WorldWideScience

Sample records for events dose-response framework

  1. Alcohol and Immediate Risk of Cardiovascular Events: A Systematic Review and Dose-Response Meta-Analysis.

    Science.gov (United States)

    Mostofsky, Elizabeth; Chahal, Harpreet S; Mukamal, Kenneth J; Rimm, Eric B; Mittleman, Murray A

    2016-03-08

    Although considerable research describes the cardiovascular effects of habitual moderate and heavy alcohol consumption, the immediate risks following alcohol intake have not been well characterized. Based on its physiological effects, alcohol may have markedly different effects on immediate and long-term risk. We searched CINAHL, Embase, and PubMed from inception to March 12, 2015, supplemented with manual screening for observational studies assessing the association between alcohol intake and cardiovascular events in the following hours and days. We calculated pooled relative risks and 95% confidence intervals for the association between alcohol intake and myocardial infarction, ischemic stroke, and hemorrhagic stroke using DerSimonian and Laird random-effects models to model any alcohol intake or dose-response relationships of alcohol intake and cardiovascular events. Among 1056 citations and 37 full-text articles reviewed, 23 studies (29 457 participants) were included. Moderate alcohol consumption was associated with an immediately higher cardiovascular risk that was attenuated after 24 hours, and even protective for myocardial infarction and hemorrhagic stroke (≈2-4 drinks: relative risk=30% lower risk) and protective against ischemic stroke within 1 week (≈6 drinks: 19% lower risk). In contrast, heavy alcohol drinking was associated with higher cardiovascular risk in the following day (≈6-9 drinks: relative risk=1.3-2.3) and week (≈19-30 drinks: relative risk=2.25-6.2). There appears to be a consistent finding of an immediately higher cardiovascular risk following any alcohol consumption, but, by 24 hours, only heavy alcohol intake conferred continued risk. © 2016 American Heart Association, Inc.

  2. Repetitive TASER X26 discharge resulted in adverse physiologic events with a dose-response relationship related to the duration of discharge in anesthetized swine model.

    Science.gov (United States)

    Park, Eun-Jung; Choi, Sang-Cheon; Ahn, Jung-Hwan; Min, Young-Gi

    2013-01-01

    The objectives of our study were to investigate the dose-response relationship of the TASER X26 discharge duration in an anesthetized swine model. Fourteen swines were anesthetized and then exposed to TASER X26 discharge for 5 sec (n = 5) or for 10 sec (n = 6). The sham control group (n = 3) was anesthetized and studied using the same protocol except TASER X26 discharges during the experiments. Hemodynamic parameters were obtained. Blood pressure and total peripheral resistance decreased significantly after TASER discharge and returned to baseline value at 15 min after 5 sec of TASER discharge but did not return to baseline values during the 30-min observation period after 10 sec of TASER discharge. Repetitive TASER X26 discharge resulted in adverse physiologic events with a dose-response relationship related to the duration of TASER X26 discharge in an anesthetized swine model. © 2012 American Academy of Forensic Sciences.

  3. Dose-response modeling of early molecular and cellular key events in the CAR-mediated hepatocarcinogenesis pathway.

    Science.gov (United States)

    Geter, David R; Bhat, Virunya S; Gollapudi, B Bhaskar; Sura, Radhakrishna; Hester, Susan D

    2014-04-01

    Low-dose extrapolation and dose-related transitions are paramount in the ongoing debate regarding the quantification of cancer risks for nongenotoxic carcinogens. Phenobarbital (PB) is a prototypical nongenotoxic carcinogen that activates the constitutive androstane receptor (CAR) resulting in rodent liver tumors. In this study, male and female CD-1 mice administered dietary PB at 0, 0.15, 1.5, 15, 75, or 150 mg/kg-day for 2 or 7 days to characterize multiple apical and molecular endpoints below, at (∼75 mg/kg-day), and above the carcinogenic dose level of PB and examine these responses using benchmark dose modeling. Linear toxicokinetics were observed for all doses. Increased liver weight, hepatocellular hypertrophy, and mitotic figures were seen at 75 and 150 mg/kg-day. CAR activation, based on Cyp2b qPCR and pentoxyresorufin dealkylase activity, occurred at doses ≥ 1.5 mg/kg-day. The no-observable transcriptional effect level for global gene expression was 15 mg/kg-day. At 2 days, several xenobiotic metabolism and cell protective pathways were activated at lower doses and to a greater degree in females. However, hepatocellular proliferation, quantified by bromodeoxyuridine immunohistochemistry, was the most sensitive indicator of PB exposure with female mice more sensitive than males, contrary to sex-specific differences in sensitivity to hepatocarcinogenesis. Taken together, the identification of low-dose cellular and molecular transitions in the subtumorigenic dose range aids the understanding of early key events in CAR-mediated hepatocarcinogenesis.

  4. A general framework for statistical inference on discrete event systems.

    NARCIS (Netherlands)

    R.P. Nicolai (Robin); A.J. Koning (Alex)

    2006-01-01

    textabstractWe present a framework for statistical analysis of discrete event systems which combines tools such as simulation of marked point processes, likelihood methods, kernel density estimation and stochastic approximation to enable statistical analysis of the discrete event system, even if

  5. Biological Extreme Events: A Research Framework

    Science.gov (United States)

    Gutschick, Vincent P.; BassiriRad, Hormoz

    2010-03-01

    Efforts designed to understand and predict adaptation responses of organisms and populations to global climate change must make a clear distinction between responses to changes in average conditions (e.g., doubling of atmospheric carbon dioxide concentration accompanied by an average increase of 1°-3°C in global air temperature by the end of this century) and responses resulting from increased incidence of extreme events [Loehle and LeBlanc, 1996; Easterling et al., 2000; Garrett et al., 2006]. Such distinction is critical because, unlike changes in average conditions, extremes (e.g., megadroughts, fire, flooding, hurricanes, heat waves, and pest outbreaks) are typically short in duration but challenge organisms and populations considerably further beyond their ability to acclimate than those expected from average trends in climate changes. There is growing evidence that climatic extremes have been rising in frequency or magnitude during the last part of the twentieth century and will continue to increase during the remainder of this century [Easterling et al., 2000; Meehl et al., 2000; Parmesan and Yohe, 2003; Barnett et al., 2006]. More important, the frequency of extremes is likely to increase even if the climatic means do not change substantially [Intergovernmental Panel on Climate Change (IPCC), 2001, chapter 10]. Therefore, it makes sense to pay special attention to extremes as major agents of biological adaption (genetic change) when considering global climate change.

  6. EventView - The Design Behind an Analysis Framework

    CERN Document Server

    Cranmer, K; Shibata, A

    2007-01-01

    The development of software used to process petabytes of data per year is an elaborate project. The complexity of the detector means components of very diverse nature are required to process the data and one needs well defined frameworks that are both flexible and maintainable. Modern programming architecture based on object-oriented component design supports desirable features of such frameworks. The principle has been applied in almost all sub-systems of ATLAS software and its robustness has benefited the collaboration. An implementation of such framework for physics analysis, however, did not exist before the work presented in this paper. As it turns out the realisation of object-oriented analysis framework is closely related to the design of the event data object. In this paper, we well review the design behind the analysis framework developed around a data class called ``EventView''. It is a highly integrated part of the ATLAS software framework and is now becoming a standard platform for physics analysi...

  7. A statistical framework for conditional extreme event attribution

    Science.gov (United States)

    Yiou, Pascal; Jézéquel, Aglaé; Naveau, Philippe; Otto, Frederike E. L.; Vautard, Robert; Vrac, Mathieu

    2017-04-01

    The goal of the attribution of individual events is to estimate whether and to what extent the probability of an extreme climate event evolves when external conditions (e.g., due to anthropogenic forcings) change. Many types of climate extremes are linked to the variability of the large-scale atmospheric circulation. It is hence essential to decipher the roles of atmospheric variability and increasing mean temperature in the change of probabilities of extremes. It is also crucial to define a background state (or counterfactual) to which recent observations are compared. In this paper we present a statistical framework to determine the dynamical (linked to the atmospheric circulation) and thermodynamical (linked to slow forcings) contributions to the probability of extreme climate events. We illustrate this methodology on a record precipitation event that hit southern United Kingdom in January 2014. We compare possibilities for the creation of two states (or worlds) in which probability change is determined. These two worlds are defined in a large ensemble of atmospheric model simulations (Weather@Home factual and counterfactual simulations) and separate periods (new: 1951-2014, and old: 1900-1950) in reanalyses and observations. We discuss how the atmospheric circulation conditioning can affect the interpretation of extreme event attribution. We eventually show the qualitative coherence of results between the choice of worlds (factual/counterfactual vs. new/old).

  8. Dose-response analysis using R

    DEFF Research Database (Denmark)

    Ritz, Christian; Baty, Florent; Streibig, Jens Carl

    2015-01-01

    Dose-response analysis can be carried out using multi-purpose commercial statistical software, but except for a few special cases the analysis easily becomes cumbersome as relevant, non-standard output requires manual programming. The extension package drc for the statistical environment R provides...

  9. Dose-response-a challenge for allelopathy?

    Science.gov (United States)

    Belz, Regina G; Hurle, Karl; Duke, Stephen O

    2005-04-01

    The response of an organism to a chemical depends, among other things, on the dose. Nonlinear dose-response relationships occur across a broad range of research fields, and are a well established tool to describe the basic mechanisms of phytotoxicity. The responses of plants to allelochemicals as biosynthesized phytotoxins, relate as well to nonlinearity and, thus, allelopathic effects can be adequately quantified by nonlinear mathematical modeling. The current paper applies the concept of nonlinearity to assorted aspects of allelopathy within several bioassays and reveals their analysis by nonlinear regression models. Procedures for a valid comparison of effective doses between different allelopathic interactions are presented for both, inhibitory and stimulatory effects. The dose-response applications measure and compare the responses produced by pure allelochemicals [scopoletin (7-hydroxy-6-methoxy-2H-1-benzopyran-2-one); DIBOA (2,4-dihydroxy-2H-1,4-benzoxaxin-3(4H)-one); BOA (benzoxazolin-2(3H)-one); MBOA (6-methoxy-benzoxazolin-2(3H)-one)], involved in allelopathy of grain crops, to demonstrate how some general principles of dose responses also relate to allelopathy. Hereupon, dose-response applications with living donor plants demonstrate the validity of these principles for density-dependent phytotoxicity of allelochemicals produced and released by living plants (Avena sativa L., Secale cereale L., Triticum L. spp.), and reveal the use of such experiments for initial considerations about basic principles of allelopathy. Results confirm that nonlinearity applies to allelopathy, and the study of allelopathic effects in dose-response experiments allows for new and challenging insights into allelopathic interactions.

  10. Bayesian penalized log-likelihood ratio approach for dose response clinical trial studies.

    Science.gov (United States)

    Tang, Yuanyuan; Cai, Chunyan; Sun, Liangrui; He, Jianghua

    2017-02-13

    In literature, there are a few unified approaches to test proof of concept and estimate a target dose, including the multiple comparison procedure using modeling approach, and the permutation approach proposed by Klingenberg. We discuss and compare the operating characteristics of these unified approaches and further develop an alternative approach in a Bayesian framework based on the posterior distribution of a penalized log-likelihood ratio test statistic. Our Bayesian approach is much more flexible to handle linear or nonlinear dose-response relationships and is more efficient than the permutation approach. The operating characteristics of our Bayesian approach are comparable to and sometimes better than both approaches in a wide range of dose-response relationships. It yields credible intervals as well as predictive distribution for the response rate at a specific dose level for the target dose estimation. Our Bayesian approach can be easily extended to continuous, categorical, and time-to-event responses. We illustrate the performance of our proposed method with extensive simulations and Phase II clinical trial data examples.

  11. The Event Coordination Notation: Execution Engine and Programming Framework

    DEFF Research Database (Denmark)

    Kindler, Ekkart

    2012-01-01

    that was written manually. In this paper, we rephrase the main concepts of ECNO. The focus of this paper, however, is on the architecture of the ECNO execution engine and its programming framework. We will show how this framework allows us to integrate ECNO with object-oriented models, how it works without any...

  12. Unified Behavior Framework for Discrete Event Simulation Systems

    Science.gov (United States)

    2015-03-26

    Layered Behaviors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 2.3 UML Diagram for the UBF...Framework UML Unified Modeling Language VESPA Visual Environment for Scenario Preparation and Analysis x UNIFIED BEHAVIOR FRAMEWORK FOR DISCRETE...Unified Modeling Language ( UML ) is also assumed, specifically in regards to UML notation as discussion of the UBF includes its depiction through a UML

  13. Lurasidone Dose Response in Bipolar Depression: A Population Dose-response Analysis.

    Science.gov (United States)

    Chapel, Sunny; Chiu, Yu-Yuan; Hsu, Jay; Cucchiaro, Josephine; Loebel, Antony

    2016-01-01

    Characterization of dose-response relationships for psychotropic agents may be difficult to determine based on results of individual clinical studies, particularly those with a flexible dose design. The goal of this pharmacometric analysis was to characterize the dose-response profile for lurasidone in patients with bipolar depression. The statistical modeling and simulation analyses reported here were derived from 2 randomized, 6-week, double-blind, placebo-controlled, flexible-dose studies (20-60 mg/d or 80-120 mg/d of lurasidone as monotherapy or 20-120 mg/d adjunct to lithium or valproate) in patients with bipolar depression. Pooled data included 5245 Montgomery-Åsberg Depression Rating Scale (MADRS) observations from 825 patients who had received lurasidone or placebo treatments, with or without lithium or valproate background medication. The time course of placebo effect on the MADRS score was adequately described by an exponential asymptotic placebo model. A linear dose-response model best described the effect of lurasidone. The net improvement in MADRS score due to lurasidone treatment (the drug effect) was significant (P related to demographic covariates. This population dose-response modeling analysis indicates that higher doses of lurasidone are likely to produce greater therapeutic effects in patients with bipolar depression. The linear dose response was consistent for both lurasidone monotherapy and adjunctive therapy in patients with bipolar depression. ClinicalTrials.gov identifiers: NCT00868452, NCT00868699. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Dose response relationship in anti-stress gene regulatory networks.

    Directory of Open Access Journals (Sweden)

    Qiang Zhang

    2007-03-01

    Full Text Available To maintain a stable intracellular environment, cells utilize complex and specialized defense systems against a variety of external perturbations, such as electrophilic stress, heat shock, and hypoxia, etc. Irrespective of the type of stress, many adaptive mechanisms contributing to cellular homeostasis appear to operate through gene regulatory networks that are organized into negative feedback loops. In general, the degree of deviation of the controlled variables, such as electrophiles, misfolded proteins, and O2, is first detected by specialized sensor molecules, then the signal is transduced to specific transcription factors. Transcription factors can regulate the expression of a suite of anti-stress genes, many of which encode enzymes functioning to counteract the perturbed variables. The objective of this study was to explore, using control theory and computational approaches, the theoretical basis that underlies the steady-state dose response relationship between cellular stressors and intracellular biochemical species (controlled variables, transcription factors, and gene products in these gene regulatory networks. Our work indicated that the shape of dose response curves (linear, superlinear, or sublinear depends on changes in the specific values of local response coefficients (gains distributed in the feedback loop. Multimerization of anti-stress enzymes and transcription factors into homodimers, homotrimers, or even higher-order multimers, play a significant role in maintaining robust homeostasis. Moreover, our simulation noted that dose response curves for the controlled variables can transition sequentially through four distinct phases as stressor level increases: initial superlinear with lesser control, superlinear more highly controlled, linear uncontrolled, and sublinear catastrophic. Each phase relies on specific gain-changing events that come into play as stressor level increases. The low-dose region is intrinsically nonlinear

  15. A Framework for Event Prioritization in Cyber Network Defense

    Science.gov (United States)

    2014-07-15

    value for highly connected networks can become artificially inflated and convergent in a way that does not make sense. The connectivity component...scanning results from SCCVI/ RETINA • Event data from a Security Information and Event Management (SIEM) tool such as NetIQ Sentinel (aggregated from...and host connection values. This is not only useful in real-time mode when cyber warriors may want to artificially raise the value of specific hosts

  16. Modeling and Analysis of Real-Time Database Systems in the Framework of Discrete Event Systems

    National Research Council Canada - National Science Library

    Ghosh, Anunoy

    1994-01-01

    .... Such database systems are called Real-Time Database Systems (RTDBS). The problem of concurrency control and scheduling of transactions in real time database systems is studied in the framework of discrete event dynamical systems (DEDS...

  17. The Event Chain of Survival in the Context of Music Festivals: A Framework for Improving Outcomes at Major Planned Events.

    Science.gov (United States)

    Lund, Adam; Turris, Sheila

    2017-08-01

    Despite the best efforts of event producers and on-site medical teams, there are sometimes serious illnesses, life-threatening injuries, and fatalities related to music festival attendance. Producers, clinicians, and researchers are actively seeking ways to reduce the mortality and morbidity associated with these events. After analyzing the available literature on music festival health and safety, several major themes emerged. Principally, stakeholder groups planning in isolation from one another (ie, in silos) create fragmentation, gaps, and overlap in plans for major planned events (MPEs). The authors hypothesized that one approach to minimizing this fragmentation may be to create a framework to "connect the dots," or join together the many silos of professionals responsible for safety, security, health, and emergency planning at MPEs. Adapted from the well-established literature regarding the management of cardiac arrests, both in and out of hospital, the "chain of survival" concept is applied to the disparate groups providing services that support event safety in the context of music festivals. The authors propose this framework for describing, understanding, coordinating and planning around the integration of safety, security, health, and emergency service for events. The adapted Event Chain of Survival contains six interdependent links, including: (1) event producers; (2) police and security; (3) festival health; (4) on-site medical services; (5) ambulance services; and (6) off-site medical services. The authors argue that adapting and applying this framework in the context of MPEs in general, and music festivals specifically, has the potential to break down the current disconnected approach to event safety, security, health, and emergency planning. It offers a means of shifting the focus from a purely reactive stance to a more proactive, collaborative, and integrated approach. Improving health outcomes for music festival attendees, reducing gaps in planning

  18. A Branch-and-Bound Framework for Unsupervised Common Event Discovery.

    Science.gov (United States)

    Chu, Wen-Sheng; De la Torre, Fernando; Cohn, Jeffrey F; Messinger, Daniel S

    2017-07-01

    Event discovery aims to discover a temporal segment of interest, such as human behavior, actions or activities. Most approaches to event discovery within or between time series use supervised learning. This becomes problematic when some relevant event labels are unknown, are difficult to detect, or not all possible combinations of events have been anticipated. To overcome these problems, this paper explores Common Event Discovery (CED), a new problem that aims to discover common events of variable-length segments in an unsupervised manner. A potential solution to CED is searching over all possible pairs of segments, which would incur a prohibitive quartic cost. In this paper, we propose an efficient branch-and-bound (B&B) framework that avoids exhaustive search while guaranteeing a globally optimal solution. To this end, we derive novel bounding functions for various commonality measures and provide extensions to multiple commonality discovery and accelerated search. The B&B framework takes as input any multidimensional signal that can be quantified into histograms. A generalization of the framework can be readily applied to discover events at the same or different times (synchrony and event commonality, respectively). We consider extensions to video search and supervised event detection. The effectiveness of the B&B framework is evaluated in motion capture of deliberate behavior and in video of spontaneous facial behavior in diverse interpersonal contexts: interviews, small groups of young adults, and parent-infant face-to-face interaction.

  19. A novel probabilistic framework for event-based speech recognition

    Science.gov (United States)

    Juneja, Amit; Espy-Wilson, Carol

    2003-10-01

    One of the reasons for unsatisfactory performance of the state-of-the-art automatic speech recognition (ASR) systems is the inferior acoustic modeling of low-level acoustic-phonetic information in the speech signal. An acoustic-phonetic approach to ASR, on the other hand, explicitly targets linguistic information in the speech signal, but such a system for continuous speech recognition (CSR) is not known to exist. A probabilistic and statistical framework for CSR based on the idea of the representation of speech sounds by bundles of binary valued articulatory phonetic features is proposed. Multiple probabilistic sequences of linguistically motivated landmarks are obtained using binary classifiers of manner phonetic features-syllabic, sonorant and continuant-and the knowledge-based acoustic parameters (APs) that are acoustic correlates of those features. The landmarks are then used for the extraction of knowledge-based APs for source and place phonetic features and their binary classification. Probabilistic landmark sequences are constrained using manner class language models for isolated or connected word recognition. The proposed method could overcome the disadvantages encountered by the early acoustic-phonetic knowledge-based systems that led the ASR community to switch to systems highly dependent on statistical pattern analysis methods and probabilistic language or grammar models.

  20. Grid-Brick Event Processing Framework in GEPS

    CERN Document Server

    Amorim, A; Fei, H; Almeida, N; Trezentos, P; Villate, J E; Amorim, Antonio; Pedro, Luis; Fei, Han; Almeida, Nuno; Trezentos, Paulo; Villate, Jaime E.

    2003-01-01

    Experiments like ATLAS at LHC involve a scale of computing and data management that greatly exceeds the capability of existing systems, making it necessary to resort to Grid-based Parallel Event Processing Systems (GEPS). Traditional Grid systems concentrate the data in central data servers which have to be accessed by many nodes each time an analysis or processing job starts. These systems require very powerful central data servers and make little use of the distributed disk space that is available in commodity computers. The Grid-Brick system, which is described in this paper, follows a different approach. The data storage is split among all grid nodes having each one a piece of the whole information. Users submit queries and the system will distribute the tasks through all the nodes and retrieve the result, merging them together in the Job Submit Server. The main advantage of using this system is the huge scalability it provides, while its biggest disadvantage appears in the case of failure of one of the n...

  1. The flood event explorer - a web based framework for rapid flood event analysis

    Science.gov (United States)

    Schröter, Kai; Lüdtke, Stefan; Kreibich, Heidi; Merz, Bruno

    2015-04-01

    Flood disaster management, recovery and reconstruction planning benefit from rapid evaluations of flood events and expected impacts. The near real time in-depth analysis of flood causes and key drivers for flood impacts requires a close monitoring and documentation of hydro-meteorological and socio-economic factors. Within the CEDIM's Rapid Flood Event Analysis project a flood event analysis system is developed which enables the near real-time evaluation of large scale floods in Germany. The analysis system includes functionalities to compile event related hydro-meteorological data, to evaluate the current flood situation, to assess hazard intensity and to estimate flood damage to residential buildings. A German flood event database is under development, which contains various hydro-meteorological information - in the future also impact information -for all large-scale floods since 1950. This data base comprises data on historic flood events which allow the classification of ongoing floods in terms of triggering processes and pre-conditions, critical controls and drivers for flood losses. The flood event analysis system has been implemented in a database system which automatically retrieves and stores data from more than 100 online discharge gauges on a daily basis. The current discharge observations are evaluated in a long term context in terms of flood frequency analysis. The web-based frontend visualizes the current flood situation in comparison to any past flood from the flood catalogue. The regional flood data base for Germany contains hydro-meteorological data and aggregated severity indices for a set of 76 historic large-scale flood events in Germany. This data base has been used to evaluate the key drivers for the flood in June 2013.

  2. Analysis of Transcriptomic Dose Response Data in the ...

    Science.gov (United States)

    Slide presentation at the HESI-HEALTH Canada-McGill Workshop on Transcriptomic Dose Response Data in the Context of Chemical Risk Assessment Slide presentation at the HESI-HEALTH Canada-McGill Workshop on Transcriptomic Dose Response Data in the Context of Chemical Risk Assessment

  3. A framework for synthesis of communicating decentralised supervisors for discrete-event systems

    Science.gov (United States)

    Mannani, Amin; Gohari, Peyman

    2014-05-01

    We propose a framework to study communication among decentralised supervisors for a (distributed) discrete-event system (DES), where system specifications lack co-observability. Using agent-wise labeling maps (ALMs), the framework explores the observation and control structures of an already designed centralised supervisor in a distributed manner, and represent them as polynomial equations over a finite field. Communication is naturally required to re-evaluate the equations, which depend on distributed information, correctly, and is formalised and implemented using communication events. The framework generalises the authors' previous work on extended finite-state machines (EFSMs) by formalising system representation and communication events, proving the correctness of proposed communication policies, and algorithmic simplification of polynomial equations. This provides a systematic procedure for the synthesis of decentralised supervisors and formalisation, computation and implementation of the communication.

  4. A semi-supervised learning framework for biomedical event extraction based on hidden topics.

    Science.gov (United States)

    Zhou, Deyu; Zhong, Dayou

    2015-05-01

    Scientists have devoted decades of efforts to understanding the interaction between proteins or RNA production. The information might empower the current knowledge on drug reactions or the development of certain diseases. Nevertheless, due to the lack of explicit structure, literature in life science, one of the most important sources of this information, prevents computer-based systems from accessing. Therefore, biomedical event extraction, automatically acquiring knowledge of molecular events in research articles, has attracted community-wide efforts recently. Most approaches are based on statistical models, requiring large-scale annotated corpora to precisely estimate models' parameters. However, it is usually difficult to obtain in practice. Therefore, employing un-annotated data based on semi-supervised learning for biomedical event extraction is a feasible solution and attracts more interests. In this paper, a semi-supervised learning framework based on hidden topics for biomedical event extraction is presented. In this framework, sentences in the un-annotated corpus are elaborately and automatically assigned with event annotations based on their distances to these sentences in the annotated corpus. More specifically, not only the structures of the sentences, but also the hidden topics embedded in the sentences are used for describing the distance. The sentences and newly assigned event annotations, together with the annotated corpus, are employed for training. Experiments were conducted on the multi-level event extraction corpus, a golden standard corpus. Experimental results show that more than 2.2% improvement on F-score on biomedical event extraction is achieved by the proposed framework when compared to the state-of-the-art approach. The results suggest that by incorporating un-annotated data, the proposed framework indeed improves the performance of the state-of-the-art event extraction system and the similarity between sentences might be precisely

  5. Climate Change Risks – Methodological Framework and Case Study of Damages from Extreme Events in Cambodia

    DEFF Research Database (Denmark)

    Halsnæs, Kirsten; Kaspersen, Per Skougaard; Trærup, Sara Lærke Meltofte

    2016-01-01

    Climate change imposes some special risks on Least Developed Countries, and the chapter presents a methodological framework, which can be used to assess the impacts of key assumptions related to damage costs, risks and equity implications on current and future generations. The methodological...... framework is applied to a case study of severe storms in Cambodia based on statistical information on past storm events including information about buildings damaged and victims. Despite there is limited data available on the probability of severe storm events under climate change as well on the actual...... damage costs associated with the events in the case of Cambodia, we are using the past storm events as proxy data in a sensitivity analysis. It is here demonstrated how key assumptions on future climate change, income levels of victims, and income distribution over time, reflected in discount rates...

  6. Accelerated Simulation of Discrete Event Dynamic Systems via a Multi-Fidelity Modeling Framework

    Directory of Open Access Journals (Sweden)

    Seon Han Choi

    2017-10-01

    Full Text Available Simulation analysis has been performed for simulation experiments of all possible input combinations as a “what-if” analysis, which causes the simulation to be extremely time-consuming. To resolve this problem, this paper proposes a multi-fidelity modeling framework for enhancing simulation speed while minimizing simulation accuracy loss. A target system for this framework is a discrete event dynamic system. The dynamic property of the system facilitates the development of variable fidelity models for the target system due to its high computational cost; and the discrete event property allows for determining when to change the fidelity within a simulation scenario. For formal representation, the paper defines several key concepts such as an interest region, a fidelity change condition, and a selection model. These concepts are integrated into the framework to allow for the achievement of a condition-based disjunction of high- and low-fidelity simulations within a scenario. The proposed framework is applied to two case studies: unmanned underwater and urban transportation vehicles. The results show that simulation speed increases at least 1.21 times with a 5% accuracy loss. We expect that the proposed framework will resolve a computationally expensive problem in the simulation analysis of discrete event dynamic systems.

  7. Establishing a Numerical Modeling Framework for Hydrologic Engineering Analyses of Extreme Storm Events

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Xiaodong; Hossain, Faisal; Leung, L. Ruby

    2017-08-01

    In this study a numerical modeling framework for simulating extreme storm events was established using the Weather Research and Forecasting (WRF) model. Such a framework is necessary for the derivation of engineering parameters such as probable maximum precipitation that are the cornerstone of large water management infrastructure design. Here this framework was built based on a heavy storm that occurred in Nashville (USA) in 2010, and verified using two other extreme storms. To achieve the optimal setup, several combinations of model resolutions, initial/boundary conditions (IC/BC), cloud microphysics and cumulus parameterization schemes were evaluated using multiple metrics of precipitation characteristics. The evaluation suggests that WRF is most sensitive to IC/BC option. Simulation generally benefits from finer resolutions up to 5 km. At the 15km level, NCEP2 IC/BC produces better results, while NAM IC/BC performs best at the 5km level. Recommended model configuration from this study is: NAM or NCEP2 IC/BC (depending on data availability), 15km or 15km-5km nested grids, Morrison microphysics and Kain-Fritsch cumulus schemes. Validation of the optimal framework suggests that these options are good starting choices for modeling extreme events similar to the test cases. This optimal framework is proposed in response to emerging engineering demands of extreme storm events forecasting and analyses for design, operations and risk assessment of large water infrastructures.

  8. Meta-analysis framework for exact inferences with application to the analysis of rare events.

    Science.gov (United States)

    Yang, Guang; Liu, Dungang; Wang, Junyuan; Xie, Min-Ge

    2016-12-01

    The usefulness of meta-analysis has been recognized in the evaluation of drug safety, as a single trial usually yields few adverse events and offers limited information. For rare events, conventional meta-analysis methods may yield an invalid inference, as they often rely on large sample theories and require empirical corrections for zero events. These problems motivate research in developing exact methods, including Tian et al.'s method of combining confidence intervals (2009, Biostatistics, 10, 275-281) and Liu et al.'s method of combining p-value functions (2014, JASA, 109, 1450-1465). This article shows that these two exact methods can be unified under the framework of combining confidence distributions (CDs). Furthermore, we show that the CD method generalizes Tian et al.'s method in several aspects. Given that the CD framework also subsumes the Mantel-Haenszel and Peto methods, we conclude that the CD method offers a general framework for meta-analysis of rare events. We illustrate the CD framework using two real data sets collected for the safety analysis of diabetes drugs. © 2016, The International Biometric Society.

  9. Characterization of a developmental toxicity dose-response model

    Energy Technology Data Exchange (ETDEWEB)

    Faustman, E.M.; Wellington, D.G.; Smith, W.P.; Kimmel, C.A.

    1989-02-01

    The Rai and Van Ryzin dose-response model proposed for teratology experiments has been characterized for its appropriateness and applicability in modeling the dichotomous response data from developmental toxicity studies. Modifications were made in the initial probability statements to reflect more accurately biological events underlying developmental toxicity. Data sets used for the evaluation were obtained from the National Toxicology Program and U.S. EPA laboratories. The studies included developmental evaluations of ethylene glycol, diethylhexyl phthalate, di- and triethylene glycol dimethyl ethers, and nitrofen in rats, mice, or rabbits. Graphic examination and statistical evaluation demonstrate that this model is sensitive to the data when compared to directly measured experimental outcomes. The model was used to interpolate to low-risk dose levels, and comparisons were made between the values obtained and the no-observed-adverse-effect levels (NOAELs) divided by an uncertainty factor. Our investigation suggests that the Rai and Van Ryzin model is sensitive to the developmental toxicity end points, prenatal deaths, and malformations, and appears to model closely their relationship to dose.

  10. Assembled cross-species perchlorate dose-response data

    Data.gov (United States)

    U.S. Environmental Protection Agency — This data set contains dose-response data for perchlorate exposure in multiple species. These data were assembled from peer-reviewed studies. Species included in...

  11. A conceptual modeling framework for discrete event simulation using hierarchical control structures.

    Science.gov (United States)

    Furian, N; O'Sullivan, M; Walker, C; Vössner, S; Neubacher, D

    2015-08-01

    Conceptual Modeling (CM) is a fundamental step in a simulation project. Nevertheless, it is only recently that structured approaches towards the definition and formulation of conceptual models have gained importance in the Discrete Event Simulation (DES) community. As a consequence, frameworks and guidelines for applying CM to DES have emerged and discussion of CM for DES is increasing. However, both the organization of model-components and the identification of behavior and system control from standard CM approaches have shortcomings that limit CM's applicability to DES. Therefore, we discuss the different aspects of previous CM frameworks and identify their limitations. Further, we present the Hierarchical Control Conceptual Modeling framework that pays more attention to the identification of a models' system behavior, control policies and dispatching routines and their structured representation within a conceptual model. The framework guides the user step-by-step through the modeling process and is illustrated by a worked example.

  12. Observational-Interventional Priors for Dose-Response Learning

    OpenAIRE

    Silva, R.

    2016-01-01

    Controlled interventions provide the most direct source of information for learning causal effects. In particular, a dose-response curve can be learned by varying the treatment level and observing the corresponding outcomes. However, interventions can be expensive and time-consuming. Observational data, where the treatment is not controlled by a known mechanism, is sometimes available. Under some strong assumptions, observational data allows for the estimation of dose-response curves. Estimat...

  13. NEVESIM: event-driven neural simulation framework with a Python interface.

    Science.gov (United States)

    Pecevski, Dejan; Kappel, David; Jonke, Zeno

    2014-01-01

    NEVESIM is a software package for event-driven simulation of networks of spiking neurons with a fast simulation core in C++, and a scripting user interface in the Python programming language. It supports simulation of heterogeneous networks with different types of neurons and synapses, and can be easily extended by the user with new neuron and synapse types. To enable heterogeneous networks and extensibility, NEVESIM is designed to decouple the simulation logic of communicating events (spikes) between the neurons at a network level from the implementation of the internal dynamics of individual neurons. In this paper we will present the simulation framework of NEVESIM, its concepts and features, as well as some aspects of the object-oriented design approaches and simulation strategies that were utilized to efficiently implement the concepts and functionalities of the framework. We will also give an overview of the Python user interface, its basic commands and constructs, and also discuss the benefits of integrating NEVESIM with Python. One of the valuable capabilities of the simulator is to simulate exactly and efficiently networks of stochastic spiking neurons from the recently developed theoretical framework of neural sampling. This functionality was implemented as an extension on top of the basic NEVESIM framework. Altogether, the intended purpose of the NEVESIM framework is to provide a basis for further extensions that support simulation of various neural network models incorporating different neuron and synapse types that can potentially also use different simulation strategies.

  14. NEVESIM: Event-Driven Neural Simulation Framework with a Python Interface

    Directory of Open Access Journals (Sweden)

    Dejan ePecevski

    2014-08-01

    Full Text Available NEVESIM is a software package for event-driven simulation of networks of spiking neurons with a fast simulation core in C++, and a scripting user interface in the Python programming language. It supports simulation of heterogeneous networks with different types of neurons and synapses, and can be easily extended by the user with new neuron and synapse types. To enable heterogeneous networks and extensibility, NEVESIM is designed to decouple the simulation logic of communicating events (spikes between the neurons at a network level from the implementation of the internal dynamics of individual neurons. In this paper we will present the simulation framework of NEVESIM, its concepts and features, as well as some aspects of the object-oriented design approaches and simulation strategies that were utilized to efficiently implement the concepts and functionalities of the framework. We will also give an overview of the Python user interface, its basic commands and constructs, and also discuss the benefits of integrating NEVESIM with Python. One of the valuable capabilities of the simulator is to simulate exactly and efficiently networks of stochastic spiking neurons from the recently developed theoretical framework of neural sampling. This functionality was implemented as an extension on top of the basic NEVESIM framework. Altogether, the intended purpose of the NEVESIM framework is to provide a basis for further extensions that support simulation of various neural network models incorporating different neuron and synapse types that can potentially also use different simulation strategies.

  15. A strategic framework for responding to coral bleaching events in a changing climate.

    Science.gov (United States)

    Maynard, J A; Johnson, J E; Marshall, P A; Eakin, C M; Goby, G; Schuttenberg, H; Spillman, C M

    2009-07-01

    The frequency and severity of mass coral bleaching events are predicted to increase as sea temperatures continue to warm under a global regime of rising ocean temperatures. Bleaching events can be disastrous for coral reef ecosystems and, given the number of other stressors to reefs that result from human activities, there is widespread concern about their future. This article provides a strategic framework from the Great Barrier Reef to prepare for and respond to mass bleaching events. The framework presented has two main inter-related components: an early warning system and assessment and monitoring. Both include the need to proactively and consistently communicate information on environmental conditions and the level of bleaching severity to senior decision-makers, stakeholders, and the public. Managers, being the most timely and credible source of information on bleaching events, can facilitate the implementation of strategies that can give reefs the best chance to recover from bleaching and to withstand future disturbances. The proposed framework is readily transferable to other coral reef regions, and can easily be adapted by managers to local financial, technical, and human resources.

