through and interact with the world, as well as understand the movements performed by other people. In recent years, there has been increasing interest in the semantics of actions as differentiated from the semantics of objects. However, as the understanding of action semantics has evolved, it is evident that the existing literature conflates two senses of the word 'action'-one that stems from studies of tool use and the other from event representation. In this paper, we suggest that this issue can be clarified by closely examining differences in how the human parietal and temporal cortices of the brain process action-related stimuli. By contrasting the posterior parietal cortex to the posterolateral temporal cortex, we characterize two complementary action systems in the human brain, each with its own specialization of function. We suggest that these two systems be referred to as the parietal Action Implementation System, and the posterolateral temporal Action Association System. While the frontoparietal system is concerned primarily with how we perform actions, and simulate others' actions, the temporal action system is more involved with processing actions from a third-person, conceptual standpoint. Recent work in cognitive neuroscience of perception and language, as well as the neuroanatomical organization of these brain regions support this distinction. We will discuss the implications of this work for cognition-, language-, and neuroscience-based action research. © 2015 Wiley Periodicals, Inc.

  17. [18F]fluoroethylcholine-PET/CT imaging for radiation treatment planning of recurrent and primary prostate cancer with dose escalation to PET/CT-positive lymph nodes

    Directory of Open Access Journals (Sweden)

    Wahl Andreas

    2011-05-01

    Full Text Available Abstract Background At present there is no consensus on irradiation treatment volumes for intermediate to high-risk primary cancers or recurrent disease. Conventional imaging modalities, such as CT, MRI and transrectal ultrasound, are considered suboptimal for treatment decisions. Choline-PET/CT might be considered as the imaging modality in radiooncology to select and delineate clinical target volumes extending the prostate gland or prostate fossa. In conjunction with intensity modulated radiotherapy (IMRT and imaged guided radiotherapy (IGRT, it might offer the opportunity of dose escalation to selected sites while avoiding unnecessary irradiation of healthy tissues. Methods Twenty-six patients with primary (n = 7 or recurrent (n = 19 prostate cancer received Choline-PET/CT planned 3D conformal or intensity modulated radiotherapy. The median age of the patients was 65 yrs (range 45 to 78 yrs. PET/CT-scans with F18-fluoroethylcholine (FEC were performed on a combined PET/CT-scanner equipped for radiation therapy planning. The majority of patients had intermediate to high risk prostate cancer. All patients received 3D conformal or intensity modulated and imaged guided radiotherapy with megavoltage cone beam CT. The median dose to primary tumours was 75.6 Gy and to FEC-positive recurrent lymph nodal sites 66,6 Gy. The median follow-up time was 28.8 months. Results The mean SUVmax in primary cancer was 5,97 in the prostate gland and 3,2 in pelvic lymph nodes. Patients with recurrent cancer had a mean SUVmax of 4,38. Two patients had negative PET/CT scans. At 28 months the overall survival rate is 94%. Biochemical relapse free survival is 83% for primary cancer and 49% for recurrent tumours. Distant disease free survival is 100% and 75% for primary and recurrent cancer, respectively. Acute normal tissue toxicity was mild in 85% and moderate (grade 2 in 15%. No or mild late side effects were observed in the majority of patients (84%. One patient had

  18. ARID5B, IKZF1 and non-genetic factors in the etiology of childhood acute lymphoblastic leukemia: the ESCALE study.

    Directory of Open Access Journals (Sweden)

    Jérémie Rudant

    Full Text Available Genome-wide association studies (GWAS have identified that frequent polymorphisms in ARID5B and IKZF1, two genes involved in lymphoid differentiation, increase the risk of childhood acute lymphoblastic leukemia (ALL. These findings markedly modified the current field of research on the etiology of ALL. In this new context, the present exploratory study investigated the possible interactions between these at-risk alleles and the non-genetic suspected ALL risk factors that were of sufficient prevalence in the French ESCALE study: maternal use of home insecticides during pregnancy, preconception paternal smoking, and some proxies for early immune modulation, i.e. breastfeeding, history of common infections before age one year, and birth order. The analyses were based on 434 ALL cases and 442 controls of European origin, drawn from the nationwide population-based case-control study ESCALE. Information on non-genetic factors was obtained by standardized telephone interview. Interactions between rs10740055 in ARID5B or rs4132601 in IKZF1 and each of the suspected non-genetic factors were tested, with the SNPs coded as counts of minor alleles (trend variable. Statistical interactions were observed between rs4132601 and maternal insecticide use (p = 0.012, breastfeeding p = 0.017 and repeated early common infections (p = 0.0070, with allelic odds ratios (OR which were only increased among the children not exposed to insecticides (OR = 1.8, 95%CI: 1.3, 2.4, those who had been breastfed (OR = 1.8, 95%CI: 1.3, 2.5 and those who had had repeated early common infections (OR = 2.4, 95%CI: 1.5, 3.8. The allelic ORs were close to one among children exposed to insecticides, who had not been breastfed and who had had no or few common infections. Repeated early common infections interacted with rs10740055 (p = 0.018 in the case-only design. Further studies are needed to evaluate whether these observations of a modification of the effect of the at-risk alleles by

  19. Risk of Late Toxicity in Men Receiving Dose-Escalated Hypofractionated Intensity Modulated Prostate Radiation Therapy: Results From a Randomized Trial

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, Karen E., E-mail: khoffman1@mdanderson.org; Voong, K. Ranh; Pugh, Thomas J.; Skinner, Heath; Levy, Lawrence B.; Takiar, Vinita; Choi, Seungtaek; Du, Weiliang; Frank, Steven J.; Johnson, Jennifer; Kanke, James; Kudchadker, Rajat J.; Lee, Andrew K.; Mahmood, Usama; McGuire, Sean E.; Kuban, Deborah A.

    2014-04-01

    Objective: To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. Methods and Materials: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. Results: 101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). Conclusions: Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this

  20. ARID5B, IKZF1 and non-genetic factors in the etiology of childhood acute lymphoblastic leukemia: the ESCALE study.

    Science.gov (United States)

    Rudant, Jérémie; Orsi, Laurent; Bonaventure, Audrey; Goujon-Bellec, Stéphanie; Baruchel, André; Petit, Arnaud; Bertrand, Yves; Nelken, Brigitte; Pasquet, Marlène; Michel, Gérard; Saumet, Laure; Chastagner, Pascal; Ducassou, Stéphane; Réguerre, Yves; Hémon, Denis; Clavel, Jacqueline

    2015-01-01

    Genome-wide association studies (GWAS) have identified that frequent polymorphisms in ARID5B and IKZF1, two genes involved in lymphoid differentiation, increase the risk of childhood acute lymphoblastic leukemia (ALL). These findings markedly modified the current field of research on the etiology of ALL. In this new context, the present exploratory study investigated the possible interactions between these at-risk alleles and the non-genetic suspected ALL risk factors that were of sufficient prevalence in the French ESCALE study: maternal use of home insecticides during pregnancy, preconception paternal smoking, and some proxies for early immune modulation, i.e. breastfeeding, history of common infections before age one year, and birth order. The analyses were based on 434 ALL cases and 442 controls of European origin, drawn from the nationwide population-based case-control study ESCALE. Information on non-genetic factors was obtained by standardized telephone interview. Interactions between rs10740055 in ARID5B or rs4132601 in IKZF1 and each of the suspected non-genetic factors were tested, with the SNPs coded as counts of minor alleles (trend variable). Statistical interactions were observed between rs4132601 and maternal insecticide use (p = 0.012), breastfeeding p = 0.017) and repeated early common infections (p = 0.0070), with allelic odds ratios (OR) which were only increased among the children not exposed to insecticides (OR = 1.8, 95%CI: 1.3, 2.4), those who had been breastfed (OR = 1.8, 95%CI: 1.3, 2.5) and those who had had repeated early common infections (OR = 2.4, 95%CI: 1.5, 3.8). The allelic ORs were close to one among children exposed to insecticides, who had not been breastfed and who had had no or few common infections. Repeated early common infections interacted with rs10740055 (p = 0.018) in the case-only design. Further studies are needed to evaluate whether these observations of a modification of the effect of the at-risk alleles by non

  1. Efficacy and safety of deferasirox, an oral iron chelator, in heavily iron-overloaded patients with β-thalassaemia: the ESCALATOR study

    Science.gov (United States)

    Taher, Ali; El-Beshlawy, Amal; Elalfy, Mohsen S; Al Zir, Kusai; Daar, Shahina; Habr, Dany; Kriemler-Krahn, Ulrike; Hmissi, Abdel; Al Jefri, Abdullah