  16. An adaptation framework for turning Real-Life Events into Games

    DEFF Research Database (Denmark)

    Kjærhus Therkildsen, Sacha; Cassøe Bunkenborg, Nanna; Larsen, Lasse Juel

    Many games are intended to change the players’ minds or actions. The presented design framework for persuasive board games is derived from the Syrian refugee crisis, which is used as backdrop to communicate the experience of being a refugee traveling through Europe. We applied an agile development...... method and participatory design to achieve our ambition. In conclusion we found that a framework for persuasive board games can be advanced by balancing five interrelated layers: 1) real life events (game fiction), 2) rules (formal game elements), 3) movement system (game mechanisms), 4) destiny...... (randomness), and 5) meaning (player choice) which prioritise game over story....

  17. Curious cases: Altered dose-response relationships in addiction genetics.

    Science.gov (United States)

    Uhl, George R; Drgonova, Jana; Hall, F Scott

    2014-03-01

    Dose-response relationships for most addictive substances are "inverted U"-shaped. Addictive substances produce both positive features that include reward, euphoria, anxiolysis, withdrawal-relief, and negative features that include aversion, dysphoria, anxiety and withdrawal symptoms. A simple model differentially associates ascending and descending limbs of dose-response curves with rewarding and aversive influences, respectively. However, Diagnostic and Statistical Manual (DSM) diagnoses of substance dependence fail to incorporate dose-response criteria and don't directly consider balances between euphoric and dysphoric drug effects. Classical genetic studies document substantial heritable influences on DSM substance dependence. Linkage and genome-wide association studies identify modest-sized effects at any locus. Nevertheless, clusters of SNPs within selected genes display 10(-2)>p>10(-8) associations with dependence in many independent samples. For several of these genes, evidence for cis-regulatory, level-of-expression differences supports the validity of mouse models in which levels of expression are also altered. This review documents surprising, recently defined cases in which convergent evidence from humans and mouse models supports central influences of altered dose-response relationships in mediating the impact of relevant genomic variation on addiction phenotypes. For variation at loci for the α5 nicotinic acetylcholine receptor, cadherin 13, receptor type protein tyrosine phosphatase Δ and neuronal cell adhesion molecule genes, changed dose-response relationships conferred by gene knockouts in mice are accompanied by supporting human data. These observations emphasize desirability of carefully elucidating dose-response relationships for both rewarding and aversive features of abused substances wherever possible. They motivate consideration of individual differences in dose-response relationships in addiction nosology and therapeutics. © 2013.

  18. Dose-Response Calculator for ArcGIS

    Science.gov (United States)

    Hanser, Steven E.; Aldridge, Cameron L.; Leu, Matthias; Nielsen, Scott E.

    2011-01-01

    The Dose-Response Calculator for ArcGIS is a tool that extends the Environmental Systems Research Institute (ESRI) ArcGIS 10 Desktop application to aid with the visualization of relationships between two raster GIS datasets. A dose-response curve is a line graph commonly used in medical research to examine the effects of different dosage rates of a drug or chemical (for example, carcinogen) on an outcome of interest (for example, cell mutations) (Russell and others, 1982). Dose-response curves have recently been used in ecological studies to examine the influence of an explanatory dose variable (for example, percentage of habitat cover, distance to disturbance) on a predicted response (for example, survival, probability of occurrence, abundance) (Aldridge and others, 2008). These dose curves have been created by calculating the predicted response value from a statistical model at different levels of the explanatory dose variable while holding values of other explanatory variables constant. Curves (plots) developed using the Dose-Response Calculator overcome the need to hold variables constant by using values extracted from the predicted response surface of a spatially explicit statistical model fit in a GIS, which include the variation of all explanatory variables, to visualize the univariate response to the dose variable. Application of the Dose-Response Calculator can be extended beyond the assessment of statistical model predictions and may be used to visualize the relationship between any two raster GIS datasets (see example in tool instructions). This tool generates tabular data for use in further exploration of dose-response relationships and a graph of the dose-response curve.

  19. A framework for analysis of sentinel events in medical student education.

    Science.gov (United States)

    Cohen, Daniel M; Clinchot, Daniel M; Werman, Howard A

    2013-11-01

    Although previous studies have addressed student factors contributing to dismissal or withdrawal from medical school for academic reasons, little information is available regarding institutional factors that may hinder student progress. The authors describe the development and application of a framework for sentinel event (SE) root cause analysis to evaluate cases in which students are dismissed or withdraw because of failure to progress in the medical school curriculum. The SE in medical student education (MSE) framework was piloted at the Ohio State University College of Medicine (OSUCOM) during 2010-2012. Faculty presented cases using the framework during academic oversight committee discussions. Nine SEs in MSE were presented using the framework. Major institution-level findings included the need for improved communication, documentation of cognitive and noncognitive (e.g., mental health) issues, clarification of requirements for remediation and fitness for duty, and additional psychological services. Challenges related to alternative and combined programs were identified as well. The OSUCOM undertook system changes based on the action plans developed through the discussions of these SEs. An SE analysis process appears to be a useful method for making system changes in response to institutional issues identified in evaluation of cases in which students fail to progress in the medical school curriculum. The authors plan to continue to refine the SE in MSE framework and analysis process. Next steps include assessing whether analysis using this framework yields improved student outcomes with universal applications for other institutions.

  20. Review of dose-response curves for acute antimigraine drugs

    DEFF Research Database (Denmark)

    Hougaard, Anders; Tfelt-Hansen, Peer

    2015-01-01

    INTRODUCTION: Dose-response curves for efficacy and tolerability are the important determinants for the choice of doses of acute migraine drugs. Areas covered: Dose-response curves for the efficacy of seven triptans (5-HT1B/1D receptor agonists), a 5-HT1F receptor agonist (lasmiditan) and four or......, there are many unmet needs. Although upcoming drugs may not be superior to triptans, migraine patients will potentially benefit greatly from these, especially patients who are triptan non-responders and patients with cardiovascular disease.......INTRODUCTION: Dose-response curves for efficacy and tolerability are the important determinants for the choice of doses of acute migraine drugs. Areas covered: Dose-response curves for the efficacy of seven triptans (5-HT1B/1D receptor agonists), a 5-HT1F receptor agonist (lasmiditan) and four oral......, whereas AEs often increase with increasing doses. The two other groups of drugs also have flat dose-response curves for efficacy. Overall, the triptans still have the most favorable efficacy-tolerability profile. Current acute antimigraine drugs do not fulfill the expectations of the patients, and thus...

  1. WE-G-BRA-02: SafetyNet: Automating Radiotherapy QA with An Event Driven Framework

    Energy Technology Data Exchange (ETDEWEB)

    Hadley, S; Kessler, M [The University of Michigan, Ann Arbor, MI (United States); Litzenberg, D [Univ Michigan, Ann Arbor, MI (United States); Lee, C; Irrer, J; Chen, X; Acosta, E; Weyburne, G; Lam, K; Younge, K; Matuszak, M [University of Michigan, Ann Arbor, MI (United States); Keranen, W [Varian Medical Systems, Palo Alto, CA (United States); Covington, E [University of Michigan Hospital and Health System, Ann Arbor, MI (United States); Moran, J [Univ Michigan Medical Center, Ann Arbor, MI (United States)

    2015-06-15

    Purpose: Quality assurance is an essential task in radiotherapy that often requires many manual tasks. We investigate the use of an event driven framework in conjunction with software agents to automate QA and eliminate wait times. Methods: An in house developed subscription-publication service, EventNet, was added to the Aria OIS to be a message broker for critical events occurring in the OIS and software agents. Software agents operate without user intervention and perform critical QA steps. The results of the QA are documented and the resulting event is generated and passed back to EventNet. Users can subscribe to those events and receive messages based on custom filters designed to send passing or failing results to physicists or dosimetrists. Agents were developed to expedite the following QA tasks: Plan Revision, Plan 2nd Check, SRS Winston-Lutz isocenter, Treatment History Audit, Treatment Machine Configuration. Results: Plan approval in the Aria OIS was used as the event trigger for plan revision QA and Plan 2nd check agents. The agents pulled the plan data, executed the prescribed QA, stored the results and updated EventNet for publication. The Winston Lutz agent reduced QA time from 20 minutes to 4 minutes and provided a more accurate quantitative estimate of radiation isocenter. The Treatment Machine Configuration agent automatically reports any changes to the Treatment machine or HDR unit configuration. The agents are reliable, act immediately, and execute each task identically every time. Conclusion: An event driven framework has inverted the data chase in our radiotherapy QA process. Rather than have dosimetrists and physicists push data to QA software and pull results back into the OIS, the software agents perform these steps immediately upon receiving the sentinel events from EventNet. Mr Keranen is an employee of Varian Medical Systems. Dr. Moran’s institution receives research support for her effort for a linear accelerator QA project from

  2. A Coupled Earthquake-Tsunami Simulation Framework Applied to the Sumatra 2004 Event

    Science.gov (United States)

    Vater, Stefan; Bader, Michael; Behrens, Jörn; van Dinther, Ylona; Gabriel, Alice-Agnes; Madden, Elizabeth H.; Ulrich, Thomas; Uphoff, Carsten; Wollherr, Stephanie; van Zelst, Iris

    2017-04-01

    Large earthquakes along subduction zone interfaces have generated destructive tsunamis near Chile in 1960, Sumatra in 2004, and northeast Japan in 2011. In order to better understand these extreme events, we have developed tools for physics-based, coupled earthquake-tsunami simulations. This simulation framework is applied to the 2004 Indian Ocean M 9.1-9.3 earthquake and tsunami, a devastating event that resulted in the loss of more than 230,000 lives. The earthquake rupture simulation is performed using an ADER discontinuous Galerkin discretization on an unstructured tetrahedral mesh with the software SeisSol. Advantages of this approach include accurate representation of complex fault and sea floor geometries and a parallelized and efficient workflow in high-performance computing environments. Accurate and efficient representation of the tsunami evolution and inundation at the coast is achieved with an adaptive mesh discretizing the shallow water equations with a second-order Runge-Kutta discontinuous Galerkin (RKDG) scheme. With the application of the framework to this historic event, we aim to better understand the involved mechanisms between the dynamic earthquake within the earth's crust, the resulting tsunami wave within the ocean, and the final coastal inundation process. Earthquake model results are constrained by GPS surface displacements and tsunami model results are compared with buoy and inundation data. This research is part of the ASCETE Project, "Advanced Simulation of Coupled Earthquake and Tsunami Events", funded by the Volkswagen Foundation.

  3. Confidence bounds for nonlinear dose-response relationships

    DEFF Research Database (Denmark)

    Baayen, C; Hougaard, P

    2015-01-01

    An important aim of drug trials is to characterize the dose-response relationship of a new compound. Such a relationship can often be described by a parametric (nonlinear) function that is monotone in dose. If such a model is fitted, it is useful to know the uncertainty of the fitted curve...... intervals for the dose-response curve. These confidence bounds have better coverage than Wald intervals and are more precise and generally faster than bootstrap methods. Moreover, if monotonicity is assumed, the profile likelihood approach takes this automatically into account. The approach is illustrated...

  4. Analysis framework for systematically studying ionospheric response to impulsive events from below

    Science.gov (United States)

    Haaser, Robert A.; Lay, Erin H.; Junor, William

    2017-09-01

    Impulsive phenomena in the Earth's atmosphere produce acoustic and gravity waves which perturb the ionosphere. Such perturbations are often measured using total electron content fluctuations (TEC), derived from ground-based Global Positioning System data. Using TEC data from the Japanese GEONET ground network after the Tōhoku earthquake on 11 March 2011, we demonstrate capabilities of a new framework of methodologies for analyzing ionospheric perturbations. The framework consists of several new techniques: calculating velocity along a single direction to reduce error due to anisotropic propagation, producing normalized bidirectional band-pass spectra that preserve relative timing between various frequencies and allowing a more systematic determination of broadband pulses, and utilizing a wavelet-based technique that considers instantaneous wave phase changes, rather than best fit time differences, to evaluate wave characteristics (speed, direction, and wavelength) within spectral ranges of interest. Using these techniques together decreases subjectivity and reduces errors in attributing fluctuations to given sources. In validating this framework using the Tōhoku case, we consistently identify three kinds of waves: a broad-band pulse (speed: >2000 m/s, max range: >1400 km) arriving in the ionosphere 10-15 min after the quake, acoustic waves following the pulse (period: 3-5 min, speed: 700-1000 m/s, max range: 1400 km) propagating away from the epicenter, consistent with theory and demonstrated in previous studies. This framework also can be applied to other impulsive events in the atmosphere that are more difficult to detect and attribute to sources.

  5. Dose-response meta-analysis of differences in means

    Directory of Open Access Journals (Sweden)

    Alessio Crippa

    2016-08-01

    Full Text Available Abstract Background Meta-analytical methods are frequently used to combine dose-response findings expressed in terms of relative risks. However, no methodology has been established when results are summarized in terms of differences in means of quantitative outcomes. Methods We proposed a two-stage approach. A flexible dose-response model is estimated within each study (first stage taking into account the covariance of the data points (mean differences, standardized mean differences. Parameters describing the study-specific curves are then combined using a multivariate random-effects model (second stage to address heterogeneity across studies. Results The method is fairly general and can accommodate a variety of parametric functions. Compared to traditional non-linear models (e.g. E max, logistic, spline models do not assume any pre-specified dose-response curve. Spline models allow inclusion of studies with a small number of dose levels, and almost any shape, even non monotonic ones, can be estimated using only two parameters. We illustrated the method using dose-response data arising from five clinical trials on an antipsychotic drug, aripiprazole, and improvement in symptoms in shizoaffective patients. Using the Positive and Negative Syndrome Scale (PANSS, pooled results indicated a non-linear association with the maximum change in mean PANSS score equal to 10.40 (95 % confidence interval 7.48, 13.30 observed for 19.32 mg/day of aripiprazole. No substantial change in PANSS score was observed above this value. An estimated dose of 10.43 mg/day was found to produce 80 % of the maximum predicted response. Conclusion The described approach should be adopted to combine correlated differences in means of quantitative outcomes arising from multiple studies. Sensitivity analysis can be a useful tool to assess the robustness of the overall dose-response curve to different modelling strategies. A user-friendly R package has been developed to facilitate

  6. Radiation Dose-Response Relationships and Risk Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Strom, Daniel J.

    2005-07-05

    The notion of a dose-response relationship was probably invented shortly after the discovery of poisons, the invention of alcoholic beverages, and the bringing of fire into a confined space in the forgotten depths of ancient prehistory. The amount of poison or medicine ingested can easily be observed to affect the behavior, health, or sickness outcome. Threshold effects, such as death, could be easily understood for intoxicants, medicine, and poisons. As Paracelsus (1493-1541), the 'father' of modern toxicology said, 'It is the dose that makes the poison.' Perhaps less obvious is the fact that implicit in such dose-response relationships is also the notion of dose rate. Usually, the dose is administered fairly acutely, in a single injection, pill, or swallow; a few puffs on a pipe; or a meal of eating or drinking. The same amount of intoxicants, medicine, or poisons administered over a week or month might have little or no observable effect. Thus, before the discovery of ionizing radiation in the late 19th century, toxicology ('the science of poisons') and pharmacology had deeply ingrained notions of dose-response relationships. This chapter demonstrates that the notion of a dose-response relationship for ionizing radiation is hopelessly simplistic from a scientific standpoint. While useful from a policy or regulatory standpoint, dose-response relationships cannot possibly convey enough information to describe the problem from a quantitative view of radiation biology, nor can they address societal values. Three sections of this chapter address the concepts, observations, and theories that contribute to the scientific input to the practice of managing risks from exposure to ionizing radiation. The presentation begins with irradiation regimes, followed by responses to high and low doses of ionizing radiation, and a discussion of how all of this can inform radiation risk management. The knowledge that is really needed for prediction of

  7. Stability and coherence of health experts' upper and lower subjective probabilities about dose-response functions.

    Science.gov (United States)

    Wallsten, T S; Forsyth, B H

    1983-06-01

    As part of a method for assessing health risks associated with primary National Ambient Air Quality Standards. T. B. Feagans and W. F. Biller (Research Triangle Park, North Carolina. EPA Office of Air Quality Planning and Standards, May 1981) developed a technique for encoding experts' subjective probabilities regarding dose--response functions. The encoding technique is based on B. O. Koopman's (Bulletin of the American Mathematical Society, 1940, 46, 763-764; Annals of Mathematics, 1940, 41, 269-292) probability theory, which does not require probabilities to be sharp, but rather allows lower and upper probabilities to be associated with an event. Uncertainty about a dose--response function can be expressed either in terms of the response rate expected at a given concentration or, conversely, in terms of the concentration expected to support a given response rate. Feagans and Biller (1981, cited above) derive the relation between the two conditional probabilities, which is easily extended to upper and lower conditional probabilities. These relations were treated as coherence requirements in an experiment utilizing four ozone and four lead experts as subjects, each providing judgments on two separate occasions. Four subjects strongly satisfied the coherence requirements in both conditions. and three more did no in the second session only. The eighth subject also improved in Session 2. Encoded probabilities were highly correlated between the two sessions, but changed from the first to the second in a manner that improved coherence and reflected greater attention to certain parameters of the dose--response function.

  8. Magnetic storms and solar flares: can be analysed within similar mathematical framework with other extreme events?

    Science.gov (United States)

    Balasis, Georgios; Potirakis, Stelios M.; Papadimitriou, Constantinos; Zitis, Pavlos I.; Eftaxias, Konstantinos

    2015-04-01

    The field of study of complex systems considers that the dynamics of complex systems are founded on universal principles that may be used to describe a great variety of scientific and technological approaches of different types of natural, artificial, and social systems. We apply concepts of the nonextensive statistical physics, on time-series data of observable manifestations of the underlying complex processes ending up to different extreme events, in order to support the suggestion that a dynamical analogy characterizes the generation of a single magnetic storm, solar flare, earthquake (in terms of pre-seismic electromagnetic signals) , epileptic seizure, and economic crisis. The analysis reveals that all the above mentioned different extreme events can be analyzed within similar mathematical framework. More precisely, we show that the populations of magnitudes of fluctuations included in all the above mentioned pulse-like-type time series follow the traditional Gutenberg-Richter law as well as a nonextensive model for earthquake dynamics, with similar nonextensive q-parameter values. Moreover, based on a multidisciplinary statistical analysis we show that the extreme events are characterized by crucial common symptoms, namely: (i) high organization, high compressibility, low complexity, high information content; (ii) strong persistency; and (iii) existence of clear preferred direction of emerged activities. These symptoms clearly discriminate the appearance of the extreme events under study from the corresponding background noise.

  9. A Probabilistic Framework for Risk Analysis of Widespread Flood Events: A Proof-of-Concept Study.

    Science.gov (United States)

    Schneeberger, Klaus; Huttenlau, Matthias; Winter, Benjamin; Steinberger, Thomas; Achleitner, Stefan; Stötter, Johann

    2017-07-27

    This article presents a flood risk analysis model that considers the spatially heterogeneous nature of flood events. The basic concept of this approach is to generate a large sample of flood events that can be regarded as temporal extrapolation of flood events. These are combined with cumulative flood impact indicators, such as building damages, to finally derive time series of damages for risk estimation. Therefore, a multivariate modeling procedure that is able to take into account the spatial characteristics of flooding, the regionalization method top-kriging, and three different impact indicators are combined in a model chain. Eventually, the expected annual flood impact (e.g., expected annual damages) and the flood impact associated with a low probability of occurrence are determined for a study area. The risk model has the potential to augment the understanding of flood risk in a region and thereby contribute to enhanced risk management of, for example, risk analysts and policymakers or insurance companies. The modeling framework was successfully applied in a proof-of-concept exercise in Vorarlberg (Austria). The results of the case study show that risk analysis has to be based on spatially heterogeneous flood events in order to estimate flood risk adequately. © 2017 Society for Risk Analysis.

  10. Framework for modeling urban restoration resilience time in the aftermath of an extreme event

    Science.gov (United States)

    Ramachandran, Varun; Long, Suzanna K.; Shoberg, Thomas G.; Corns, Steven; Carlo, Héctor

    2015-01-01

    The impacts of extreme events continue long after the emergency response has terminated. Effective reconstruction of supply-chain strategic infrastructure (SCSI) elements is essential for postevent recovery and the reconnectivity of a region with the outside. This study uses an interdisciplinary approach to develop a comprehensive framework to model resilience time. The framework is tested by comparing resilience time results for a simulated EF-5 tornado with ground truth data from the tornado that devastated Joplin, Missouri, on May 22, 2011. Data for the simulated tornado were derived for Overland Park, Johnson County, Kansas, in the greater Kansas City, Missouri, area. Given the simulated tornado, a combinatorial graph considering the damages in terms of interconnectivity between different SCSI elements is derived. Reconstruction in the aftermath of the simulated tornado is optimized using the proposed framework to promote a rapid recovery of the SCSI. This research shows promising results when compared with the independent quantifiable data obtained from Joplin, Missouri, returning a resilience time of 22 days compared with 25 days reported by city and state officials.

  11. Model Averaging Software for Dichotomous Dose Response Risk Estimation

    Directory of Open Access Journals (Sweden)

    Matthew W. Wheeler

    2008-02-01

    Full Text Available Model averaging has been shown to be a useful method for incorporating model uncertainty in quantitative risk estimation. In certain circumstances this technique is computationally complex, requiring sophisticated software to carry out the computation. We introduce software that implements model averaging for risk assessment based upon dichotomous dose-response data. This software, which we call Model Averaging for Dichotomous Response Benchmark Dose (MADr-BMD, fits the quantal response models, which are also used in the US Environmental Protection Agency benchmark dose software suite, and generates a model-averaged dose response model to generate benchmark dose and benchmark dose lower bound estimates. The software fulfills a need for risk assessors, allowing them to go beyond one single model in their risk assessments based on quantal data by focusing on a set of models that describes the experimental data.

  12. Analytical modelling of regional radiotherapy dose response of lung

    Science.gov (United States)

    Lee, Sangkyu; Stroian, Gabriela; Kopek, Neil; AlBahhar, Mahmood; Seuntjens, Jan; El Naqa, Issam

    2012-06-01

    Knowledge of the dose-response of radiation-induced lung disease (RILD) is necessary for optimization of radiotherapy (RT) treatment plans involving thoracic cavity irradiation. This study models the time-dependent relationship between local radiation dose and post-treatment lung tissue damage measured by computed tomography (CT) imaging. Fifty-eight follow-up diagnostic CT scans from 21 non-small-cell lung cancer patients were examined. The extent of RILD was segmented on the follow-up CT images based on the increase of physical density relative to the pre-treatment CT image. The segmented RILD was locally correlated with dose distribution calculated by analytical anisotropic algorithm and the Monte Carlo method to generate the corresponding dose-response curves. The Lyman-Kutcher-Burman (LKB) model was fit to the dose-response curves at six post-RT time periods, and temporal change in the LKB parameters was recorded. In this study, we observed significant correlation between the probability of lung tissue damage and the local dose for 96% of the follow-up studies. Dose-injury correlation at the first three months after RT was significantly different from later follow-up periods in terms of steepness and threshold dose as estimated from the LKB model. Dependence of dose response on superior-inferior tumour position was also observed. The time-dependent analytical modelling of RILD might provide better understanding of the long-term behaviour of the disease and could potentially be applied to improve inverse treatment planning optimization.

  13. A Visual Analytics Framework for Identifying Topic Drivers in Media Events.

    Science.gov (United States)

    Lu, Yafeng; Wang, Hong; Landis, Steven; Maciejewski, Ross

    2017-09-14

    Media data has been the subject of large scale analysis with applications of text mining being used to provide overviews of media themes and information flows. Such information extracted from media articles has also shown its contextual value of being integrated with other data, such as criminal records and stock market pricing. In this work, we explore linking textual media data with curated secondary textual data sources through user-guided semantic lexical matching for identifying relationships and data links. In this manner, critical information can be identified and used to annotate media timelines in order to provide a more detailed overview of events that may be driving media topics and frames. These linked events are further analyzed through an application of causality modeling to model temporal drivers between the data series. Such causal links are then annotated through automatic entity extraction which enables the analyst to explore persons, locations, and organizations that may be pertinent to the media topic of interest. To demonstrate the proposed framework, two media datasets and an armed conflict event dataset are explored.

  14. iROCS: Integrated accident management framework for coping with beyond-design-basis external events

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jaewhan; Park, Soo-Yong; Ahn, Kwang-Il, E-mail: kiahn@kaeri.re.kr; Yang, Joon-Eon

    2016-03-15

    Highlights: • An integrated mitigating strategy to cope with extreme external events, iROCS, is proposed. • The strategy aims to preserve the integrity of the reactor vessel as well as core cooling. • A case study for an extreme damage state is performed to assess the effectiveness and feasibility of candidate mitigation strategies under an extreme event. - Abstract: The Fukushima Daiichi accident induced by the Great East Japan earthquake and tsunami on March 11, 2011, poses a new challenge to the nuclear society, especially from an accident management viewpoint. This paper presents a new accident management framework called an integrated, RObust Coping Strategy (iROCS) to cope with beyond-design-basis external events (BDBEEs). The iROCS approach is characterized by classification of various plant damage conditions (PDCs) that might be impacted by BDBEEs and corresponding integrated coping strategies for each of PDCs, aiming to maintain and restore core cooling (i.e., to prevent core damage) and to maintain the integrity of the reactor pressure vessel if it is judged that core damage may not be preventable in view of plant conditions. From a case study for an extreme damage condition, it showed that candidate accident management strategies should be evaluated from the viewpoint of effectiveness and feasibility against accident scenarios and extreme damage conditions of the site, especially when employing mobile or portable equipment under BDBEEs within the limited time available to achieve desired goals such as prevention of core damage as well as a reactor vessel failure.

  15. Controlled Optimal Design Program for the Logit Dose Response Model

    Directory of Open Access Journals (Sweden)

    Jiaqiao Hu

    2010-10-01

    Full Text Available The assessment of dose-response is an integral component of the drug development process. Parallel dose-response studies are conducted, customarily, in preclinical and phase 1, 2 clinical trials for this purpose. Practical constraints on dose range, dose levels and dose proportions are intrinsic issues in the design of dose response studies because of drug toxicity, efficacy, FDA regulations, protocol requirements, clinical trial logistics, and marketing issues. We provide a free on-line software package called Controlled Optimal Design 2.0 for generating controlled optimal designs that can incorporate prior information and multiple objectives, and meet multiple practical constraints at the same time. Researchers can either run the web-based design program or download its stand-alone version to construct the desired multiple-objective controlled Bayesian optimal designs. Because researchers often adopt ad-hoc design schemes such as the equal allocation rules without knowing how efficient such designs would be for the design problem, the program also evaluates the efficiency of user-supplied designs.

  16. Dose-response of pregabalin for diabetic peripheral neuropathy, postherpetic neuralgia, and fibromyalgia.

    Science.gov (United States)

    Arnold, Lesley M; McCarberg, Bill H; Clair, Andrew G; Whalen, Ed; Thomas, Neal; Jorga, Anamaria; Pauer, Lynne; Vissing, Richard; Park, Peter W

    2017-11-01

    The pregabalin dose-response for pain, Patient Global Impression of Change (PGIC), and sleep quality measures in painful diabetic peripheral neuropathy (pDPN), postherpetic neuralgia (PHN), and fibromyalgia (FM) is relevant for physicians treating these patients. This analysis aimed to demonstrate the dose-response of pregabalin for each indication and describe the onset (incidence), onset/continuation (prevalence), and resolution of adverse events (AEs) occurring during treatment. Data from 14 placebo-controlled, fixed-dose pregabalin trials in pDPN, PHN, and FM were pooled within each indication. Patients had mean baseline pain scores ≥6 on an 11-point numeric rating scale. A hyperbolic Emax dose-response model examined the dose-response of pregabalin for pain, PGIC, and sleep quality. Safety assessments included onset and prevalence of common AEs each week, and resolution in the first 2 months of treatment. In all indications, the likelihood of patients experiencing pain relief and improvements in PGIC and sleep quality increased in a dose-dependent manner with increasing doses. In all indications, new incidences of dizziness and somnolence were highest after 1 week of treatment, with few subsequent new reports at a given dose. Prevalence rates decreased steadily after 1 week of treatment. In FM, new onset weight gain emerged 6-8 weeks following treatment; prevalence rates generally increased then remained steady over time. With the exception of weight gain, many AEs resolved in month 1. The dose-response of pregabalin for pain, PGIC, and sleep quality was demonstrated, highlighting the benefit of achieving the maximum recommended dose of 300 mg/day for pDPN, 300-600 mg/day for PHN, and 300-450 mg/day for FM. Common AEs are generally seen within 1 week of starting treatment, with few subsequent new reports at a given dose. New onset weight gain occurs after 6 weeks of treatment, reinforcing the need for regular monitoring of weight.

  17. The theory of event coding (TEC) as embodied-cognition framework.

    Science.gov (United States)

    Hommel, Bernhard

    2015-01-01

    The concept of embodied cognition attracts enormous interest but neither is the concept particularly well-defined nor is the related research guided by systematic theorizing. To improve this situation the theory of event coding (TEC) is suggested as a suitable theoretical framework for theorizing about cognitive embodiment-which, however, presupposes giving up the anti-cognitivistic attitude inherent in many embodiment approaches. The article discusses the embodiment-related potential of TEC, and the way and degree to which it addresses Wilson's (2002) six meanings of the embodiment concept. In particular, it is discussed how TEC considers human cognition to be situated, distributed, and body-based, how it deals with time pressure, how it delegates work to the environment, and in which sense it subserves action.

  18. The theory of event coding (TEC as embodied-cognition framework

    Directory of Open Access Journals (Sweden)

    Bernhard eHommel

    2015-09-01

    Full Text Available The concept of embodied cognition attracts enormous interest but neither is the concept particularly well-defined nor is the related research guided by systematic theorizing. To improve this situation the Theory of Event Coding (TEC is suggested as a suitable theoretical framework for theorizing about cognitive embodiment—which however presupposes giving up the anti-cognitivistic attitude inherent in many embodiment approaches. The article discusses the embodiment-related potential of TEC, and the way and degree to which it addresses Wilson’s (2002 six meanings of the embodiment concept. In particular, it is discussed how TEC considers human cognition to be situated, distributed, and body-based, how it deals with time pressure, how it delegates work to the environment, and in which sense it subserves action.

  19. Research toward the development of a biologically based dose response assessment for inorganic arsenic carcinogenicity: a progress report.

    Science.gov (United States)

    Clewell, Harvey J; Thomas, Russell S; Gentry, P Robinan; Crump, Kenny S; Kenyon, Elaina M; El-Masri, Hisham A; Yager, Janice W

    2007-08-01

    Cancer risk assessments for inorganic arsenic have been based on human epidemiological data, assuming a linear dose response below the range of observation of tumors. Part of the reason for the continued use of the linear approach in arsenic risk assessments is the lack of an adequate biologically based dose response (BBDR) model that could provide a quantitative basis for an alternative nonlinear approach. This paper describes elements of an ongoing collaborative research effort between the CIIT Centers for Health Research, the U.S. Environmental Protection Agency, ENVIRON International, and EPRI to develop BBDR modeling approaches that could be used to inform a nonlinear cancer dose response assessment for inorganic arsenic. These efforts are focused on: (1) the refinement of physiologically based pharmacokinetic (PBPK) models of the kinetics of inorganic arsenic and its metabolites in the mouse and human; (2) the investigation of mathematical solutions for multi-stage cancer models involving multiple pathways of cell transformation; (3) the review and evaluation of the literature on the dose response for the genomic effects of arsenic; and (4) the collection of data on the dose response for genomic changes in the urinary bladder (a human target tissue for arsenic carcinogenesis) associated with in vivo drinking water exposures in the mouse as well as in vitro exposures of both mouse and human cells. An approach is proposed for conducting a biologically based margin of exposure risk assessment for inorganic arsenic using the in vitro dose response for the expression of genes associated with the obligatory precursor events for arsenic tumorigenesis.

  20. Events as a Framework for Tourist Destination Branding – Case Studies of Two Cultural Events in Croatia

    Directory of Open Access Journals (Sweden)

    Klara Trošt

    2012-04-01

    Full Text Available Events have become an increasingly significant component of destination branding. Many destinations throughout the world have developed events portfolios as a strategic initiative to attract tourists and to reinforce their brand. In this paper, the focus of research will be on tourist destination branding by means of events. The relationship between events and destination branding is examined through six phases of the process of building a destination brand identity with the use of events. When it comes to destination branding, a need for an analysis of strategic documents of destination development imposes because event tourism strategies help destinations plan how to use events in a tourism role. The purpose of this study is to examine which factors are of the top priorities when using events as a marketing approach. The method of case study will be used, by which two cultural events which take place in the Republic of Croatia will be analyzed, namely, “Špancirfest” in Varaždin and “Trka na prstenac” in Barban. Varaždin and Barban are on different levels in their branding work. The different sizes and locations of the destinations naturally affect the operating procedures. This article may be of interest to destination marketers and event organizers, especially in developing destinations which intend to differentiate themselves from the competitive market.

  1. An Urban Resilience to Extreme Weather Events Framework for Development of Post Event Learning and Transformative Adaptation in Cities

    Science.gov (United States)

    Solecki, W. D.; Friedman, E. S.; Breitzer, R.

    2016-12-01

    Increasingly frequent extreme weather events are becoming an immediate priority for urban coastal practitioners and stakeholders, adding complexity to decisions concerning risk management for short-term action and long-term needs of city climate stakeholders. The conflict between the prioritization of short versus long-term events by decision-makers creates disconnect between climate science and its applications. The Consortium for Climate Risk in the Urban Northeast (CCRUN), a NOAA RISA team, is developing a set of mechanisms to help bridge this gap. The mechanisms are designed to promote the application of climate science on extreme weather events and their aftermath. It is in the post event policy window where significant opportunities for science-policy linkages exist. In particular, CCRUN is interested in producing actionable and useful information for city managers to use in decision-making processes surrounding extreme weather events and climate change. These processes include a sector specific needs assessment survey instrument and two tools for urban coastal practitioners and stakeholders. The tools focus on post event learning and connections between resilience and transformative adaptation. Elements of the two tools are presented. Post extreme event learning supports urban coastal practitioners and decision-makers concerned about maximizing opportunities for knowledge transfer and assimilation, and policy initiation and development following an extreme weather event. For the urban U.S. Northeast, post event learning helps coastal stakeholders build the capacity to adapt to extreme weather events, and inform and develop their planning capacity through analysis of past actions and steps taken in response to Hurricane Sandy. Connecting resilience with transformative adaptation is intended to promote resilience in urban Northeast coastal settings to the long-term negative consequences of extreme weather events. This is done through a knowledge co

  2. Neuromuscular dose-response studies: determining sample size.

    Science.gov (United States)

    Kopman, A F; Lien, C A; Naguib, M

    2011-02-01

    Investigators planning dose-response studies of neuromuscular blockers have rarely used a priori power analysis to determine the minimal sample size their protocols require. Institutional Review Boards and peer-reviewed journals now generally ask for this information. This study outlines a proposed method for meeting these requirements. The slopes of the dose-response relationships of eight neuromuscular blocking agents were determined using regression analysis. These values were substituted for γ in the Hill equation. When this is done, the coefficient of variation (COV) around the mean value of the ED₅₀ for each drug is easily calculated. Using these values, we performed an a priori one-sample two-tailed t-test of the means to determine the required sample size when the allowable error in the ED₅₀ was varied from ±10-20%. The COV averaged 22% (range 15-27%). We used a COV value of 25% in determining the sample size. If the allowable error in finding the mean ED₅₀ is ±15%, a sample size of 24 is needed to achieve a power of 80%. Increasing 'accuracy' beyond this point requires increasing greater sample sizes (e.g. an 'n' of 37 for a ±12% error). On the basis of the results of this retrospective analysis, a total sample size of not less than 24 subjects should be adequate for determining a neuromuscular blocking drug's clinical potency with a reasonable degree of assurance.

  3. Characterization of statin dose response in electronic medical records.

    Science.gov (United States)

    Wei, W-Q; Feng, Q; Jiang, L; Waitara, M S; Iwuchukwu, O F; Roden, D M; Jiang, M; Xu, H; Krauss, R M; Rotter, J I; Nickerson, D A; Davis, R L; Berg, R L; Peissig, P L; McCarty, C A; Wilke, R A; Denny, J C

    2014-03-01

    Efforts to define the genetic architecture underlying variable statin response have met with limited success, possibly because previous studies were limited to effect based on a single dose. We leveraged electronic medical records (EMRs) to extract potency (ED50) and efficacy (Emax) of statin dose-response curves and tested them for association with 144 preselected variants. Two large biobanks were used to construct dose-response curves for 2,026 and 2,252 subjects on simvastatin and atorvastatin, respectively. Atorvastatin was more efficacious, was more potent, and demonstrated less interindividual variability than simvastatin. A pharmacodynamic variant emerging from randomized trials (PRDM16) was associated with Emax for both. For atorvastatin, Emax was 51.7 mg/dl in subjects homozygous for the minor allele vs. 75.0 mg/dl for those homozygous for the major allele. We also identified several loci associated with ED50. The extraction of rigorously defined traits from EMRs for pharmacogenetic studies represents a promising approach to further understand the genetic factors contributing to drug response.

  4. Integrated survival analysis using an event-time approach in a Bayesian framework

    Science.gov (United States)

    Walsh, Daniel P.; Dreitz, VJ; Heisey, Dennis M.