    2009-01-01

    Objective: Many patients with transfusional iron overload are at risk for progressive organ dysfunction and early death and poor compliance with older chelation therapies is believed to be a major contributing factor. Phase II/III studies have shown that oral deferasirox 20–30 mg/kg/d reduces iron burden, depending on transfusional iron intake. Methods: The prospective, open-label, 1-yr ESCALATOR study in the Middle East was designed to evaluate once-daily deferasirox in patients ≥2 yr with β-thalassaemia major and iron overload who were previously chelated with deferoxamine and/or deferiprone. Most patients began treatment with deferasirox 20 mg/kg/d; doses were adjusted in response to markers of over- or under-chelation. The primary endpoint was treatment success, defined as a reduction in liver iron concentration (LIC) of ≥3 mg Fe/g dry weight (dw) if baseline LIC was ≥10 mg Fe/g dw, or final LIC of 1–7 mg Fe/g dw for patients with baseline LIC of 2 to <10 mg Fe/g dw. Results: Overall, 233/237 enrolled patients completed 1 yr’s treatment. Mean baseline LIC was 18.0 ± 9.1 mg Fe/g dw, while median serum ferritin was 3356 ng/mL. After 1 yr’s deferasirox treatment, the intent-to-treat population experienced a significant treatment success rate of 57.0% (P = 0.016) and a mean reduction in LIC of 3.4 mg Fe/g dw. Changes in serum ferritin appeared to parallel dose increases at around 24 wk. Most patients (78.1%) underwent dose increases above 20 mg/kg/d, primarily to 30 mg/kg/d. Drug-related adverse events were mostly mild to moderate and resolved without discontinuing treatment. Conclusions: The results of the ESCALATOR study in primarily heavily iron-overloaded patients confirm previous observations in patients with β-thalassaemia, highlighting the importance of timely deferasirox dose adjustments based on serum ferritin levels and transfusional iron intake to ensure patients achieve their therapeutic goal of maintenance or reduction in iron burden

  2. SU-E-T-69: A Radiobiological Investigation of Dose Escalation in Lower Oesophageal Tumours with a Focus On Gastric Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Carrington, R [Cardiff University, Cardiff, Wales (United Kingdom); Staffurth, J; Spezi, E; Crosby, T [Velindre Cancer Centre, Cardiff, Wales (United Kingdom); Warren, S; Partridge, M; Hawkins, M [CRUK/MRC Oxford Institute for Radiation Oncology, Oxford (United Kingdom); Gwynne, S [Singleton Hospital, Swansea, Wales (United Kingdom)

    2015-06-15

    The incidence of lower third oesophageal tumours is increasing in most Western populations. With the role of radiotherapy dose escalation being identified as a research priority in improving outcomes, it is important to quantify the increased toxicity that this may pose to sites such as the lower oesophagus. This study therefore aims to investigate the feasibility of lower oesophageal dose escalation with a focus on stomach tissue toxicity.The original 3D-conformal plans (50Gy3D) from 10 patients in the SCOPE1 trial were reviewed and compared to two RapidArc plans created retrospectively to represent the treatment arms of the forthcoming SCOPE2 trial: 50GyRA and 60GyRA (50Gy to PTV1 with a simultaneously integrated boost of 60Gy to PTV2). The stomach was contoured as stomach wall and dose constraints set according to QUANTEC. Normal tissue complication probability (NTCP) was estimated for the stomach wall for an endpoint of gastric bleeding. There was a mean increase of 5.93% in NTCP from 50Gy3D to 60GyRA and a mean increase of 8.15% in NTCP from the 50GyRA to 60GyRA. With NTCP modelling restricted to volumes outside PTV2, there was a mean decrease of 0.92% in NTCP from the 50Gy3D to 60GyRA, and a mean increase of 2.25% from 50GyRA to 60GyRA. There was a strong correlation between the NTCP and Stomach Wall/PTV1 overlap volume for all plans (R=0.80, 0.77 and 0.77 for 60GyRA, 50GyRA and 50Gy3D respectively). There was also a strong correlation between NTCP and the Stomach Wall/PTV2 overlap volume for 60GyRA (R= 0.82).Radiobiological modelling suggests that increasing the prescribed dose to 60Gy may be associated with a significantly increased risk of toxicity to the stomach within the boost volume. It is recommended that stomach toxicity be closely monitored prospectively when treating patients with lower oesophageal tumours in the forthcoming SCOPE 2 trial. Rhys Carrington received a PhD studentship grant from Cancer Research Wales. Grant number: 2445; Dr Warren and

  3. 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.

  4. Brane actions and string dualities

    NARCIS (Netherlands)

    Eyras, E; Lozano, Y; Ceresole, A; Kounnas, C; Lust, D; Theisen, S

    1999-01-01

    An effective action for the M9-brane is proposed. We study its relation with other branes via dualities. Among these, we find actions for branes which are not suggested by the central charges of the Type II superalgebras.

  5. Digital computers in action

    CERN Document Server

    Booth, A D

    1965-01-01

    Digital Computers in Action is an introduction to the basics of digital computers as well as their programming and various applications in fields such as mathematics, science, engineering, economics, medicine, and law. Other topics include engineering automation, process control, special purpose games-playing devices, machine translation and mechanized linguistics, and information retrieval. This book consists of 14 chapters and begins by discussing the history of computers, from the idea of performing complex arithmetical calculations to the emergence of a modern view of the structure of a ge

  6. Action Research for Sustainability

    DEFF Research Database (Denmark)

    Egmose, Jonas

    by analysing processes of social learning. The book addresses the need to move towards sustainability at societal level as a democratic challenge questioning the way we live on planet earth. By conceptualising sustain-ability as an immanent and emergent ability of ecological and social life, continuously...... to provide local citizens with a greater say in the future of urban sustainability research, this book shows how action research can make important methodological contributions to processes of social learning between citizens and scientists by enabling free spaces in peoples everyday life and within academia...

  7. Action Research for Sustainability

    DEFF Research Database (Denmark)

    Egmose, Jonas

    on urban sustainability the need to move towards sustainability at societal level is conceptualised as a democratic challenge questioning the way we live on planet earth. By understanding sustainability as an immanent and emergent ability of ecological and social life, continuously to renew itself without...... with a greater say in the future of urban sustainability research, the work shows how action research can make important methodological contributions to processes of social learning between citizens and scientists by enabling free spaces in peoples everyday life and within academia, where aspects...

  8. Complexity Equals Action

    CERN Document Server

    Brown, Adam R; Susskind, Leonard; Swingle, Brian; Zhao, Ying

    2015-01-01

    We conjecture that the quantum complexity of a holographic state is dual to the action of a certain spacetime region that we call a Wheeler-DeWitt patch. We illustrate and test the conjecture in the context of neutral, charged, and rotating black holes in AdS, as well as black holes perturbed with static shells and with shock waves. This conjecture evolved from a previous conjecture that complexity is dual to spatial volume, but appears to be a major improvement over the original. In light of our results, we discuss the hypothesis that black holes are the fastest computers in nature.

  9. VIOLENT FRAMES IN ACTION

    Energy Technology Data Exchange (ETDEWEB)

    Sanfilippo, Antonio P.; McGrath, Liam R.; Whitney, Paul D.

    2011-11-17

    We present a computational approach to radical rhetoric that leverages the co-expression of rhetoric and action features in discourse to identify violent intent. The approach combines text mining and machine learning techniques with insights from Frame Analysis and theories that explain the emergence of violence in terms of moral disengagement, the violation of sacred values and social isolation in order to build computational models that identify messages from terrorist sources and estimate their proximity to an attack. We discuss a specific application of this approach to a body of documents from and about radical and terrorist groups in the Middle East and present the results achieved.

  10. Action Research: Some basic issues

    DEFF Research Database (Denmark)

    Rasmussen, Lauge Baungaard

    2003-01-01

    The article introduces the main characteristica of action research as well as its origin. In addition the epistmological criteria are presented and discussed. Finally power relationships and ethical concerns are reflected in relation to the practice of action research.......The article introduces the main characteristica of action research as well as its origin. In addition the epistmological criteria are presented and discussed. Finally power relationships and ethical concerns are reflected in relation to the practice of action research....

  11. Action Research and Interactive Research

    DEFF Research Database (Denmark)

    Svensson, lennart; Nielsen, Kurt Aagaard

    2006-01-01

    The authors present trends in Nordic action research. They ask critical questions in the development towards mode 2 and points out alternative roads for a scientific consolidation of action research and interactive research.......The authors present trends in Nordic action research. They ask critical questions in the development towards mode 2 and points out alternative roads for a scientific consolidation of action research and interactive research....

  12. Action Research and Interactive Research

    DEFF Research Database (Denmark)

    Svensson, lennart; Nielsen, Kurt Aagaard

    2006-01-01

    The authors present trends in Nordic action research. They ask critical questions in the development towards mode 2 and points out alternative roads for a scientific consolidation of action research and interactive research.......The authors present trends in Nordic action research. They ask critical questions in the development towards mode 2 and points out alternative roads for a scientific consolidation of action research and interactive research....