    2015-01-01

    Event-time or continuous-time statistical approaches have been applied throughout the biostatistical literature and have led to numerous scientific advances. However, these techniques have traditionally relied on knowing failure times. This has limited application of these analyses, particularly, within the ecological field where fates of marked animals may be unknown. To address these limitations, we developed an integrated approach within a Bayesian framework to estimate hazard rates in the face of unknown fates. We combine failure/survival times from individuals whose fates are known and times of which are interval-censored with information from those whose fates are unknown, and model the process of detecting animals with unknown fates. This provides the foundation for our integrated model and permits necessary parameter estimation. We provide the Bayesian model, its derivation, and use simulation techniques to investigate the properties and performance of our approach under several scenarios. Lastly, we apply our estimation technique using a piece-wise constant hazard function to investigate the effects of year, age, chick size and sex, sex of the tending adult, and nesting habitat on mortality hazard rates of the endangered mountain plover (Charadrius montanus) chicks. Traditional models were inappropriate for this analysis because fates of some individual chicks were unknown due to failed radio transmitters. Simulations revealed biases of posterior mean estimates were minimal (≤ 4.95%), and posterior distributions behaved as expected with RMSE of the estimates decreasing as sample sizes, detection probability, and survival increased. We determined mortality hazard rates for plover chicks were highest at weights and/or whose nest was within agricultural habitats. Based on its performance, our approach greatly expands the range of problems for which event-time analyses can be used by eliminating the need for having completely known fate data.

  5. Alcohol and cirrhosis: dose--response or threshold effect?

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads; Grønbaek, Morten; Tolstrup, Janne

    2004-01-01

    BACKGROUND/AIMS: General population studies have shown a strong association between alcohol intake and death from alcoholic cirrhosis, but whether this is a dose-response or a threshold effect remains unknown, and the relation among alcohol misusers has not been studied. METHODS: A cohort of 6152...... alcohol misusing men and women aged 15-83 were interviewed about drinking pattern and social issues and followed for 84,257 person-years. Outcome was alcoholic cirrhosis mortality. Data was analyzed by means of Cox-regression models. RESULTS: In this large prospective cohort study of alcohol misusers...... there was a 27 fold increased mortality from alcoholic cirrhosis in men and a 35 fold increased mortality from alcoholic cirrhosis in women compared to the Danish population. Number of drinks per day was not significantly associated with death from alcoholic cirrhosis, since there was no additional risk of death...

  6. A discrete event modelling framework for simulation of long-term outcomes of sequential treatment strategies for ankylosing spondylitis

    NARCIS (Netherlands)

    Tran-Duy, A.; Boonen, A.; Laar, M.A.F.J.; Franke, A.C.; Severens, J.L.

    2011-01-01

    Objective To develop a modelling framework which can simulate long-term quality of life, societal costs and cost-effectiveness as affected by sequential drug treatment strategies for ankylosing spondylitis (AS). Methods Discrete event simulation paradigm was selected for model development. Drug

  7. Dose-response studies with ethylenediurea (EDU) and radish.

    Science.gov (United States)

    Kostka-Rick, R; Manning, W J

    1993-01-01

    There is some concern that the antiozonant ethylenediurea (EDU), used for crop loss assessment due to ambient ozone (O3) may per se affect plant growth and yield. In view of this, and to provide knowledge for later field experiments, dose-response studies with EDU and O3 were carried out in greenhouses in winter and spring 1989, using radish (Raphanus sativus L.) cv. 'Cherry Belle' and 'Red Prince', grown in two different substrates. EDU was applied as a single or repeated soil drench in concentrations ranging from 300 to 800 mg litre(-1) in the first, and from 100 to 400 mg litre(-1) in the second trial. In the second experiment, plants were exposed to a chronic level of O3, mimicking ambient patterns, or to filtered air after the EDU-treatment. When applied in concentrations above 300 mg litre(-1), EDU reduced growth, thereby affecting the development of the thickened hypocotyl far more than the shoot growth that was partially stimulated by lower doses of EDU. Phytotoxic symptoms on the leaves, attributable to EDU, were observed at concentrations above 200 mg litre(-1), but complete protection from visible O3-injury was provided by a single application of EDU at a concentration as low as 100 mg litre(-1). Significant interactions on growth characters measured between O3-exposure and EDU application were observed only in one of the substrates. While these results demonstrate the need for careful dose-response studies prior to field assessments, they also provide evidence of a dosage that is effective in protecting radish from O3 damage without interfering with plant growth itself.

  8. Bayesian Dose-Response Modeling in Sparse Data

    Science.gov (United States)

    Kim, Steven B.

    This book discusses Bayesian dose-response modeling in small samples applied to two different settings. The first setting is early phase clinical trials, and the second setting is toxicology studies in cancer risk assessment. In early phase clinical trials, experimental units are humans who are actual patients. Prior to a clinical trial, opinions from multiple subject area experts are generally more informative than the opinion of a single expert, but we may face a dilemma when they have disagreeing prior opinions. In this regard, we consider compromising the disagreement and compare two different approaches for making a decision. In addition to combining multiple opinions, we also address balancing two levels of ethics in early phase clinical trials. The first level is individual-level ethics which reflects the perspective of trial participants. The second level is population-level ethics which reflects the perspective of future patients. We extensively compare two existing statistical methods which focus on each perspective and propose a new method which balances the two conflicting perspectives. In toxicology studies, experimental units are living animals. Here we focus on a potential non-monotonic dose-response relationship which is known as hormesis. Briefly, hormesis is a phenomenon which can be characterized by a beneficial effect at low doses and a harmful effect at high doses. In cancer risk assessments, the estimation of a parameter, which is known as a benchmark dose, can be highly sensitive to a class of assumptions, monotonicity or hormesis. In this regard, we propose a robust approach which considers both monotonicity and hormesis as a possibility. In addition, We discuss statistical hypothesis testing for hormesis and consider various experimental designs for detecting hormesis based on Bayesian decision theory. Past experiments have not been optimally designed for testing for hormesis, and some Bayesian optimal designs may not be optimal under a

  9. An investigation of gene-gene interactions in dose-response studies with Bayesian nonparametrics.

    Science.gov (United States)

    Beam, Andrew L; Motsinger-Reif, Alison A; Doyle, Jon

    2015-01-01

    Best practice for statistical methodology in cell-based dose-response studies has yet to be established. We examine the ability of MANOVA to detect trait-associated genetic loci in the presence of gene-gene interactions. We present a novel Bayesian nonparametric method designed to detect such interactions. MANOVA and the Bayesian nonparametric approach show good ability to detect trait-associated genetic variants under various possible genetic models. It is shown through several sets of analyses that this may be due to marginal effects being present, even if the underlying genetic model does not explicitly contain them. Understanding how genetic interactions affect drug response continues to be a critical goal. MANOVA and the novel Bayesian framework present a trade-off between computational complexity and model flexibility.

  10. Integrating Visualization Applications, such as ParaView, into HEP Software Frameworks for In-situ Event Displays

    Energy Technology Data Exchange (ETDEWEB)

    Lyon, A. L. [Fermilab; Kowalkowski, J. B. [Fermilab; Jones, C. D. [Fermilab

    2017-11-22

    ParaView is a high performance visualization application not widely used in High Energy Physics (HEP). It is a long standing open source project led by Kitware and involves several Department of Energy (DOE) and Department of Defense (DOD) laboratories. Futhermore, it has been adopted by many DOE supercomputing centers and other sites. ParaView is unique in speed and efficiency by using state-of-the-art techniques developed by the academic visualization community that are often not found in applications written by the HEP community. In-situ visualization of events, where event details are visualized during processing/analysis, is a common task for experiment software frameworks. Kitware supplies Catalyst, a library that enables scientific software to serve visualization objects to client ParaView viewers yielding a real-time event display. Connecting ParaView to the Fermilab art framework will be described and the capabilities it brings discussed.

  11. Integrating Visualization Applications, such as ParaView, into HEP Software Frameworks for In-situ Event Displays

    Science.gov (United States)

    Lyon, A. L.; Kowalkowski, J. B.; Jones, C. D.

    2017-10-01

    ParaView is a high performance visualization application not widely used in High Energy Physics (HEP). It is a long standing open source project led by Kitware and involves several Department of Energy (DOE) and Department of Defense (DOD) laboratories. Futhermore, it has been adopted by many DOE supercomputing centers and other sites. ParaView is unique in speed and efficiency by using state-of-the-art techniques developed by the academic visualization community that are often not found in applications written by the HEP community. In-situ visualization of events, where event details are visualized during processing/analysis, is a common task for experiment software frameworks. Kitware supplies Catalyst, a library that enables scientific software to serve visualization objects to client ParaView viewers yielding a real-time event display. Connecting ParaView to the Fermilab art framework will be described and the capabilities it brings discussed.

  12. Using a New Event-Based Simulation Framework for Investigating Resource Provisioning in Clouds

    Directory of Open Access Journals (Sweden)

    Simon Ostermann

    2011-01-01

    Full Text Available Today, Cloud computing proposes an attractive alternative to building large-scale distributed computing environments by which resources are no longer hosted by the scientists' computational facilities, but leased from specialised data centres only when and for how long they are needed. This new class of Cloud resources raises new interesting research questions in the fields of resource management, scheduling, fault tolerance, or quality of service, requiring hundreds to thousands of experiments for finding valid solutions. To enable such research, a scalable simulation framework is typically required for early prototyping, extensive testing and validation of results before the real deployment is performed. The scope of this paper is twofold. In the first part we present GroudSim, a Grid and Cloud simulation toolkit for scientific computing based on a scalable simulation-independent discrete-event engine. GroudSim provides a comprehensive set of features for complex simulation scenarios from simple job executions on leased computing resources to file transfers, calculation of costs and background load on resources. Simulations can be parameterised and are easily extendable by probability distribution packages for failures which normally occur in complex distributed environments. Experimental results demonstrate the improved scalability of GroudSim compared to a related process-based simulation approach. In the second part, we show the use of the GroudSim simulator to analyse the problem of dynamic provisioning of Cloud resources to scientific workflows that do not benefit from sufficient Grid resources as required by their computational demands. We propose and study four strategies for provisioning and releasing Cloud resources that take into account the general leasing model encountered in today's commercial Cloud environments based on resource bulks, fuzzy descriptions and hourly payment intervals. We study the impact of our techniques to the

  13. [Oral health in asthmatic children: a dose-response study].

    Science.gov (United States)

    Eloot, A; Vanobbergen, J; Martens, L

    2004-01-01

    In literature there is a lack of consensus regarding the relationship between dental caries risk and asthma in a child population. Despite these divergent views, all studies conclude that asthmatic children are at risk and that special preventive programs are needed. The asthmatic through either its disease status or its pharmacotherapy carries several factors for an increased caries risk. PH values of most inhalant powders are less than 5.5. A decrease of the salivary and plaque pH has been detected in asthmatic children after use of these inhalers. This low pH value associated with a reduced salivary flow rate (caused by beta-adrenergic agonists and by anti-histaminic medication) makes asthmatics more susceptible to caries and erosion. There are only a few studies that take into account that asthma is a disease with a large diversity of severity and duration. This approach could help to clarify some variability in caries risk. The aim of the present study (a dose-response study) was to examine the oral health status of asthmatic children and to compare the oral health condition and oral health habits within different groups of asthmatic children.

  14. A normal tissue dose response model of dynamic repair processes

    Science.gov (United States)

    Alber, Markus; Belka, Claus

    2006-01-01

    A model is presented for serial, critical element complication mechanisms for irradiated volumes from length scales of a few millimetres up to the entire organ. The central element of the model is the description of radiation complication as the failure of a dynamic repair process. The nature of the repair process is seen as reestablishing the structural organization of the tissue, rather than mere replenishment of lost cells. The interactions between the cells, such as migration, involved in the repair process are assumed to have finite ranges, which limits the repair capacity and is the defining property of a finite-sized reconstruction unit. Since the details of the repair processes are largely unknown, the development aims to make the most general assumptions about them. The model employs analogies and methods from thermodynamics and statistical physics. An explicit analytical form of the dose response of the reconstruction unit for total, partial and inhomogeneous irradiation is derived. The use of the model is demonstrated with data from animal spinal cord experiments and clinical data about heart, lung and rectum. The three-parameter model lends a new perspective to the equivalent uniform dose formalism and the established serial and parallel complication models. Its implications for dose optimization are discussed.

  15. Toolkit for determination of dose-response relations, validation of radiobiological parameters and treatment plan optimization based on radiobiological measures.

    Science.gov (United States)

    Mavroidis, Panayiotis; Tzikas, Athanasios; Papanikolaou, Nikos; Lind, Bengt K

    2010-10-01

    Accurately determined dose-response relations of the different tumors and normal tissues should be estimated and used in the clinic. The aim of this study is to demonstrate developed tools that are necessary for determining the dose-response parameters of tumors and normal tissues, for clinically verifying already published parameter sets using local patient materials and for making use of all this information in the optimization and comparison of different treatment plans and radiation techniques. One of the software modules (the Parameter Determination Module) is designed to determine the dose-response parameters of tumors and normal tissues. This is accomplished by performing a maximum likelihood fitting to calculate the best estimates and confidence intervals of the parameters used by different radiobiological models. Another module of this software (the Parameter Validation Module) concerns the validation and compatibility of external or reported dose-response parameters describing tumor control and normal tissue complications. This is accomplished by associating the expected response rates, which are calculated using different models and published parameter sets, with the clinical follow-up records of the local patient population. Finally, the last module of the software (the Radiobiological Plan Evaluation Module) is used for estimating and optimizing the effectiveness a treatment plan in terms of complication-free tumor control, P(+). The use of the Parameter Determination Module is demonstrated by deriving the dose-response relation of proximal esophagus from head and neck cancer radiotherapy. The application of the Parameter Validation Module is illustrated by verifying the clinical compatibility of those dose-response parameters with the examined treatment methodologies. The Radiobiological Plan Evaluation Module is demonstrated by evaluating and optimizing the effectiveness of head and neck cancer treatment plans. The results of the radiobiological

  16. Defining a quantitative framework for evaluation and optimisation of the environmental impacts of mega-event projects.

    Science.gov (United States)

    Parkes, Olga; Lettieri, Paola; Bogle, I David L

    2016-02-01

    This paper presents a novel quantitative methodology for the evaluation and optimisation of the environmental impacts of the whole life cycle of a mega-event project: construction and staging the event and post-event site redevelopment and operation. Within the proposed framework, a mathematical model has been developed that takes into account greenhouse gas (GHG) emissions resulting from use of transportation fuel, energy, water and construction materials used at all stages of the mega-event project. The model is applied to a case study - the London Olympic Park. Three potential post-event site design scenarios of the Park have been developed: Business as Usual (BAU), Commercial World (CW) and High Rise High Density (HRHD). A quantitative summary of results demonstrates that the highest GHG emissions associated with the actual event are almost negligible compared to those associated with the legacy phase. The highest share of emissions in the legacy phase is attributed to embodied emissions from construction materials (almost 50% for the BAU and HRHD scenarios) and emissions resulting from the transportation of residents, visitors and employees to/from the site (almost 60% for the CW scenario). The BAU scenario is the one with the lowest GHG emissions compared to the other scenarios. The results also demonstrate how post-event site design scenarios can be optimised to minimise the GHG emissions. The overall outcomes illustrate how the proposed framework can be used to support decision making process for mega-event projects planning. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Handling of the Generation of Primary Events in Gauss, the LHCb Simulation Framework

    CERN Multimedia

    Corti, G; Brambach, T; Brook, N H; Gauvin, N; Harrison, K; Harrison, P; He, J; Ilten, P J; Jones, C R; Lieng, M H; Manca, G; Miglioranzi, S; Robbe, P; Vagnoni, V; Whitehead, M; Wishahi, J

    2010-01-01

    The LHCb simulation application, Gauss, consists of two independent phases, the generation of the primary event and the tracking of particles produced in the experimental setup. For the LHCb experimental program it is particularly important to model B meson decays: the EvtGen code developed in CLEO and BaBar has been chosen and customized for non coherent B production as occuring in pp collisions at the LHC. The initial proton-proton collision is provided by a different generator engine, currently Pythia 6 for massive production of signal and generic pp collisions events. Beam gas events, background events originating from proton halo, cosmics and calibration events for different detectors can be generated in addition to pp collisions. Different generator packages are available in the physics community or specifically developed in LHCb, and are used for the different purposes. Running conditions affecting the events generated such as the size of the luminous region, the number of collisions occuring in a bunc...

  18. Shared dosimetry error in epidemiological dose-response analyses.

    Directory of Open Access Journals (Sweden)

    Daniel O Stram

    Full Text Available Radiation dose reconstruction systems for large-scale epidemiological studies are sophisticated both in providing estimates of dose and in representing dosimetry uncertainty. For example, a computer program was used by the Hanford Thyroid Disease Study to provide 100 realizations of possible dose to study participants. The variation in realizations reflected the range of possible dose for each cohort member consistent with the data on dose determinates in the cohort. Another example is the Mayak Worker Dosimetry System 2013 which estimates both external and internal exposures and provides multiple realizations of "possible" dose history to workers given dose determinants. This paper takes up the problem of dealing with complex dosimetry systems that provide multiple realizations of dose in an epidemiologic analysis. In this paper we derive expected scores and the information matrix for a model used widely in radiation epidemiology, namely the linear excess relative risk (ERR model that allows for a linear dose response (risk in relation to radiation and distinguishes between modifiers of background rates and of the excess risk due to exposure. We show that treating the mean dose for each individual (calculated by averaging over the realizations as if it was true dose (ignoring both shared and unshared dosimetry errors gives asymptotically unbiased estimates (i.e. the score has expectation zero and valid tests of the null hypothesis that the ERR slope β is zero. Although the score is unbiased the information matrix (and hence the standard errors of the estimate of β is biased for β≠0 when ignoring errors in dose estimates, and we show how to adjust the information matrix to remove this bias, using the multiple realizations of dose. The use of these methods in the context of several studies including, the Mayak Worker Cohort, and the U.S. Atomic Veterans Study, is discussed.

  19. Shared dosimetry error in epidemiological dose-response analyses.

    Science.gov (United States)

    Stram, Daniel O; Preston, Dale L; Sokolnikov, Mikhail; Napier, Bruce; Kopecky, Kenneth J; Boice, John; Beck, Harold; Till, John; Bouville, Andre

    2015-01-01

    Radiation dose reconstruction systems for large-scale epidemiological studies are sophisticated both in providing estimates of dose and in representing dosimetry uncertainty. For example, a computer program was used by the Hanford Thyroid Disease Study to provide 100 realizations of possible dose to study participants. The variation in realizations reflected the range of possible dose for each cohort member consistent with the data on dose determinates in the cohort. Another example is the Mayak Worker Dosimetry System 2013 which estimates both external and internal exposures and provides multiple realizations of "possible" dose history to workers given dose determinants. This paper takes up the problem of dealing with complex dosimetry systems that provide multiple realizations of dose in an epidemiologic analysis. In this paper we derive expected scores and the information matrix for a model used widely in radiation epidemiology, namely the linear excess relative risk (ERR) model that allows for a linear dose response (risk in relation to radiation) and distinguishes between modifiers of background rates and of the excess risk due to exposure. We show that treating the mean dose for each individual (calculated by averaging over the realizations) as if it was true dose (ignoring both shared and unshared dosimetry errors) gives asymptotically unbiased estimates (i.e. the score has expectation zero) and valid tests of the null hypothesis that the ERR slope β is zero. Although the score is unbiased the information matrix (and hence the standard errors of the estimate of β) is biased for β≠0 when ignoring errors in dose estimates, and we show how to adjust the information matrix to remove this bias, using the multiple realizations of dose. The use of these methods in the context of several studies including, the Mayak Worker Cohort, and the U.S. Atomic Veterans Study, is discussed.

  20. Chronic periodontitis and smoking. Prevalence and dose-response relationship.

    Science.gov (United States)

    Khan, Shahrukh; Khalid, Taimur; Awan, Kamran H

    2016-08-01

    To determine the prevalence and dose-response relationship of chronic periodontitis among smokers in Pakistan.   This is a cross-sectional study among participants seeking dental care in Karachi Medical and Dental College, Karachi, Pakistan. A total of 443 participants with a mean age of 44.3 (±6.5) participated in the study from April 2011 to December 2011. Males comprised 64.7%, and females comprised 35.2%. Participants were interviewed on social demographics and oral habits. Participants with shallow pockets (3.5-5.5 mm) and deep pockets (greater than 5.5 mm) were considered suffering from chronic periodontitis. The characteristics of participants were assessed using frequency distribution for categorical variables and mean (standard deviation) for continuous variables.  Among 443 participants, smokers were distributed as 55.1% and non-smokers as 44.9%. Smoking was found to be significantly related to young adults (p less than 0.007), male gender (p less than 0.001), and lower education level (p less than 0.01). Overall prevalence of chronic periodontitis among smokers was estimated at 81.6%. Heavy smoking was found to have significantly high prevalence (p less than 0.001) and severity (p less than 0.001) of periodontitis as compared with moderate and light smokers. The multivariate unadjusted model depicted 3.5 times higher risk of chronic periodontitis among smokers (p less than 0.001). Chronic periodontitis had a high prevalence among smokers. Heavy smoking was found to have a higher risk for having periodontitis.

  1. Human cardiovascular dose-response to supplemental oxygen.

    Science.gov (United States)

    Bak, Z; Sjöberg, F; Rousseau, A; Steinvall, I; Janerot-Sjoberg, B

    2007-09-01

    The aim of the study was to examine the central and peripheral cardiovascular adaptation and its coupling during increasing levels of hyperoxaemia. We hypothesized a dose-related effect of hyperoxaemia on left ventricular performance and the vascular properties of the arterial tree. Oscillometrically calibrated arterial subclavian pulse trace data were combined with echocardiographic recordings to obtain non-invasive estimates of left ventricular volumes, aortic root pressure and flow data. For complementary vascular parameters and control purposes whole-body impedance cardiography was applied. In nine (seven males) supine, resting healthy volunteers, aged 23-48 years, data was collected after 15 min of air breathing and at increasing transcutaneous oxygen tensions (20, 40 and 60 kPa), accomplished by a two group, random order and blinded hyperoxemic protocol. Left ventricular stroke volume [86 +/- 13 to 75 +/- 9 mL (mean +/- SD)] and end-diastolic area (19.3 +/- 4.4 to 16.8 +/- 4.3 cm(2)) declined (P arterial oxygen levels in a regression model. Peripheral resistance and characteristic impedance increased in a similar manner. Heart rate, left ventricular fractional area change, end-systolic area, mean arterial pressure, arterial compliance or carbon dioxide levels did not change. There is a linear dose-response relationship between arterial oxygen and cardiovascular parameters when the systemic oxygen tension increases above normal. A direct effect of supplemental oxygen on the vessels may therefore not be excluded. Proximal aortic and peripheral resistance increases from hyperoxaemia, but a decrease of venous return implies extra cardiac blood-pooling and compensatory relaxation of the capacitance vessels.

  2. Depressive disorder, coronary heart disease, and stroke: dose-response and reverse causation effects in the Whitehall II cohort study.

    Science.gov (United States)

    Brunner, Eric J; Shipley, Martin J; Britton, Annie R; Stansfeld, Stephen A; Heuschmann, Peter U; Rudd, Anthony G; Wolfe, Charles D A; Singh-Manoux, Archana; Kivimaki, Mika

    2014-03-01

    Systematic reviews examining associations of depressive disorder with coronary heart disease and stroke produce mixed results. Failure to consider reverse causation and dose-response patterns may have caused inconsistencies in evidence. This prospective cohort study on depressive disorder, coronary heart disease, and stroke analysed reverse causation and dose-response effects using four 5-year and three 10-year observation cycles (total follow up 24 years) based on multiple repeat measures of exposure. Participants in the Whitehall II study (n = 10,036, 31,395 person-observations, age at start 44.4 years) provided up to six repeat measures of depressive symptoms via the 30-item General Health Questionnaire (GHQ-30) and one measure via Center for Epidemiologic Studies Depression Scale (CES-D). The cohort was followed up for major coronary events (coronary death/nonfatal myocardial infarction) and stroke (stroke death/morbidity) through the national mortality register Hospital Episode Statistics, ECG-screening, medical records, and self-report questionnaires. GHQ-30 caseness predicted stroke over 0-5 years (age-, sex- and ethnicity-adjusted HR 1.60, 95% CI 1.1-2.3) but not over 5-10 years (HR 0.94, 95% CI 0.6-1.4). Using the last 5-year observation cycle, cumulative GHQ-30 caseness was associated with incident coronary heart disease in a dose-response manner (1-2 times a case: HR 1.12, 95% CI 0.7-1.7; 3-4 times: HR 2.06, 95% CI 1.2-3.7), and CES-D caseness predicted coronary heart disease (HR 1.81, 95% CI 1.1-3.1). There was evidence of a dose-response effect of depressive symptoms on risk of coronary heart disease. In contrast, prospective associations of depressive symptoms with stroke appeared to arise wholly or partly through reverse causation.

  3. SSEL-ADE: A semi-supervised ensemble learning framework for extracting adverse drug events from social media.

    Science.gov (United States)

    Liu, Jing; Zhao, Songzheng; Wang, Gang

    2017-10-27

    With the development of Web 2.0 technology, social media websites have become lucrative but under-explored data sources for extracting adverse drug events (ADEs), which is a serious health problem. Besides ADE, other semantic relation types (e.g., drug indication and beneficial effect) could hold between the drug and adverse event mentions, making ADE relation extraction - distinguishing ADE relationship from other relation types - necessary. However, conducting ADE relation extraction in social media environment is not a trivial task because of the expertise-dependent, time-consuming and costly annotation process, and the feature space's high-dimensionality attributed to intrinsic characteristics of social media data. This study aims to develop a framework for ADE relation extraction using patient-generated content in social media with better performance than that delivered by previous efforts. To achieve the objective, a general semi-supervised ensemble learning framework, SSEL-ADE, was developed. The framework exploited various lexical, semantic, and syntactic features, and integrated ensemble learning and semi-supervised learning. A series of experiments were conducted to verify the effectiveness of the proposed framework. Empirical results demonstrate the effectiveness of each component of SSEL-ADE and reveal that our proposed framework outperforms most of existing ADE relation extraction methods The SSEL-ADE can facilitate enhanced ADE relation extraction performance, thereby providing more reliable support for pharmacovigilance. Moreover, the proposed semi-supervised ensemble methods have the potential of being applied to effectively deal with other social media-based problems. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Framework for Modeling High-Impact, Low-Frequency Power Grid Events to Support Risk-Informed Decisions

    Energy Technology Data Exchange (ETDEWEB)

    Veeramany, Arun; Unwin, Stephen D.; Coles, Garill A.; Dagle, Jeffery E.; Millard, W. David; Yao, Juan; Glantz, Clifford S.; Gourisetti, Sri Nikhil Gup

    2015-12-03

    Natural and man-made hazardous events resulting in loss of grid infrastructure assets challenge the electric power grid’s security and resilience. However, the planning and allocation of appropriate contingency resources for such events requires an understanding of their likelihood and the extent of their potential impact. Where these events are of low likelihood, a risk-informed perspective on planning can be problematic as there exists an insufficient statistical basis to directly estimate the probabilities and consequences of their occurrence. Since risk-informed decisions rely on such knowledge, a basis for modeling the risk associated with high-impact low frequency events (HILFs) is essential. Insights from such a model can inform where resources are most rationally and effectively expended. The present effort is focused on development of a HILF risk assessment framework. Such a framework is intended to provide the conceptual and overarching technical basis for the development of HILF risk models that can inform decision makers across numerous stakeholder sectors. The North American Electric Reliability Corporation (NERC) 2014 Standard TPL-001-4 considers severe events for transmission reliability planning, but does not address events of such severity that they have the potential to fail a substantial fraction of grid assets over a region, such as geomagnetic disturbances (GMD), extreme seismic events, and coordinated cyber-physical attacks. These are beyond current planning guidelines. As noted, the risks associated with such events cannot be statistically estimated based on historic experience; however, there does exist a stable of risk modeling techniques for rare events that have proven of value across a wide range of engineering application domains. There is an active and growing interest in evaluating the value of risk management techniques in the State transmission planning and emergency response communities, some of this interest in the context of

  5. A method to adjust radiation dose-response relationships for clinical risk factors

    DEFF Research Database (Denmark)

    Appelt, Ane Lindegaard; Vogelius, Ivan R

    2012-01-01

    Several clinical risk factors for radiation induced toxicity have been identified in the literature. Here, we present a method to quantify the effect of clinical risk factors on radiation dose-response curves and apply the method to adjust the dose-response for radiation pneumonitis for patients...

  6. Health damage of air pollution : an estimate of a dose-response relationship for The Netherlands

    NARCIS (Netherlands)

    Nentjes, A; Schneider, T

    1998-01-01

    This paper estimates the dose-response relationship between air pollution and the number of work loss days for The Netherlands. The study is based on illness data (work loss days) for the Dutch labor population and average year concentrations of air pollution in 29 districts. The dose-response

  7. Dose-response relationships and threshold levels in skin and respiratory allergy

    NARCIS (Netherlands)

    Arts, J.H.E.; Mommers, C.; Heer, C.de

    2006-01-01

    A literature study was performed to evaluate dose-response relationships and no-effect levels for sensitization and elicitation in skin- and respiratory allergy. With respect to the skin, dose-response relationships and no-effect levels were found for both intradermal and topical induction, as well

  8. Framework for modeling high-impact, low-frequency power grid events to support risk-informed decisions

    Energy Technology Data Exchange (ETDEWEB)

    Veeramany, Arun; Unwin, Stephen D.; Coles, Garill A.; Dagle, Jeffery E.; Millard, David W.; Yao, Juan; Glantz, Cliff S.; Gourisetti, Sri N. G.

    2016-06-25

    Natural and man-made hazardous events resulting in loss of grid infrastructure assets challenge the security and resilience of the electric power grid. However, the planning and allocation of appropriate contingency resources for such events requires an understanding of their likelihood and the extent of their potential impact. Where these events are of low likelihood, a risk-informed perspective on planning can be difficult, as the statistical basis needed to directly estimate the probabilities and consequences of their occurrence does not exist. Because risk-informed decisions rely on such knowledge, a basis for modeling the risk associated with high-impact, low-frequency events (HILFs) is essential. Insights from such a model indicate where resources are most rationally and effectively expended. A risk-informed realization of designing and maintaining a grid resilient to HILFs will demand consideration of a spectrum of hazards/threats to infrastructure integrity, an understanding of their likelihoods of occurrence, treatment of the fragilities of critical assets to the stressors induced by such events, and through modeling grid network topology, the extent of damage associated with these scenarios. The model resulting from integration of these elements will allow sensitivity assessments based on optional risk management strategies, such as alternative pooling, staging and logistic strategies, and emergency contingency planning. This study is focused on the development of an end-to-end HILF risk-assessment framework. Such a framework is intended to provide the conceptual and overarching technical basis for the development of HILF risk models that can inform decision-makers across numerous stakeholder groups in directing resources optimally towards the management of risks to operational continuity.

  9. Application of stochastic discrete event system framework for detection of induced low rate TCP attack.

    Science.gov (United States)

    Barbhuiya, F A; Agarwal, Mayank; Purwar, Sanketh; Biswas, Santosh; Nandi, Sukumar

    2015-09-01

    TCP is the most widely accepted transport layer protocol. The major emphasis during the development of TCP was its functionality and efficiency. However, not much consideration was given on studying the possibility of attackers exploiting the protocol, which has lead to several attacks on TCP. This paper deals with the induced low rate TCP attack. Since the attack is relatively new, only a few schemes have been proposed to mitigate it. However, the main issues with these schemes are scalability, change in TCP header, lack of formal frameworks, etc. In this paper, we have adapted the stochastic DES framework for detecting the attack, which addresses most of these issues. We have successfully deployed and tested the proposed DES based IDS on a test bed. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

  10. An integrative framework identifies alternative splicing events in colorectal cancer development.

    Science.gov (United States)

    Bisognin, Andrea; Pizzini, Silvia; Perilli, Lisa; Esposito, Giovanni; Mocellin, Simone; Nitti, Donato; Zanovello, Paola; Bortoluzzi, Stefania; Mandruzzato, Susanna

    2014-02-01

    Alternative splicing (AS) is a common mechanism which creates diverse RNA isoforms from a single gene, potentially increasing protein variety. Growing evidence suggests that this mechanism is closely related to cancer progression. In this study, whole transcriptome analysis was performed with GeneChip Human exon 1.0 ST Array from 80 samples comprising 23 normal colon mucosa, 30 primary colorectal cancer and 27 liver metastatic specimens from 46 patients, to identify AS events in colorectal cancer progression. Differentially expressed genes and exons were estimated and AS events were reconstructed by combining exon-level analyses with AltAnalyze algorithms and transcript-level estimations (MMBGX probabilistic method). The number of AS genes in the transition from normal colon mucosa to primary tumor was the most abundant, but fell considerably in the next transition to liver metastasis. 206 genes with probable AS events in colon cancer development and progression were identified, that are involved in processes and pathways relevant to tumor biology, as cell-cell and cell-matrix interactions. Several AS events in VCL, CALD1, B3GNT6 and CTHRC1 genes, differentially expressed during tumor development were validated, at RNA and at protein level. Taken together, these results demonstrate that cancer-specific AS is common in early phases of colorectal cancer natural history. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  11. A Strategic E-Marketing Framework For Sport Mega-Events

    National Research Council Canada - National Science Library

    Paul S. Radikonyana; Ernie Heath; Felicité Fairer-Wessels Fairer-Wessels; J.J. Prinsloo; Theuns G. Pelser

    2015-01-01

      This article reports on a study that was conducted which aims to understand the optimal usage of e-marketing in sport mega-events with reference to the 2010 FIFA Soccer World Cup, which was held in South Africa...

  12. ATLAS Event Data Organization and I/O Framework Capabilities in Support of Heterogeneous Data Access and Processing Models

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00219732; The ATLAS collaboration; Cranshaw, Jack; van Gemmeren, Peter; Nowak, Marcin

    2016-01-01

    Choices in persistent data models and data organization have significant performance ramifications for data-intensive scientific computing. In experimental high energy physics, organizing file-based event data for efficient per-attribute retrieval may improve the I/O performance of some physics analyses but hamper the performance of processing that requires full-event access. In-file data organization tuned for serial access by a single process may be less suitable for opportunistic sub-file-based processing on distributed computing resources. Unique I/O characteristics of high-performance computing platforms pose additional challenges. The ATLAS experiment at the Large Hadron Collider employs a flexible I/O framework and a suite of tools and techniques for persistent data organization to support an increasingly heterogeneous array of data access and processing models.

  13. ATLAS Event Data Organization and I/O Framework Capabilities in Support of Heterogeneous Data Access and Processing Models

    CERN Document Server

    Malon, David; The ATLAS collaboration; van Gemmeren, Peter

    2016-01-01

    Choices in persistent data models and data organization have significant performance ramifications for data-intensive scientific computing. In experimental high energy physics, organizing file-based event data for efficient per-attribute retrieval may improve the I/O performance of some physics analyses but hamper the performance of processing that requires full-event access. In-file data organization tuned for serial access by a single process may be less suitable for opportunistic sub-file-based processing on distributed computing resources. Unique I/O characteristics of high-performance computing platforms pose additional challenges. This paper describes work in the ATLAS experiment at the Large Hadron Collider to provide an I/O framework and tools for persistent data organization to support an increasingly heterogenous array of data access and processing models.

  14. Dose response severity functions for acoustic disturbance in cetaceans using recurrent event survival analysis

    NARCIS (Netherlands)

    Harris, C.M.; Sadykova, D.; DeRuiter, S.L.; Tyack, P.L.; Miller, P.J.O.; Kvadsheim, P.H.; Lam, F.P.A.; Thomas, L.

    2015-01-01

    Behavioral response studies (BRSs) aim to enhance our understanding of the behavior changes made by animals in response to specific exposure levels of different stimuli, often presented in an increasing dosage. Here, we focus on BRSs that aim to understand behavioral responses of free-ranging whales

  15. Events

    Directory of Open Access Journals (Sweden)

    Igor V. Karyakin

    2016-02-01

    Full Text Available The 9th ARRCN Symposium 2015 was held during 21st–25th October 2015 at the Novotel Hotel, Chumphon, Thailand, one of the most favored travel destinations in Asia. The 10th ARRCN Symposium 2017 will be held during October 2017 in the Davao, Philippines. International Symposium on the Montagu's Harrier (Circus pygargus «The Montagu's Harrier in Europe. Status. Threats. Protection», organized by the environmental organization «Landesbund für Vogelschutz in Bayern e.V.» (LBV was held on November 20-22, 2015 in Germany. The location of this event was the city of Wurzburg in Bavaria.

  16. A framework for estimating the adverse health effects of contamination events in water distribution systems and its application.