  13. Developing an Action Concept Inventory

    CERN Document Server

    McGinness, Lachlan P

    2016-01-01

    We report on progress towards the development of an Action Concept Inventory (ACI), a test that measures student understanding of action principles in introductory mechanics and optics. The ACI also covers key concepts of many-paths quantum mechanics, from which classical action physics arises. We used a multi-stage iterative development cycle for incorporating expert and student feedback into successive revisions of the ACI. The student feedback, including think-aloud interviews, enabled us to identify their misconceptions about action physics.

  14. 76 FR 80847 - Enforcement Actions

    Science.gov (United States)

    2011-12-27

    ... into compliance before an enforcement action is taken by the Chair. Voluntary compliance is the goal of... existing compliance issues. The amendment retains the Chair's authority to issue an enforcement action at... compliance. In the Preliminary draft, the second action was called a ``non-compliance notice.''...

  15. Unsupervised Learning of Action Primitives

    DEFF Research Database (Denmark)

    Baby, Sanmohan; Krüger, Volker; Kragic, Danica

    2010-01-01

    Action representation is a key issue in imitation learning for humanoids. With the recent finding of mirror neurons there has been a growing interest in expressing actions as a combination meaningful subparts called primitives. Primitives could be thought of as an alphabet for the human actions. ...

  16. Collaborative Action Research: Historical Trends.

    Science.gov (United States)

    Smulyan, Lisa

    This paper presents a historical overview of the use of action research in education and describes the basic assumptions and expectations that continue to characterize collaborative research projects today. Action research was initiated in the 1930's by Kurt Lewin and adapted by educators in the 1940's. Interest in action research declined between…

  17. Escalating morphine exposures followed by withdrawal in feline immunodeficiency virus-infected cats: a model for HIV infection in chronic opiate abusers.

    Science.gov (United States)

    Barr, Margaret C; Huitron-Resendiz, Salvador; Sanchez-Alavez, Manuel; Henriksen, Steven J; Phillips, Tom R

    2003-11-24

    Opiate abuse is a risk factor for human immunodeficiency virus (HIV) infection. Because the direct effects of opiates on HIV infection are difficult to determine epidemiologically, animal models of lentivirus infection are relied upon to study the effects of opiates in the absence of confounding factors. Morphine, the predominant metabolite of heroin, is used in most experimental systems examining heroin abuse. In this study, morphine treatment of feline immunodeficiency virus (FIV)-infected cats modeled a typical pattern of escalating drug use interspersed with withdrawals. Plasma cortisol levels were measured for evidence of stress associated with morphine withdrawal. In the morphine-treated cats, cortisol levels peaked at time points corresponding to morphine withdrawal and returned to baseline levels during treatment and several weeks after the final withdrawal. Morphine-treated cats displayed clear behavioral and physical signs of opiate exposure and evidence of withdrawal when the drug was stopped. Morphine-exposed cats did not experience enhanced severity of FIV-related disease; in fact, morphine demonstrated a protective effect on FIV-associated changes in brainstem auditory evoked potentials. Our research suggests that opiate exposure is unlikely to adversely affect the progression of acute lentivirus infection and might be beneficial in controlling associated neurological disease.

  18. The Christian church’s role in the escalating mob justice system in our black townships – An African pastoral view

    Directory of Open Access Journals (Sweden)

    Elijah Baloyi

    2015-02-01

    Full Text Available Among the crimes in the South African black townships, mob justice has become a growing concern. Some questions that need to be asked are: Is our police force doing enough to protect the ordinary citizens of this country? If the situation continues, will all suspects be killed in the same manner or will there be a solution to change the situation? What is the impact of mob justice on the families of the victims and the witnesses of the brutal acts? How long are we going to live as a traumatised nation as a result of these violent acts? Is there any hope that our nation will ever have the peace it deserves in the context of democracy? This article intends to investigate the impact of the mob justice system and find out what the role of the Christian church should be in the midst of this escalating violence. This study aims to unveil the negative impact of mob justice on the lives of many township South Africans and giving pastoral-biblical suggestions of the church’s role in the elimination of this kind of brutality.

  19. Recombinant T-Cell Receptor Ligand (RTL for Treatment of Multiple Sclerosis: A Double-Blind, Placebo-Controlled, Phase 1, Dose-Escalation Study

    Directory of Open Access Journals (Sweden)

    Vijayshree Yadav

    2012-01-01

    Full Text Available Background. Recombinant T-cell receptor ligand 1000 (RTL1000 is a single-chain protein construct containing the outer two domains of HLA-DR2 linked to myelin-oligodendrocyte-glycoprotein- (MOG- 35–55 peptide. Analogues of RTL1000 induce T-cell tolerance, reverse clinical and histological disease, and promote repair in experimental autoimmune encephalomyelitis (EAE in DR2 transgenic, C57BL/6, and SJL/J mice. Objective. Determining the maximum tolerated dose, safety, and tolerability of RTL1000 in multiple sclerosis (MS subjects. Methods. This was a multicenter, Phase I dose-escalation study in HLA-DR2+ MS subjects. Consecutive cohorts received RTL1000 doses of 2, 6, 20, 60, 200, and 100 mg, respectively. Subjects within each cohort randomly received a single intravenous infusion of RTL1000 or placebo at a 4 : 2 ratio. Safety monitoring included clinical, laboratory, and brain magnetic resonance imaging (MRI evaluations. Results. Thirty-four subjects completed the protocol. All subjects tolerated the 2–60 mg doses of RTL1000. Doses ≥100 mg caused hypotension and diarrhea in 3 of 4 subjects, leading to discontinuation of further enrollment. Conclusions. The maximum tolerated dose of RTL1000 in MS subjects is 60 mg, comparable to effective RTL doses in EAE. RTL1000 is a novel approach for MS treatment that may induce immunoregulation without immunosuppression and promote neural repair.

  20. A Phase I Dose Escalation Study Demonstrates Quercetin Safety and Explores Potential for Bioflavonoid Antivirals in Patients with Chronic Hepatitis C.

    Science.gov (United States)

    Lu, Nu T; Crespi, Catherine M; Liu, Natalie M; Vu, James Q; Ahmadieh, Yasaman; Wu, Sheng; Lin, Sherry; McClune, Amy; Durazo, Francisco; Saab, Sammy; Han, Steven; Neiman, David C; Beaven, Simon; French, Samuel W

    2016-01-01

    The hepatitis C virus (HCV) infects more than 180 million people worldwide, with long-term consequences including liver failure and hepatocellular carcinoma. Quercetin bioflavonoids can decrease HCV production in tissue culture, in part through inhibition of heat shock proteins. If quercetin demonstrates safety and antiviral activity in patients, then it could be developed into an inexpensive HCV treatment for third world countries or other affected populations that lack financial means to cover the cost of mainstream antivirals. A phase 1 dose escalation study was performed to evaluate the safety of quercetin in 30 untreated patients with chronic HCV infection and to preliminarily characterize quercetin's potential in suppressing viral load and/or liver injury. Quercetin displayed safety in all trial participants. Additionally, 8 patients showed a "clinically meaningful" 0.41-log viral load decrease. There was a positive correlation (r = 0.41, p = 0.03) indicating a tendency for HCV decrease in patients with a lower ratio of plasma quercetin relative to dose. No significant changes in aspartate transaminase and alanine transaminase were detected. In conclusion, quercetin exhibited safety (up to 5 g daily) and there was a potential for antiviral activity in some hepatitis C patients.

  1. Safety, tolerability and pharmacokinetics of 2-pyridylacetic acid, a major metabolite of betahistine, in a phase 1 dose escalation study in subjects with ADHD.

    Science.gov (United States)

    Moorthy, Ganesh; Sallee, Floyd; Gabbita, Prasad; Zemlan, Frank; Sallans, Larry; Desai, Pankaj B

    2015-10-01

    Betahistine, a potent histamine H3 receptor antagonist, is being developed for the treatment of attention deficit hyperactivity disorder (ADHD) that manifests with symptoms such as hyperactivity, impulsivity and inattention. This study describes the pharmacokinetics of betahistine in ADHD subjects at doses higher than 50 mg. These assessments were made during a randomized, placebo-controlled, single blind, dose escalation study to determine the safety, tolerability and pharmacokinetics of once daily doses of 50 mg, 100 mg and 200 mg of betahistine in subjects with ADHD. Plasma levels of 2-pyridylacetic acid (2-PAA), a major metabolite of betahistine were quantified using a validated LC-MS/MS method and used for pharmacokinetic analysis and dose proportionality of betahistine. A linear relationship was observed in Cmax and AUC0-4 of 2-PAA with the betahistine dose (R2 0.9989 and 0.9978, respectively) and dose proportionality coefficients (β) for the power model were 0.8684 (Cmax) and 1.007 (AUC0-4). A population pharmacokinetic model with first-order absorption of betahistine and metabolism to 2-PAA, followed by a first-order elimination of 2-PAA provides estimates of clearance that underscored the linear increase in systemic exposure with dose. There were no serious adverse events reported in the study, betahistine was safe and well tolerated at all the dose levels tested.