    Science.gov (United States)

    Davis, Michael J; Janke, Robert; Magnuson, Matthew L

    2014-03-01

    Intentional or accidental releases of contaminants into a water distribution system (WDS) have the potential to cause significant adverse health effects among individuals consuming water from the system. A flexible analysis framework is presented here for estimating the magnitude of such potential effects and is applied using network models for 12 actual WDSs of varying sizes. Upper bounds are developed for the magnitude of adverse effects of contamination events in WDSs and evaluated using results from the 12 systems. These bounds can be applied in cases in which little system-specific information is available. The combination of a detailed, network-specific approach and a bounding approach allows consequence assessments to be performed for systems for which varying amounts of information are available and addresses important needs of individual utilities as well as regional or national assessments. The approach used in the analysis framework allows contaminant injections at any or all network nodes and uses models that (1) account for contaminant transport in the systems, including contaminant decay, and (2) provide estimates of ingested contaminant doses for the exposed population. The approach can be easily modified as better transport or exposure models become available. The methods presented here provide the ability to quantify or bound potential adverse effects of contamination events for a wide variety of possible contaminants and WDSs, including systems without a network model. © 2013 Society for Risk Analysis.

  17. Bonsai: An event-based framework for processing and controlling data streams

    Directory of Open Access Journals (Sweden)

    Gonçalo eLopes

    2015-04-01

    Full Text Available The design of modern scientific experiments requires the control and monitoring of many different data streams. However, the serial execution of programming instructions in a computer makes it a challenge to develop software that can deal with the asynchronous, parallel nature of scientific data. Here we present Bonsai, a modular, high-performance, open-source visual programming framework for the acquisition and online processing of data streams. We describe Bonsai's core principles and architecture and demonstrate how it allows for the rapid and flexible prototyping of integrated experimental designs in neuroscience. We specifically highlight some applications that require the combination of many different hardware and software components, including video tracking of behavior, electrophysiology and closed-loop control of stimulation.

  18. Bonsai: an event-based framework for processing and controlling data streams.

    Science.gov (United States)

    Lopes, Gonçalo; Bonacchi, Niccolò; Frazão, João; Neto, Joana P; Atallah, Bassam V; Soares, Sofia; Moreira, Luís; Matias, Sara; Itskov, Pavel M; Correia, Patrícia A; Medina, Roberto E; Calcaterra, Lorenza; Dreosti, Elena; Paton, Joseph J; Kampff, Adam R

    2015-01-01

    The design of modern scientific experiments requires the control and monitoring of many different data streams. However, the serial execution of programming instructions in a computer makes it a challenge to develop software that can deal with the asynchronous, parallel nature of scientific data. Here we present Bonsai, a modular, high-performance, open-source visual programming framework for the acquisition and online processing of data streams. We describe Bonsai's core principles and architecture and demonstrate how it allows for the rapid and flexible prototyping of integrated experimental designs in neuroscience. We specifically highlight some applications that require the combination of many different hardware and software components, including video tracking of behavior, electrophysiology and closed-loop control of stimulation.

  19. Lack-of-fit tests for assessing mean structures for continuous dose-response data

    DEFF Research Database (Denmark)

    Ritz, Christian; Martinussen, Torben

    2011-01-01

    We review a range of lack-of-fit tests suitable for assessing the appropriateness of the mean function in dose-response models. The review encompasses both well-known tests and new tests based on recent developments in statistics, which we have extended to the dose-response case. We argue...... that the classical methods are inadequate in certain situations, where the new tests may be applied. Power comparisons are carried out by means of extensive simulation studies, covering both designs with and without replicates at small and large sample sizes. Three datasets from dose-response applications illustrate...

  20. Dose - response relationship between noise exposure and the risk of occupational injury

    Directory of Open Access Journals (Sweden)

    Jin-Ha Yoon

    2015-01-01

    Full Text Available Many workers worldwide experience fatality and disability caused by occupational injuries. This study examined the relationship between noise exposure and occupational injuries at factories in Korea. A total of 1790 factories located in northern Gyeonggi Province, Korea was evaluated. The time-weighted average levels of dust and noise exposure were taken from Workplace Exposure Assessment data. Apart occupational injuries, sports events, traffic accidents, and other accidents occurring outside workplaces were excluded. The incidences of occupational injury in each factory were calculated by data from the Korea Workers′ Compensation and Welfare Services. Workplaces were classified according to the incidence of any occupational injuries (incident or nonincident workplaces, respectively. Workplace dust exposure was classified as 90 dB. Workplaces with high noise exposure were significantly associated with being incident workplaces, whereas workplaces with high dust exposure were not. The odds ratios (95% confidence intervals derived from a logistic regression model were 1.68 (1.27-2.24 and 3.42 (2.26-5.17 at 80-89 dB and ≥90 dB versus <80 dB. These associations remained significant when in a separate analysis according to high or low dust exposure level. Noise exposure increases the risk of occupational injury in the workplace. Furthermore, the risk of occupational injury increases with noise exposure level in a dose-response relationship. Therefore, strategies for reducing noise exposure level are required to decrease the risk of occupational injury.

  1. Dose - response relationship between noise exposure and the risk of occupational injury.

    Science.gov (United States)

    Yoon, Jin-Ha; Hong, Jeong-Suk; Roh, Jaehoon; Kim, Chi-Nyon; Won, Jong-Uk

    2015-01-01

    Many workers worldwide experience fatality and disability caused by occupational injuries. This study examined the relationship between noise exposure and occupational injuries at factories in Korea. A total of 1790 factories located in northern Gyeonggi Province, Korea was evaluated. The time-weighted average levels of dust and noise exposure were taken from Workplace Exposure Assessment data. Apart occupational injuries, sports events, traffic accidents, and other accidents occurring outside workplaces were excluded. The incidences of occupational injury in each factory were calculated by data from the Korea Workers' Compensation and Welfare Services. Workplaces were classified according to the incidence of any occupational injuries (incident or nonincident workplaces, respectively). Workplace dust exposure was classified as noise exposure as 90 dB. Workplaces with high noise exposure were significantly associated with being incident workplaces, whereas workplaces with high dust exposure were not. The odds ratios (95% confidence intervals) derived from a logistic regression model were 1.68 (1.27-2.24) and 3.42 (2.26-5.17) at 80-89 dB and ≥ 90 dB versus exposure level. Noise exposure increases the risk of occupational injury in the workplace. Furthermore, the risk of occupational injury increases with noise exposure level in a dose-response relationship. Therefore, strategies for reducing noise exposure level are required to decrease the risk of occupational injury.

  2. Assessing the impact of an alternative biochemical failure definition on radiation dose response for high-risk prostate cancer treated with external beam radiotherapy.

    Science.gov (United States)

    Cheung, Rex; Tucker, Susan L; Lee, Andrew L; Dong, Lei; Kamat, Ashish; Pisters, Louis; Kuban, Deborah A

    2005-01-01

    The American Society for Therapeutic Radiology and Oncology (ASTRO) biochemical failure definition has recently been compared with various alternative definitions. We assessed the effect of using an alternative failure definition on the dose-response characteristics of high-risk prostate cancer treated with radiotherapy alone. This study included 363 high-risk prostate cancer patients treated with external beam radiotherapy alone from 1987 to 1999. These patients have one or more of the following: 1992 American Joint Committee on Cancer (AJCC) digital rectal examination (DRE) stage > or = cT3, prostate-specific antigen (PSA) > 20 ng/mL, and/or biopsy Gleason score > or = 8. We previously reported the dose response based on the ASTRO definition for these patients. In this study, a biochemical failure is defined as a PSA rise > or = 2 ng/mL above the current nadir PSA (CN + 2). The failure date is defined as the time at which the event occurred (i.e., the call date). Using CN + 2, the tumor control probability (TCP) continues to decrease with time as opposed to reaching a plateau as with the ASTRO definition. At 5 years, TCD50 (95% CI), the dose to achieve 50% tumor control, for high-risk prostate cancer, is 70.4 (68.0-72.9) Gy using CN + 2 [ASTRO: 75.5 (70.7-80.2) Gy]. The relative slope, gamma50 (95% CI) is 1.8 (0.8-2.8) [ASTRO: 1.7 (0.7-2.7)]. Recursive partitioning again identified two subgroups: PSA or = 13 ng/mL (ASTRO: PSA 20 ng/mL). The difference in TCD50 between the two subgroups is about 20 Gy at 5 years (ASTRO: about 15 Gy at 5 years). This analysis using the CN + 2 failure definition continues to show a dose response for the high-risk group of patients. However, the dose-response characteristics differ from those estimated using the ASTRO definition. We observed that the position (TCD50) and steepness (gamma50) of the dose-response curve changed with time as long as the TCP continued to decrease. This suggests that the dose response characteristics

  3. Unified framework for triaxial accelerometer-based fall event detection and classification using cumulants and hierarchical decision tree classifier.

    Science.gov (United States)

    Kambhampati, Satya Samyukta; Singh, Vishal; Manikandan, M Sabarimalai; Ramkumar, Barathram

    2015-08-01

    In this Letter, the authors present a unified framework for fall event detection and classification using the cumulants extracted from the acceleration (ACC) signals acquired using a single waist-mounted triaxial accelerometer. The main objective of this Letter is to find suitable representative cumulants and classifiers in effectively detecting and classifying different types of fall and non-fall events. It was discovered that the first level of the proposed hierarchical decision tree algorithm implements fall detection using fifth-order cumulants and support vector machine (SVM) classifier. In the second level, the fall event classification algorithm uses the fifth-order cumulants and SVM. Finally, human activity classification is performed using the second-order cumulants and SVM. The detection and classification results are compared with those of the decision tree, naive Bayes, multilayer perceptron and SVM classifiers with different types of time-domain features including the second-, third-, fourth- and fifth-order cumulants and the signal magnitude vector and signal magnitude area. The experimental results demonstrate that the second- and fifth-order cumulant features and SVM classifier can achieve optimal detection and classification rates of above 95%, as well as the lowest false alarm rate of 1.03%.

  4. Effects of fluticasone propionate on methacholine dose-response curves in nonsmoking atopic asthmatics

    NARCIS (Netherlands)

    S.E. Overbeek (Shelley); P.R. Rijnbeek (Peter); C. Vons; H.C. Hoogsteden (Henk); J.M. Bogaard (Jan); P.G.H. Mulder (Paul)

    1996-01-01

    textabstractMethacholine is frequently used to determine bronchial hyperresponsiveness (BHR) and to generate dose-response curves. These curves are characterized by a threshold (provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second

  5. Eosinophils in the bronchial mucosa in relation to methacholine dose-response curves in atopic asthma

    NARCIS (Netherlands)

    G.M. Moller (Trude); S.E. Overbeek (Shelley); C.G. van Helden-Meeuwsen; H.C. Hoogsteden (Henk); J.M. Bogaard (Jan)

    1999-01-01

    textabstractAsthma is characterized by both local infiltration of eosinophils in the bronchial mucosa and bronchial hyperreactivity (BHR). A detailed characterization of BHR implies analysis of a histamine or methacholine dose-response curve yielding not only the dose

  6. Dose-response regressions for algal growth and similar continuous endpoints: Calculation of effective concentrations

    DEFF Research Database (Denmark)

    Christensen, Erik R.; Kusk, Kresten Ole; Nyholm, Niels

    2009-01-01

    % inhibition). For illustration, data from closed, freshwater algal assays are analyzed using the green alga Pseudokirchneriella subcapitata with growth rate as the response parameter. Dose-response regressions for four test chemicals (tetraethylammonium bromide, musculamine, benzonitrile, and 4...

  7. Dose-response relationship of autonomic nervous system responses to individualized training impulse in marathon runners

    National Research Council Canada - National Science Library

    Vincenzo Manzi; Carlo Castagna; Elvira Padua; Mauro Lombardo; Stefano D'Ottavio; Michele Massaro; Maurizio Volterrani; Ferdinando Iellamo

    2009-01-01

    .... We tested the hypothesis that in long-distance athletes, changes in ANS parameters are dose-response related to individual volume/intensity training load and could predict athletic performance...

  8. Framework for Research on Children’s Reactions to Disasters and Terrorist Events

    Science.gov (United States)

    Pfefferbaum, Betty; Noffsinger, Mary A.; Sherrieb, Kathleen; Norris, Fran H.

    2012-01-01

    Clinical work and research relative to child mental health during and following disaster are especially challenging due to the complex child maturational processes and family and social contexts of children’s lives. The effects of disasters and terrorist events on children and adolescents necessitate diligent and responsible preparation and implementation of research endeavors. Disasters present numerous practical and methodological barriers that may influence the selection of participants, timing of assessments, and constructs being investigated. This article describes an efficient approach to guide both novice and experienced researchers as they prepare to conduct disaster research involving children. The approach is based on five fundamental research questions: “Why?, Who?, When?, What?, and How?” Addressing each of the “four Ws” will assist researchers in determining “How” to construct and implement a study from start to finish. A simple diagram of the five questions guides the reader through the components involved in studying children’s reactions to disasters. The use of this approach is illustrated with examples from disaster mental health studies in children, thus simultaneously providing a review of the literature. PMID:23034149

  9. Robust Initial Wetness Condition Framework of an Event-Based Rainfall–Runoff Model Using Remotely Sensed Soil Moisture

    Directory of Open Access Journals (Sweden)

    Wooyeon Sunwoo

    2017-01-01

    Full Text Available Runoff prediction in limited-data areas is vital for hydrological applications, such as the design of infrastructure and flood defenses, runoff forecasting, and water management. Rainfall–runoff models may be useful for simulation of runoff generation, particularly event-based models, which offer a practical modeling scheme because of their simplicity. However, there is a need to reduce the uncertainties related to the estimation of the initial wetness condition (IWC prior to a rainfall event. Soil moisture is one of the most important variables in rainfall–runoff modeling, and remotely sensed soil moisture is recognized as an effective way to improve the accuracy of runoff prediction. In this study, the IWC was evaluated based on remotely sensed soil moisture by using the Soil Conservation Service-Curve Number (SCS-CN method, which is one of the representative event-based models used for reducing the uncertainty of runoff prediction. Four proxy variables for the IWC were determined from the measurements of total rainfall depth (API5, ground-based soil moisture (SSMinsitu, remotely sensed surface soil moisture (SSM, and soil water index (SWI provided by the advanced scatterometer (ASCAT. To obtain a robust IWC framework, this study consists of two main parts: the validation of remotely sensed soil moisture, and the evaluation of runoff prediction using four proxy variables with a set of rainfall–runoff events in the East Asian monsoon region. The results showed an acceptable agreement between remotely sensed soil moisture (SSM and SWI and ground based soil moisture data (SSMinsitu. In the proxy variable analysis, the SWI indicated the optimal value among the proposed proxy variables. In the runoff prediction analysis considering various infiltration conditions, the SSM and SWI proxy variables significantly reduced the runoff prediction error as compared with API5 by 60% and 66%, respectively. Moreover, the proposed IWC framework with

  10. Time-to-event analysis as a framework for quantifying fish passage performance: Chapter 9.1

    Science.gov (United States)

    Castro-Santos, Theodore R.; Perry, Russell W.; Adams, Noah S.; Beeman, John W.; Eiler, John H.

    2012-01-01

    Fish passage is the result of a sequence of processes, whereby fish must approach, enter, and pass a structure. Each of these processes takes time, and fishway performance is best quantified in terms of the rates at which each process is completed. Optimal performance is achieved by maximizing the rates of approach, entry, and passage through safe and desirable routes. Sometimes, however, it is necessary to reduce rates of passage through less desirable routes in order to increase proportions passing through the preferred route. Effectiveness of operational or structural modifications for achieving either of these goals is best quantified by applying time-to-event analysis, commonly known as survival analysis methods, to telemetry data. This set of techniques allows for accurate estimation of passage rates and covariate effects on those rates. Importantly, it allows researchers to quantify rates that vary over time, as well as the effects of covariates that also vary over time. Finally, these methods are able to control for competing risks, i.e., the presence of alternate passage routes, failure to pass, or other fates that remove fish from the pool of candidates available to pass through a particular route. In this chapter, we present a model simulation of telemetered fish passing a hydroelectric dam, and provide step-by-step guidance and rationales for performing time-to-event analysis on the resulting data. We demonstrate how this approach removes bias from performance estimates that can result from using methods that focus only on proportions passing each route. Time-to-event analysis, coupled with multinomial models for measuring survival, provides a comprehensive set of techniques for quantifying fish passage, and a framework from which performance among different sites can be better understood.

  11. Effect of Photon Hormesis on Dose Responses to Alpha Particles in Zebrafish Embryos.

    Science.gov (United States)

    Ng, Candy Yuen Ping; Cheng, Shuk Han; Yu, Kwan Ngok

    2017-02-11

    Photon hormesis refers to the phenomenon where the biological effect of ionizing radiation with a high linear energy transfer (LET) value is diminished by photons with a low LET value. The present paper studied the effect of photon hormesis from X-rays on dose responses to alpha particles using embryos of the zebrafish (Danio rerio) as the in vivo vertebrate model. The toxicity of these ionizing radiations in the zebrafish embryos was assessed using the apoptotic counts at 20, 24, or 30 h post fertilization (hpf) revealed through acridine orange (AO) staining. For alpha-particle doses ≥ 4.4 mGy, the additional X-ray dose of 10 mGy significantly reduced the number of apoptotic cells at 24 hpf, which proved the presence of photon hormesis. Smaller alpha-particle doses might not have inflicted sufficient aggregate damages to trigger photon hormesis. The time gap T between the X-ray (10 mGy) and alpha-particle (4.4 mGy) exposures was also studied. Photon hormesis was present when T ≤ 30 min, but was absent when T = 60 min, at which time repair of damage induced by alpha particles would have completed to prevent their interactions with those induced by X-rays. Finally, the drop in the apoptotic counts at 24 hpf due to photon hormesis was explained by bringing the apoptotic events earlier to 20 hpf, which strongly supported the removal of aberrant cells through apoptosis as an underlying mechanism for photon hormesis.

  12. Two-Stage Experimental Design for Dose-Response Modeling in Toxicology Studies.

    Science.gov (United States)

    Wang, Kai; Yang, Feng; Porter, Dale W; Wu, Nianqiang

    The efficient design of experiments (i.e., selection of experimental doses and allocation of animals) is important to establishing dose-response relationships in toxicology studies. The proposed procedure for design of experiments is distinct from those in the literature because it is able to adequately accommodate the special features of the dose-response data, which include non-normality, variance heterogeneity, possibly nonlinearity of the dose-response curve, and data scarcity. The design procedure is built in a sequential two-stage paradigm that allows for a learning process. In the first stage, preliminary experiments are performed to gain information regarding the underlying dose-response curve and variance structure. In the second stage, the prior information obtained from the previous stage is utilized to guide the second-stage experiments. An optimization algorithm is developed to search for the design of experiments that will lead to dose-response models of the highest quality. To evaluate model quality (or uncertainty), which is the basis of design optimization, a bootstrapping method is employed; unlike standard statistical methods, bootstrapping is not subject to restrictive assumptions such as normality or large sample sizes. The design procedure in this paper will help to reduce the experimental cost/time in toxicology studies and alleviate the sustainability concerns regarding the tremendous new materials and chemicals.

  13. Dose-response characteristics of low- and intermediate-risk prostate cancer treated with external beam radiotherapy.

    Science.gov (United States)

    Cheung, Rex; Tucker, Susan L; Lee, Andrew K; de Crevoisier, Renaud; Dong, Lei; Kamat, Ashish; Pisters, Louis; Kuban, Deborah

    2005-03-15

    In this era of dose escalation, the benefit of higher radiation doses for low-risk prostate cancer remains controversial. For intermediate-risk patients, the data suggest a benefit from higher doses. However, the quantitative characterization of the benefit for these patients is scarce. We investigated the radiation dose-response relation of tumor control probability in low-risk and intermediate-risk prostate cancer patients treated with radiotherapy alone. We also investigated the differences in the dose-response characteristics using the American Society for Therapeutic Radiology and Oncology (ASTRO) definition vs. an alternative biochemical failure definition. This study included 235 low-risk and 387 intermediate-risk prostate cancer patients treated with external beam radiotherapy without hormonal treatment between 1987 and 1998. The low-risk patients had 1992 American Joint Committee on Cancer Stage T2a or less disease as determined by digital rectal examination, prostate-specific antigen (PSA) levels of 10 ng/mL, and/or Gleason score of 7, without any of the following high-risk features: Stage T3 or greater, PSA >20 ng/mL, or Gleason score > or =8. The logistic models were fitted to the data at varying points after treatment, and the dose-response parameters were estimated. We used two biochemical failure definitions. The ASTRO PSA failure was defined as three consecutive PSA rises, with the time to failure backdated to the mid-point between the nadir and the first rise. The second biochemical failure definition used was a PSA rise of > or =2 ng/mL above the current PSA nadir (CN + 2). The failure date was defined as the time at which the event occurred. Local, nodal, and distant relapses and the use of salvage hormonal therapy were also failures. On the basis of the ASTRO definition, at 5 years after radiotherapy, the dose required for 50% tumor control (TCD(50)) for low-risk patients was 57.3 Gy (95% confidence interval [CI], 47.6-67.0). The gamma50 was 1

  14. A review of the use of human factors classification frameworks that identify causal factors for adverse events in the hospital setting.

    Science.gov (United States)

    Mitchell, R J; Williamson, A M; Molesworth, B; Chung, A Z Q

    2014-01-01

    Various human factors classification frameworks have been used to identified causal factors for clinical adverse events. A systematic review was conducted to identify human factors classification frameworks that identified the causal factors (including human error) of adverse events in a hospital setting. Six electronic databases were searched, identifying 1997 articles and 38 of these met inclusion criteria. Most studies included causal contributing factors as well as error and error type, but the nature of coding varied considerably between studies. The ability of human factors classification frameworks to provide information on specific causal factors for an adverse event enables the focus of preventive attention on areas where improvements are most needed. This review highlighted some areas needing considerable improvement in order to meet this need, including better definition of terms, more emphasis on assessing reliability of coding and greater sophistication in analysis of results of the classification. Practitioner Summary: Human factors classification frameworks can be used to identify causal factors of clinical adverse events. However, this review suggests that existing frameworks are diverse, limited in their identification of the context of human error and have poor reliability when used by different individuals.

  15. Exposure- and Dose-response Analyses in Dose Selection and Labeling of FDA-approved Biologics.

    Science.gov (United States)

    Ogasawara, Ken; Breder, Christopher D; Lin, Dora H; Alexander, G Caleb

    2018-01-01

    Biological drug products, or products derived from living cells, represent an increasingly important part of the pharmaceutical market. Despite this, little is known about how sponsors determine the dose to be studied in registrational trials or to be proposed in labeling for biologics. We examined how exposure-response and dose-response analyses were used to determine dosing in pivotal trials or the labeling for all biologics approved by the Center for Drug Evaluation and Research, the US Food and Drug Administration (FDA) between 2003 and 2016. We extracted relevant characteristics of each biologic from its review package by FDA. We used descriptive statistics to characterize the rationale for the selected dose(s) in registration trials, with a particular focus on the role of exposure-response/dose-response analyses. We also examined how exposure-response/dose-response analyses were used to support the labeling dose and the basis for postmarketing requirements or commitments related to dose optimization. A total of 79 biologics license applications were examined. Dose selection in registrational trials was more often attributed to clinical efficacy (73% of applications) than to clinical safety (42%). The dosing of products whose dose was apparently selected based on clinical efficacy was often (72%) determined by the dose-response relationship. In support of doses that were described in labeling, exposure-response analyses for efficacy were performed more commonly (53%) than dose-response analyses (21%). This trend was apparent after 2012. This is the first study to summarize the justification of dose selection and the labeled dose of biologics approved by the FDA. Dose-response analyses have been often used as the rationale for dose selection of registrational studies, although exposure-response analyses are becoming more prevalent in support of the dosing guidelines in labeling. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

  16. Dose response of subcutaneous GLP-1 infusion in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Torekov, Signe Sørensen; Kipnes, M S; Harley, R E

    2011-01-01

    To evaluate the dose-response relationship of the recombinant glucagon-like peptide-1 (7-36) amide (rGLP-1) administered by continuous subcutaneous infusion (CSCI) in subjects with type 2 diabetes, with respect to reductions in fasting, postprandial and 11-h serum glucose profiles.......To evaluate the dose-response relationship of the recombinant glucagon-like peptide-1 (7-36) amide (rGLP-1) administered by continuous subcutaneous infusion (CSCI) in subjects with type 2 diabetes, with respect to reductions in fasting, postprandial and 11-h serum glucose profiles....

  17. Dose-Response Curve of Chromosome Aberrations in Human Lymphocytes Induced by Gamma-Rays

    Directory of Open Access Journals (Sweden)

    Y. Lusiyanti

    2013-12-01

    Full Text Available Chromosome aberration is a biomarker to predict the level of cell damage caused by exposure to ionizing radiation on human body. Dicentric chromosome is a specific chromosome aberration caused by ionizing radiation and is used as a gold standard biodosimetry of individuals over exposed to ionizing radiation. In radiation accident the dicentric assays has been applied as biological dosimetry to estimate radiation absorbed dose and also to confirm the radiation dose received to radiation workers.The purpose of this study was to generate a dose response curve of chromosome aberration (dicentric in human lymphocyte induced by gamma radiation. Peripheral blood samples from three non smoking healthy volunteers aged between 25-48 years old with informed consent were irradiated with dose between 0.1-4.0 Gy and a control using gamma teletherapy source. The culture procedure was conducted following the IAEA standard procedures with slight modifications. Analysis of dose-response curves used was LQ model Y = a + αD + βD2. The result showed that α and β values of the curve obtained were 0.018 ± 0.006 and 0.013 ± 0.002, respectively. Dose response calibration curve for dicentric chromosome aberrations in human lymphocytes induced by gamma-radiation fitted to linear quadratic model. In order to apply the dose response curve of chromosome aberration disentric for biodosimetry, this standar curve still need to be validated.

  18. An in vitro biofilm model for enamel demineralization and antimicrobial dose-response studies

    NARCIS (Netherlands)

    Sande, F.H. van de; Azevedo, M.S.; Lund, R.G.; Huysmans, M.C.D.N.J.M.; Cenci, M.S.

    2011-01-01

    Microcosm biofilms formed in microplates have demonstrated complex community dynamics similar to natural dental biofilm. No simplified microcosm models to evaluate enamel demineralization and dose-response effect to anticariogenic therapies have yet been established, thus this study was designed to

  19. Dose response association of pregnancy cigarette smoke exposure, childhood stature, overweight and obesity

    NARCIS (Netherlands)

    Koshy, Gibby; Delpisheh, Ali; Brabin, Bernard J.

    2011-01-01

    The combined dose response effects of pregnancy cigarette smoke exposure on childhood overweight, obesity and short stature have not been reported. A community based cross-sectional survey of 3038 children aged 5-11 years from 15 primary schools in Merseyside, UK. Self-completed parental

  20. Dose-response characteristics of ketamine effect on locomotion, cognitive function and central neuronal activity

    NARCIS (Netherlands)

    Imre, G; Fokkema, DS; Den Boer, JA; Ter Horst, GJ

    2006-01-01

    The present dose-response study sought to determine the effects of subanesthetic dosages (4-16 mg/kg) of ketamine on locomotion, sensorimotor gating (PP1), working memory, as well as c-fos expression in various limbic regions implicated in the pathogenesis of schizophrenia. In addition, we examined

  1. Empirical Evaluation of Meta-Analytic Approaches for Nutrient and Health Outcome Dose-Response Data

    Science.gov (United States)

    Yu, Winifred W.; Schmid, Christopher H.; Lichtenstein, Alice H.; Lau, Joseph; Trikalinos, Thomas A.

    2013-01-01

    The objective of this study is to empirically compare alternative meta-analytic methods for combining dose-response data from epidemiological studies. We identified meta-analyses of epidemiological studies that analyzed the association between a single nutrient and a dichotomous outcome. For each topic, we performed meta-analyses of odds ratios…

  2. Concord grape juice polyphenols and cardiovascular risk factors: dose-response relationships

    Science.gov (United States)

    Pure fruit juices provide nutritional value with evidence suggesting some of their benefits on biomarkers of cardiovascular disease risk may be derived from their constituent polyphenols, particularly flavonoids. However, few data from clinical trials are available on the dose-response relationship ...

  3. Accelerometer-measured dose-response for physical activity, sedentary time, and mortality in US adults

    DEFF Research Database (Denmark)

    Matthews, Charles E; Keadle, S. K.; Troiano, Richard P

    2016-01-01

    Background: Moderate-to-vigorous-intensity physical activity is recommended to maintain and improve health, but the mortality benefits of light activity and risk for sedentary time remain uncertain. Objectives: Using accelerometer-based measures, we 1) described the mortality dose-response for se...

  4. A free software for the evaluation and comparison of dose response models in clinical radiotherapy (DORES).

    Science.gov (United States)

    Tsougos, Ioannis; Grout, Ioannis; Theodorou, Kyriaki; Kappas, Constantin

    2009-03-01

    The aim of this work was to develop a user-friendly and simple tool for fast and accurate estimation of Normal Tissue Complication Probabilities (NTCP) for several radiobiological models, which can be used as a valuable complement to the clinical experience. The software which has been named DORES (Dose Response Evaluation Software) has been developed in Visual Basic, and includes three NTCP models (Lyman-Kuther-Burman (LKB), Relative Seriality and Parallel). Required input information includes the Dose-Volume Histogram (DVH) for the Organs at Risk (OAR) of each treatment, the number of fractions and the total dose of therapy. NTCP values are computed, and subsequently placed in a spreadsheet file for further analysis. A Dose Response curve for every model is automatically generated. Every patient of the study population can be found on the curve since by definition their corresponding dose-response points fall exactly on the theoretical dose-response curve, when plotted on the same diagram. Distributions of absorbed dose alone do not provide information on the biological response of tissues to irradiation, so the use of this software may aid in the comparison of outcomes for different treatment plans or types of treatment, and also aid the evaluation of the sensitivity of different model predictions to uncertainties in parameter values. This was illustrated in a clinical case of breast cancer radiotherapy.

  5. Dose-response curve for blood exposed to gamma-neutron mixed field by conventional cytogenetic method

    Energy Technology Data Exchange (ETDEWEB)

    Brandao, Jose Odinilson de C.; Souza, Priscilla L.G.; Santos, Joelan A.L.; Vilela, Eudice C.; Lima, Fabiana F., E-mail: jodinilson@cnen.gov.b, E-mail: fflima@cnen.gov.b, E-mail: jasantos@cnen.gov.b [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Calixto, Merilane S.; Santos, Neide, E-mail: santos_neide@yahoo.com.b [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Genetica

    2009-07-01

    There is increasing concern about airline crew members (about one million worldwide) are exposed to measurable neutrons doses. Historically, cytogenetic biodosimetry assays have been based on quantifying asymmetrical chromosome alterations (dicentrics, centric rings and acentric fragments) in mytogen-stimulated T-lymphocytes in their first mitosis after radiation exposure. Increased levels of chromosome damage in peripheral blood lymphocytes are a sensitive indicator of radiation exposure and they are routinely exploited for assessing radiation absorbed dose after accidental or occupational exposure. Since radiological accidents are not common, not all nations feel that it is economically justified to maintain biodosimetry competence. However, dependable access to biological dosimetry capabilities is completely critical in event of an accident. In this paper the dose-response curve was measured for the induction of chromosomal alterations in peripheral blood lymphocytes after chronic exposure in vitro to neutron-gamma mixes field. Blood was obtained from one healthy donor and exposed to two neutron-gamma mixed field from sources {sup 241}AmBe (20 Ci) at the Neutron Calibration Laboratory (NCL-CRCN/NE-PE-Brazil). The evaluated absorbed doses were 0.2 Gy; 1.0 Gy and 2.5 Gy. The dicentric chromosomes were observed at metaphase, following colcemid accumulation and 1000 well-spread metaphase figures were analyzed for the presence of dicentrics by two experienced scorers after painted by giemsa 5%. Our preliminary results showed a linear dependence between radiations absorbed dose and dicentric chromosomes frequencies. Dose-response curve described in this paper will contribute to the construction of calibration curve that will be used in our laboratory for biological dosimetry. (author)

  6. Odor frequency and odor annoyance Part II: dose-response associations and their modification by hedonic tone.

    Science.gov (United States)

    Sucker, Kirsten; Both, Ralf; Bischoff, Michael; Guski, Rainer; Krämer, Ursula; Winneke, Gerhard

    2008-05-01

    Risk-assessment for environmental odors and the development of an appropriate guideline for protection against undue odor annoyance have long been hampered by the difficulties of assessing odor exposure and community annoyance responses. In recent years, however, dose-response associations between frequency of odor events and odor annoyance level in the affected population were established. However, the influence of hedonic tone (pleasantness-unpleasantness) and perceived odor strength (intensity) on the degree of odor annoyance have long been neglected in such studies and accompanying guidelines. In order to close this gap a pertinent field study was conducted in the vicinity of six odor emitting plants, two with pleasant (sweets production, rusk bakery), with neutral (textile production, seed oil production), and with presumably unpleasant odor emissions (fat refinery, cast iron production). A standardized sensory method was developed (described in Part I in the accompanying paper) to quantify intensity and hedonic tone within the assessment of odor exposure by systematic field inspection with trained observers. Additionally, exposure-information, the degree of annoyance, and the frequency of general health complaints and irritation symptoms were collected from the exposed residents through direct interviews. Multiple logistic regression analysis was used to establish dose-response associations between odor frequency, intensity and hedonic tone as independent variables and annoyance or symptom reporting as the dependent variable. It is shown that exposure-annoyance as well as exposure-symptom associations are strongly influenced by odor hedonic. Whereas pleasant odors induced little to no annoyance, both neutral and unpleasant ones did. Additional inclusion of odor intensity did not improve the prediction of odor annoyance. Frequency of reported symptoms was found to be exclusively mediated by annoyance. The results are discussed in terms of environmental stress

  7. Dose-response curve to salbutamol during acute and chronic treatment with formoterol in COPD

    Directory of Open Access Journals (Sweden)

    La Piana GE

    2011-07-01

    Full Text Available Giuseppe Emanuele La Piana¹, Luciano Corda², Enrica Bertella¹, Luigi Taranto Montemurro¹, Laura Pini¹, Claudio Tantucci¹¹Cattedra di Malattie dell'Apparato Respiratorio, Università di Brescia, ²Prima Divisione di Medicina Interna, Spedali Civili, Brescia, ItalyBackground: Use of short-acting ß2-agonists in chronic obstructive pulmonary disease (COPD during treatment with long-acting ß2-agonists is recommended as needed, but its effectiveness is unclear. The purpose of this study was to assess the additional bronchodilating effect of increasing doses of salbutamol during acute and chronic treatment with formoterol in patients with COPD.Methods: Ten patients with COPD underwent a dose-response curve to salbutamol (until 800 µg of cumulative dose after a 1-week washout (baseline, 8 hours after the first administration of formoterol 12 µg (day 1, and after a 12-week and 24-week period of treatment with formoterol (12 µg twice daily by dry powder inhaler. Peak expiratory flow, forced expiratory volume in one second (FEV1, forced vital capacity, and inspiratory capacity were measured at the different periods of treatment and at different steps of the dose-response curve.Results: Despite acute or chronic administration of formoterol, maximal values of peak expiratory flow, FEV1, and forced vital capacity after 800 µg of salbutamol were unchanged compared with baseline. The baseline FEV1 dose-response curve was steeper than that at day 1, week 12, or week 24 (P < 0.0001. Within each dose-response curve, FEV1 was different only at baseline and at day 1 (P < 0.001, when FEV1 was still greater at 800 µg than at 0 µg (P < 0.02. In contrast, the forced vital capacity dose-response curves were similar at the different periods, while within each dose-response curve, forced vital capacity was different in all instances (P < 0.001, always being higher at 800 µg than at 0 µg (P < 0.05.Conclusion: In patients with stable COPD, the maximal effect

  8. Dose Effects of Ion Beam Exposure on Deinococcus Radiodurans: Survival and Dose Response

    Science.gov (United States)

    Song, Dao-jun; Wu, Li-fang; Wu, Li-jun; Yu, Zeng-liang

    2001-02-01

    To explore the survival and dose response of organism for different radiation sources is of great importance in the research of radiobiology. In this study, the survival-dose response of Deinococcus radiodurans (E.coli, as the control) for ultra-violet (UV), γ-rays radiation and ion beam exposure was investigated. The shoulder type of survival curves were found for both UV and γ-ray ionizing radiation, but the saddle type of survival curves were shown for H+, N+(20keV and 30keV) and Ar+ beam exposure. This dose effect of the survival initially decreased with the increase in dose and then increased in the high dose range and finally decreased again in the higher dose range. Our experimental results suggest that D. radiodurans, which is considerably radio-resistant to UV and x-ray and γ-ray ionizing radiation, do not resist ion beam exposure.

  9. Aspartame tablets-gamma dose response and usability for routine radiation processing dosimetry using spectrophotometry

    Energy Technology Data Exchange (ETDEWEB)

    Shinde, S.H. [Radiation Safety Systems Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)]. E-mail: shs_barc@yahoo.com; Mukherjee, T. [Radiation Safety Systems Division, Chemistry Group, Bhabha Atomic Research Centre, Mumbai 400 085 (India)

    2007-02-15

    Aspartame tablets were studied for gamma dose response, using spectrophotometric read-out method. The optimum concentration for ferrous ions was 2x10{sup -4}moldm{sup -3} and xylenol orange with 2.5x10{sup -1}moldm{sup -3} of sulphuric acid for the optimum acidity in FX solution. Wavelength of maximum absorbance is 548nm. Post-irradiation stability is appreciable i.e. for not less than one month. Dose response is non-linear with third order polynomial fit, in the dose range of 1000-10000Gy. This system of aspartame was further used for carrying out relative percentage dose profile measurement in Gamma Cell-220. Results obtained were inter-compared with that of a glutamine dosimeter, which showed that maximum difference between the values of aspartame and glutamine systems is within +/-10%.