  2. Predictors of Rectal Tolerance Observed in a Dose-Escalated Phase 1-2 Trial of Stereotactic Body Radiation Therapy for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, D.W. Nathan [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Cho, L. Chinsoo [Department of Radiation Oncology, University of Minnesota, Minneapolis, Minnesota (United States); Straka, Christopher [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Christie, Alana [Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Lotan, Yair [Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Pistenmaa, David [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Kavanagh, Brian D. [Department of Radiation Oncology, University of Colorado, Denver, Colorado (United States); Nanda, Akash [Department of Radiation Oncology, University of Florida Health Cancer Center at Orlando Health, Orlando, Florida (United States); Kueplian, Patrick [Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, California (United States); Brindle, Jeffrey [Prairie Lakes Hospital, Watertown, South Dakota (United States); Cooley, Susan; Perkins, Alida [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Raben, David [Department of Radiation Oncology, University of Colorado, Denver, Colorado (United States); Xie, Xian-Jin [Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Timmerman, Robert D., E-mail: robert.timmerman@utsouthwestern.edu [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States)

    2014-07-01

    Purpose: To convey the occurrence of isolated cases of severe rectal toxicity at the highest dose level tested in 5-fraction stereotactic body radiation therapy (SBRT) for localized prostate cancer; and to rationally test potential causal mechanisms to guide future studies and experiments to aid in mitigating or altogether avoiding such severe bowel injury. Methods and Materials: Clinical and treatment planning data were analyzed from 91 patients enrolled from 2006 to 2011 on a dose-escalation (45, 47.5, and 50 Gy in 5 fractions) phase 1/2 clinical study of SBRT for localized prostate cancer. Results: At the highest dose level, 6.6% of patients treated (6 of 91) developed high-grade rectal toxicity, 5 of whom required colostomy. Grade 3+ delayed rectal toxicity was strongly correlated with volume of rectal wall receiving 50 Gy >3 cm{sup 3} (P<.0001), and treatment of >35% circumference of rectal wall to 39 Gy (P=.003). Grade 2+ acute rectal toxicity was significantly correlated with treatment of >50% circumference of rectal wall to 24 Gy (P=.010). Conclusion: Caution is advised when considering high-dose SBRT for treatment of tumors near bowel structures, including prostate cancer. Threshold dose constraints developed from physiologic principles are defined, and if respected can minimize risk of severe rectal toxicity.

  3. Learning to Avoid Risky Actions

    OpenAIRE

    Malfaz, María; Miguel A. Salichs

    2011-01-01

    When a reinforcement learning agent executes actions that can cause frequent damage to itself, it can learn, by using Q-learning, that these actions must not be executed again. However, there are other actions that do not cause damage frequently but only once in a while, for example, risky actions such as parachuting. These actions may imply punishment to the agent and, depending on its personality, it would be better to avoid them. Nevertheless, using the standard Q-learning algorithm, the a...

  4. Learning Actions Models: Qualitative Approach

    DEFF Research Database (Denmark)

    Bolander, Thomas; Gierasimczuk, Nina

    2015-01-01

    identifiability (conclusively inferring the appropriate action model in finite time) and identifiability in the limit (inconclusive convergence to the right action model). We show that deterministic actions are finitely identifiable, while non-deterministic actions require more learning power......—they are identifiable in the limit.We then move on to a particular learning method, which proceeds via restriction of a space of events within a learning-specific action model. This way of learning closely resembles the well-known update method from dynamic epistemic logic. We introduce several different learning...

  5. Action feedback affects the perception of action-related objects beyond actual action success

    OpenAIRE

    2014-01-01

    Successful object-oriented action typically increases the perceived size of aimed target objects. This phenomenon has been assumed to reflect an impact of an actor's current action ability on visual perception. The actual action ability and the explicit knowledge of action outcome, however, were confounded in previous studies. The present experiments aimed at disentangling these two factors. Participants repeatedly tried to hit a circular target varying in size with a stylus movement under re...

  6. Controlling Attention through Action: Observing Actions Primes Action-Related Stimulus Dimensions

    Science.gov (United States)

    Fagioli, Sabrina; Ferlazzo, Fabio; Hommel, Bernhard

    2007-01-01

    Previous findings suggest that planning an action "backward-primes" perceptual dimension related to this action: planning a grasp facilitates the processing of visual size information, while planning a reach facilitates the processing of location information. Here we show that dimensional priming of perception through action occurs even in the…

  7. The minimalist grammar of action.

    Science.gov (United States)

    Pastra, Katerina; Aloimonos, Yiannis

    2012-01-12

    Language and action have been found to share a common neural basis and in particular a common 'syntax', an analogous hierarchical and compositional organization. While language structure analysis has led to the formulation of different grammatical formalisms and associated discriminative or generative computational models, the structure of action is still elusive and so are the related computational models. However, structuring action has important implications on action learning and generalization, in both human cognition research and computation. In this study, we present a biologically inspired generative grammar of action, which employs the structure-building operations and principles of Chomsky's Minimalist Programme as a reference model. In this grammar, action terminals combine hierarchically into temporal sequences of actions of increasing complexity; the actions are bound with the involved tools and affected objects and are governed by certain goals. We show, how the tool role and the affected-object role of an entity within an action drives the derivation of the action syntax in this grammar and controls recursion, merge and move, the latter being mechanisms that manifest themselves not only in human language, but in human action too.

  8. Unsupervised Learning of Action Primitives

    DEFF Research Database (Denmark)

    Baby, Sanmohan; Krüger, Volker; Kragic, Danica

    2010-01-01

    and scale, the use of the object can provide a strong invariant for the detection of motion primitives. In this paper we propose an unsupervised learning approach for action primitives that makes use of the human movements as well as the object state changes. We group actions according to the changes......Action representation is a key issue in imitation learning for humanoids. With the recent finding of mirror neurons there has been a growing interest in expressing actions as a combination meaningful subparts called primitives. Primitives could be thought of as an alphabet for the human actions....... In this paper we observe that human actions and objects can be seen as being intertwined: we can interpret actions from the way the body parts are moving, but as well from how their effect on the involved object. While human movements can look vastly different even under minor changes in location, orientation...

  9. Viewpoint Manifolds for Action Recognition

    Directory of Open Access Journals (Sweden)

    Souvenir Richard

    2009-01-01

    Full Text Available Abstract Action recognition from video is a problem that has many important applications to human motion analysis. In real-world settings, the viewpoint of the camera cannot always be fixed relative to the subject, so view-invariant action recognition methods are needed. Previous view-invariant methods use multiple cameras in both the training and testing phases of action recognition or require storing many examples of a single action from multiple viewpoints. In this paper, we present a framework for learning a compact representation of primitive actions (e.g., walk, punch, kick, sit that can be used for video obtained from a single camera for simultaneous action recognition and viewpoint estimation. Using our method, which models the low-dimensional structure of these actions relative to viewpoint, we show recognition rates on a publicly available dataset previously only achieved using multiple simultaneous views.

  10. Viewpoint Manifolds for Action Recognition

    Directory of Open Access Journals (Sweden)

    Richard Souvenir

    2009-01-01

    Full Text Available Action recognition from video is a problem that has many important applications to human motion analysis. In real-world settings, the viewpoint of the camera cannot always be fixed relative to the subject, so view-invariant action recognition methods are needed. Previous view-invariant methods use multiple cameras in both the training and testing phases of action recognition or require storing many examples of a single action from multiple viewpoints. In this paper, we present a framework for learning a compact representation of primitive actions (e.g., walk, punch, kick, sit that can be used for video obtained from a single camera for simultaneous action recognition and viewpoint estimation. Using our method, which models the low-dimensional structure of these actions relative to viewpoint, we show recognition rates on a publicly available dataset previously only achieved using multiple simultaneous views.

  11. Networks for Collective Action

    CERN Document Server

    Bruggeman, Jeroen

    2016-01-01

    A significant challenge is to explain how people cooperate for public goods. The problem is more difficult for people when their public good and its benefits are unclear at the outset and its timing and costs are uncertain. However, history shows that even under adverse conditions, people can cooperate. As a prelude to cooperation, people can establish (or reinforce) social ties through communication. Consequently, individuals' cognitive states may synchronize, so that they can depend on like-minded people rather than on a situation beyond their control. Whether this succeeds largely depends on the network that is formed (or used), which should also help them to overcome misunderstandings and to synchronize relatively fast. From a well-known model of social influence it is inferred that network patterns with high algebraic connectivity, featuring multiple independent connections, are optimal for collective action.

  12. CLICing into action

    CERN Multimedia

    Barbara Warmbein

    2015-01-01

    Putting its acronym into action, the Compact Linear Collider (CLIC) collaboration is testing its first compact accelerator module in the CTF3 test facility. Fed by high-power waveguides, cables and cooling tubes, the module has all the functions of future CLIC modules and allows the experts to test all the features, including frequency, losses, damping, acceleration and deceleration.   The new CLIC module in the CTF3 test facility. CLIC is one of the potential follow-up projects to the LHC, alongside the International Linear Collider (ILC) and the Future Circular Collider (FCC) studies. Instead of smashing protons into protons, it is designed to collide electrons with positrons. Following the publication of its CDR in 2012, the CLIC collaboration entered the project preparation phase - testing its unique technology, making improvements and taking a closer look at the cost of the individual components. This is where the new module comes in. While many of the techniques and technologies neede...

  13. Structure learning in action

    Science.gov (United States)

    Braun, Daniel A.; Mehring, Carsten; Wolpert, Daniel M.

    2010-01-01

    ‘Learning to learn’ phenomena have been widely investigated in cognition, perception and more recently also in action. During concept learning tasks, for example, it has been suggested that characteristic features are abstracted from a set of examples with the consequence that learning of similar tasks is facilitated—a process termed ‘learning to learn’. From a computational point of view such an extraction of invariants can be regarded as learning of an underlying structure. Here we review the evidence for structure learning as a ‘learning to learn’ mechanism, especially in sensorimotor control where the motor system has to adapt to variable environments. We review studies demonstrating that common features of variable environments are extracted during sensorimotor learning and exploited for efficient adaptation in novel tasks. We conclude that structure learning plays a fundamental role in skill learning and may underlie the unsurpassed flexibility and adaptability of the motor system. PMID:19720086

  14. The Quench Action

    Science.gov (United States)

    Caux, Jean-Sébastien

    2016-06-01

    We give a pedagogical introduction to the methodology of the Quench Action, which is an effective representation for the calculation of time-dependent expectation values of physical operators following a generic out-of-equilibrium state preparation protocol (for example a quantum quench). The representation, originally introduced in Caux and Essler (2013 Phys. Rev. Lett. 110 257203), is founded on a mixture of exact data for overlaps together with variational reasonings. It is argued to be quite generally valid and thermodynamically exact for arbitrary times after the quench (from short times all the way up to the steady state), and applicable to a wide class of physically relevant observables. Here, we introduce the method and its language, give an overview of some recent results, suggest a roadmap and offer some perspectives on possible future research directions.

  15. Testing Fractional Action Cosmology

    CERN Document Server

    Shchigolev, V K

    2015-01-01

    The present work deals with a combined test of the so-called Fractional Action Cosmology (FAC) on the example of a specific model obtained by the author earlier. In this model, the effective cosmological term is proportional to the Hubble parameter squared through the so-called kinematic induction. The reason of studying this cosmological model could be explained by its ability to describe two periods of accelerated expansion, that is in agreement with the recent observations and the cosmological inflation paradigm. First of all, we put our model through the theoretical tests that gives a general conception of the influence of the model parameters on its behavior. Then, we obtain some restrictions on the principal parameters of the model, including the fractional index, by means of the observational data. Finally, the cosmography parameters and the observational data compared to the theoretical predictions are presented both analytically and graphically.

  16. Testing fractional action cosmology

    Science.gov (United States)

    Shchigolev, V. K.

    2016-08-01

    The present work deals with a combined test of the so-called Fractional Action Cosmology (FAC) on the example of a specific model obtained by the author earlier. In this model, the effective cosmological term is proportional to the Hubble parameter squared through the so-called kinematic induction. The reason of studying this cosmological model could be explained by its ability to describe two periods of accelerated expansion, that is in agreement with the recent observations and the cosmological inflation paradigm. First of all, we put our model through the theoretical tests, which gives a general conception of the influence of the model parameters on its behavior. Then, we obtain some restrictions on the principal parameters of the model, including the fractional index, by means of the observational data. Finally, the cosmography parameters and the observational data compared to the theoretical predictions are presented both analytically and graphically.

  17. Guam Energy Action Plan

    Energy Technology Data Exchange (ETDEWEB)

    Conrad, M. D.; Ness, J. E.

    2013-07-01

    Describes the four near-term strategies selected by the Guam Energy Task Force during action planning workshops conducted in March 2013, and outlines the steps being taken to implement those strategies. Each strategy addresses one of the energy sectors identified in the earlier Guam strategic energy plan as being an essential component of diversifying Guam's fuel sources and reducing fossil energy consumption 20% by 2020. The four energy strategies selected are: (1) expanding public outreach on energy efficiency and conservation, (2) establishing a demand-side management revolving loan program, (3) exploring waste-to-energy options, and (4) influencing the transportation sector via anti-idling legislation, vehicle registration fees, and electric vehicles.

  18. Entrepreneurial learning requires action

    DEFF Research Database (Denmark)

    Brink, Tove; Madsen, Svend Ole

    2014-01-01

    apply in industry. The findings of this study show that SME managers employ a practice-shaped holistic multi- and cross-disciplinary approach to learning. This learning approach is supported by theory dissemination, business challenge applications, and organisational prerequisites. Diversified learning......This paper reveals how managers of small- and medium-sized enterprises (SMEs) can utilise their participation in research-based training. Empirical research from a longitudinal study of 10 SMEs managers in the wind turbine industry is provided to describe a learning approach that SME managers can...... that is enhanced by essential large-scale industry players and other SME managers are required to create action and value in learning. An open-mindedness to new learning approaches by SME managers and an open-mindedness to multi- and cross-disciplinary collaboration with SME managers by facilitators is required....

  19. An agenda for action.

    Science.gov (United States)

    1987-01-01

    Participants at the 1985 Maseru Seminar on Another Development for Southern African Development Coordination Conference (SADCC) Countries developed an agenda for action aimed at ending the exploitation of people in the region. Another Development, a concept first introduced into the worldwide debate about economic development in 1975, is based on 5 premises: development should be need-oriented, self-reliant, endogenous, ecologically sound, and based on structural transformations. It should be viewed as an integrated socioeconomic, political, and cultural process. Participants noted that conventional development policies are becoming increasingly incapable of satisfying the basic needs of people in the SADCC region for food, health, housing, education, and employment. The Agenda for Action recognizes that the problems of dependency cannot be solved by the more intensive application of development strategies that created the problems in the first place. Needed, instead, is: 1) effective popular participation in all decision-making processes; 2) the transformation of social structures to facilitate effective participation in decision-making; 3) the full exercise of human rights; 4) the establishment of local, district, and national papers and publishing houses dedicated to the right to be informed; 5) the gearing of agricultural production primarily to the growing of food for domestic markets, with exports limited to surpluses; 6) the production of raw materials for manufactured goods that meet local needs; 7) land reform; 8) the coordinated development of both light and heavy industry and mining, with an emphasis on decentralization of industries to rural areas; 9) the allocation of higher priority to resources for housing; 10) the integration of meaningful productive work into the educational system at every level; 11) the development of an endogenous science and technology base; and 12) the allocation of the resources needed for a primary health care system.

  20. 旁路变频控制系统原理及其在扶梯节能中的应用%BYPASS FREQUENCY CONTROL SYSTEM IN ESCALATOR ENERGY-SAVING PROGRAM

    Institute of Scientific and Technical Information of China (English)

    黄德雄

    2011-01-01

    Briefly introduce for Standby-vF system's theory and application in Escalator saving energy, system composing cost, system's affection on the motor, and the description about the systemic superiority capability. And this thesis indicates the trend of the escalator on the saving energy development.%简要介绍旁路变频控制系统的原理及在扶梯节能中的应用.系统构成费用.系统对于电动机的影响.论述该系统的优越性能.指出这一系统必是扶梯节能发展方向的一大必然趋势。

  1. 一种自动扶梯梯级踏陷安全性能检测仪的设计%Design of an Escalator Safety Performance Testing Instrument

    Institute of Scientific and Technical Information of China (English)

    付红; 许林

    2012-01-01

      This paper developed in a new escalator stave collapses safety performance detector,and discussed the general design of the tester and technical features,it provided a safe and effective technical method for the safety performance testing and rerifying of escalator and automatic sidewalk.%  在研制一种新型自动扶梯梯级踏陷安全性能检测仪的基础上,阐述了该测试仪的总体设计和技术特点,该检测仪为自动扶梯及自动人行道的检测和验证提供了一种安全有效的技术手段。

  2. Retrospective Evaluation Reveals That Long-term Androgen Deprivation Therapy Improves Cause-Specific and Overall Survival in the Setting of Dose-Escalated Radiation for High-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Felix Y., E-mail: ffeng@med.umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Radiation Oncology, Veterans Affairs Medical Center, Ann Arbor, Michigan (United States); Blas, Kevin; Olson, Karin; Stenmark, Matthew [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Sandler, Howard [Cedars Sinai Medical Center, Los Angeles, California (United States); Hamstra, Daniel A. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)