  10. Radiation dose-response curves: cell repair mechanisms vs. ion track overlapping

    Science.gov (United States)

    Kowalska, Agata; Czerski, Konrad; Nasonova, Elena; Kutsalo, Polina; Krasavin, Eugen

    2017-12-01

    Chromosome aberrations in human lymphocytes exposed to different doses of particle radiation: 150 MeV and spread out Bragg peak proton beams, 22 MeV/u boron beam and 199 V/u carbon beam were studied. For comparison, an experiment with 60Co γ-rays was also performed. We investigated distributions of aberration frequency and the shape of dose-response curves for the total aberration yield as well as for exchange and non-exchange aberrations, separately. Applying the linear-quadratic model, we could derive a relation between the fitted parameters and the ion track radius which could explain experimentally observed curvature of the dose-response curves. The results compared with physical expectations clearly show that the biological effects of cell repair are much more important than the ion track overlapping. Contribution to the Topical Issue "Dynamics of Systems at the Nanoscale", edited by Andrey Solov'yov and Andrei Korol.

  11. Dose-response association between leisure time physical activity and work ability

    DEFF Research Database (Denmark)

    Calatayud, Joaquin; Jakobsen, Markus D.; Sundstrup, Emil

    2015-01-01

    INTRODUCTION: Regular physical activity is important for longevity and health, but knowledge about the optimal dose of physical activity for maintaining good work ability is unknown. This study investigates the association between intensity and duration of physical activity during leisure time......, lifestyle and chronic disease showed that the duration of high-intensity physical activity during leisure was positively associated with work ability, in a dose-response fashion (p activity per week had on average 8 points higher work ability...... than those not performing such activities. The duration of low-intensity leisure-time physical activity was not associated with work ability (p = 0.5668). CONCLUSIONS: The duration of high-intensity physical activity during leisure time is associated in a dose-response fashion with work ability...

  12. Effects of measurement strategy and statistical analysis on dose-response relations between physical workload and low back pain

    NARCIS (Netherlands)

    J.J.P. Jansen (Justin); A. Burdorf (Alex)

    2003-01-01

    textabstractBACKGROUND: In epidemiological studies on physical workloads and back complaints, among the important features in modelling dose-response relations are the measurement strategy of the exposure and the nature of the dose-response relation that is assumed. AIM: To

  13. Dose-response relationship between periodontal inflamed surface area and HbA1c in type 2 Diabetics

    NARCIS (Netherlands)

    Nesse, Willem; Linde, Annemiek; Abbas, Frank; Spijkervet, Frederik Karst Lucien; Dijkstra, Pieter Ubele; de Brabander, Eric Carl; Gerstenbluth, Izzy; Vissink, Arjan

    Nesse W, Linde A, Abbas F, Spijkervet FKL, Dijkstra PU, de Brabander EC, Gerstenbluth I, Vissink A. Dose-response relationship between periodontal inflamed surface area and HbA1c in type 2 diabetics. J Clin Periodontol 2009; 36: 295-300. doi: 10.1111/j.1600-051X.2009.01377.x. A dose-response

  14. Analysis of Dose Response for Circulatory Disease After Radiotherapy for Benign Disease

    Energy Technology Data Exchange (ETDEWEB)

    Little, Mark P., E-mail: mark.little@nih.gov [Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza South, Rockville, Maryland (United States); Kleinerman, Ruth A. [Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza South, Rockville, Maryland (United States); Stovall, Marilyn; Smith, Susan A. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mabuchi, Kiyohiko [Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza South, Rockville, Maryland (United States)

    2012-12-01

    Purpose: To assess the shape of the dose-response for various circulatory disease endpoints, and modifiers by age and time since exposure. Methods and Materials: This was an analysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by circulatory disease endpoint (ischemic heart, cerebrovascular, other circulatory disease). Results: There were significant excess risks for all circulatory disease, with an excess relative risk Gy{sup -1} of 0.082 (95% CI 0.031-0.140), and ischemic heart disease, with an excess relative risk Gy{sup -1} of 0.102 (95% CI 0.039-0.174) (both p = 0.01), and indications of excess risk for stroke. There were no statistically significant (p > 0.2) differences between risks by endpoint, and few indications of curvature in the dose-response. There were significant (p < 0.001) modifications of relative risk by time since exposure, the magnitude of which did not vary between endpoints (p > 0.2). Risk modifications were similar if analysis was restricted to patients receiving radiation, although the relative risks were slightly larger and the risk of stroke failed to be significant. The slopes of the dose-response were generally consistent with those observed in the Japanese atomic bomb survivors and in occupationally and medically exposed groups. Conclusions: There were excess risks for a variety of circulatory diseases in this dataset, with significant modification of risk by time since exposure. The consistency of the dose-response slopes with those observed in radiotherapeutically treated groups at much higher dose, as well as in lower dose-exposed cohorts such as the Japanese atomic bomb survivors and nuclear workers, implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.

  15. Diethylene glycol-induced toxicities show marked threshold dose response in rats

    Energy Technology Data Exchange (ETDEWEB)

    Landry, Greg M., E-mail: Landry.Greg@mayo.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Dunning, Cody L., E-mail: cdunni@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Abreo, Fleurette, E-mail: fabreo@lsuhsc.edu [Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Latimer, Brian, E-mail: blatim@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Orchard, Elysse, E-mail: eorcha@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Division of Animal Resources, Louisiana State University Health Sciences Center, Shreveport, LA (United States); McMartin, Kenneth E., E-mail: kmcmar@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States)

    2015-02-01

    Diethylene glycol (DEG) exposure poses risks to human health because of widespread industrial use and accidental exposures from contaminated products. To enhance the understanding of the mechanistic role of metabolites in DEG toxicity, this study used a dose response paradigm to determine a rat model that would best mimic DEG exposure in humans. Wistar and Fischer-344 (F-344) rats were treated by oral gavage with 0, 2, 5, or 10 g/kg DEG and blood, kidney and liver tissues were collected at 48 h. Both rat strains treated with 10 g/kg DEG had equivalent degrees of metabolic acidosis, renal toxicity (increased BUN and creatinine and cortical necrosis) and liver toxicity (increased serum enzyme levels, centrilobular necrosis and severe glycogen depletion). There was no liver or kidney toxicity at the lower DEG doses (2 and 5 g/kg) regardless of strain, demonstrating a steep threshold dose response. Kidney diglycolic acid (DGA), the presumed nephrotoxic metabolite of DEG, was markedly elevated in both rat strains administered 10 g/kg DEG, but no DGA was present at 2 or 5 g/kg, asserting its necessary role in DEG-induced toxicity. These results indicate that mechanistically in order to produce toxicity, metabolism to and significant target organ accumulation of DGA are required and that both strains would be useful for DEG risk assessments. - Highlights: • DEG produces a steep threshold dose response for kidney injury in rats. • Wistar and F-344 rats do not differ in response to DEG-induced renal injury. • The dose response for renal injury closely mirrors that for renal DGA accumulation. • Results demonstrate the importance of DGA accumulation in producing kidney injury.

  16. Dose-response relations for occupational exposure to arsenic and cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Jaerup, L. [Dept. of Environmental Hygiene and Inst. of Environmental Medicine, Dept. of Epidemiology, Karolinska Inst. and Dept. of Occupational Medicine, Karolinska Hospital, Stockholm (Sweden)

    1992-12-31

    The dose-response relationship between arsenic exposure and lung cancer in occupationally exposed workers and between occupational cadmium exposure and various kidney effects was studied. A cohort of 3916 Swedish smelter workers showed an increased over-all mortality as well as excess relative risks of deaths due to cancer of the lung and stomach, cardiovascular and cerebrovascular disease, compared with the Swedish general population, When a regional reference population was used, only lung cancer mortality remained significantly elevated. A positive dose-response relation was found between cumulative arsenic exposure and lung cancer risk, the relative risk among the highest exposed workers being more than ten-fold (SMR=1137) (95% confidence interval=588-1986). The dose-response relation was further strengthened when smoking data was added in a nested case-referent study within the smelter cohort. The interaction between arsenic and smoking appeared to be more than additive, but less than multiplicative. Cadmium in the blood has been considered to reflect recent exposure. It was shown in a group of cadmium copper alloy workers that the decay of cadmium in blood followed a two-exponential model. Blood cadmium can thus also be regarded as an estimate of the body burden after cessation of exposure. The use of blood cadmium as a dose estimate was further explored in a group of 440 cadmium exposed battery workers. A clear dose-response relation was found between cumulative blood cadmium and tubular proteinuria. It is recognised that highly exposed workers may develop a glomerula dysfunction in addition to their tubular damage. A questionnaire including questions of the history of kidney stones was sent to the living individuals and the next of kin to the deceased workers in a cohort of 902 cadmium exposed battery workers. There was in increased incidence of renal stones among the medium and highly exposed workers.

  17. Radiation-induced heart disease: review of experimental data on dose response and pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Schultz-Hector, S. (Institut fuer Strahlenbiologie, Neuherberg (Germany))

    1992-02-01

    Clinical and experimental heart irradiation can cause a variety of sequelae. A single dose of {>=} 15 Gy leads to a reversible exudative pericarditis, occurring in dogs, rabbits or rats at around 100 days. Its time-course is very similar in all species investigated, but there are considerable species and strain differences in severity and incidence. After longer, dose-dependent latency times chronic congestive myocardial failure develops. The paper reviews experimental data concerning dose response and pathogenesis. (author).

  18. Dose-response expectancies for alcohol: Validation and implications for brief interventions.

    Science.gov (United States)

    Adey, Gwen E; Moore, Simon C; Chestnutt, Ivor G

    2010-11-01

    Brief interventions for alcohol problems are informed by elements of behavioural motivation theories and behaviour change models. However, motivations across drinking occasions have yet to be explored. This paper addresses this need and presents initial validity statistics for a new construct, Dose Response Expectancies for Alcohol Metrics (DREAM) that can be used to investigate expectancies across the drinking session and thus inform novel interventions. Twenty-seven participants completed a test-retest reliability assessment. Hypothesised systematic relationships between the hypothetical number of drinks consumed across a drinking session and anticipated affective responses were assessed. The DREAM questionnaire yielded good test-retest statistics for anticipated happiness and nausea in the hours following drinking. Consistent with hypotheses, DREAM yielded a systematic relationship between anticipated alcohol dose and affective response. DREAM offers a novel means to investigate alcohol dose-response expectancies across drinking sessions and to therefore provide a theoretical platform that can be used to inform effective brief interventions for young people.[Adey GE, Moore SC, Chestnutt IG. Dose-response expectancies for alcohol: Validation and implications for brief interventions. © 2010 Australasian Professional Society on Alcohol and other Drugs.

  19. [Polymer gel dosimetry--the dose response for X-ray irradiation].

    Science.gov (United States)

    Tominaga, Takahiro; Usui, Shuji; Hayashi, Shin-Ichiro; Yoshioka, Munenori; Haneda, Kiyofumi

    2012-01-01

    Polymer gel dosimetry has been considered a promising technique for clinical use, but this potential has not yet been fully realized in Japan. One reason may be because the commercialized gel detector, BANG gel, is expensive and it is only produced abroad. A second reason is the difficulty of controlling dose sensitivity of the gel so that it is stable under ordinary clinical conditions. In this work we introduce two types of gel detectors (MAG and PAG) which we produced in-house. First the method of fabrication of gel is presented in detail, then the dose responses of MAG and PAG for X-ray irradiation are evaluating for MRI and X-ray CT scanning. The MAG-type gel is useful in low contrast dosimetry because of the high sensitivity in its dose response (R2). The PAG-type gel is effective for dosimetry in multiple field irradiations because its dose response (CT value) has reproducibility independent of the different irradiation conditions. Finally, we summarize the potential for clinical use of polymer gel dosimetry with these gel detectors.

  20. Dose-response effects of water supplementation on cognitive performance and mood in children and adults.

    Science.gov (United States)

    Edmonds, Caroline J; Crosbie, Laura; Fatima, Fareeha; Hussain, Maryam; Jacob, Nicole; Gardner, Mark

    2017-01-01

    Water supplementation has been found to facilitate visual attention and short-term memory, but the dose required to improve performance is not yet known. We assessed the dose response effect of water on thirst, mood and cognitive performance in both adults and children. Participants were offered either no water, 25 ml or 300 ml water to drink. Study 1 assessed 96 adults and in Study 2, data are presented from 60 children aged 7-9 years. In both studies, performance was assessed at baseline and 20 min after drinking (or no drink); on thirst and mood scales, letter cancellation and a digit span test. For both children and adults, a large drink (300 ml) was necessary to reduce thirst, while a small drink (25 ml) was sufficient to improve visual attention (letter cancellation). In adults, a large drink improved digit span, but there was no such effect in children. In children, but not adults, a small drink resulted in increased thirst ratings. Both children and adults show dose-response effects of drinking on visual attention. Visual attention is enhanced by small amounts of fluid and appears not to be contingent on thirst reduction. Memory performance may be related to thirst, but differently for children and adults. These contrasting dose-response characteristics could imply cognitive enhancement by different mechanisms for these two domains. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Concord Grape Juice Polyphenols and Cardiovascular Risk Factors: Dose-Response Relationships.

    Science.gov (United States)

    Blumberg, Jeffrey B; Vita, Joseph A; Chen, C-Y Oliver

    2015-12-02

    Pure fruit juices provide nutritional value with evidence suggesting some of their benefits on biomarkers of cardiovascular disease risk may be derived from their constituent polyphenols, particularly flavonoids. However, few data from clinical trials are available on the dose-response relationship of fruit juice flavonoids to these outcomes. Utilizing the results of clinical trials testing single doses, we have analyzed data from studies of 100% Concord grape juice by placing its flavonoid content in the context of results from randomized clinical trials of other polyphenol-rich foods and beverages describing the same outcomes but covering a broader range of intake. We selected established biomarkers determined by similar methods for measuring flow-mediated vasodilation (FMD), blood pressure, platelet aggregation, and the resistance of low density lipoprotein cholesterol (LDL) to oxidation. Despite differences among the clinical trials in the treatment, subjects, and duration, correlations were observed between the dose and FMD. Inverse dose-response relationships, albeit with lower correlation coefficients, were also noted for the other outcomes. These results suggest a clear relationship between consumption of even modest serving sizes of Concord grape juice, flavonoid intake, and effects on risk factors for cardiovascular disease. This approach to dose-response relationships may prove useful for testing other individual foods and beverages.

  2. Dose-response modelling of umeclidinium and fluticasone furoate/umeclidinium in asthma.

    Science.gov (United States)

    Yang, Shuying; Goyal, Navin; Beerahee, Misba; Trivedi, Roopa; Lee, Laurie; Pascoe, Steven

    2015-09-01

    In two dose-ranging crossover studies, the long-acting muscarinic antagonist umeclidinium (UMEC) was assessed as monotherapy in patients with asthma not treated with inhaled corticosteroids (ICS) (NCT01641692 [study 1]) and combined with the ICS fluticasone furoate (FF) in patients with asthma symptomatic on ICS (NCT01573624 [study 2]). The present study aimed to further characterise the UMEC dose-response relationship with change from baseline trough forced expiratory volume in one second (FEV1) (day 15). A model-based approach using non-linear mixed-effects analyses was used to assess data from studies 1 and 2. Within the Study 1 dose range, no significant dose-response was demonstrated. In study 2, the slope-intercept on log-dose model showed a mild dose-response, with a 10 % probability of a 0.075-L FEV1 improvement with FF/UMEC 100/250 mcg; period 1 data (with an absent carryover effect) indicated an 88 % probability of a 0.075-L FEV1 improvement. The model-based approach in study 2 identified FF/UMEC doses warranting further investigation.

  3. Dose-response model of Rocky Mountain spotted fever (RMSF) for human.

    Science.gov (United States)

    Tamrakar, Sushil B; Haas, Charles N

    2011-10-01

    Rickettsia rickettsii is the causative agent of Rocky Mountain spotted fever (RMSF) and is the prototype bacterium in the spotted fever group of rickettsiae, which is found in North, Central, and South America. The bacterium is gram negative and an obligate intracellular pathogen. The disease is transmitted to humans and vertebrate host through tick bites; however, some cases of aerosol transmission also have been reported. The disease can be difficult to diagnose in the early stages, and without prompt and appropriate treatment, it can be fatal. This article develops dose-response models of different routes of exposure for RMSF in primates and humans. The beta-Poisson model provided the best fit to the dose-response data of aerosol-exposed rhesus monkeys, and intradermally inoculated humans (morbidity as end point of response). The average 50% infectious dose among (ID₅₀) exposed human population, N₅₀, is 23 organisms with 95% confidence limits of 1 to 89 organisms. Similarly, ID₁₀ and ID₂₀ are 2.2 and 5.0, respectively. Moreover, the data of aerosol-exposed rhesus monkeys and intradermally inoculated humans could be pooled. This indicates that the dose-response models fitted to different data sets are not significantly different and can be described by the same relationship. © 2011 Society for Risk Analysis.

  4. Arsenite Effects on Mitochondrial Bioenergetics in Human and Mouse Primary Hepatocytes Follow a Nonlinear Dose Response

    Directory of Open Access Journals (Sweden)

    Hemantkumar Chavan

    2017-01-01

    Full Text Available Arsenite is a known carcinogen and its exposure has been implicated in a variety of noncarcinogenic health concerns. Increased oxidative stress is thought to be the primary cause of arsenite toxicity and the toxic effect is thought to be linear with detrimental effects reported at all concentrations of arsenite. But the paradigm of linear dose response in arsenite toxicity is shifting. In the present study we demonstrate that arsenite effects on mitochondrial respiration in primary hepatocytes follow a nonlinear dose response. In vitro exposure of primary hepatocytes to an environmentally relevant, moderate level of arsenite results in increased oxidant production that appears to arise from changes in the expression and activity of respiratory Complex I of the mitochondrial proton circuit. In primary hepatocytes the excess oxidant production appears to elicit adaptive responses that promote resistance to oxidative stress and a propensity to increased proliferation. Taken together, these results suggest a nonlinear dose-response characteristic of arsenite with low-dose arsenite promoting adaptive responses in a process known as mitohormesis, with transient increase in ROS levels acting as transducers of arsenite-induced mitohormesis.

  5. Individualisation of speed thresholds does not enhance the dose-response determination in football training.

    Science.gov (United States)

    Scott, Dawn; Lovell, Ric

    2017-11-03

    This study examined the utility of a range of approaches used to develop player-dependent speed zones in time-motion analysis (TMA), in determining the dose-response (internal load) of daily football training. Daily external (10 Hz GPS) and internal load (heart rate metrics, ratings of perceived exertion [RPE], wellness ratings) measures were tracked for 22 International women's football players during a 21-day training camp. High-speed (HSR) and very high speed running (VHSR) were determined according to arbitrary speed thresholds, as well as using a range of different individualization approaches that included the velocities corresponding to the heart rate deflection point, maximal aerobic speed, YYIR1 performance, and maximal sprint speed (MSS). Within-player correlations between the TMA approaches versus internal load measures quantified the dose-response to training. Correlations between HSR and VHSR vs. RPE were large (r = 0.53-0.67), with the exception of VHSR for the MSS technique (moderate; r = 0.44). HSR was very-largely associated with heart rate indices (r = 0.72-0.78), again with the exception of MSS (large; r = 0.60-0.67). Using a range of different fitness characteristics to individualise speed thresholds did not enhance the dose-response determination to daily fluctuations in external load, and was worsened with MSS per se.

  6. A Statistical Framework to Evaluate Extreme Weather Definitions from A Health Perspective: A Demonstration Based on Extreme Heat Events.

    Science.gov (United States)

    Vaidyanathan, Ambarish; Kegler, Scott R; Saha, Shubhayu S; Mulholland, James A

    2016-10-01

    A statistical framework for evaluating definitions of extreme weather phenomena can help weather agencies and health departments identify the definition(s) most applicable for alerts nd other preparedness operations related to extreme weather episodes.

  7. A Statistical Framework to Evaluate Extreme Weather Definitions from A Health Perspective: A Demonstration Based on Extreme Heat Events

    OpenAIRE

    Vaidyanathan, Ambarish; Kegler, Scott R; Saha, Shubhayu S.; Mulholland, James A.

    2016-01-01

    A statistical framework for evaluating definitions of extreme weather phenomena can help weather agencies and health departments identify the definition(s) most applicable for alerts nd other preparedness operations related to extreme weather episodes.

  8. Dose response of selected solid state detectors in applied homogeneous transverse and longitudinal magnetic fields

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, M., E-mail: michaelreynolds@ualberta.net [Department of Oncology, Medical Physics Division, University of Alberta, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 (Canada); Fallone, B. G. [Department of Medical Physics, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2, Canada and Departments of Oncology and Physics, University of Alberta, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 (Canada); Rathee, S. [Department of Medical Physics, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2, Canada and Department of Oncology, Medical Physics Division, University of Alberta, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 (Canada)

    2014-09-15

    Purpose: MR-Linac devices under development worldwide will require standard calibration, commissioning, and quality assurance. Solid state radiation detectors are often used for dose profiles and percent depth dose measurements. The dose response of selected solid state detectors is therefore evaluated in varying transverse and longitudinal magnetic fields for this purpose. Methods: The Monte Carlo code PENELOPE was used to model irradiation of a PTW 60003 diamond detector and IBA PFD diode detector in the presence of a magnetic field. The field itself was varied in strength, and oriented both transversely and longitudinally with respect to the incident photon beam. The long axis of the detectors was oriented either parallel or perpendicular to the photon beam. The dose to the active volume of each detector in air was scored, and its ratio to dose with zero magnetic field strength was determined as the “dose response” in magnetic field. Measurements at low fields for both detectors in transverse magnetic fields were taken to evaluate the accuracy of the simulations. Additional simulations were performed in a water phantom to obtain few representative points for beam profile and percent depth dose measurements. Results: Simulations show significant dose response as a function of magnetic field in transverse field geometries. This response can be near 20% at 1.5 T, and it is highly dependent on the detectors’ relative orientation to the magnetic field, the energy of the photon beam, and detector composition. Measurements at low transverse magnetic fields verify the simulations for both detectors in their relative orientations to radiation beam. Longitudinal magnetic fields, in contrast, show little dose response, rising slowly with magnetic field, and reaching 0.5%–1% at 1.5 T regardless of detector orientation. Water tank and in air simulation results were the same within simulation uncertainty where lateral electronic equilibrium is present and expectedly

  9. Mysteries of LiF TLD response following high ionisation density irradiation: nanodosimetry and track structure theory, dose response and glow curve shapes.

    Science.gov (United States)

    Horowitz, Y; Fuks, E; Datz, H; Oster, L; Livingstone, J; Rosenfeld, A

    2011-06-01

    Three outstanding effects of ionisation density on the thermoluminescence (TL) mechanisms giving rise to the glow peaks of LiF:Mg,Ti (TLD-100) are currently under investigation: (1) the dependence of the heavy charged particle (HCP) relative efficiency with increasing ionisation density and the effectiveness of its modelling by track structure theory (TST), (2) the behaviour of the TL efficiency, f(D), as a function of photon energy and dose. These studies are intended to promote the development of a firm theoretical basis for the evaluation of relative TL efficiencies to assist in their application in mixed radiation fields. And (3) the shape of composite peak 5 in the glow curve for various HCP types and energies and following high-dose electron irradiation, i.e. the ratio of the intensity of peak 5a to peak 5. Peak 5a is a low-temperature satellite of peak 5 arising from electron-hole capture in a spatially correlated trapping centre/luminescent centre (TC/LC) complex that has been suggested to possess a potential as a solid-state nanodosemeter due to the preferential electron/hole population of the TC/LC at high ionisation density. It is concluded that (1) the predictions of TST are very strongly dependent on the choice of photon energy used in the determination of f(D); (2) modified TST employing calculated values of f(D) at 2 keV is in agreement with 5-MeV alpha particle experimental results for composite peak 5 but underestimates the 1.5-MeV proton relative efficiencies. Both the proton and alpha particle relative TL efficiencies of the high-temperature TL (HTTL) peaks 7 and 8 are underestimated by an order of magnitude suggesting that the HTTL efficiencies are affected by other factors in addition to radial electron dose; (3) the dose-response supralinearity of peaks 7 and 8 change rapidly with photon energy: this behaviour is explained in the framework of the unified interaction model as due to a very strong dependence on photon energy of the relative

  10. Coupling a continuous watershed-scale microbial fate and transport model with a stochastic dose-response model to estimate risk of illness in an urban watershed

    Energy Technology Data Exchange (ETDEWEB)

    Liao, Hehuan, E-mail: hehuan86@vt.edu [Department of Biological Systems Engineering, Virginia Tech, 155 Ag Quad Lane, Blacksburg, VA 24061 (United States); Krometis, Leigh-Anne H. [Department of Biological Systems Engineering, Virginia Tech, 155 Ag Quad Lane, Blacksburg, VA 24061 (United States); Kline, Karen [Department of Biological Systems Engineering, Virginia Tech, 155 Ag Quad Lane, Blacksburg, VA 24061 (United States); Center for Watershed Studies, Virginia Tech, 155 Ag Quad Lane, Blacksburg, VA 24061 (United States)

    2016-05-01

    Within the United States, elevated levels of fecal indicator bacteria (FIB) remain the leading cause of surface water-quality impairments requiring formal remediation plans under the federal Clean Water Act's Total Maximum Daily Load (TMDL) program. The sufficiency of compliance with numerical FIB criteria as the targeted endpoint of TMDL remediation plans may be questionable given poor correlations between FIB and pathogenic microorganisms and varying degrees of risk associated with exposure to different fecal pollution sources (e.g. human vs animal). The present study linked a watershed-scale FIB fate and transport model with a dose-response model to continuously predict human health risks via quantitative microbial risk assessment (QMRA), for comparison to regulatory benchmarks. This process permitted comparison of risks associated with different fecal pollution sources in an impaired urban watershed in order to identify remediation priorities. Results indicate that total human illness risks were consistently higher than the regulatory benchmark of 36 illnesses/1000 people for the study watershed, even when the predicted FIB levels were in compliance with the Escherichia coli geometric mean standard of 126 CFU/100 mL. Sanitary sewer overflows were associated with the greatest risk of illness. This is of particular concern, given increasing indications that sewer leakage is ubiquitous in urban areas, yet not typically fully accounted for during TMDL development. Uncertainty analysis suggested the accuracy of risk estimates would be improved by more detailed knowledge of site-specific pathogen presence and densities. While previous applications of the QMRA process to impaired waterways have mostly focused on single storm events or hypothetical situations, the continuous modeling framework presented in this study could be integrated into long-term water quality management planning, especially the United States' TMDL program, providing greater clarity to

  11. QMRA for Drinking Water: 1. Revisiting the Mathematical Structure of Single-Hit Dose-Response Models.

    Science.gov (United States)

    Nilsen, Vegard; Wyller, John

    2016-01-01

    Dose-response models are essential to quantitative microbial risk assessment (QMRA), providing a link between levels of human exposure to pathogens and the probability of negative health outcomes. In drinking water studies, the class of semi-mechanistic models known as single-hit models, such as the exponential and the exact beta-Poisson, has seen widespread use. In this work, an attempt is made to carefully develop the general mathematical single-hit framework while explicitly accounting for variation in (1) host susceptibility and (2) pathogen infectivity. This allows a precise interpretation of the so-called single-hit probability and precise identification of a set of statistical independence assumptions that are sufficient to arrive at single-hit models. Further analysis of the model framework is facilitated by formulating the single-hit models compactly using probability generating and moment generating functions. Among the more practically relevant conclusions drawn are: (1) for any dose distribution, variation in host susceptibility always reduces the single-hit risk compared to a constant host susceptibility (assuming equal mean susceptibilities), (2) the model-consistent representation of complete host immunity is formally demonstrated to be a simple scaling of the response, (3) the model-consistent expression for the total risk from repeated exposures deviates (gives lower risk) from the conventional expression used in applications, and (4) a model-consistent expression for the mean per-exposure dose that produces the correct total risk from repeated exposures is developed. © 2016 Society for Risk Analysis.

  12. Searching for Drug Synergy in Complex Dose-Response Landscapes Using an Interaction Potency Model.

    Science.gov (United States)

    Yadav, Bhagwan; Wennerberg, Krister; Aittokallio, Tero; Tang, Jing

    2015-01-01

    Rational design of multi-targeted drug combinations is a promising strategy to tackle the drug resistance problem for many complex disorders. A drug combination is usually classified as synergistic or antagonistic, depending on the deviation of the observed combination response from the expected effect calculated based on a reference model of non-interaction. The existing reference models were proposed originally for low-throughput drug combination experiments, which make the model assumptions often incompatible with the complex drug interaction patterns across various dose pairs that are typically observed in large-scale dose-response matrix experiments. To address these limitations, we proposed a novel reference model, named zero interaction potency (ZIP), which captures the drug interaction relationships by comparing the change in the potency of the dose-response curves between individual drugs and their combinations. We utilized a delta score to quantify the deviation from the expectation of zero interaction, and proved that a delta score value of zero implies both probabilistic independence and dose additivity. Using data from a large-scale anticancer drug combination experiment, we demonstrated empirically how the ZIP scoring approach captures the experimentally confirmed drug synergy while keeping the false positive rate at a low level. Further, rather than relying on a single parameter to assess drug interaction, we proposed the use of an interaction landscape over the full dose-response matrix to identify and quantify synergistic and antagonistic dose regions. The interaction landscape offers an increased power to differentiate between various classes of drug combinations, and may therefore provide an improved means for understanding their mechanisms of action toward clinical translation.

  13. Flow characterization and patch clamp dose responses using jet microfluidics in a tubeless microfluidic device.

    Science.gov (United States)

    Resto, Pedro J; Bhat, Abhishek; Stava, Eric; Lor, Chong; Merriam, Elliot; Diaz-Rivera, Ruben E; Pearce, Robert; Blick, Robert; Williams, Justin C

    2017-11-01

    Surface tension passive pumping is a way to actuate flow without the need for pumps, tubing or valves by using the pressure inside small drop to move liquid via a microfluidic channel. These types of tubeless devices have typically been used in cell biology. Herein we present the use of tubeless devices as a fluid exchange platform for patch clamp electrophysiology. Inertia from high-speed droplets and jets is used to create flow and perform on-the-fly mixing of solutions. These are then flowed over GABA transfected HEK cells under patch in order to perform a dose response analysis. TIRF imaging and electrical recordings are used to study the fluid exchange properties of the microfluidic device, resulting in 0-90% fluid exchange times of hundreds of milliseconds. COMSOL is used to model flow and fluid exchange within the device. Patch-clamping experiments show the ability to use high-speed passive pumping and its derivatives for studying peak dose responses, but not for studying ion channel kinetics. Our system results in fluid exchange times slower than when using a standard 12-barrel application system and is not as stable as traditional methods, but it offers a new platform with added functionality. Surface tension passive pumping and tubeless devices can be used in a limited fashion for electrophysiology. Users may obtain peak dose responses but the system, in its current form, is not capable of fluid exchange fast enough to study the kinetics of most ion channels. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Coffee consumption and risk of hypertension: a dose-response meta-analysis of prospective studies.

    Science.gov (United States)

    D'Elia, Lanfranco; La Fata, Ersilia; Galletti, Ferruccio; Scalfi, Luca; Strazzullo, Pasquale

    2017-12-08

    Recently, a large prospective study provided additional information concerning the debated possible association between habitual coffee consumption and risk of hypertension (HPT). Therefore, we updated the state of knowledge on this issue by carrying out a comprehensive new systematic review of the literature and a meta-analysis of the available relevant studies. We performed a systematic search for prospective studies on general population, published without language restrictions (1966-August 2017). A random-effects dose-response meta-analysis was conducted to combine study specific relative risks (RRs) and 95% confidence intervals. Potential non-linear relation was investigated using restricted cubic splines. Four studies (196,256 participants, 41,184 diagnosis of HPT) met the inclusion criteria. Coffee intake was assessed by dietary questionnaire. Dose-response meta-analysis showed a non-linear relationship between coffee consumption and risk of HPT (p for non-linearity < 0.001). Whereas the habitual drinking of one or two cups of coffee per day, compared with non-drinking, was not associated with risk of HPT, a significantly protective effect of coffee consumption was found starting from the consumption of three cups of coffee per day (RR = 0.97, 95% CI = 0.94 to 0.99), and was confirmed for greater consumption. The results of this analysis indicate that habitual moderate coffee intake is not associated with higher risk of HPT in the general population and that in fact a non-linear inverse dose-response relationship occurs between coffee consumption and risk of HPT.

  15. Dose-Response of Aerobic Exercise on Cognition: A Community-Based, Pilot Randomized Controlled Trial.

    Science.gov (United States)

    Vidoni, Eric D; Johnson, David K; Morris, Jill K; Van Sciver, Angela; Greer, Colby S; Billinger, Sandra A; Donnelly, Joseph E; Burns, Jeffrey M

    2015-01-01

    Epidemiological studies suggest a dose-response relationship exists between physical activity and cognitive outcomes. However, no direct data from randomized trials exists to support these indirect observations. The purpose of this study was to explore the possible relationship of aerobic exercise dose on cognition. Underactive or sedentary participants without cognitive impairment were randomized to one of four groups: no-change control, 75, 150, and 225 minutes per week of moderate-intensity semi-supervised aerobic exercise for 26-weeks in a community setting. Cognitive outcomes were latent residual scores derived from a battery of 16 cognitive tests: Verbal Memory, Visuospatial Processing, Simple Attention, Set Maintenance and Shifting, and Reasoning. Other outcome measures were cardiorespiratory fitness (peak oxygen consumption) and measures of function functional health. In intent-to-treat (ITT) analyses (n = 101), cardiorespiratory fitness increased and perceived disability decreased in a dose-dependent manner across the 4 groups. No other exercise-related effects were observed in ITT analyses. Analyses restricted to individuals who exercised per-protocol (n = 77) demonstrated that Simple Attention improved equivalently across all exercise groups compared to controls and a dose-response relationship was present for Visuospatial Processing. A clear dose-response relationship exists between exercise and cardiorespiratory fitness. Cognitive benefits were apparent at low doses with possible increased benefits in visuospatial function at higher doses but only in those who adhered to the exercise protocol. An individual’s cardiorespiratory fitness response was a better predictor of cognitive gains than exercise dose (i.e., duration) and thus maximizing an individual’s cardiorespiratory fitness may be an important therapeutic target for achieving cognitive benefits. ClinicalTrials.gov NCT01129115.

  16. Modeling and regression analysis of semiochemical dose-response curves of insect antennal reception and behavior.

    Science.gov (United States)

    Byers, John A

    2013-08-01

    Dose-response curves of the effects of semiochemicals on neurophysiology and behavior are reported in many articles in insect chemical ecology. Most curves are shown in figures representing points connected by straight lines, in which the x-axis has order of magnitude increases in dosage vs. responses on the y-axis. The lack of regression curves indicates that the nature of the dose-response relationship is not well understood. Thus, a computer model was developed to simulate a flux of various numbers of pheromone molecules (10(3) to 5 × 10(6)) passing by 10(4) receptors distributed among 10(6) positions along an insect antenna. Each receptor was depolarized by at least one strike by a molecule, and subsequent strikes had no additional effect. The simulations showed that with an increase in pheromone release rate, the antennal response would increase in a convex fashion and not in a logarithmic relation as suggested previously. Non-linear regression showed that a family of kinetic formation functions fit the simulated data nearly perfectly (R(2) >0.999). This is reasonable because olfactory receptors have proteins that bind to the pheromone molecule and are expected to exhibit enzyme kinetics. Over 90 dose-response relationships reported in the literature of electroantennographic and behavioral bioassays in the laboratory and field were analyzed by the logarithmic and kinetic formation functions. This analysis showed that in 95% of the cases, the kinetic functions explained the relationships better than the logarithmic (mean of about 20% better). The kinetic curves become sigmoid when graphed on a log scale on the x-axis. Dose-catch relationships in the field are similar to dose-EAR (effective attraction radius, in which a spherical radius indicates the trapping effect of a lure) and the circular EARc in two dimensions used in mass trapping models. The use of kinetic formation functions for dose-response curves of attractants, and kinetic decay curves for

  17. Time course and dose response of alpha tocopherol on oxidative stress in haemodialysis patients

    Directory of Open Access Journals (Sweden)

    Coombes Jeff S

    2009-10-01

    Full Text Available Abstract Background Oxidative stress is associated with increased cardiovascular morbidity and mortality particularly in patients with end stage kidney disease. Although observational data from the general population has shown dietary antioxidant intake is associated with reduced cardiovascular morbidity and mortality, most clinical intervention trials have failed to support this relationship. This may be a consequence of not using an effective antioxidant dose and/or not investigating patients with elevated oxidative stress. The SPACE study, conducted in haemodialysis patients, reported that 800 IU/day of alpha tocopherol significantly reduced cardiovascular disease endpoints. A recent time course and dose response study conducted in hypercholesterolaemic patients that found 1600 IU/day of alpha tocopherol was an optimal dose. There is no such dose response data available for haemodialysis patients. Therefore the aim of this study is to investigate the effect of different doses of oral alpha tocopherol on oxidative stress in haemodialysis patients with elevated oxidative stress and the time taken to achieve this effect. Methods The study will consist of a time-course followed by a dose response study. In the time course study 20 haemodialysis patients with elevated oxidative stress will take either 1600 IU/day natural (RRR alpha tocopherol for 20 weeks or placebo. Blood will be collected every two weeks and analysed for a marker of oxidative stress (plasma F2-isoprostanes and alpha tocopherol. The optimum time period to significantly decrease plasma F2-isoprostanes will be determined from this study. In the dose response study 60 patients will be randomised to receive either placebo, 100, 200, 400, 800 or 1600 IU/day of natural (RRR alpha tocopherol for a time period determined from the time course study. Blood will be collected at baseline and every two weeks and analysed for plasma F2-isoprostanes and alpha tocopherol. It is hypothesised that

  18. Dose-response of strengthening exercise for treatment of severe neck pain in women

    DEFF Research Database (Denmark)

    Andersen, Christoffer H; Andersen, Lars Louis; Pedersen, Mogens T

    2013-01-01

    Specific strength training is shown relieves neck pain in office workers. The purpose of this study is to evaluate the effectiveness of specific strength training in women with severe neck pain and to analyze the dose-response relationship between training adherence and pain reduction. 118...... untrained women with severe neck pain (>30 mm VAS pain) were included from a larger study, in which the subjects were randomized to 20-weeks specific strength training for the neck/shoulders or to a control group. In the intention-to-treat analysis, the training group experienced greater pain relief than...

  19. A proposed case-control framework to probabilistically classify individual deaths as expected or excess during extreme hot weather events.

    Science.gov (United States)

    Henderson, Sarah B; Gauld, Jillian S; Rauch, Stephen A; McLean, Kathleen E; Krstic, Nikolas; Hondula, David M; Kosatsky, Tom

    2016-11-15

    Most excess deaths that occur during extreme hot weather events do not have natural heat recorded as an underlying or contributing cause. This study aims to identify the specific individuals who died because of hot weather using only secondary data. A novel approach was developed in which the expected number of deaths was repeatedly sampled from all deaths that occurred during a hot weather event, and compared with deaths during a control period. The deaths were compared with respect to five factors known to be associated with hot weather mortality. Individuals were ranked by their presence in significant models over 100 trials of 10,000 repetitions. Those with the highest rankings were identified as probable excess deaths. Sensitivity analyses were performed on a range of model combinations. These methods were applied to a 2009 hot weather event in greater Vancouver, Canada. The excess deaths identified were sensitive to differences in model combinations, particularly between univariate and multivariate approaches. One multivariate and one univariate combination were chosen as the best models for further analyses. The individuals identified by multiple combinations suggest that marginalized populations in greater Vancouver are at higher risk of death during hot weather. This study proposes novel methods for classifying specific deaths as expected or excess during a hot weather event. Further work is needed to evaluate performance of the methods in simulation studies and against clinically identified cases. If confirmed, these methods could be applied to a wide range of populations and events of interest.

  20. Syn-depositional alteration of coral reef framework through bioerosion, encrustation and cementation: Taphonomic signatures of reef accretion and reef depositional events

    Science.gov (United States)

    Perry, C. T.; Hepburn, L. J.

    2008-01-01

    The development of coral reef framework and the preservational character of both in-situ and rubble coral is strongly influenced by a range of physical, chemical and biologically-mediated taphonomic processes. These operate at, or just below, the reef framework-water interface and can be defined as having either a constructive or destructive effect upon primary reef framework (i.e., coral) constituents. Constructional activities add additional calcium carbonate to the primary framework structure via secondary framework growth and early cementation. Destructive processes, which remove or degrade primary (and secondary) framework carbonate, are associated with the effects of either physical (mainly storm) disturbance or biological erosion (termed bioerosion). Key bioeroding groups include the grazing fish and echinoid groups, as well as the activities of an array of infaunal borers. These include specific groups of sponges, bivalves and worms (termed macroborers), as well as cyanobacteria, chlorophytes, rhodophytes and fungi (termed microborers). The relative importance of each process and the rates at which they operate vary spatially across individual reef systems. In addition, many of these processes leave distinctive signatures on, or in, the coral framework. In some cases (e.g., calcareous encrusters) these are the skeletons of the organisms themselves, whilst in other cases the organism may leave behind a trace of their activity (e.g., macro- and microborers). These represent useful palaeoenvironmental tools, firstly because they often have good preservation potential and, secondly because the range and extent of many of the individual species, groups and processes involved exhibit reasonably well-constrained environment and/or depth-related distributions. As a result these taphonomically important organisms or processes can be used to delineate between reef environments in core or outcrop, and to aid the interpretation of reef depositional processes and

  1. A framework for collaborative review of candidate events in high data rate streams: The V-FASTR experiment as a case study

    Energy Technology Data Exchange (ETDEWEB)

    Hart, Andrew F.; Cinquini, Luca; Khudikyan, Shakeh E.; Thompson, David R.; Mattmann, Chris A.; Wagstaff, Kiri; Lazio, Joseph; Jones, Dayton, E-mail: andrew.f.hart@jpl.nasa.gov [Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109 (United States)

    2015-01-01

    “Fast radio transients” are defined here as bright millisecond pulses of radio-frequency energy. These short-duration pulses can be produced by known objects such as pulsars or potentially by more exotic objects such as evaporating black holes. The identification and verification of such an event would be of great scientific value. This is one major goal of the Very Long Baseline Array (VLBA) Fast Transient Experiment (V-FASTR), a software-based detection system installed at the VLBA. V-FASTR uses a “commensal” (piggy-back) approach, analyzing all array data continually during routine VLBA observations and identifying candidate fast transient events. Raw data can be stored from a buffer memory, which enables a comprehensive off-line analysis. This is invaluable for validating the astrophysical origin of any detection. Candidates discovered by the automatic system must be reviewed each day by analysts to identify any promising signals that warrant a more in-depth investigation. To support the timely analysis of fast transient detection candidates by V-FASTR scientists, we have developed a metadata-driven, collaborative candidate review framework. The framework consists of a software pipeline for metadata processing composed of both open source software components and project-specific code written expressly to extract and catalog metadata from the incoming V-FASTR data products, and a web-based data portal that facilitates browsing and inspection of the available metadata for candidate events extracted from the VLBA radio data.

  2. Dose-Response Modeling of the Visual Pathway Tolerance to Single-Fraction and Hypofractionated Stereotactic Radiosurgery.

    Science.gov (United States)

    Hiniker, Susan M; Modlin, Leslie A; Choi, Clara Y; Atalar, Banu; Seiger, Kira; Binkley, Michael S; Harris, Jeremy P; Liao, Yaping Joyce; Fischbein, Nancy; Wang, Lei; Ho, Anthony; Lo, Anthony; Chang, Steven D; Harsh, Griffith R; Gibbs, Iris C; Hancock, Steven L; Li, Gordon; Adler, John R; Soltys, Scott G

    2016-04-01

    Patients with tumors adjacent to the optic nerves and chiasm are frequently not candidates for single-fraction stereotactic radiosurgery (SRS) due to concern for radiation-induced optic neuropathy. However, these patients have been successfully treated with hypofractionated SRS over 2-5 days, though dose constraints have not yet been well defined. We reviewed the literature on optic tolerance to radiation and constructed a dose-response model for visual pathway tolerance to SRS delivered in 1-5 fractions. We analyzed optic nerve and chiasm dose-volume histogram (DVH) data from perioptic tumors, defined as those within 3mm of the optic nerves or chiasm, treated with SRS from 2000-2013 at our institution. Tumors with subsequent local progression were excluded from the primary analysis of vision outcome. A total of 262 evaluable cases (26 with malignant and 236 with benign tumors) with visual field and clinical outcomes were analyzed. Median patient follow-up was 37 months (range: 2-142 months). The median number of fractions was 3 (1 fraction n = 47, 2 fraction n = 28, 3 fraction n = 111, 4 fraction n = 10, and 5 fraction n = 66); doses were converted to 3-fraction equivalent doses with the linear quadratic model using α/β = 2Gy prior to modeling. Optic structure dose parameters analyzed included Dmin, Dmedian, Dmean, Dmax, V30Gy, V25Gy, V20Gy, V15Gy, V10Gy, V5Gy, D50%, D10%, D5%, D1%, D1cc, D0.50cc, D0.25cc, D0.20cc, D0.10cc, D0.05cc, D0.03cc. From the plan DVHs, a maximum-likelihood parameter fitting of the probit dose-response model was performed using DVH Evaluator software. The 68% CIs, corresponding to one standard deviation, were calculated using the profile likelihood method. Of the 262 analyzed, 2 (0.8%) patients experienced common terminology criteria for adverse events grade 4 vision loss in one eye, defined as vision of 20/200 or worse in the affected eye. One of these patients had received 2 previous courses of radiotherapy to the optic structures

  3. A new method for synthesizing radiation dose-response data from multiple trials applied to prostate cancer

    DEFF Research Database (Denmark)

    Diez, Patricia; Vogelius, Ivan S; Bentzen, Søren M

    2010-01-01

    A new method is presented for synthesizing dose-response data for biochemical control of prostate cancer according to study design (randomized vs. nonrandomized) and risk group (low vs. intermediate-high)....

  4. Influence of lung parenchymal destruction on the different indexes of the methacholine dose-response curve in COPD patients

    NARCIS (Netherlands)

    G.T. Verhoeven; A.F.M. Verbraak (Anton); S. Boere-van der Straat; H.C. Hoogsteden (Henk); J.M. Bogaard (Jan)

    2000-01-01

    textabstractSTUDY OBJECTIVES: The interpretation of nonspecific bronchial provocation dose-response curves in COPD is still a matter of debate. Bronchial hyperresponsiveness (BHR) in patients with COPD could be influenced by the destruction of the parenchyma and the

  5. Dose-response relationship of the cardiovascular adaptation to endurance training in healthy adults: how much training for what benefit?

    National Research Council Canada - National Science Library

    Ken-ichi Iwasaki; Rong Zhang; Julie H. Zuckerman; Benjamin D. Levine

    2003-01-01

    .... Therefore, we conducted the present long-term longitudinal study to quantify the dose-response relationship between the volume and intensity of exercise training, and regulation of heart rate (HR) and BP...

  6. Planning and evaluating clinical trials with composite time-to-first-event endpoints in a competing risk framework.

    Science.gov (United States)

    Rauch, G; Beyersmann, J

    2013-09-20

    Composite endpoints combine several events of interest within a single variable. These are often time-to-first-event data, which are analyzed via survival analysis techniques. To demonstrate the significance of an overall clinical benefit, it is sufficient to assess the test problem formulated for the composite. However, the effect observed for the composite does not necessarily reflect the effects for the components. Therefore, it would be desirable that the sample size for clinical trials using composite endpoints provides enough power not only to detect a clinically relevant superiority for the composite but also to address the components in an adequate way. The single components of a composite endpoint assessed as time-to-first-event define competing risks. We consider multiple test problems based on the cause-specific hazards of competing events to address the problem of analyzing both a composite endpoint and its components. Thereby, we use sequentially rejective test procedures to reduce the power loss to a minimum. We show how to calculate the sample size for the given multiple test problem by using a simply applicable simulation tool in SAS. Our ideas are illustrated by two clinical study examples. Copyright © 2013 John Wiley & Sons, Ltd.

  7. Using Information Communication Technologies to Develop Dynamic Curriculum Frameworks for Diverse Cohorts: A Case Study from Event Management

    Science.gov (United States)

    Hadley, Bree Jamila

    2012-01-01

    This article investigates the role of information communication technologies (ICTs) in establishing a well-aligned, authentic learning environment for a diverse cohort of non-cognate and cognate students studying event management in a higher education context. Based on a case study which examined the way ICTs assisted in accommodating diverse…

  8. Cancer risk assessment: Optimizing human health through linear dose-response models.

    Science.gov (United States)

    Calabrese, Edward J; Shamoun, Dima Yazji; Hanekamp, Jaap C

    2015-07-01

    This paper proposes that generic cancer risk assessments be based on the integration of the Linear Non-Threshold (LNT) and hormetic dose-responses since optimal hormetic beneficial responses are estimated to occur at the dose associated with a 10(-4) risk level based on the use of a LNT model as applied to animal cancer studies. The adoption of the 10(-4) risk estimate provides a theoretical and practical integration of two competing risk assessment models whose predictions cannot be validated in human population studies or with standard chronic animal bioassay data. This model-integration reveals both substantial protection of the population from cancer effects (i.e. functional utility of the LNT model) while offering the possibility of significant reductions in cancer incidence should the hormetic dose-response model predictions be correct. The dose yielding the 10(-4) cancer risk therefore yields the optimized toxicologically based "regulatory sweet spot". Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Folate intake and pancreatic cancer risk: an overall and dose-response meta-analysis.

    Science.gov (United States)

    Lin, H L; An, Q Z; Wang, Q Z; Liu, C X

    2013-07-01

    Inconsistent findings of association between supplemental folate consumption and pancreatic cancer risk have been observed in the literature. This study aims to summarize the relationship between folate intake and risk of pancreatic cancer. Pertinent studies published before November 2011 were identified by searching PubMed and Embase and by reviewing the reference lists of retrieved articles. The summary relative risks were estimated by the random effects model. A linear regression analysis of the natural logarithm of the relative risk (RR) was carried out to assess a possible dose-response relationship between folate intake and pancreatic cancer risk. Ten studies on dietary and supplemental folate intake and pancreatic cancer (4 case-control and 6 cohort studies) were included in the meta-analysis. The pooled RRs of pancreatic cancer for the highest vs lowest categories of dietary folate intake and supplemental folate intake were 0.66 (95% CI: 0.49-0.88) and 1.08 (95% CI, 0.82-1.41), respectively. The dose-response meta-analysis indicated that a 100 μg/day increment in dietary folate intake conferred a RR of 0.93 (95% CI: 0.90-0.97). These findings support the hypothesis that dietary folate may play a protective role in carcinogenesis of pancreatic cancer. Copyright © 2013 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  10. Dose Response Association between Physical Activity and Biological, Demographic, and Perceptions of Health Variables

    Directory of Open Access Journals (Sweden)

    Paul D. Loprinzi

    2013-08-01

    Full Text Available Background: Few population-based studies have examined the association between physical activity (PA and cardiovascular disease risk factors, demographic variables, and perceptions of health status, and we do not have a clear understanding of the dose-response relationship among these variables. Methods: Data from the 2003-2006 National Health and Nutrition Examination Survey was used to examine the dose-response relationship between objectively measured PA and metabolic syndrome (and its individual cardiovascular disease risk factors, demographic variables, and perceptions of health. After exclusions, 5,538 participants 18 years or older were included in the present study, with 2,538 participants providing fasting glucose and 2,527 providing fasting triglyceride data. PA was categorized into deciles. Results: Overall, the health benefits showed a general pattern of increase with each increasing levels of PA. Of the ten PA classifications examined, participants in the highest moderate-to-vigorous physical activity (MVPA category (at least 71 min/day had the lowest odds of developing metabolic syndrome. Conclusion: At a minimum, sedentary adults should strive to meet current PA guidelines (i.e., 150 min/week of MVPA, with additional positive benefits associated with engaging in three times this level of PA.

  11. Transcriptional profiling of the dose response: a more powerful approach for characterizing drug activities.

    Directory of Open Access Journals (Sweden)

    Rui-Ru Ji

    2009-09-01

    Full Text Available The dose response curve is the gold standard for measuring the effect of a drug treatment, but is rarely used in genomic scale transcriptional profiling due to perceived obstacles of cost and analysis. One barrier to examining transcriptional dose responses is that existing methods for microarray data analysis can identify patterns, but provide no quantitative pharmacological information. We developed analytical methods that identify transcripts responsive to dose, calculate classical pharmacological parameters such as the EC50, and enable an in-depth analysis of coordinated dose-dependent treatment effects. The approach was applied to a transcriptional profiling study that evaluated four kinase inhibitors (imatinib, nilotinib, dasatinib and PD0325901 across a six-logarithm dose range, using 12 arrays per compound. The transcript responses proved a powerful means to characterize and compare the compounds: the distribution of EC50 values for the transcriptome was linked to specific targets, dose-dependent effects on cellular processes were identified using automated pathway analysis, and a connection was seen between EC50s in standard cellular assays and transcriptional EC50s. Our approach greatly enriches the information that can be obtained from standard transcriptional profiling technology. Moreover, these methods are automated, robust to non-optimized assays, and could be applied to other sources of quantitative data.

  12. Dose-response plasma appearance of coffee chlorogenic and phenolic acids in adults.

    Science.gov (United States)

    Renouf, Mathieu; Marmet, Cynthia; Giuffrida, Francesca; Lepage, Mélissa; Barron, Denis; Beaumont, Maurice; Williamson, Gary; Dionisi, Fabiola

    2014-02-01

    Coffee contains phenolic compounds, mainly chlorogenic acids (CGAs). Even though coffee intake has been associated with some health benefits in epidemiological studies, the bioavailability of coffee phenolics is not fully understood. We performed a dose-response study measuring plasma bioavailability of phenolics after drinking three increasing, but still nutritionally relevant doses of instant pure soluble coffee. The study design was a one treatment (coffee) three-dose randomized cross-over design, with a washout period of 2 wks between visits. CGAs, phenolic acids, and late-appearing metabolites all increased with increasing ingested dose. Hence, the sum of area under the curve was significantly higher for the medium to low dose, and high to medium dose, by 2.23- and 2.38-fold, respectively. CGAs were not well absorbed in their intact form, regardless of the dose. CGA and phenolic acids appeared rapidly in plasma, indicating an early absorption in the gastrointestinal tract. Late-appearing metabolites were the most abundant, regardless of the dose. This study confirmed previous findings about coffee bioavailability but also showed that coffee phenolics appear in a positive dose-response manner in plasma when drank at nutritionally relevant doses. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. RadFET dose response in the CHARM mixed-field: FLUKA MC simulations

    Directory of Open Access Journals (Sweden)

    Marzo Matteo

    2017-01-01

    Full Text Available This paper focuses on Monte Carlo simulations aimed at calculating the dose response of the RadFET dosimeter, when exposed to the complex CHARM mixed-fields, at CERN. We study how the dose deposited in the gate oxide (SiO2 of the RadFET is affected by the energy threshold variation in the Monte Carlo simulations as well as the materials and sizes of scoring volumes. Also the characteristics of the input spectra will be taken into account and their impact on the final simulated dose will be studied. Dose variation as a function of the position of the RadFET in the test facility will be then examined and comparisons with experimental results will be shown. The contribution to the total dose due to all particles of the mixed-field, under different target-shielding configurations, is finally presented, aiming at a complete characterization of the RadFETs dose response in the CHARM mixed-fields.

  14. RadFET dose response in the CHARM mixed-field: FLUKA MC simulations

    Directory of Open Access Journals (Sweden)

    Marzo M.

    2017-01-01

    Full Text Available This paper focuses on Monte Carlo simulations aiming at calculating the dose response of the Rad- FET dosimeter, when exposed to the complex CHARM mixed-fields, at CERN. We study how the dose deposited in the Gate Oxide (SiO2 of the RadFET is a_ected by the energy threshold variation in the Monte Carlo simulations as well as the materials and sizes of scoring volumes. Also the characteristics of the input spectra will be taken into account and their impact on the final simulated dose will be studied. Dose variation as a function of the position of the RadFET in the test facility will be then examined and comparisons with experimental results will be shown. The contribution to the total dose due to every single particles of the mixed-field, under di_erent target-shielding configurations, will be finally presented, aiming at a complete characterization of the RadFETs dose response in the CHARM mixed-fields.

  15. Radiation dose response of N channel MOSFET submitted to filtered X-ray photon beam

    Science.gov (United States)

    Gonçalves Filho, Luiz C.; Monte, David S.; Barros, Fabio R.; Santos, Luiz A. P.

    2018-01-01

    MOSFET can operate as a radiation detector mainly in high-energy photon beams, which are normally used in cancer treatments. In general, such an electronic device can work as a dosimeter from threshold voltage shift measurements. The purpose of this article is to show a new way for measuring the dose-response of MOSFETs when they are under X-ray beams generated from 100kV potential range, which is normally used in diagnostic radiology. Basically, the method consists of measuring the MOSFET drain current as a function of the radiation dose. For this the type of device, it has to be biased with a high value resistor aiming to see a substantial change in the drain current after it has been irradiated with an amount of radiation dose. Two types of N channel device were used in the experiment: a signal transistor and a power transistor. The delivered dose to the device was varied and the electrical curves were plotted. Also, a sensitivity analysis of the power MOSFET response was made, by varying the tube potential of about 20%. The results show that both types of devices have responses very similar, the shift in the electrical curve is proportional to the radiation dose. Unlike the power MOSFET, the signal transistor does not provide a linear function between the dose rate and its drain current. We also have observed that the variation in the tube potential of the X-ray equipment produces a very similar dose-response.

  16. Dose-response relationship between cigarette smoking and site-specific cancer risk: protocol for a systematic review with an original design combining umbrella and traditional reviews.

    Science.gov (United States)

    Lugo, Alessandra; Bosetti, Cristina; Peveri, Giulia; Rota, Matteo; Bagnardi, Vincenzo; Gallus, Silvano

    2017-11-01

    Only a limited number of meta-analyses providing risk curve functions of dose-response relationships between various smoking-related variables and cancer-specific risk are available. To identify all relevant original publications on the issue, we will conduct a series of comprehensive systematic reviews based on three subsequent literature searches: (1) an umbrella review, to identify meta-analyses, pooled analyses and systematic reviews published before 28 April 2017 on the association between cigarette smoking and the risk of 28 (namely all) malignant neoplasms; (2) for each cancer site, an updated review of original publications on the association between cigarette smoking and cancer risk, starting from the last available comprehensive review identified through the umbrella review; and (3) a review of all original articles on the association between cigarette smoking and site-specific cancer risk included in the publications identified through the umbrella review and the updated reviews. The primary outcomes of interest will be (1) the excess incidence/mortality of various cancers for smokers compared with never smokers; and (2) the dose-response curves describing the association between smoking intensity, duration and time since stopping and incidence/mortality for various cancers. For each cancer site, we will perform a meta-analysis by pooling study-specific estimates for smoking status. We will also estimate the dose-response curves for other smoking-related variables through random-effects meta-regression models based on a non-linear dose-response relationship framework. Ethics approval is not required for this study. Main results will be published in peer-reviewed journals and will also be included in a publicly available website. We will provide therefore the most complete and updated estimates on the association between various measures of cigarette smoking and site-specific cancer risk. This will allow us to obtain precise estimates on the cancer burden

  17. X-ray dose response of calcite—A comprehensive analysis for optimal application in TL dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Kalita, J.M., E-mail: jitukalita09@gmail.com; Wary, G.

    2016-09-15

    Highlights: • Effect of annealing temperature on TL signal of calcite has been studied. • Specific annealing treatment for optimal dose response has been evaluated. • The dose response of natural calcite has been analyzed quantitatively. - Abstract: The effect of various annealing treatments on dosimetric characteristics of orange calcite (CaCO{sub 3}) mineral has been studied in detail. Quantitative analysis on the dose response shows that the 573 K annealed sample showed sublinear dose response from 10 mGy to 1 Gy. The fading and reproducibility of this sample are also good enough for dosimetric application. However, a specific annealing treatment after irradiation shows some significant improvements in the dosimetric characteristics of the sample. The 773 K pre-annealed sample, after X-ray irradiation post-annealing at 340 K for 6 min provides linear dose response from 10 mGy to 3.60 Gy, very less fading and good reproducibility. Moreover, this sample after post-annealing at 380 K for 6 min shows linear dose response from 10 mGy to 5.40 Gy when analyzed from the ∼408 K thermoluminescence (TL) glow peak. Analysis of TL glow curves confirmed that the 1.30 eV trap center in calcite crystal is the most effective trapping site for dosimetric application.

  18. Hormesis: changing view of the dose-response, a personal account of the history and current status.

    Science.gov (United States)

    Calabrese, Edward J

    2002-07-01

    This paper provides a personal account of the history of the hormesis concept, and of the role of the dose response in toxicology and pharmacology. A careful evaluation of the toxicology and pharmacology literatures suggests that the biphasic dose response that characterizes hormesis may be much more widespread than is commonly recognized, and may come to rival our currently favored ideas about toxicological dose responses confined to the linear and threshold representations used in risk assessment. Although hormesis-like biphasic dose responses were already well-established in chemical and radiation toxicology by the early decades of the 20th century, they were all but expunged from mainstream toxicology in the 1930s. The reasons may be found in a complex set of unrelated problems of which difficulties in replication of low-dose stimulatory responses resulting from poor study designs, greater societal interest in high-dose effects, linking of the concept of hormesis to the practice of homeopathy, and perhaps most crucially a complete lack of strong leadership to advocate its acceptance in the right circles. I believe that if hormesis achieves widespread recognition as a valid and valuable interpretation of dose-response results, we would expect an increase in the breadth of evaluations of the dose-response relationship which could be of great value in hazard and risk assessment as well as in future approaches to drug development and/or chemotherapeutics.

  19. Modification of the SAS4A Safety Analysis Code for Integration with the ADAPT Discrete Dynamic Event Tree Framework.

    Energy Technology Data Exchange (ETDEWEB)

    Jankovsky, Zachary Kyle [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Denman, Matthew R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-05-01

    It is difficult to assess the consequences of a transient in a sodium-cooled fast reactor (SFR) using traditional probabilistic risk assessment (PRA) methods, as numerous safety-related sys- tems have passive characteristics. Often there is significant dependence on the value of con- tinuous stochastic parameters rather than binary success/failure determinations. One form of dynamic PRA uses a system simulator to represent the progression of a transient, tracking events through time in a discrete dynamic event tree (DDET). In order to function in a DDET environment, a simulator must have characteristics that make it amenable to changing physical parameters midway through the analysis. The SAS4A SFR system analysis code did not have these characteristics as received. This report describes the code modifications made to allow dynamic operation as well as the linking to a Sandia DDET driver code. A test case is briefly described to demonstrate the utility of the changes.

  20. SU-F-J-147: Magnetic Field Dose Response Considerations for a Linac Monitor Chamber

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, M; Fallone, B [Cross Cancer Institute, Edmonton, AB (Canada)

    2016-06-15

    Purpose: The impact of magnetic fields on the readings of a linac monitor chamber have not yet been investigated. Herein we examine the total dose response as well as any deviations in the beam parameters of flatness and symmetry when a Varian monitor chamber is irradiated within an applied magnetic field. This work has direct application to the development of Linac-MR systems worldwide. Methods: A Varian monitor chamber was modeled in the Monte Carlo code PENELOPE and irradiated in the presence of a magnetic field with a phase space generated from a model of a Linac-MR prototype system. The magnetic field strength was stepped from 0 to 3.0T in both parallel and perpendicular directions with respect to the normal surface of the phase space. Dose to each of the four regions in the monitor chamber were scored separately for every magnetic field adaptation to evaluate the effect of the magnetic field on flatness and symmetry. Results: When the magnetic field is perpendicular to the phase space normal we see a change in dose response with a maximal deviation (10–25% depending on the chamber region) near 0.75T. In the direction of electron deflection we expectedly see opposite responses in chamber regions leading to a measured asymmetry. With a magnetic field parallel to the phase space normal we see no measured asymmetries, however there is a monotonic rise in dose response leveling off at about +12% near 2.5T. Conclusion: Attention must be given to correct for the strength and direction of the magnetic field at the location of the linac monitor chamber in hybrid Linac-MR devices. Elsewise the dose sampled by these chambers may not represent the actual dose expected at isocentre; additionally there may be a need to correct for the symmetry of the beam recorded by the monitor chamber. Fallone is a co-founder and CEO of MagnetTx Oncology Solutions (under discussions to license Alberta bi-planar linac MR for commercialization).

  1. Dose-response analysis indicating time-dependent neurotoxicity caused by organic and inorganic mercury-Implications for toxic effects in the developing brain.

    Science.gov (United States)

    Pletz, Julia; Sánchez-Bayo, Francisco; Tennekes, Henk A

    2016-03-10

    A latency period preceding neurotoxicity is a common characteristic in the dose-response relationship induced by organic mercury. Latency periods have typically been observed with genotoxicants in carcinogenesis, with cancer being manifested a long time after the initiating event. These observations indicate that even a very small dose may cause extensive adverse effects later in life, so the toxicity of the genotoxic compound is dose and time-dependent. In children, methylmercury exposure during pregnancy (in utero) has been associated with delays in reaching developmental milestones (e.g., age at first walking) and decreases in intelligence, increasing in severity with increasing exposure. Ethylmercury exposure from thimerosal in some vaccines has been associated, in some studies, with autism and other neurological disorders in children. In this paper, we have examined whether dose-response data from in vitro and in vivo organic mercury toxicity studies fit the Druckrey-Küpfmüller equation c·t(n)=constant (c=exposure concentration, t=latency period), first established for genotoxic carcinogens, and whether or not irreversible effects are enhanced by time of exposure (n≥1), or else toxic effects are dose-dependent while time has only minor influence on the adverse outcome (nmercury induced neurotoxic effects. This amounts to a paradigm shift in chemical risk assessment of mercurial compounds and highlights that it is vital to perform toxicity testing geared to investigate time-dependent effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Development and Evaluation of Vectorised and Multi-Core Event Reconstruction Algorithms within the CMS Software Framework

    CERN Multimedia

    CERN. Geneva

    2012-01-01

    The processing of data acquired by the CMS detector at LHC is carried out with an object-oriented C++ software framework: CMSSW. With the increasing luminosity delivered by the LHC, the treatment of recorded data requires extraordinary large computing resources, also in terms of CPU usage. A possible solution to cope with this task is the exploitation of the features offered by the latest microprocessor architectures. Modern CPUs present several vector units, the capacity of which is growing steadily with the introduction of new processor generations. Moreover, an increasing number of cores per die is offered by the main vendors, even on consumer hardware. Most recent C++ compilers provide facilities to take advantage of such innovations, either by explicit statements in the programs’ sources or automatically adapting the generated machine instructions to the available hardware, without the need of modifying the existing code base. Programming techniques to implement reconstruction algorithms and optimised ...

  3. SynergyFinder: a web application for analyzing drug combination dose-response matrix data.

    Science.gov (United States)

    Ianevski, Aleksandr; He, Liye; Aittokallio, Tero; Tang, Jing

    2017-08-01

    Rational design of drug combinations has become a promising strategy to tackle the drug sensitivity and resistance problem in cancer treatment. To systematically evaluate the pre-clinical significance of pairwise drug combinations, functional screening assays that probe combination effects in a dose-response matrix assay are commonly used. To facilitate the analysis of such drug combination experiments, we implemented a web application that uses key functions of R-package SynergyFinder, and provides not only the flexibility of using multiple synergy scoring models, but also a user-friendly interface for visualizing the drug combination landscapes in an interactive manner. The SynergyFinder web application is freely accessible at https://synergyfinder.fimm.fi ; The R-package and its source-code are freely available at http://bioconductor.org/packages/release/bioc/html/synergyfinder.html . jing.tang@helsinki.fi.

  4. Dose-response model for Listeria monocytogenes-induced stillbirths in nonhuman primates.

    Science.gov (United States)

    Smith, Mary Alice; Takeuchi, Kazue; Anderson, Gary; Ware, Glenn O; McClure, Harold M; Raybourne, Richard B; Mytle, Nutan; Doyle, Michael P

    2008-02-01

    A dose-response model using rhesus monkeys as a surrogate for pregnant women indicates that oral exposure to 10(7) CFU of Listeria monocytogenes results in about 50% stillbirths. Ten of 33 pregnant rhesus monkeys exposed orally to a single dose of 10(2) to 10(10) CFU of L. monocytogenes had stillbirths. A log-logistic model predicts a dose affecting 50% of animals at 10(7) CFU, comparable to an estimated 10(6) CFU based on an outbreak among pregnant women but much less than the extrapolated estimate (10(13) CFU) from the FDA-U.S. Department of Agriculture-CDC risk assessment using an exponential curve based on mouse data. Exposure and etiology of the disease are the same in humans and primates but not in mice. This information will aid in risk assessment, assist policy makers, and provide a model for mechanistic studies of L. monocytogenes-induced stillbirths.

  5. Dose-response of acute urinary toxicity of long-course preoperative chemoradiotherapy for rectal cancer

    DEFF Research Database (Denmark)

    Appelt, Ane L.; Bentzen, Søren M.; Jakobsen, Anders

    2015-01-01

    BACKGROUND: Long-course preoperative chemoradiotherapy (chemo-RT) improves outcomes for rectal cancer patients, but acute side effects during treatment may cause considerable patient discomfort and may compromise treatment compliance. We developed a dose-response model for acute urinary toxicity...... based on a large, single-institution series. MATERIAL AND METHODS: In total 345 patients were treated with (chemo-)RT for primary rectal cancer from January 2007 to May 2012. Urinary toxicity during RT was scored prospectively using the CTCAE v 3.0 cystitis score (grade 0-5). Clinical variables...... and radiation dose to the bladder were related to graded toxicity using multivariate ordinal logistic regression. Three models were optimized, each containing all available clinical variables and one of three dose metrics: Mean dose (Dmean), equivalent uniform dose (EUD), or relative volume given x Gy or above...

  6. Glucocorticoid treatment earlier in childhood and adolescence show dose-response associations with diurnal cortisol levels

    DEFF Research Database (Denmark)

    Vestergaard, Martin; Holm, Sara K; Uldall, Peter

    2017-01-01

    Heightened levels of glucocorticoids in children and adolescents have previously been linked to prolonged changes in the diurnal regulation of the stress-hormone cortisol, a glucocorticoid regulated by the hypothalamic-pituitary-adrenal-axis (HPA-axis). To address this question, we examined...... the salivary cortisol awakening response (CAR) and daily cortisol output in 36 children and adolescents (25 girls/11 boys) aged 7-16 years previously treated with glucocorticoids for nephrotic syndrome or rheumatic disorder and 36 healthy controls. Patients and controls did not significantly differ in the CAR...... patients showed a positive linear relationship with the mean daily glucocorticoid doses administered during treatment. The observed dose-response associations suggest that glucocorticoid therapy during childhood and adolescence might trigger long-term changes in HPA-axis regulation, which may differ...

  7. Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

    DEFF Research Database (Denmark)

    Appelt, A. L.; Ploen, J.; Vogelius, I. R.

    2013-01-01

    Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we...... estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination...... of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect...

  8. SO/sub 2/ dose-response sensitivity classification data for crops and natural vegetation species

    Energy Technology Data Exchange (ETDEWEB)

    Irving, P.M.; Ballou, S.W.

    1980-09-01

    Over the past several years studies have been made on the interaction of sulfur dioxide (SO/sub 2/) and vegetation by performing field research and by developing analytical procedures for applying field observation data to energy impact assessments. As a result of this work, numerous reports have been prepared on crop-pollutant interactions, such as dose-response data; on the applications of such data to screening approaches for identifying crops at risk; and on models that predict crop yield reductions from point source emissions of SO/sub 2/. Data that were used for these studies, such as the crop-at-risk screening procedure, are presented in this report. Maps are also presented that show the national distribution of SO/sub 2/-sensitive crops and natural vegetation.

  9. Childhood adversity specificity and dose-response effect in non-affective first-episode psychosis

    DEFF Research Database (Denmark)

    Trauelsen, Anne Marie; Bendall, Sarah; Jansen, Jens Einar

    2015-01-01

    BACKGROUND: Reviews conclude that childhood and adolescence sexual, physical, emotional abuse and emotional and physical neglect are all risk factors for psychosis. However, studies suggest only some adversities are associated with psychosis. Dose-response effects of several adversities on risk......-clinical control persons matched by gender, age and parents' socio-economic status. Assessment included the Childhood Trauma Questionnaire and parts of the Childhood Experience of Care and Abuse Questionnaire. RESULTS: Eighty-nine percent of the FEP group reported one or more adversities compared to 37......% of the control group. Childhood and adolescent sexual, physical, emotional abuse, and physical and emotional neglect, separation and institutionalization were about four to 17 times higher for the FEP group (all p

  10. Mass shootings: a meta-analysis of the dose-response relationship.

    Science.gov (United States)

    Wilson, Laura C

    2014-12-01

    A meta-analysis was conducted to examine the dose-response theory as it relates to posttraumatic stress symptoms (PTSSs) following mass shootings. It was hypothesized that greater exposure to a mass shooting would be associated with greater PTSSs. Trauma exposure in the current study was broadly defined as the extent to which a person experienced or learned about a mass shooting. The meta-analysis identified 11 qualifying studies that included 13 independent effect sizes from a total of 8,047 participants. The overall weighted mean effect size, based on a random effects model, was r = .19, p shooting on the relationship between exposure and PTSSs. Because so few studies satisfied the inclusion criteria, the present study also documents that this area of the literature is underresearched. Copyright © 2014 International Society for Traumatic Stress Studies.