    2013-05-01

    Purpose: To evaluate the role of androgen deprivation therapy (ADT) and duration for high-risk prostate cancer patients treated with dose-escalated radiation therapy (RT). Methods and Materials: A retrospective analysis of high-risk prostate cancer patients treated with dose-escalated RT (minimum 75 Gy) with or without ADT was performed. The relationship between ADT use and duration with biochemical failure (BF), metastatic failure (MF), prostate cancer-specific mortality (PCSM), non-prostate cancer death (NPCD), and overall survival (OS) was assessed as a function of pretreatment characteristics, comorbid medical illness, and treatment using Fine and Gray's cumulative incidence methodology. Results: The median follow-up time was 64 months. In men with National Comprehensive Cancer Network defined high-risk prostate cancer treated with dose-escalated RT, on univariate analysis, both metastasis (P<.0001; hazard ratio 0.34; 95% confidence interval 0.18-0.67; cumulative incidence at 60 months 13% vs 35%) and PCSM (P=.015; hazard ratio 0.41; 95% confidence interval 0.2-1.0; cumulative incidence at 60 months 6% vs 11%) were improved with the use of ADT. On multivariate analysis for all high-risk patients, Gleason score was the strongest negative prognostic factor, and long-term ADT (LTAD) improved MF (P=.002), PCSM (P=.034), and OS (P=.001). In men with prostate cancer and Gleason scores 8 to 10, on multivariate analysis after adjustment for other risk features, there was a duration-dependent improvement in BF, metastasis, PCSM, and OS, all favoring LTAD in comparison with STAD or RT alone. Conclusion: For men with high-risk prostate cancer treated with dose-escalated EBRT, this retrospective study suggests that the combination of LTAD and RT provided a significant improvement in clinical outcome, which was especially true for those with Gleason scores of 8 to 10.

  3. Everyday robotic action: Lessons from human action control

    Directory of Open Access Journals (Sweden)

    Roy eDe Kleijn

    2014-03-01

    Full Text Available Robots are increasingly capable of performing everyday human activities such as cooking, cleaning, and doing the laundry. This requires the real-time planning and execution of complex, temporally-extended sequential actions under high degrees of uncertainty, which provides many challenges to traditional approaches to robot action control. We argue that important lessons in this respect can be learned from research on human action control. We provide a brief overview of available psychological insights into this issue and focus on four principles that we think could be particularly beneficial for robot control: the integration of symbolic and subsymbolic planning of action sequences, the integration of feedforward and feedback control, the clustering of complex actions into subcomponents, and the contextualization of action-control structures through goal representations.

  4. Action-based flood forecasting for triggering humanitarian action

    Science.gov (United States)

    Coughlan de Perez, Erin; van den Hurk, Bart; van Aalst, Maarten K.; Amuron, Irene; Bamanya, Deus; Hauser, Tristan; Jongma, Brenden; Lopez, Ana; Mason, Simon; Mendler de Suarez, Janot; Pappenberger, Florian; Rueth, Alexandra; Stephens, Elisabeth; Suarez, Pablo; Wagemaker, Jurjen; Zsoter, Ervin

    2016-09-01

    Too often, credible scientific early warning information of increased disaster risk does not result in humanitarian action. With financial resources tilted heavily towards response after a disaster, disaster managers have limited incentive and ability to process complex scientific data, including uncertainties. These incentives are beginning to change, with the advent of several new forecast-based financing systems that provide funding based on a forecast of an extreme event. Given the changing landscape, here we demonstrate a method to select and use appropriate forecasts for specific humanitarian disaster prevention actions, even in a data-scarce location. This action-based forecasting methodology takes into account the parameters of each action, such as action lifetime, when verifying a forecast. Forecasts are linked with action based on an understanding of (1) the magnitude of previous flooding events and (2) the willingness to act "in vain" for specific actions. This is applied in the context of the Uganda Red Cross Society forecast-based financing pilot project, with forecasts from the Global Flood Awareness System (GloFAS). Using this method, we define the "danger level" of flooding, and we select the probabilistic forecast triggers that are appropriate for specific actions. Results from this methodology can be applied globally across hazards and fed into a financing system that ensures that automatic, pre-funded early action will be triggered by forecasts.

  5. Tracking in Object Action Space

    DEFF Research Database (Denmark)

    Krüger, Volker; Herzog, Dennis

    2013-01-01

    In this paper we focus on the joint problem of tracking humans and recognizing human action in scenarios such as a kitchen scenario or a scenario where a robot cooperates with a human, e.g., for a manufacturing task. In these scenarios, the human directly interacts with objects physically by using....../manipulating them or by, e.g., pointing at them such as in “Give me that…”. To recognize these types of human actions is difficult because (a) they ought to be recognized independent of scene parameters such as viewing direction and (b) the actions are parametric, where the parameters are either object...... tracking and action recognition should be seen as an intertwined problem that is primed by the objects on which the actions are applied. In this paper, we are looking at human body tracking and action recognition from a object-driven perspective. Instead of the space of human body poses we consider...

  6. Long-term outcomes from dose-escalated image-guided intensity-modulated radiotherapy with androgen deprivation: encouraging results for intermediate- and high-risk prostate cancer

    Directory of Open Access Journals (Sweden)

    Wilcox SW

    2014-08-01

    Full Text Available Shea W Wilcox,1,4 Noel J Aherne,2,4 Linus C Benjamin,1 Bosco Wu,1 Thomaz de Campos Silva,3 Craig S McLachlan,4 Michael J McKay,3,5 Andrew J Last,1 Thomas P Shakespeare1–4 1North Coast Cancer Institute, Port Macquarie, NSW, Australia; 2North Coast Cancer Institute, Coffs Harbour, NSW, Australia; 3North Coast Cancer Institute, Lismore, NSW, Australia; 4The University of New South Wales, Rural Clinical School, Sydney, NSW, Australia; 5The University of Sydney, Sydney, NSW, Australia Purpose: Dose-escalated (DE radiotherapy in the setting of localized prostate cancer has been shown to improve biochemical disease-free survival (bDFS in several studies. In the same group of patients, androgen deprivation therapy (ADT has been shown to confer a survival benefit when combined with radiotherapy doses of up to 70 Gy; however, there is currently little long-term data on patients who have received high-dose intensity-modulated radiotherapy (IMRT with ADT. We report the long-term outcomes in a large cohort of patients treated with the combination of DE image-guided IMRT (IG-IMRT and ADT. Methods and materials: Patients with localized prostate cancer were identified from a centralized database across an integrated cancer center. All patients received DE IG-IMRT, combined with ADT, and had a minimum follow up of 12 months post-radiotherapy. All relapse and toxicity data were collected prospectively. Actuarial bDFS, metastasis-free survival, prostate cancer-specific survival, and multivariate analyses were calculated using the SPSS v20.0 statistical package. Results: Seven hundred and eighty-two eligible patients were identified with a median follow up of 46 months. Overall, 4.3% of patients relapsed, 2.0% developed distant metastases, and 0.6% died from metastatic prostate cancer. At 5-years, bDFS was 88%, metastasis-free survival was 95%, and prostate cancer-specific survival was 98%. Five-year grade 2 genitourinary and gastrointestinal toxicity was 2

  7. Is credit for early action credible early action?

    Energy Technology Data Exchange (ETDEWEB)

    Rolfe, C. [West Coast Environmental Law Research Foundation, Vancouver, BC (Canada); Michaelowa, A.; Dutschke, M. [Hamburg Institute for Economic Research, Hamburg, (Germany)

    1999-12-01

    Credit for early action as a tool for greenhouse gas emissions reduction is compared with various market instruments as a means of narrowing the gap between projected emssions and those of the Kyoto Protocol. Market instruments work by creating a market price for emissions and use the market to encourage reductions at the lowest price, which is done by placing limits on greenhouse gas emissions and allowing the market to decide where reductions occur, or by imposing a carbon tax or emissions charge. While they can be applied within a sector, they are usually used to encourage reductions throughout the economy or across large sectors. Credit for early action also creates an incentive for emissions reductions throughout the economy or at least across many sectors. Credit for early action tools do not work by either imposing a carbon tax or emissions charge or placing limits on emissions, rather they promise that entities that take action against greenhouse gases prior to the imposition of a carbon tax or emissions limits will receive a credit against future taxes or limits. An overview is provided of the Kyoto Protocol and the rationale for taking early action, and a review is included of the theory and specific proposals for market instruments and credit for early action. A comparative analysis is provided of these approaches by examining their relative efficiency, environmental effectiveness, and impacts on the redistribution of wealth. Credit for early action is viewed as problematic on a number of counts and is seen as an interim strategy for imposition while political support for market instruments develop. The environmental effectiveness of credit for early action is very difficult to predict, and credit for early action programs do not yield the lowest cost emissions reductions. Credit for early action programs will not achieve compliance with the Kyoto Protocol at the lowest cost, and credits for early action will increase the compliance costs for those who

  8. Numbers in Action.

    Science.gov (United States)

    Rugani, Rosa; Sartori, Luisa

    2016-01-01

    Humans show a remarkable tendency to describe and think of numbers as being placed on a mental number line (MNL), with smaller numbers located on the left and larger ones on the right. Faster responses to small numbers are indeed performed on the left side of space, while responses to large numbers are facilitated on the right side of space (spatial-numerical association of response codes, SNARC effect). This phenomenon is considered the experimental demonstration of the MNL and has been extensively replicated throughout a variety of paradigms. Nevertheless, the majority of previous literature has mainly investigated this effect by means of response times and accuracy, whereas studies considering more subtle and automatic measures such as kinematic parameters are rare (e.g., in a reaching-to-grasp movement, the grip aperture is enlarged in responding to larger numbers than in responding to small numbers). In this brief review we suggest that numerical magnitude can also affect the what and how of action execution (i.e., temporal and spatial components of movement). This evidence could have large implications in the strongly debated issue concerning the effect of experience and culture on the orientation of MNL.