  11. IncucyteDRC: An R package for the dose response analysis of live cell imaging data

    Science.gov (United States)

    Chapman, Philip J.; James, Dominic I.; Watson, Amanda J.; Hopkins, Gemma V.; Waddell, Ian D.; Ogilvie, Donald J.

    2016-01-01

    We present IncucyteDRC, an R package for the analysis of data from live cell imaging cell proliferation experiments carried out on the Essen Biosciences IncuCyte ZOOM instrument. The package provides a simple workflow for summarising data into a form that can be used to calculate dose response curves and EC50 values for small molecule inhibitors. Data from different cell lines, or cell lines grown under different conditions, can be normalised as to their doubling time. A simple graphical web interface, implemented using shiny, is provided for the benefit of non-R users. The software is potentially useful to any research group studying the impact of small molecule inhibitors on cell proliferation using the IncuCyte ZOOM. PMID:27703665

  12. Nano-silver induces dose-response effects on the nematode Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Ellegaard-Jensen, Lea; Alstrup Jensen, Keld; Johansen, Anders

    2012-01-01

    Toxicity of nano-formulated silver to eukaryotes was assessed by exposing nematodes (Caenorhabditis elegans) to two types of silver nanoparticles (AgNPs): with average primary particle diameters of 1 nm (AgNP1) and 28 nm (AgNP28, PVP coated), respectively. Tests were performed with and without...... adverse dose-response effects and mortality on C. elegans. LC50 for AgNP28 was lower than for AgNP1 and, hence, at the present test conditions the PVP-coated AgNP28 was more toxic than AgNP1. Including E. coil in the test medium as a food source increased AgNPs toxicity towards nematodes compared to when...

  13. Accelerometer-measured dose-response for physical activity, sedentary time, and mortality in US adults

    DEFF Research Database (Denmark)

    Matthews, Charles E; Keadle, S. K.; Troiano, Richard P

    2016-01-01

    behavior-mortality relation. Isotemporal models estimated replacement associations for sedentary time, and separate models were fit for low-(,5.8 h total activity/d) and high-active participants to account for nonlinear associations. Results: Over a mean of 6.6 y, 700 deaths occurred. Compared with less-sedentary......Background: Moderate-to-vigorous-intensity physical activity is recommended to maintain and improve health, but the mortality benefits of light activity and risk for sedentary time remain uncertain. Objectives: Using accelerometer-based measures, we 1) described the mortality dose......-response for sedentary time and light-and moderateto-vigorous-intensity activity using restricted cubic splines, and 2) estimated the mortality benefits associated with replacing sedentary time with physical activity, accounting for total activity. Design: US adults (n = 4840) from NHANES (2003-2006) wore...

  14. Radiation dose response correlation between thermoluminescence and optically stimulated luminescence in quartz

    Energy Technology Data Exchange (ETDEWEB)

    Oniya, E.O. [Archaeometry Laboratory, Cultural and Educational Technology Institute (C.E.T.I.), R.C. ' Athena' , Tsimiski 58, GR-67100 Xanthi (Greece); Physics and Electronics Department, Adekunle Ajasin University, PMB 01, Akungba Akoko (Nigeria); Polymeris, G.S.; Tsirliganis, N.C. [Archaeometry Laboratory, Cultural and Educational Technology Institute (C.E.T.I.), R.C. ' Athena' , Tsimiski 58, GR-67100 Xanthi (Greece); Kitis, G., E-mail: gkitis@auth.gr [Aristotle University of Thessaloniki, Nuclear Physics Laboratory, 54124 Thessaloniki (Greece)

    2012-07-15

    The fast, linearly modulated optically stimulated luminescence (LM-OSL) component in quartz is the main dosimetric signal used for the dating applications of this material. Since the blue light stimulation (470 nm, 40 mW cm {sup -2}) time needed to obtain the fast LM-OSL component is less than 50 s the electron trapping levels responsible for it are still highly populated. In this way an active radiation history is created which could play an important role in the dosimetric characteristics of the fast OSL signal. In the present work the dose response behavior of the fast OSL signal is investigated in quartz samples with an annealed radiation history and quartz samples possessing an artificial radiation history. A computerized curve de-convolution analysis of the LM-OSL curves for 50 s stimulation time showed that it consists of three individual OSL components. The faster component C{sub 1} with peak maximum time around 5 s has a linear dose response in virgin samples, which turns to a slight superlinearity as a function of the artificial radiation history. On the other hand the component C{sub 2} with peak maximum time at 12 s is slightly superlinear which turns into strong superlinearity as a function of artificial radiation history. Finally, component C{sub 3} with peak maximum time at about 45 s is strongly superlinear for both virgin samples and as a function of artificial radiation history. The implications to practical application are discussed. - Highlights: Black-Right-Pointing-Pointer The fast OSL component consists of three components. Black-Right-Pointing-Pointer The linearity of first fast component does not depend on radiation history. Black-Right-Pointing-Pointer The linearity of second and third components depend on radiation history. Black-Right-Pointing-Pointer The TL between 180 and 300 Degree-Sign C is the major source of OSL.

  15. The Dose-Response Relationship Between Training Load and Aerobic Fitness in Academy Rugby Union Players.

    Science.gov (United States)

    Taylor, Richard J; Sanders, Dajo; Myers, Tony; Abt, Grant; Taylor, Celia A; Akubat, Ibrahim

    2018-02-13

    To identify the dose-response relationship between measures of training load (TL) and changes in aerobic fitness in academy rugby union players. Training data from 10 academy rugby union players were collected during a 6-wk in-season period. Participants completed a lactate-threshold test that was used to assess VO 2 max, velocity at VO 2 max, velocity at 2 mmol/L (lactate threshold), and velocity at 4 mmol/L (onset of lactate accumulation; vOBLA) as measures of aerobic fitness. Internal-TL measures calculated were Banister training impulse (bTRIMP), Edwards TRIMP, Lucia TRIMP, individualized TRIMP (iTRIMP), and session RPE (sRPE). External-TL measures calculated were total distance, PlayerLoad™, high-speed distance >15 km/h, very-high-speed distance >18 km/h, and individualized high-speed distance based on each player's vOBLA. A second-order-regression (quadratic) analysis found that bTRIMP (R 2  = .78, P = .005) explained 78% of the variance and iTRIMP (R 2  = .55, P = .063) explained 55% of the variance in changes in VO 2 max. All other HR-based internal-TL measures and sRPE explained less than 40% of variance with fitness changes. External TL explained less than 42% of variance with fitness changes. In rugby players, bTRIMP and iTRIMP display a curvilinear dose-response relationship with changes in maximal aerobic fitness.

  16. Triphasic low-dose response in zebrafish embryos irradiated by microbeam protons.

    Science.gov (United States)

    Choi, Viann Wing Yan; Yum, Emily Hoi Wa; Konishi, Teruaki; Oikawa, Masakazu; Cheng, Shuk Han; Yu, Kwan Ngok

    2012-01-01

    The microbeam irradiation system (Single-Particle Irradiation System to Cell, acronym as SPICE) at the National Institute of Radiological Sciences (NIRS), Japan, was employed to irradiate dechorionated zebrafish embryos at the 2-cell stage at 0.75 h post fertilization (hpf) by microbeam protons. Either one or both of the cells of the embryos were irradiated with 10, 20, 40, 50, 80, 100, 160, 200, 300 and 2000 protons each with an energy of 3.37 MeV. The embryos were then returned back to the incubator until 24 hpf for analyses. The levels of apoptosis in zebrafish embryos at 25 hpf were quantified through terminal dUTP transferase-mediated nick end-labeling (TUNEL) assay, with the apoptotic signals captured by a confocal microscope. The results revealed a triphasic dose-response for zebrafish embryos with both cells irradiated at the 2-cell stage, namely, (1) increase in apoptotic signals for protons (protons (at doses of 30-60 mGy), and (3) increase in apoptotic signals again for > 600 protons (at doses > 90 mGy). The dose response for zebrafish embryos with only one cell irradiated at the 2-cell stage was also likely a triphasic one, but the apoptotic signals in the first zone (protons or < 30 mGy) did not have significant differences from those of the background. At the same time, the experimental data were in line with induction of radiation-induced bystander effect as well as rescue effect in the zebrafish embryos, particular in those embryos with unirradiated cells.

  17. Coffee consumption and risk of fractures: a systematic review and dose-response meta-analysis.

    Science.gov (United States)

    Lee, Dong Ryul; Lee, Jungun; Rota, Matteo; Lee, Juneyoung; Ahn, Hyeong Sik; Park, Sang Min; Shin, Doosup

    2014-06-01

    The data on the association between coffee consumption and the risk of fractures are inconclusive. We performed a comprehensive literature review and meta-analysis to better quantify this association. We identified all potentially relevant articles by searching MEDLINE, EMBASE, Cochrane Library, Web of Science, SCOPUS, and CINAHL (until February 2013). The keywords "coffee," "caffeine," "drink," and "beverage" were used as the exposure factors, and the keyword "fracture" was used as the outcome factor. We determined the overall relative risk (RR) and confidence interval (CI) for the highest and lowest levels of coffee consumption. A dose-response analysis was performed to assess the risk of fractures based on the level of coffee consumption. We included 253,514 participants with 12,939 fracture cases from 9 cohort and 6 case-control studies. The estimated RR of fractures at the highest level of coffee consumption was 1.14 (95% CI: 1.05-1.24; I(2)=0.0%) in women and 0.76 (95% CI: 0.62-0.94; I(2)=7.3%) in men. In the dose-response analysis, the pooled RRs of fractures in women who consumed 2 and 8 cups of coffee per day were 1.02 (95% CI: 1.01-1.04) and 1.54 (95% CI: 1.19-1.99), respectively. Our meta-analysis suggests that daily consumption of coffee is associated with an increased risk of fractures in women and a contrasting decreased risk in men. However, future well-designed studies should be performed to confirm these findings. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. The dose-response relationship between in-ear occupational noise exposure and hearing loss.

    Science.gov (United States)

    Rabinowitz, Peter M; Galusha, Deron; Dixon-Ernst, Christine; Clougherty, Jane E; Neitzel, Richard L

    2013-10-01

    Current understanding of the dose-response relationship between occupational noise and hearing loss is based on cross-sectional studies prior to the widespread use of hearing protection, and with limited data regarding noise exposures below 85 dBA. We report on the hearing loss experience of a unique cohort of industrial workers, with daily monitoring of noise inside of hearing protection devices. At an industrial facility, workers exhibiting accelerated hearing loss were enrolled in a mandatory programme to monitor daily noise exposures inside of hearing protection. We compared these noise measurements (as time-weighted LAVG) to interval rates of high-frequency hearing loss over a 6-year period using a mixed-effects model, adjusting for potential confounders. Workers' high-frequency hearing levels at study inception averaged more than 40 dB Hearing threshold level (HTL). Most noise exposures were less than 85 dBA (mean LAVG 76 dBA, IQR 74-80 dBA). We found no statistical relationship between LAvg and high-frequency hearing loss (p=0.53). Using a metric for monthly maximum noise exposure did not improve model fit. At-ear noise exposures below 85 dBA did not show an association with risk of high-frequency hearing loss among workers with substantial past noise exposure and hearing loss at baseline. Therefore, effective noise control to below 85 dBA may lead to significant reduction in occupational hearing loss risk in such individuals. Further research is needed on the dose-response relationship of noise and hearing loss in individuals with normal hearing and little prior noise exposure.

  19. [Occlusion treatment for amblyopia. Age dependence and dose-response relationship].

    Science.gov (United States)

    Fronius, M

    2016-04-01

    Based on clinical experience and studies on animal models the age of 6-7 years was regarded as the limit for treatment of amblyopia, although functional improvement was also occasionally reported in older patients. New technical developments as well as insights from clinical studies and the neurosciences have attracted considerable attention to this topic. Various aspects of the age dependence of amblyopia treatment are discussed in this article, e. g. prescription, electronic monitoring of occlusion dosage, calculation of indicators for age-dependent plasticity of the visual system, and novel, alternative treatment approaches. Besides a discussion of the recent literature, results of studies by our "Child Vision Research Unit" in Frankfurt are presented: results of a questionnaire about prescription habits concerning age limits of patching, electronic recording of occlusion in patients beyond the conventional treatment age, calculation of dose-response function and efficiency of patching and their age dependence. The results of the questionnaire illustrate the uncertainty about age limits of prescription with significant deviations from the guideline of the German Ophthalmological Society (DOG). Electronic recording of occlusion allowed the quantification of declining dose-response function and treatment efficiency between 5 and 16 years of age. Reports about successful treatment with conventional and novel methods in adults are at variance with the notion of a rigid adult visual system lacking plasticity. Electronic recording of patching allowed new insights into the age-dependent susceptibility of the visual system and contributes to a more evidence-based treatment of amblyopia. Alternative approaches for adults challenge established notions about age limits of amblyopia therapy. Further studies comparing different treatment options are urgently needed.

  20. Cancer dose-response modeling of epidemiological data on worker exposures to aldrin and dieldrin.

    Science.gov (United States)

    Sielken, R L; Bretzlaff, R S; Valdez-Flores, C; Stevenson, D E; de Jong, G

    1999-12-01

    The paper applies classical statistical principles to yield new tools for risk assessment and makes new use of epidemiological data for human risk assessment. An extensive clinical and epidemiological study of workers engaged in the manufacturing and formulation of aldrin and dieldrin provides occupational hygiene and biological monitoring data on individual exposures over the years of employment and provides unusually accurate measures of individual lifetime average daily doses. In the cancer dose-response modeling, each worker is treated as a separate experimental unit with his own unique dose. Maximum likelihood estimates of added cancer risk are calculated for multistage, multistage-Weibull, and proportional hazards models. Distributional characterizations of added cancer risk are based on bootstrap and relative likelihood techniques. The cancer mortality data on these male workers suggest that low-dose exposures to aldrin and dieldrin do not significantly increase human cancer risk and may even decrease the human hazard rate for all types of cancer combined at low doses (e.g., 1 microgram/kg/day). The apparent hormetic effect in the best fitting dose-response models for this data set is statistically significant. The decrease in cancer risk at low doses of aldrin and dieldrin is in sharp contrast to the U.S. Environmental Protection Agency's upper bound on cancer potency based on mouse liver tumors. The EPA's upper bound implies that lifetime average daily doses of 0.0000625 and 0.00625 microgram/kg body weight/day would correspond to increased cancer risks of 0.000001 and 0.0001, respectively. However, the best estimate from the Pernis epidemiological data is that there is no increase in cancer risk in these workers at these doses or even at doses as large as 2 micrograms/kg/day.

  1. An Experimental Toxoplasma gondii Dose Response Challenge Model to Study Therapeutic or Vaccine Efficacy in Cats

    Science.gov (United States)

    Cornelissen, Jan B. W. J.; van der Giessen, Joke W. B.; Takumi, Katsuhisa; Teunis, Peter F. M.; Wisselink, Henk J.

    2014-01-01

    High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment. Previous studies have indicated that bradyzoites are highly infectious for cats. To infect cats, tissue cysts were isolated from the brains of mice infected with oocysts of T. gondii M4 strain, and bradyzoites were released by pepsin digestion. Free bradyzoites were counted and graded doses (1000, 100, 50, 10), and 250 intact tissue cysts were inoculated orally into three cats each. Oocysts shed by these five groups of cats were collected from faeces by flotation techniques, counted microscopically and estimated by real time PCR. Additionally, the number of T. gondii in heart, tongue and brains were estimated, and serology for anti T. gondii antibodies was performed. A Beta-Poisson dose-response model was used to estimate the infectivity of single bradyzoites and linear regression was used to determine the relation between inoculated dose and numbers of oocyst shed. We found that real time PCR was more sensitive than microscopic detection of oocysts, and oocysts were detected by PCR in faeces of cats fed 10 bradyzoites but by microscopic examination. Real time PCR may only detect fragments of T. gondii DNA without the presence of oocysts in low doses. Prevalence of tissue cysts of T. gondii in tongue, heart and brains, and anti T. gondii antibody concentrations were all found to depend on the inoculated bradyzoite dose. The combination of the experimental challenge model and the dose response analysis provides a suitable reference for quantifying the potential reduction in human health risk due to a treatment of domestic cats by vaccination or by therapeutic drug application. PMID:25184619

  2. Cerebral radioprotection by pentobarbital: Dose-response characteristics and association with GABA agonist activity

    Energy Technology Data Exchange (ETDEWEB)

    Olson, J.J.; Friedman, R.; Orr, K.; Delaney, T.; Oldfield, E.H. (National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (USA))

    1990-05-01

    Pentobarbital reduces cerebral radiation toxicity; however, the mechanism of this phenomenon remains unknown. As an anesthetic and depressant of cerebral metabolism, pentobarbital induces its effects on the central nervous system by stimulating the binding of gamma-aminobutyric acid (GABA) to its receptor and by inhibiting postsynaptic excitatory amino acid activity. The purpose of this study is to investigate the role of these actions as well as other aspects of the radioprotective activity of pentobarbital. Fischer 344 rats were separated into multiple groups and underwent two dose-response evaluations. In one set of experiments to examine the relationship of radioprotection to pentobarbital dose, a range of pentobarbital doses (0 to 75 mg/kg) were given intraperitoneally prior to a constant-level radiation dose (70 Gy). In a second series of experiments to determine the dose-response relationship of radiation protection to radiation dose, a range of radiation doses (10 to 90 Gy) were given with a single pentobarbital dose. Further groups of animals were used to evaluate the importance of the timing of pentobarbital administration, the function of the (+) and (-) isomers of pentobarbital, and the role of an alternative GABA agonist (diazepam). In addition, the potential protective effects of alternative methods of anesthesia (ketamine) and induction of cerebral hypometabolism (hypothermia) were examined. Enhancement of survival time from acute radiation injury due to high-dose single-fraction whole-brain irradiation was maximal with 60 mg/kg of pentobarbital, and occurred over the range of all doses examined between 30 to 90 Gy. Protection was seen only in animals that received the pentobarbital before irradiation. Administration of other compounds that enhance GABA binding (Saffan and diazepam) also significantly enhanced survival time.

  3. Dose-response relationship for breast cancer induction at radiotherapy dose

    Directory of Open Access Journals (Sweden)

    Gruber Günther

    2011-06-01

    Full Text Available Abstract Purpose Cancer induction after radiation therapy is known as a severe side effect. It is therefore of interest to predict the probability of second cancer appearance for the patient to be treated including breast cancer. Materials and methods In this work a dose-response relationship for breast cancer is derived based on (i the analysis of breast cancer induction after Hodgkin's disease, (ii a cancer risk model developed for high doses including fractionation based on the linear quadratic model, and (iii the reconstruction of treatment plans for Hodgkin's patients treated with radiotherapy, (iv the breast cancer induction of the A-bomb survivor data. Results The fitted model parameters for an α/β = 3 Gy were α = 0.067Gy-1 and R = 0.62. The risk for breast cancer is according to this model for small doses consistent with the finding of the A-bomb survivors, has a maximum at doses of around 20 Gy and drops off only slightly at larger doses. The predicted EAR for breast cancer after radiotherapy of Hodgkin's disease is 11.7/10000PY which can be compared to the findings of several epidemiological studies where EAR for breast cancer varies between 10.5 and 29.4/10000PY. The model was used to predict the impact of the reduction of radiation volume on breast cancer risk. It was estimated that mantle field irradiation is associated with a 3.2-fold increased risk compared with mediastinal irradiation alone, which is in agreement with a published value of 2.7. It was also shown that the modelled age dependency of breast cancer risk is in satisfying agreement with published data. Conclusions The dose-response relationship obtained in this report can be used for the prediction of radiation induced secondary breast cancer of radiotherapy patients.

  4. Caffeine intake and atrial fibrillation incidence: dose response meta-analysis of prospective cohort studies.

    Science.gov (United States)

    Cheng, Min; Hu, Zunsong; Lu, Xiangfeng; Huang, Jianfeng; Gu, Dongfeng

    2014-04-01

    The association between habitual caffeine intake with incident atrial fibrillation (AF) was unknown. We conducted a meta-analysis to investigate the association between chronic exposure of caffeine and the risk of AF and to evaluate the potential dose-response relation. We searched PubMed, EMBASE, and the Cochrane Library up to November 2013 and references of relevant retrieved articles. Prospective cohort studies were included with relative risk (RR) or hazard ratio and 95% confidence intervals (CIs) for AF according to coffee/caffeine intake. Six prospective cohort studies with 228,465 participants were included. In the primary meta-analysis, caffeine exposure was weakly associated with a reduced risk of AF (RR, 0.90; 95% CI, 0.81-1.01; P = 0.07; I(2) = 73%). In subgroup analyses, pooled results from studies with adjustment of potential confounders showed an 11% reduction for low doses (RR, 0.89; 95% CI, 0.80-0.99, P = 0.032; I(2) = 30.9%, P = 0.227) and 16% for high doses (RR, 0.84; 95% CI, 0.75-0.94, P = 0.002; I(2) = 24.1%, P = 0.267) of caffeine consumption in AF risk. An inverse relation was found between habitual caffeine intake and AF risk (P for overall trend = 0.015; P for nonlinearity = 0.27) in dose-response meta-analysis and the incidence of AF decreased by 6% (RR, 0.94; 95% CI, 0.90-0.99) for every 300 mg/d increment in habitual caffeine intake. It is unlikely that caffeine consumption causes or contributes to AF. Habitual caffeine consumption might reduce AF risk. Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  5. Dose-response relationship for breast cancer induction at radiotherapy dose

    Science.gov (United States)

    2011-01-01

    Purpose Cancer induction after radiation therapy is known as a severe side effect. It is therefore of interest to predict the probability of second cancer appearance for the patient to be treated including breast cancer. Materials and methods In this work a dose-response relationship for breast cancer is derived based on (i) the analysis of breast cancer induction after Hodgkin's disease, (ii) a cancer risk model developed for high doses including fractionation based on the linear quadratic model, and (iii) the reconstruction of treatment plans for Hodgkin's patients treated with radiotherapy, (iv) the breast cancer induction of the A-bomb survivor data. Results The fitted model parameters for an α/β = 3 Gy were α = 0.067Gy-1 and R = 0.62. The risk for breast cancer is according to this model for small doses consistent with the finding of the A-bomb survivors, has a maximum at doses of around 20 Gy and drops off only slightly at larger doses. The predicted EAR for breast cancer after radiotherapy of Hodgkin's disease is 11.7/10000PY which can be compared to the findings of several epidemiological studies where EAR for breast cancer varies between 10.5 and 29.4/10000PY. The model was used to predict the impact of the reduction of radiation volume on breast cancer risk. It was estimated that mantle field irradiation is associated with a 3.2-fold increased risk compared with mediastinal irradiation alone, which is in agreement with a published value of 2.7. It was also shown that the modelled age dependency of breast cancer risk is in satisfying agreement with published data. Conclusions The dose-response relationship obtained in this report can be used for the prediction of radiation induced secondary breast cancer of radiotherapy patients. PMID:21651799

  6. Meta-analysis on occupational exposure to pesticides--neurobehavioral impact and dose-response relationships.

    Science.gov (United States)

    Meyer-Baron, Monika; Knapp, Guido; Schäper, Michael; van Thriel, Christoph

    2015-01-01

    While the health impact of high exposures to pesticides is acknowledged, the impact of chronic exposures in the absence of acute poisonings is controversial. A systematic analysis of dose-response relationships is still missing. Its absence may provoke alternative explanations for altered performances. Consequently, opportunities for health prevention in the occupational and environmental field may be missed. Objectives were (1) quantification of the neurotoxic impact of pesticides by an analysis of functional alterations in workers measured by neuropsychological performance tests, (2) estimates of dose-response relationships on the basis of exposure duration, and (3) exploration of susceptible subgroups. The meta-analysis employed a random effects model to obtain overall effects for individual performance tests. Twenty-two studies with a total of 1758 exposed and 1260 reference individuals met the inclusion criteria. At least three independent outcomes were available for twenty-six performance variables. Significant performance effects were shown in adults and referred to both cognitive and motor performances. Effect sizes ranging from dRE=-0.14 to dRE=-0.67 showed consistent outcomes for memory and attention. Relationships between effect sizes and exposure duration were indicated for individual performance variables and the total of measured performances. Studies on adolescents had to be analyzed separately due to numerous outliers. The large variation among outcomes hampered the analysis of the susceptibility in this group, while data on female workers was too scant for the analysis. Relationships exist between the impact of pesticides on performances and exposure duration. A change in test paradigms would help to decipher the impact more specifically. The use of biomarkers appropriate for lower exposures would allow a better prevention of neurotoxic effects due to occupational and environmental exposure. Intervention studies in adolescents seem warranted to

  7. A method for inverse bifurcation of biochemical switches: inferring parameters from dose response curves.

    Science.gov (United States)

    Otero-Muras, Irene; Yordanov, Pencho; Stelling, Joerg

    2014-11-20

    Within cells, stimuli are transduced into cell responses by complex networks of biochemical reactions. In many cell decision processes the underlying networks behave as bistable switches, converting graded stimuli or inputs into all or none cell responses. Observing how systems respond to different perturbations, insight can be gained into the underlying molecular mechanisms by developing mathematical models. Emergent properties of systems, like bistability, can be exploited to this purpose. One of the main challenges in modeling intracellular processes, from signaling pathways to gene regulatory networks, is to deal with high structural and parametric uncertainty, due to the complexity of the systems and the difficulty to obtain experimental measurements. Formal methods that exploit structural properties of networks for parameter estimation can help to overcome these problems. We here propose a novel method to infer the kinetic parameters of bistable biochemical network models. Bistable systems typically show hysteretic dose response curves, in which the so called bifurcation points can be located experimentally. We exploit the fact that, at the bifurcation points, a condition for multistationarity derived in the context of the Chemical Reaction Network Theory must be fulfilled. Chemical Reaction Network Theory has attracted attention from the (systems) biology community since it connects the structure of biochemical reaction networks to qualitative properties of the corresponding model of ordinary differential equations. The inverse bifurcation method developed here allows determining the parameters that produce the expected behavior of the dose response curves and, in particular, the observed location of the bifurcation points given by experimental data. Our inverse bifurcation method exploits inherent structural properties of bistable switches in order to estimate kinetic parameters of bistable biochemical networks, opening a promising route for developments in

  8. Dose-response behavior of the bacterium Vibrio fischeri exposed to pharmaceuticals and personal care products.

    Science.gov (United States)

    Ortiz de García, Sheyla; García-Encina, Pedro A; Irusta-Mata, Rubén

    2016-01-01

    The presence of pharmaceuticals and personal care products (PPCPs) in the environment has become a real and widespread concern in recent years. Therefore, the primary goal of this study was to investigate 20 common and widely used PPCPs to assess their individual and combined effect on an important species in one trophic level, i.e., bacteria. The ecotoxicological effects of PPCPs at two different concentration ranges were determined in the bacterium Vibrio fischeri using Microtox(®) and were statistically analyzed using three models in the GraphPad Prism 6 program for Windows, v.6.03. A four-parameter model best fit the majority of the compounds. The half maximal effective concentration (EC50) of each PPCP was estimated using the best-fitting model and was compared with the results from a recent study. Comparative analysis indicated that most compounds showed the same level of toxicity. Moreover, the stimulatory effects of PPCPs at environmental concentrations (low doses) were assessed. These results indicated that certain compounds have traditional inverted U- or J-shaped dose-response curves, and 55% of them presented a stimulatory effect below the zero effect-concentration point. Effective concentrations of 0 (EC0), 5 (EC5) and 50% (EC50) were calculated for each PPCP as the ecotoxicological points. All compounds that presented narcosis as a mode of toxic action at high doses also exhibited stimulation at low concentrations. The maximum stimulatory effect of a mixture was higher than the highest stimulatory effect of each individually tested compound. Moreover, when the exposure time was increased, the hormetic effect decreased. Hormesis is being increasingly included in dose-response studies because this may have a harmful, beneficial or indifferent effect in an environment. Despite the results obtained in this research, further investigations need to be conducted to elucidate the behavior of PPCPs in aquatic environments.

  9. Statin Adherence and the Risk of Stroke: A Dose-Response Meta-Analysis.

    Science.gov (United States)

    Xu, Tao; Yu, Xinyuan; Ou, Shu; Liu, Xi; Yuan, Jinxian; Chen, Yangmei

    2017-04-01

    Statins are one of the most common medications for stroke prevention. Increasing evidence indicates that the effect of statins against stroke may depend on the optimal adherence of the patients to the long-term therapies. However, the magnitude of the association between statin adherence and the risk of stroke has not been determined. We conducted a dose-response meta-analysis to investigate the association between statin adherence and the risk of stroke. The Medline and Embase databases were systematically searched to identify relevant observational studies that evaluated the association between statin adherence and stroke risk. Statin adherence was primarily quantified by the proportion of days covered by prescribed statins. Studies in which relative risks (RRs) with 95% confidence intervals (CIs) for the association between statin adherence and stroke risk were reported or could be estimated were included in this meta-analysis. A total of 15 studies with 710,504 participants were included. The pooled RR of total stroke for the categories with the highest compared with the lowest adherence to statins was 0.72 (95% CI 0.65-0.79). Stratified by stroke subtype, the pooled RR for ischemic stroke (IS) was 0.83 (95% CI 0.74-0.92) and for hemorrhagic stroke was 0.75 (95% CI 0.51-1.09). The dose-response analysis indicated that an improvement in statin adherence of 20% was associated with an 8% lower risk of total stroke (RR 0.92; 95% CI 0.89-0.94). In the subgroup analysis for IS, an improvement in statin adherence of 20% was associated with a 7% lower risk of IS (RR 0.93; 95% CI 0.88-0.99). Improved adherence to statins was associated with a lower risk of stroke, particularly of IS.

  10. Parity and risk of colorectal cancer: a dose-response meta-analysis of prospective studies.

    Directory of Open Access Journals (Sweden)

    Hong-Bo Guan

    Full Text Available BACKGROUND: Association between parity and colorectal cancer (CRC risk has been investigated by several epidemiological studies but results are controversial, yet a comprehensive and quantitative assessment of this association has not been reported so far. METHODS: Relevant published studies of parity and CRC were identified using MEDLINE, EMBASE and Web of Science databases through end of April 2013. Two authors independently assessed eligibility and extracted data. Eleven prospective studies reported relative risk (RR estimates and 95% confidence intervals (CIs of CRC risk associated with parity. We pooled the RR from individual studies using fixed- or random-effects models and carried out heterogeneity and publication bias analyses. RESULTS: The summary RR for the ever parity vs. nulliparous was 0.95 (95% CI: 0.88-1.02, with no heterogeneity (Q = 9.04, P = 0.443, I (2 = 0.5%. Likewise, no significant association was yielded for the highest vs. lowest parity number (RR = 1.02, 95% CI: 0.89-1.17, with moderate heterogeneity (Q = 17.48, P = 0.094, I (2 = 37.1%. Dose-response analysis still indicated no effect of parity on CRC risk and the summary RR of per one livebirth was 0.99 (95% CI: 0.96-1.02, with moderate of heterogeneity (Q = 16.50, P<0.021, I (2 = 57.6%. Similar results were observed among all the subgroup analyses. No evidence of publication bias and significant heterogeneity between subgroups were detected by meta-regression analyses. CONCLUSION: Results of this dose-response meta-analysis of prospective studies found that there was little evidence of an association between parity and CRC risk.

  11. Aged garlic extract reduces blood pressure in hypertensives: a dose-response trial.

    Science.gov (United States)

    Ried, K; Frank, O R; Stocks, N P

    2013-01-01

    Hypertension affects about 30% of adults worldwide. Garlic has blood pressure-lowering properties and the mechanism of action is biologically plausible. Our trial assessed the effect, dose-response, tolerability and acceptability of different doses of aged garlic extract as an adjunct treatment to existing antihypertensive medication in patients with uncontrolled hypertension. A total of 79 general practice patients with uncontrolled systolic hypertension participated in a double-blind randomised placebo-controlled dose-response trial of 12 weeks. Participants were allocated to one of three garlic groups with either of one, two or four capsules daily of aged garlic extract (240/480/960 mg containing 0.6/1.2/2.4 mg of S-allylcysteine) or placebo. Blood pressure was assessed at 4, 8 and 12 weeks and compared with baseline using a mixed-model approach. Tolerability was monitored throughout the trial and acceptability was assessed at 12 weeks by questionnaire. Mean systolic blood pressure was significantly reduced by 11.8±5.4 mm Hg in the garlic-2-capsule group over 12 weeks compared with placebo (P=0.006), and reached borderline significant reduction in the garlic-4-capsule group at 8 weeks (-7.4±4.1 mm Hg, P=0.07). Changes in systolic blood pressure in the garlic-1-capsule group and diastolic blood pressure were not significantly different to placebo. Tolerability, compliance and acceptability were high in all garlic groups (93%) and highest in the groups taking one or two capsules daily. Our trial suggests aged garlic extract to be an effective and tolerable treatment in uncontrolled hypertension, and may be considered as a safe adjunct treatment to conventional antihypertensive therapy.

  12. Mathematical modeling improves EC50 estimations from classical dose-response curves.

    Science.gov (United States)

    Nyman, Elin; Lindgren, Isa; Lövfors, William; Lundengård, Karin; Cervin, Ida; Sjöström, Theresia Arbring; Altimiras, Jordi; Cedersund, Gunnar

    2015-03-01

    The β-adrenergic response is impaired in failing hearts. When studying β-adrenergic function in vitro, the half-maximal effective concentration (EC50 ) is an important measure of ligand response. We previously measured the in vitro contraction force response of chicken heart tissue to increasing concentrations of adrenaline, and observed a decreasing response at high concentrations. The classical interpretation of such data is to assume a maximal response before the decrease, and to fit a sigmoid curve to the remaining data to determine EC50 . Instead, we have applied a mathematical modeling approach to interpret the full dose-response curve in a new way. The developed model predicts a non-steady-state caused by a short resting time between increased concentrations of agonist, which affect the dose-response characterization. Therefore, an improved estimate of EC50 may be calculated using steady-state simulations of the model. The model-based estimation of EC50 is further refined using additional time-resolved data to decrease the uncertainty of the prediction. The resulting model-based EC50 (180-525 nm) is higher than the classically interpreted EC50 (46-191 nm). Mathematical modeling thus makes it possible to re-interpret previously obtained datasets, and to make accurate estimates of EC50 even when steady-state measurements are not experimentally feasible. The mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database, and may be accessed at http://jjj.bio.vu.nl/database/nyman. © 2015 FEBS.

  13. Functional tests of a prototype for the CMS-ATLAS common non-event data handling framework

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00366910; The ATLAS collaboration; Formica, Andrea

    2017-01-01

    Since 2014 the ATLAS and CMS experiments share a common vision on the database infrastructure for the handling of the non-event data in forthcoming LHC runs. The wide commonality in the use cases has allowed to agree on a common overall design solution that is meeting the requirements of both experiments. A first prototype has been completed in 2016 and has been made available to both experiments. The prototype is based on a web service implementing a REST api with a set of functions for the management of conditions data. In this contribution, we describe this prototype architecture and the tests that have been performed within the CMS computing infrastructure, with the aim of validating the support of the main use cases and of suggesting future improvements.

  14. Functional tests of a prototype for the CMS-ATLAS common non-event data handling framework

    Science.gov (United States)

    Sipos, Roland; Formica, Andrea; Franzoni, Giovanni; Govi, Giacomo; Pfeiffer, Andreas

    2017-10-01

    Since 2014 the ATLAS and CMS experiments share a common vision on the database infrastructure for the handling of the non-event data in forthcoming LHC runs. The wide commonality in the use cases has allowed to agree on a common overall design solution that is meeting the requirements of both experiments. A first prototype has been completed in 2016 and has been made available to both experiments. The prototype is based on a web service implementing a REST api with a set of functions for the management of conditions data. In this contribution, we describe this prototype architecture and the tests that have been performed within the CMS computing infrastructure, with the aim of validating the support of the main use cases and of suggesting future improvements.