  9. Solr in action

    CERN Document Server

    Grainger, Trey

    2014-01-01

    Whether handling big data, building cloud-based services, or developing multi-tenant web applications, it's vital to have a fast, reliable search solution. Apache Solr is a scalable and ready-to-deploy open-source full-text search engine powered by Lucene. It offers key features like multi-lingual keyword searching, faceted search, intelligent matching, and relevancy weighting right out of the box. Solr in Action is the definitive guide to implementing fast and scalable search using Apache Solr 4. It uses well-documented examples ranging from basic keyword searching to scaling a system for billions of documents and queries. Readers will gain a deep understanding of how to implement core Solr capabilities such as faceted navigation through search results, matched snippet highlighting, field collapsing and search results grouping, spell checking, query auto-complete, querying by functions, and more. RETAIL SELLING POINTS Clearly-written comprehensive guide In-depth coverage of Solr 4 Uses real-world examples ba...

  10. [Antimicrobial mechanisms of action].

    Science.gov (United States)

    Calvo, Jorge; Martínez-Martínez, Luis

    2009-01-01

    A large number of families and groups of antimicrobial agents are of clinical interest. The mechanisms by which compounds with antibacterial activity inhibit growth or cause bacterial death are varied and depend on the affected targets. The bacterial cell wall-a unique structure in most bacteria that is absent in eukaryotic cells-can be affected in several ways: at different stages of synthesis (fosfomycin, cycloserine) or transport (bacitracin, mureidomycins) of its metabolic precursors, or by a direct action on its structural organization (beta-lactams, glycopeptides). The main drugs affecting the cytoplasmic membrane are polymyxins and daptomycin. Protein synthesis can be blocked by a large variety of compounds that affect any of the phases of this process, including activation (mupirocin), initiation (oxazolidinones, aminoglycosides), binding of the tRNA amino acid complex to ribosomes (tetracyclines, glycylcyclines) and elongation (amphenicols, lincosamides, macrolides, ketolides, streptogramins, fusidic acid). The metabolism of nucleic acids can be altered at the DNA-dependent RNA polymerase or in the process of DNA coiling (quinolones); some compounds affect DNA directly (nitroimidazoles, nitrofurans). Trimethoprim and sulfamides (often used in combination) are examples of antimicrobial agents that block bacterial metabolic pathways. Some compounds are unable to inhibit or kill bacteria in themselves, but can block bacterial mechanisms of resistance, enhancing the activity of other antimicrobials administered in combination. Among this group of agents, only certain beta-lactamase inhibitors are currently in clinical use.

  11. Action as ejection.

    Science.gov (United States)

    Franco, Daisy

    2006-01-01

    The systematic analysis of acting-out episodes can be used in assessing analytic progress. Variables to be considered are the nature of the wish, the type of defense, and the degree of concreteness (versus symbolization) of the mental processes used in attempting actualization (as distinct from the resort to action). Two acting-out episodes of a borderline patient who acted out as a character trait, both occurring outside the analytic setting, are presented as illustrations. In the first one, occurring relatively early in the analysis, when split-off negative and positive self-images had to be rigidly maintained, ejection of the negative self-image was actualized via the regressive use of a symbolic equation and the mechanism of displacement, obliterating the distinction between an internal feeling and an external thing that here was literally thrown out. The later episode, occurring after the split was healed and within the context of a frustrating heterosexual involvement, contained an acted-out allusion to identification and competition with the mother. As in a dream, via associations, an unconscious wish for oedipal victory was revealed. Whereas in the first episode the goal of ejection was central, with splitting and denial the underlying defenses, it was absent from the second, in which an attempt was made to actualize a repressed infantile wish and made greater use of symbolization. It is concluded that acting-out episodes at different periods of the analysis, when systematically analyzed, can serve in assessing a patient's progress.

  12. Affirmative Action at Work

    Directory of Open Access Journals (Sweden)

    Jack McKillip

    2001-04-01

    Full Text Available IMGIP and ICEOP are minority graduate fellowship programs sponsored by the State of Illinois in order to increase the number of minority faculty and professional staff at Illinois institutions of higher education through graduate fellowships, networking and mentoring support. Nearly 850 fellowships have been awarded since 1986. A performance audit examined immediate (areas of graduate study, ethnicity of awards, intermediate (graduation areas and rates, and long-range results (academic job placement. The primary source for the audit was the database maintained by the programs' administrative office. These data were compared with data sets maintained by the Illinois Board of Higher Education and with national benchmarks (NSF and Ford Foundation Minority Graduate Fellowships. Findings revealed: (a the IMGIP and ICEOP programs led to major diversification of minority doctoral study in Illinois; (b a high percentage of all fellows graduated, both absolutely and in relation to national benchmarks, and fellows made up a large percentage of doctoral degrees awarded to minorities by Illinois institutions (e.g., 46% of doctorates in the hard sciences awarded to African Americans from 1988-1998; and (c fellows made up an important proportion of all minority faculty in Illinois (9%. Most ICEOP doctoral fellows and many other fellows have taken academic positions. The audit revealed outcomes-based evidence of a successful affirmative action program in higher education—evidence that is not otherwise available.

  13. Grails in action

    CERN Document Server

    Ledbrook, Peter

    2014-01-01

    Web apps shouldn't be hard to build, right? The developers of Grails agree. This hyper-productive open-source web framework offers "code by convention", leaving developers to focus on what makes their app special. Through its use of Groovy, it gives a powerful, Java-like language and full access to all Java libraries. Grails in Action is a comprehensive guide to the Grails framework. First, it covers the basics: the domain model, controllers, views, and services. Then, the fun! It dives into a Twitter-style app with features like AJAX/JSON, animation, search, wizards-even messaging and Jabber integration. It also offers loads of great plugins that'll make apps shine. RETAIL SELLING POINTS Fast track to super productivity Covers Grails 2.1 from the ground up Tons of tips and tricks from the trenches AUDIENCE No Java or Groovy background is required, but it is helpful for readers to have a background in web development and knowledge of an object-oriented language. ABOUT THE TECHNOLOGY Grails is an open source w...

  14. Less chalk more action

    Science.gov (United States)

    Mitriceski Andelkovic, Bojana; Jovic, Sladjana

    2016-04-01

    Less chalk more action Education should not be a mechanical system that operates according to the principles of the orders and implementation. Education should respect the basic laws of the develop and progress. Curiosity is the engine of achievement and children spontaneously and happily learn only if they get interested, if teacher wake up and stimulate their creativity and individuality. We would like to present classes that are realized as thematic teaching with several subjects involved: chemistry, geography, math, art and biology. Classes were organized for students at age from 10 to 13 years, every month during autumn and winter 2015. Better students identified themselves as teachers and presented peer education .Teachers were monitoring the process of teaching and help to develop links between younger and older students, where older students were educators to younger students. Also one student with special needs was involved in this activities and was supported by other students during the workshops The benefit from this project will be represented with evaluation marks. Evaluation table shows that group of ten students(age 10 to13 years) which are selected in October as children with lack of motivation for learning, got better marks, at the end of January , then they had it in the beginning of the semester.

  15. Nonclassical Vitamin D Actions

    Directory of Open Access Journals (Sweden)

    Armin Zittermann

    2010-03-01

    Full Text Available It is becoming increasingly clear that vitamin D has a broad range of actions in the human body. Besides its well-known effects on calcium/phosphate homeostasis, vitamin D influences muscle function, cardiovascular homeostasis, nervous function, and the immune response. Vitamin D deficiency/insufficiency has been associated with muscle weakness and a high incidence of various chronic diseases such as cardiovascular disease, cancer, multiple sclerosis, and type 1 and 2 diabetes. Most importantly, low vitamin D status has been found to be an independent predictor of all-cause mortality. Several recent randomized controlled trials support the assumption that vitamin D can improve muscle strength, glucose homeostasis, and cardiovascular risk markers. In addition, vitamin D may reduce cancer incidence and elevated blood pressure. Since the prevalence of vitamin D deficiency/insufficiency is high throughout the world, there is a need to improve vitamin D status in the general adult population. However, the currently recommended daily vitamin D intake of 5–15 µg is too low to achieve an adequate vitamin D status in individuals with only modest skin synthesis. Thus, there is a need to recommend a vitamin D intake that is effective for achieving adequate circulating 25-hydroxyvitamin D concentrations (>75 nmol/L.

  16. Action-Specific Effects Underwater

    OpenAIRE

    Witt, Jessica; Schuck, Donald M; Taylor, J. Eric T.

    2011-01-01

    Action-specific effects on perception are apparent in terrestrial environments. For example, targets that require more effort to walk, jump, or throw to look farther away than when the targets require less effort. Here, we examined whether action-specific effects would generalize to an underwater environment. Instead, perception might be geometrically precise, rather than action-specific, in an environment that is novel from an evolutionary perspective. We manipulated ease to swim by giving p...

  17. Evaluation of anthrax vaccine safety in 18 to 20 year olds: A first step towards age de-escalation studies in adolescents.

    Science.gov (United States)

    King, James C; Gao, Yonghong; Quinn, Conrad P; Dreier, Thomas M; Vianney, Cabrini; Espeland, Eric M

    2015-05-15

    Anthrax vaccine adsorbed (AVA, BioThrax(®)) is recommended for post-exposure prophylaxis administration for the US population in response to large-scale Bacillus anthracis spore exposure. However, no information exists on AVA use in children and ethical barriers exist to performing pre-event pediatric AVA studies. A Presidential Ethics Commission proposed a potential pathway for such studies utilizing an age de-escalation process comparing safety and immunogenicity data from 18 to 20 year-olds to older adults and if acceptable proceeding to evaluations in younger adolescents. We conducted exploratory summary re-analyses of existing databases from 18 to 20 year-olds (n=74) compared to adults aged 21 to 29 years (n=243) who participated in four previous US government funded AVA studies. Data extracted from studies included elicited local injection-site and systemic adverse events (AEs) following AVA doses given subcutaneously at 0, 2, and 4 weeks. Additionally, proportions of subjects with ≥4-fold antibody rises from baseline to post-second and post-third AVA doses (seroresponse) were obtained. Rates of any elicited local AEs were not significantly different between younger and older age groups for local events (79.2% vs. 83.8%, P=0.120) or systemic events (45.4% vs. 50.5%, P=0.188). Robust and similar proportions of seroresponses to vaccination were observed in both age groups. AVA was safe and immunogenic in 18 to 20 year-olds compared to 21 to 29 year-olds. These results provide initial information to anthrax and pediatric specialists if AVA studies in adolescents are required. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. A phase I dose-escalation study of the safety and pharmacokinetics of a tablet formulation of voxtalisib, a phosphoinositide 3-kinase inhibitor, in patients with solid tumors.

    Science.gov (United States)

    Mehnert, Janice M; Edelman, Gerald; Stein, Mark; Camisa, Heather; Lager, Joanne; Dedieu, Jean-François; Ghuysen, Anne-Frédérique; Sharma, Jyoti; Liu, Li; LoRusso, Patricia M

    2017-04-17

    Background Voxtalisib, a PI3K/mTOR inhibitor, has shown antitumor activity in capsule formulation in patients with solid tumors. This Phase I study assessed safety and pharmacokinetics of voxtalisib administered as immediate-release tablets in patients with solid tumors (NCT01596270). Methods A "3 + 3" dose escalation design was used. Adverse events (AEs), pharmacokinetics (PK), food effect and tumor response were evaluated. Results Thirty-two patients received voxtalisib doses ranging from 50 mg to 70 mg once daily (QD) and 17 patients received voxtalisib doses ranging from 30 mg to 50 mg twice daily (BID), for two 28-day cycles. Dose-limiting toxicities (DLTs) were Grade 3 fatigue (two patients at 70 mg QD, one patient at 40 mg BID) and Grade 3 rash (two patients at 50 mg BID). The maximum tolerated dose (MTD) was 60 mg for QD and 40 mg for BID regimens. Common treatment-emergent AEs were diarrhea (41%), nausea (37%) and fatigue (33%). Voxtalisib appeared to follow linear PK, with a general increase in plasma exposure with dose and no significant accumulation. Administration with food caused a slight decrease in exposure; however, given the high variability observed in the exposure parameters, this should be interpreted with caution. Best response was stable disease in 29% and 50% of patients (QD and BID regimens, respectively). Conclusions The safety profile of voxtalisib tablets at the MTD in patients with solid tumors was consistent with that observed with voxtalisib capsules. Given the limited activity observed across multiple clinical trials, no further trials of voxtalisib are planned.

  19. Combination of Trabectedin and Gemcitabine for Advanced Soft Tissue Sarcomas: Results of a Phase I Dose Escalating Trial of the German Interdisciplinary Sarcoma Group (GISG

    Directory of Open Access Journals (Sweden)

    Bernd Kasper

    2015-01-01

    Full Text Available Background: Evaluation of the potential efficacy and safety of combination therapies for advanced soft tissue sarcomas (STS has increased substantially after approval of trabectedin and pazopanib. Trabectedin's introduction in Europe in 2007 depended mainly on its activity in so-called L-sarcomas (liposarcoma and leiomyosarcoma; combination of trabectedin with other chemotherapies used in STS seems of particular interest. Methods: We initiated within the German Interdisciplinary Sarcoma Group (GISG a phase I dose escalating trial evaluating the combination of trabectedin and gemcitabine in patients with advanced and/or metastatic L-sarcomas (GISG-02; ClinicalTrials.gov NCT01426633. Patients were treated with increasing doses of trabectedin and gemcitabine. The primary endpoint was to determine the maximum tolerated dose. Results: Five patients were included in the study. Two patients were treated on dose level 1 comprising trabectedin 0.9 mg/m2 on day 1 and gemcitabine 700 mg/m2 on days 1 + 8, every 3 weeks. Due to dose-limiting toxicity (DLT in both patients (elevated transaminases and thrombocytopenia, an additional three patients were treated on dose level −1 with trabectedin 0.7 mg/m2 plus gemcitabine 700 mg/m2. Of these three patients, two demonstrated another DLT; therefore, the trial was stopped and none of the dose levels could be recommended for phase II testing. Conclusion: The GISG-02 phase I study was stopped with the conclusion that the combination of gemcitabine and trabectedin is generally not recommended for the treatment of patients with advanced and/or metastatic leiomyosarcoma or liposarcoma. Also, this phase I study strongly supports the necessity for careful evaluation of combination therapies.

  20. A phase 1 dose-escalation study of the oral histone deacetylase inhibitor abexinostat in combination with standard hypofractionated radiotherapy in advanced solid tumors

    Science.gov (United States)

    Deutsch, Eric; Moyal, Elizabeth Cohen-Jonathan; Gregorc, Vanesa; Zucali, Paolo Andrea; Menard, Jean; Soria, Jean-Charles; Kloos, Ioana; Hsu, Jeff; Luan, Ying; Liu, Emily; Vezan, Remus; Graef, Thorsten; Rivera, Sofia

    2017-01-01

    Current treatments for advanced solid tumors tend to be only palliative. Although radiotherapy is administered with a curative intent, radioresistance and dose-limiting toxicities pose limitations to treatment. Abexinostat, an oral pan-histone deacetylase inhibitor, demonstrated enhanced sensitivity to radiation in various solid tumor cell lines. We conducted an exploratory, phase 1, dose-escalation study of abexinostat in combination with standard hypofractionated radiotherapy in patients with advanced solid tumors treated in a palliative setting. Among 58 treated patients, the median age was 61.5 years (range, 20-82); 47% of the patients had M1 stage disease, and 95% had received previous chemotherapy alone or chemotherapy in combination with surgery and/or radiotherapy. The recommended phase 2 dose was determined to be 90 mg/m2 (140 mg). Of the 51 patients evaluable for response, best overall response was 8% (1 complete response [CR], 3 partial responses [PRs]), and best loco-regional response was 12% (1 CR and 5 PRs) at a median follow-up of 16 weeks. Of note, patients with target or non-target brain lesions showed encouraging responses, with 1 patient achieving a best loco-regional response of CR. Treatment-emergent grade ≥3 adverse events (AEs) were few, with most common being thrombocytopenia (17%), lymphopenia (12%), and hypokalemia (7%). Six patients (10%) discontinued treatment due to AEs. No grade ≥3 prolongation of the QTc interval was observed, with no treatment discontinuations due to this AE. Oral abexinostat combined with radiotherapy was well tolerated in patients with advanced solid tumors. The combination may have potential for treatment of patients with brain lesions. PMID:28915584