  15. Salvage Radiation Therapy Dose Response for Biochemical Failure of Prostate Cancer After Prostatectomy—A Multi-Institutional Observational Study

    Energy Technology Data Exchange (ETDEWEB)

    Pisansky, Thomas M., E-mail: pisansky.thomas@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Agrawal, Shree [Case Western Reserve University School of Medicine, Cleveland, Ohio (United States); Hamstra, Daniel A. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Koontz, Bridget F. [Department of Radiation Oncology, Duke Cancer Institute, Durham, North Carolina (United States); Liauw, Stanley L. [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Efstathiou, Jason A. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Michalski, Jeff M. [Department of Radiation Oncology, Washington University, St. Louis, Missouri (United States); Feng, Felix Y. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Abramowitz, Matthew C.; Pollack, Alan [Department of Radiation Oncology, University of Miami, Miami, Florida (United States); Anscher, Mitchell S. [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia (United States); Moghanaki, Drew [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia (United States); Hunter Holmes McGuire Veterans Administration Medical Center, Richmond, Virginia (United States); Den, Robert B. [Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Stephans, Kevin L. [Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio (United States); Zietman, Anthony L. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Lee, W. Robert [Department of Radiation Oncology, Duke Cancer Institute, Durham, North Carolina (United States); Kattan, Michael W. [Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio (United States); and others

    2016-12-01

    Purpose: To determine whether a dose-response relationship exists for salvage radiation therapy (RT) of biochemical failure after prostatectomy for prostate cancer. Methods and Materials: Individual data from 1108 patients who underwent salvage RT at 10 academic centers were pooled. The cohort was enriched for selection criteria more likely associated with tumor recurrence in the prostate bed (margin positive and pre-RT prostate-specific antigen [PSA] level of ≤2.0 ng/mL) and without the confounding of planned androgen suppression. The cumulative incidence of biochemical failure and distant metastasis over time was computed, and competing risks hazard regression models were used to investigate the association between potential predictors and these outcomes. The association of radiation dose with outcomes was the primary focus. Results: With a 65.2-month follow-up duration, the 5- and 10-year estimates of freedom from post-RT biochemical failure (PSA level >0.2 ng/mL and rising) was 63.5% and 49.8%, respectively, and the cumulative incidence of distant metastasis was 12.4% by 10 years. A Gleason score of ≥7, higher pre-RT PSA level, extraprostatic tumor extension, and seminal vesicle invasion were associated with worse biochemical failure and distant metastasis outcomes. A salvage radiation dose of ≥66.0 Gy was associated with a reduced cumulative incidence of biochemical failure, but not of distant metastasis. Conclusions: The use of salvage radiation doses of ≥66.0 Gy are supported by evidence presented in the present multicenter pooled analysis of individual patient data. The observational reporting method, limited sample size, few distant metastasis events, modest follow-up duration, and elective use of salvage therapy might have diminished the opportunity to identify an association between the radiation dose and this endpoint.

  16. Functional tests of a prototype for the CMS-ATLAS common non-event data handling framework

    CERN Document Server

    Formica, Andrea; The ATLAS collaboration

    2016-01-01

    Since the 2014 the experiments ATLAS and CMS have started to share a common vision for the Condition Database infrastructure required for the forthcoming LHC runs. The large commonality in the use cases to be satisfied has allowed to agree to an overall design solution which could meet the requirements for both experiments. A first prototype implementing these solutions has been completed in 2015 and made available to both the experiments. The prototype is based on a web service implementing a REST api with a set of functions for the management of conditions data. The objects which constitute the elements of the data model are seen as resources on which CRUD operations can be performed via standard HTTP methods. The choice to insert a REST api in the architecture has several advantages: 1) the conditions data are exchanged in a neutral format ( JSON or XML), allowing to be processed by different technologies in different frameworks. 2) the client is agnostic with respect to the underlying technology adopted f...

  17. A unified framework for benchmark dose estimation applied to mixed models and model averaging

    DEFF Research Database (Denmark)

    Ritz, Christian; Gerhard, Daniel; Hothorn, Ludwig A.

    2013-01-01

    This article develops a framework for benchmark dose estimation that allows intrinsically nonlinear dose-response models to be used for continuous data in much the same way as is already possible for quantal data. This means that the same dose-response model equations may be applied to both...

  18. Leisure time physical activity and dementia risk: a dose-response meta-analysis of prospective studies.

    Science.gov (United States)

    Xu, Wei; Wang, Hui Fu; Wan, Yu; Tan, Chen-Chen; Yu, Jin-Tai; Tan, Lan

    2017-10-22

    There is considerable evidence of the favourable role of more physical activity (PA) in fighting against dementia. However, the shape of the dose-response relationship is still unclear. To quantitatively investigate the relationship between dementia and PA. PubMed, EMBASE, Ovid and the Cochrane Library were searched for prospective studies published from 1 January 1995 to 15 October 2016. Two types of meta-analyses were performed with a focus on the dose-response relationship using two stage generalised least squares regression. The primary analysis exhibited a dose-response trend for all-cause dementia (ACD), Alzheimer's disease (AD) but not for vascular dementia (VD). In the dose-response analysis, either ACD (ptrend linearity=0.87) or AD (p trend linearity=0.10) exhibited a linear relationship with leisure time PA (LTPA) over the observed range (0-2000 kcal/week or 0-45 metabolic equivalent of task hours per week (MET-h/week)). Specifically, for every 500 kcal or 10 MET-h increase per week, there was, on average, 10% and 13% decrease in the risk of ACD and AD, respectively. We have reported, for the first time, the dose-response relationship between LTPA and dementia, further supporting the international PA guideline from the standpoint of dementia prevention. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. The energy dependence of the lateral dose response functions of detectors with various densities in photon-beam dosimetry.

    Science.gov (United States)

    Looe, Hui Khee; Harder, Dietrich; Poppe, Björn

    2017-02-07

    The lateral dose response function is a general characteristic of the volume effect of a detector used for photon dosimetry in a water phantom. It serves as the convolution kernel transforming the true absorbed dose to water profile, which would be produced within the undisturbed water phantom, into the detector-measured signal profile. The shape of the lateral dose response function characterizes (i) the volume averaging attributable to the detector's size and (ii) the disturbance of the secondary electron field associated with the deviation of the electron density of the detector material from the surrounding water. In previous work, the characteristic dependence of the shape of the lateral dose response function upon the electron density of the detector material was studied for 6 MV photons by Monte Carlo simulation of a wall-less voxel-sized detector (Looe et al 2015 Phys. Med. Biol. 60 6585-07). This study is here continued for 60Co gamma rays and 15 MV photons in comparison with 6 MV photons. It is found (1) that throughout these photon spectra the shapes of the lateral dose response functions are retaining their characteristic dependence on the detector's electron density, and (2) that their energy-dependent changes are only moderate. This appears as a practical advantage because the lateral dose response function can then be treated as practically invariant across a clinical photon beam in spite of the known changes of the photon spectrum with increasing distance from the beam axis.

  20. Treatment of ulcerative colitis with oral mesalamine: advances in drug formulation, efficacy expectations and dose response, compliance, and chemoprevention.

    Science.gov (United States)

    Sandborn, William J

    2006-01-01

    Sulfasalazine, olsalazine, balsalazide, delayed-release mesalamine, controlled-release mesalamine, mesalamine pellets, and Multi-Matrix System mesalamine are effective first-line therapies for the treatment of mildly to moderately active ulcerative colitis and for subsequent maintenance of remission. For induction therapy it is unclear if there is a dose response above 1.5 g, and for maintenance therapy existing data do not support a dose response above 1.5 g. Sulfasalazine has more frequent side effects than olsalazine, balsalazide, and mesalamine formulations. Once-daily dosing with multi-matrix system mesalamine 1.2 g tablets may lead to optimal compliance. Mesalamine >/= 1.2 g and sulfasalazine >/= 2 g reduce the risk of colorectal cancer in patients with ulcerative colitis. Drug formulations, efficacy expectations and dose response, toxicity expectations, compliance considerations, and chemoprevention considerations are reviewed.

  1. Youth suicide attempts and the dose-response relationship to parental risk factors: a population-based study

    DEFF Research Database (Denmark)

    Christiansen, E; Goldney, R D; Beautrai, A L

    2011-01-01

    BACKGROUND: There is a lack of specific knowledge about the dose-response effect of multiple parental risk factors for suicide attempts among children and adolescents. The aim of this study was to determine the dose-response effect of multiple parental risk factors on an offspring's risk...... illness and low level of income were all significant independent risk factors for offspring's suicide attempts. CONCLUSIONS: Knowledge of the effect of multiple risk factors on the likelihood of suicide attempts in children and adolescents is important for risk assessment. Dose-response effects...... of multiple parental risk factors are multiplicative, but it is rare for children and adolescents to be exposed to multiple parental risk factors simultaneously. Nevertheless, they should be considered along with the offspring's own multiple risk factors in determining the overall risk of a suicide attempt...

  2. Paradigm lost, paradigm found: The re-emergence of hormesis as a fundamental dose response model in the toxicological sciences

    Energy Technology Data Exchange (ETDEWEB)

    Calabrese, Edward J. [Environmental Health Sciences, School of Public Health, Morrill I, N344, University of Massachusetts, Amherst, MA 01003 (United States)]. E-mail: edwardc@schoolph.umass.edu

    2005-12-15

    This paper provides an assessment of the toxicological basis of the hormetic dose-response relationship including issues relating to its reproducibility, frequency, and generalizability across biological models, endpoints measured and chemical class/physical stressors and implications for risk assessment. The quantitative features of the hormetic dose response are described and placed within toxicological context that considers study design, temporal assessment, mechanism, and experimental model/population heterogeneity. Particular emphasis is placed on an historical evaluation of why the field of toxicology rejected hormesis in favor of dose response models such as the threshold model for assessing non-carcinogens and linear no threshold (LNT) models for assessing carcinogens. The paper argues that such decisions were principally based on complex historical factors that emerged from the intense and protracted conflict between what is now called traditional medicine and homeopathy and the overly dominating influence of regulatory agencies on the toxicological intellectual agenda. Such regulatory agency influence emphasized hazard/risk assessment goals such as the derivation of no observed adverse effect levels (NOAELs) and the lowest observed adverse effect levels (LOAELs) which were derived principally from high dose studies using few doses, a feature which restricted perceptions and distorted judgments of several generations of toxicologists concerning the nature of the dose-response continuum. Such historical and technical blind spots lead the field of toxicology to not only reject an established dose-response model (hormesis), but also the model that was more common and fundamental than those that the field accepted. - The quantitative features of the hormetic dose/response are described and placed within the context of toxicology.

  3. SU-E-J-51: Dose Response of Common Solid State Detectors in Homogeneous Transverse and Longitudinal Magnetic Fields

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, M; Fallone, B; Rathee, S [Cross Cancer Institute, Edmonton, AB (Canada)

    2014-06-01

    Purpose: Solid state radiation detectors are often used for dose profiles and percent depth dose measurements. The dose response of selected solid state detectors is evaluated in varying transverse and longitudinal magnetic fields for eventual use in MR-Linac devices. Methods: A PTW 60003 and IBA PFD detector were modeled in the Monte Carlo code PENELOPE, incorporating a magnetic field which was varied in strength and oriented both transversely and longitudinally with respect to the incident photon beam. The detectors' long axis was in turn oriented either parallel or perpendicular to the photon beam. Dose to the active volume of each detector was scored, and its ratio to dose with zero magnetic field strength (dose response) was determined. Accuracy of the simulations was evaluated by measurements using both chambers taken at low field with a small electromagnet. Simulations were also performed in a water phantom to compare to the in air results. Results: Significant dose response was found in transverse field geometries, nearing 20% at 1.5T. The response is highly dependent on relative orientations to the magnetic field and photon beam, and on detector composition. Low field measurements confirm these results. In the presence of longitudinal magnetic fields, the detectors exhibit little dose response, reaching 0.5–1% at 1.5T regardless of detector orientation. Water tank simulations compared well to the in air simulations when not at the beam periphery, where in transverse magnetic fields only, the water tank simulations differed from the in air results. Conclusion: Transverse magnetic fields can cause large deviations in dose response, and are highly position orientation dependent. Comparatively, longitudinal magnetic fields exhibit little to no dose response in each detector as a function of magnetic field strength. Water tank simulations show longitudinal fields are generally easier to work with, but each detector must be evaluated separately.

  4. Dose-responses for mortality from cerebrovascular and heart diseases in atomic bomb survivors: 1950-2003.

    Science.gov (United States)

    Schöllnberger, Helmut; Eidemüller, Markus; Cullings, Harry M; Simonetto, Cristoforo; Neff, Frauke; Kaiser, Jan Christian

    2017-12-08

    The scientific community faces important discussions on the validity of the linear no-threshold (LNT) model for radiation-associated cardiovascular diseases at low and moderate doses. In the present study, mortalities from cerebrovascular diseases (CeVD) and heart diseases from the latest data on atomic bomb survivors were analyzed. The analysis was performed with several radio-biologically motivated linear and nonlinear dose-response models. For each detrimental health outcome one set of models was identified that all fitted the data about equally well. This set was used for multi-model inference (MMI), a statistical method of superposing different models to allow risk estimates to be based on several plausible dose-response models rather than just relying on a single model of choice. MMI provides a more accurate determination of the dose response and a more comprehensive characterization of uncertainties. It was found that for CeVD, the dose-response curve from MMI is located below the linear no-threshold model at low and medium doses (0-1.4 Gy). At higher doses MMI predicts a higher risk compared to the LNT model. A sublinear dose-response was also found for heart diseases (0-3 Gy). The analyses provide no conclusive answer to the question whether there is a radiation risk below 0.75 Gy for CeVD and 2.6 Gy for heart diseases. MMI suggests that the dose-response curves for CeVD and heart diseases in the Lifespan Study are sublinear at low and moderate doses. This has relevance for radiotherapy treatment planning and for international radiation protection practices in general.

  5. Parametric modelling of cardiac system multiple measurement signals: an open-source computer framework for performance evaluation of ECG, PCG and ABP event detectors.

    Science.gov (United States)

    Homaeinezhad, M R; Sabetian, P; Feizollahi, A; Ghaffari, A; Rahmani, R

    2012-02-01

    The major focus of this study is to present a performance accuracy assessment framework based on mathematical modelling of cardiac system multiple measurement signals. Three mathematical algebraic subroutines with simple structural functions for synthetic generation of the synchronously triggered electrocardiogram (ECG), phonocardiogram (PCG) and arterial blood pressure (ABP) signals are described. In the case of ECG signals, normal and abnormal PQRST cycles in complicated conditions such as fascicular ventricular tachycardia, rate dependent conduction block and acute Q-wave infarctions of inferior and anterolateral walls can be simulated. Also, continuous ABP waveform with corresponding individual events such as systolic, diastolic and dicrotic pressures with normal or abnormal morphologies can be generated by another part of the model. In addition, the mathematical synthetic PCG framework is able to generate the S4-S1-S2-S3 cycles in normal and in cardiac disorder conditions such as stenosis, insufficiency, regurgitation and gallop. In the PCG model, the amplitude and frequency content (5-700 Hz) of each sound and variation patterns can be specified. The three proposed models were implemented to generate artificial signals with varies abnormality types and signal-to-noise ratios (SNR), for quantitative detection-delineation performance assessment of several ECG, PCG and ABP individual event detectors designed based on the Hilbert transform, discrete wavelet transform, geometric features such as area curve length (ACLM), the multiple higher order moments (MHOM) metric, and the principal components analysed geometric index (PCAGI). For each method the detection-delineation operating characteristics were obtained automatically in terms of sensitivity, positive predictivity and delineation (segmentation) error rms and checked by the cardiologist. The Matlab m-file script of the synthetic ECG, ABP and PCG signal generators are available in the Appendix.

  6. Neurobehavioral Dynamics Following Chronic Sleep Restriction: Dose-Response Effects of One Night for Recovery

    Science.gov (United States)

    Banks, Siobhan; Van Dongen, Hans P. A.; Maislin, Greg; Dinges, David F.

    2010-01-01

    Objective: Establish the dose-response relationship between increasing sleep durations in a single night and recovery of neurobehavioral functions following chronic sleep restriction. Design: Intent-to-treat design in which subjects were randomized to 1 of 6 recovery sleep doses (0, 2, 4, 6, 8, or 10 h TIB) for 1 night following 5 nights of sleep restriction to 4 h TIB. Setting: Twelve consecutive days in a controlled laboratory environment. Participants: N = 159 healthy adults (aged 22-45 y), median = 29 y). Interventions: Following a week of home monitoring with actigraphy and 2 baseline nights of 10 h TIB, subjects were randomized to either sleep restriction to 4 h TIB per night for 5 nights followed by randomization to 1 of 6 nocturnal acute recovery sleep conditions (N = 142), or to a control condition involving 10 h TIB on all nights (N = 17). Measurements and Results: Primary neurobehavioral outcomes included lapses on the Psychomotor Vigilance Test (PVT), subjective sleepiness from the Karolinska Sleepiness Scale (KSS), and physiological sleepiness from a modified Maintenance of Wakefulness Test (MWT). Secondary outcomes included psychomotor and cognitive speed as measured by PVT fastest RTs and number correct on the Digit Symbol Substitution Task (DSST), respectively, and subjective fatigue from the Profile of Mood States (POMS). The dynamics of neurobehavioral outcomes following acute recovery sleep were statistically modeled across the 0 h-10 h recovery sleep doses. While TST, stage 2, REM sleep and NREM slow wave energy (SWE) increased linearly across recovery sleep doses, best-fitting neurobehavioral recovery functions were exponential across recovery sleep doses for PVT and KSS outcomes, and linear for the MWT. Analyses based on return to baseline and on estimated intersection with control condition means revealed recovery was incomplete at the 10 h TIB (8.96 h TST) for PVT performance, KSS sleepiness, and POMS fatigue. Both TST and SWE were elevated

  7. Non-Targeted Effects and the Dose Response for Heavy Ion Tumorigenesis

    Science.gov (United States)

    Chappelli, Lori J.; Cucinotta, Francis A.

    2010-01-01

    BACKGROUND: There is no human epidemiology data available to estimate the heavy ion cancer risks experienced by astronauts in space. Studies of tumor induction in mice are a necessary step to estimate risks to astronauts. Previous experimental data can be better utilized to model dose response for heavy ion tumorigenesis and plan future low dose studies. DOSE RESPONSE MODELS: The Harderian Gland data of Alpen et al.[1-3] was re-analyzed [4] using non-linear least square regression. The data set measured the induction of Harderian gland tumors in mice by high-energy protons, helium, neon, iron, niobium and lanthanum with LET s ranging from 0.4 to 950 keV/micron. We were able to strengthen the individual ion models by combining data for all ions into a model that relates both radiation dose and LET for the ion to tumor prevalence. We compared models based on Targeted Effects (TE) to one motivated by Non-targeted Effects (NTE) that included a bystander term that increased tumor induction at low doses non-linearly. When comparing fitted models to the experimental data, we considered the adjusted R2, the Akaike Information Criteria (AIC), and the Bayesian Information Criteria (BIC) to test for Goodness of fit.In the adjusted R2test, the model with the highest R2values provides a better fit to the available data. In the AIC and BIC tests, the model with the smaller values of the summary value provides the better fit. The non-linear NTE models fit the combined data better than the TE models that are linear at low doses. We evaluated the differences in the relative biological effectiveness (RBE) and found the NTE model provides a higher RBE at low dose compared to the TE model. POWER ANALYSIS: The final NTE model estimates were used to simulate example data to consider the design of new experiments to detect NTE at low dose for validation. Power and sample sizes were calculated for a variety of radiation qualities including some not considered in the Harderian Gland data

  8. Evaluation of Different Dose-Response Models for High Hydrostatic Pressure Inactivation of Microorganisms

    Science.gov (United States)

    2017-01-01

    Modeling of microbial inactivation by high hydrostatic pressure (HHP) requires a plot of the log microbial count or survival ratio versus time data under a constant pressure and temperature. However, at low pressure and temperature values, very long holding times are needed to obtain measurable inactivation. Since the time has a significant effect on the cost of HHP processing it may be reasonable to fix the time at an appropriate value and quantify the inactivation with respect to pressure. Such a plot is called dose-response curve and it may be more beneficial than the traditional inactivation modeling since short holding times with different pressure values can be selected and used for the modeling of HHP inactivation. For this purpose, 49 dose-response curves (with at least 4 log10 reduction and ≥5 data points including the atmospheric pressure value (P = 0.1 MPa), and with holding time ≤10 min) for HHP inactivation of microorganisms obtained from published studies were fitted with four different models, namely the Discrete model, Shoulder model, Fermi equation, and Weibull model, and the pressure value needed for 5 log10 (P5) inactivation was calculated for all the models above. The Shoulder model and Fermi equation produced exactly the same parameter and P5 values, while the Discrete model produced similar or sometimes the exact same parameter values as the Fermi equation. The Weibull model produced the worst fit (had the lowest adjusted determination coefficient (R2adj) and highest mean square error (MSE) values), while the Fermi equation had the best fit (the highest R2adj and lowest MSE values). Parameters of the models and also P5 values of each model can be useful for the further experimental design of HHP processing and also for the comparison of the pressure resistance of different microorganisms. Further experiments can be done to verify the P5 values at given conditions. The procedure given in this study can also be extended for enzyme

  9. Evaluation of Different Dose-Response Models for High Hydrostatic Pressure Inactivation of Microorganisms

    Directory of Open Access Journals (Sweden)

    Sencer Buzrul

    2017-09-01

    Full Text Available Modeling of microbial inactivation by high hydrostatic pressure (HHP requires a plot of the log microbial count or survival ratio versus time data under a constant pressure and temperature. However, at low pressure and temperature values, very long holding times are needed to obtain measurable inactivation. Since the time has a significant effect on the cost of HHP processing it may be reasonable to fix the time at an appropriate value and quantify the inactivation with respect to pressure. Such a plot is called dose-response curve and it may be more beneficial than the traditional inactivation modeling since short holding times with different pressure values can be selected and used for the modeling of HHP inactivation. For this purpose, 49 dose-response curves (with at least 4 log10 reduction and ≥5 data points including the atmospheric pressure value (P = 0.1 MPa, and with holding time ≤10 min for HHP inactivation of microorganisms obtained from published studies were fitted with four different models, namely the Discrete model, Shoulder model, Fermi equation, and Weibull model, and the pressure value needed for 5 log10 (P5 inactivation was calculated for all the models above. The Shoulder model and Fermi equation produced exactly the same parameter and P5 values, while the Discrete model produced similar or sometimes the exact same parameter values as the Fermi equation. The Weibull model produced the worst fit (had the lowest adjusted determination coefficient (R2adj and highest mean square error (MSE values, while the Fermi equation had the best fit (the highest R2adj and lowest MSE values. Parameters of the models and also P5 values of each model can be useful for the further experimental design of HHP processing and also for the comparison of the pressure resistance of different microorganisms. Further experiments can be done to verify the P5 values at given conditions. The procedure given in this study can also be extended for

  10. Linearization of dose-response curve of the radiochromic film dosimetry system

    Energy Technology Data Exchange (ETDEWEB)

    Devic, Slobodan; Tomic, Nada; Aldelaijan, Saad; DeBlois, Francois; Seuntjens, Jan; Chan, Maria F.; Lewis, Dave [Medical Physics Unit, McGill University, Montreal, Quebec H3G 1A4 (Canada) and Department of Radiation Oncology, SMBD Jewish General Hospital, McGill University, Montreal, Quebec H3T 1E2 (Canada); Executive Administration for Radiation Protection and Safety Medical Devices Sector, Saudi Food and Drug Authority, Riyadh, Kingdom of Saudi Arabia 13312 (Saudi Arabia); Medical Physics Unit, McGill University, Montreal, Quebec H3G 1A4 (Canada) and Department of Radiation Oncology, SMBD Jewish General Hospital, McGill University, Montreal, Quebec H3T 1E2 (Canada); Medical Physics Unit, McGill University, Montreal, Quebec H3G 1A4 (Canada); Department of Medical Physics, Memorial Sloan-Kettering Cancer Center Basking Ridge, New Jersey 07920 (United States); Ashland Inc., Wayne, New Jersey 07470 (United States)

    2012-08-15

    Purpose: Despite numerous advantages of radiochromic film dosimeter (high spatial resolution, near tissue equivalence, low energy dependence) to measure a relative dose distribution with film, one needs to first measure an absolute dose (following previously established reference dosimetry protocol) and then convert measured absolute dose values into relative doses. In this work, we present result of our efforts to obtain a functional form that would linearize the inherently nonlinear dose-response curve of the radiochromic film dosimetry system. Methods: Functional form [{zeta}= (-1){center_dot}netOD{sup (2/3)}/ln(netOD)] was derived from calibration curves of various previously established radiochromic film dosimetry systems. In order to test the invariance of the proposed functional form with respect to the film model used we tested it with three different GAFCHROMIC Trade-Mark-Sign film models (EBT, EBT2, and EBT3) irradiated to various doses and scanned on a same scanner. For one of the film models (EBT2), we tested the invariance of the functional form to the scanner model used by scanning irradiated film pieces with three different flatbed scanner models (Epson V700, 1680, and 10000XL). To test our hypothesis that the proposed functional argument linearizes the response of the radiochromic film dosimetry system, verification tests have been performed in clinical applications: percent depth dose measurements, IMRT quality assurance (QA), and brachytherapy QA. Results: Obtained R{sup 2} values indicate that the choice of the functional form of the new argument appropriately linearizes the dose response of the radiochromic film dosimetry system we used. The linear behavior was insensitive to both film model and flatbed scanner model used. Measured PDD values using the green channel response of the GAFCHROMIC Trade-Mark-Sign EBT3 film model are well within {+-}2% window of the local relative dose value when compared to the tabulated Cobalt-60 data. It was also

  11. KINETIC SIMULATIONS OF THERMOLUMINESCENCE DOSE RESPONSE: LONG OVERDUE CONFRONTATION WITH THE EFFECTS OF IONISATION DENSITY.

    Science.gov (United States)

    Horowitz, Y S; Eliyahu, I; Oster, L

    2016-12-01

    The reader will time-travel through almost seven decades of kinetic models and mathematical simulations of thermoluminescence (TL) characteristics based on the band-gap theory of the solid state. From post-World-War II, ideas concerning electron trapping mechanisms to the highly idealised one trap-one recombination (OTOR) model first elaborated in 1956 but still in 'high gear' today. The review caresses but purposely avoids in-depth discussion of the endless stream of papers discussing the intricacies of glow peak shapes arising from first-order, second-order, mixed-order and general-order kinetics predominantly based on non-interacting systems, and then on to the more physically realistic scenarios that have attempted to analyse complex systems involving ever greater numbers of interacting trapping centres, luminescent centres and non-luminescent centres. The review emphasises the difficulty the band-gap models have in the simulation of dose response linear/supralinear behaviour and especially the dependence of the supralinearity on ionisation density. The significance of the non-observation of filling-rate supralinearity in the absorption stage is emphasised since it removes from consideration the possibility of TL supralinearity arising from irradiation stage supralinearity. The importance of the simultaneous action of both localised and delocalised transitions has gradually penetrated the mindset of the community of kinetic researchers, but most simulations have concentrated on the shape of glow peaks and the extraction of the glow peak parameters, E (the thermal activation energy) and s (the attempt-to-escape frequency). The simulation of linear/supralinear dose response and its dependence on ionisation density have been largely avoided until recently due to the fundamental schism between the effects of ionisation density and some basic assumptions of the band-gap model. The review finishes with an in-depth presentation and discussion of the most recent

  12. Habitual Chocolate Consumption May Increase Body Weight in a Dose-Response Manner

    Science.gov (United States)

    Greenberg, James A.; Buijsse, Brian

    2013-01-01

    Objective Habitual chocolate intake was recently found to be associated with lower body weight in three cross-sectional epidemiological studies. Our objective was to assess whether these cross-sectional results hold up in a more rigorous prospective analysis. Methods We used data from the Atherosclerosis Risk in Communities cohort. Usual dietary intake was assessed by questionnaire at baseline (1987–98), and after six years. Participants reported usual chocolate intake as the frequency of eating a 1-oz (∼28 g) serving. Body weight and height were measured at the two visits. Missing data were replaced by multiple imputation. Linear mixed-effects models were used to evaluate cross-sectional and prospective associations between chocolate intake and adiposity. Results Data were from 15,732 and 12,830 participants at the first and second visit, respectively. More frequent chocolate consumption was associated with a significantly greater prospective weight gain over time, in a dose-response manner. For instance, compared to participants who ate a chocolate serving less often than monthly, those who ate it 1–4 times a month and at least weekly experienced an increase in Body Mass Index (kg/m2) of 0.26 (95% CI 0.08, 0.44) and 0.39 (0.23, 0.55), respectively, during the six-year study period. In cross-sectional analyses the frequency of chocolate consumption was inversely associated with body weight. This inverse association was attenuated after excluding participants with preexisting obesity-related illness. Compared to participants without such illness, those with it had higher BMI and reported less frequent chocolate intake, lower caloric intake, and diets richer in fruits and vegetables. They tended to make these dietary changes after becoming ill. Conclusions Our prospective analysis found that a chocolate habit was associated with long-term weight gain, in a dose-response manner. Our cross-sectional finding that chocolate intake was associated with lower body

  13. Dose-Response Effects of Tai Chi and Physical Therapy Exercise Interventions in Symptomatic Knee Osteoarthritis.

    Science.gov (United States)

    Lee, Augustine C; Harvey, William F; Price, Lori Lyn; Han, Xingyi; Driban, Jeffrey B; Iversen, Maura D; Desai, Sima A; Knopp, Hans E; Wang, Chenchen

    2018-01-30

    Therapeutic exercise is a currently recommended non-pharmacological treatment for knee osteoarthritis (KOA). The optimal treatment dose (frequency or duration) has not been determined. To examine dose-response relationships, minimal effective dose, and baseline factors associated with the timing of response from two exercise interventions in KOA. Secondary analysis of a single-blind, randomized trial comparing 12-week Tai Chi and Physical Therapy exercise programs (Trial Registry #NCT01258985). Urban tertiary care academic hospital PARTICIPANTS: 182 participants with symptomatic KOA (mean age 61 years; BMI 32kg/m2, 70% female; 55% white). We defined dose as cumulative attendance-weeks of intervention, and treatment response as ≥20% and ≥50% improvement in pain and function. Using log-rank tests, we compared time-to-response between interventions; and used Cox regression to examine baseline factors associated with timing of response, including physical and psychosocial health, physical performance, outcome expectations, self-efficacy, and biomechanical factors. Weekly Western Ontario and McMasters Osteoarthritis Index (WOMAC) pain (0 to 500) and function (0 to 1700) scores. Both interventions had an approximately linear dose-response effect resulting in a 9 to 11-point reduction in WOMAC pain and a 32 to 41-point improvement in function per attendance-week. There was no significant difference in overall time-to-response for pain and function between treatment groups. Median time-to-response for ≥20% improvement in pain and function was 2 attendance-weeks and 4 to 5 attendance-weeks for ≥50% improvement. On multivariable models, outcome expectations were independently associated with incident function response (Hazard Ratio: 1.47; 95% CI: 1.004 to 2.14). Both interventions have approximately linear dose-dependent effects on pain and function, their minimum effective doses range from 2-5 weeks, and patient perceived benefits of exercise influence the timing of

  14. Linearization of dose-response curve of the radiochromic film dosimetry system.

    Science.gov (United States)

    Devic, Slobodan; Tomic, Nada; Aldelaijan, Saad; Deblois, Francois; Seuntjens, Jan; Chan, Maria F; Lewis, Dave

    2012-08-01

    Despite numerous advantages of radiochromic film dosimeter (high spatial resolution, near tissue equivalence, low energy dependence) to measure a relative dose distribution with film, one needs to first measure an absolute dose (following previously established reference dosimetry protocol) and then convert measured absolute dose values into relative doses. In this work, we present result of our efforts to obtain a functional form that would linearize the inherently nonlinear dose-response curve of the radiochromic film dosimetry system. Functional form [ζ = (-1)[middle dot]netOD((2∕3))∕ln(netOD)] was derived from calibration curves of various previously established radiochromic film dosimetry systems. In order to test the invariance of the proposed functional form with respect to the film model used we tested it with three different GAFCHROMIC™ film models (EBT, EBT2, and EBT3) irradiated to various doses and scanned on a same scanner. For one of the film models (EBT2), we tested the invariance of the functional form to the scanner model used by scanning irradiated film pieces with three different flatbed scanner models (Epson V700, 1680, and 10000XL). To test our hypothesis that the proposed functional argument linearizes the response of the radiochromic film dosimetry system, verification tests have been performed in clinical applications: percent depth dose measurements, IMRT quality assurance (QA), and brachytherapy QA. Obtained R(2) values indicate that the choice of the functional form of the new argument appropriately linearizes the dose response of the radiochromic film dosimetry system we used. The linear behavior was insensitive to both film model and flatbed scanner model used. Measured PDD values using the green channel response of the GAFCHROMIC™ EBT3 film model are well within ±2% window of the local relative dose value when compared to the tabulated Cobalt-60 data. It was also found that criteria of 3%∕3 mm for an IMRT QA plan and 3%∕2

  15. The alanine detector in BNCT dosimetry: Dose response in thermal and epithermal neutron fields

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, T., E-mail: schmito@uni-mainz.de [Institute for nuclear chemistry, Johannes Gutenberg-University, Mainz D-55128 (Germany); Bassler, N. [Department of Physics and Astronomy, Aarhus University, Ny Munkegade 120, Aarhus C, Aarhus 8000 (Denmark); Blaickner, M. [AIT Austrian Institute of Technology GmbH, Vienna A-1220 (Austria); Ziegner, M. [AIT Austrian Institute of Technology GmbH, Vienna A-1220, Austria and TU Wien, Vienna University of Technology, Vienna A-1020 (Austria); Hsiao, M. C. [Insitute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Liu, Y. H. [Nuclear Science and Technology Development Center, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Koivunoro, H. [Department of Physics, University of Helsinki, POB 64, FI-00014, Finland and HUS Medical Imaging Center, Helsinki University Central Hospital, FI-00029 HUS (Finland); Auterinen, I.; Serén, T.; Kotiluoto, P. [VTT Technical Research Centre of Finland, Espoo (Finland); Palmans, H. [National Physical Laboratory, Acoustics and Ionising Radiation Division, Teddington TW11 0LW, United Kingdom and Medical Physics Group, EBG MedAustron GmbH, Wiener Neustadt A-2700 (Austria); Sharpe, P. [National Physical Laboratory, Acoustics and Ionising Radiation Division, Teddington TW11 0LW (United Kingdom); Langguth, P. [Department of Pharmacy and Toxicology, University of Mainz, Mainz D-55128 (Germany); Hampel, G. [Institut für Kernchemie, Johannes Gutenberg-Universität, Mainz D-55128 (Germany)

    2015-01-15

    Purpose: The response of alanine solid state dosimeters to ionizing radiation strongly depends on particle type and energy. Due to nuclear interactions, neutron fields usually also consist of secondary particles such as photons and protons of diverse energies. Various experiments have been carried out in three different neutron beams to explore the alanine dose response behavior and to validate model predictions. Additionally, application in medical neutron fields for boron neutron capture therapy is discussed. Methods: Alanine detectors have been irradiated in the thermal neutron field of the research reactor TRIGA Mainz, Germany, in five experimental conditions, generating different secondary particle spectra. Further irradiations have been made in the epithermal neutron beams at the research reactors FiR 1 in Helsinki, Finland, and Tsing Hua open pool reactor in HsinChu, Taiwan ROC. Readout has been performed with electron spin resonance spectrometry with reference to an absorbed dose standard in a {sup 60}Co gamma ray beam. Absorbed doses and dose components have been calculated using the Monte Carlo codes FLUKA and MCNP. The relative effectiveness (RE), linking absorbed dose and detector response, has been calculated using the Hansen and Olsen alanine response model. Results: The measured dose response of the alanine detector in the different experiments has been evaluated and compared to model predictions. Therefore, a relative effectiveness has been calculated for each dose component, accounting for its dependence on particle type and energy. Agreement within 5% between model and measurement has been achieved for most irradiated detectors. Significant differences have been observed in response behavior between thermal and epithermal neutron fields, especially regarding dose composition and depth dose curves. The calculated dose components could be verified with the experimental results in the different primary and secondary particle fields. Conclusions: The

  16. Case Study on Influence Factor Trend Analysis of the Accidents and Events of Nuclear Power Plants by applying Nuclear Safety Culture Framework

    Energy Technology Data Exchange (ETDEWEB)

    Park, J. Y.; Park, Y. W.; Park, H.G. [KAIST, Daejeon (Korea, Republic of)

    2016-05-15

    This study 1) established the standard based on frameworks of safety culture principles that show safety culture promotion goals, 2) analyzed the linkages with the frameworks that were established by analyzing each incident cause and weak point from selected 268 cases(rating over INES grade 1) among 4,088 cases (as of April 1, 2015). The 4,088 cases were selected as a result of database analysis from 702 accidents recorded in accident and rating evaluation reports that were published in the National Nuclear Safety Commission and overseas IRS (International Reporting System for operating Experience), and 3) finally conducted a trend analysis studies with these comprehensive results. From the investigations, followings were concluded. 1) In order to analyze the safety culture, analysis methodology is required. 2) Analytical methodology for building sustainable safety culture promoting a virtuous cycle system was developed 3) Among variety of process input data, 970 domestic and overseas incidents were selected as targets and 502 accidents were classified as safety culture related events by utilizing screen filter of IAEA GS-G-3.5 Appendix I and Framework (Nuclear Safety Culture Base Frame) developed by BEES, Inc. for safety culture analysis method. 4) As a result, complex safety culture influence factors for the one reason which was difficult to separate by conventional methods was able to be analyzed. 5) The cumulative data through the system was results of virtuous trend analysis rather than temporary results. Thus, it could be unique cultural factors of the domestic industry and could derive trend differences for domestic safety culture factors accordingly.

  17. Component resolved OSL dose response and sensitization of various sedimentary quartz samples

    Energy Technology Data Exchange (ETDEWEB)

    Kiyak, N.G. [Faculty of Science and Arts, ISIK University, Istanbul (Turkey)]. E-mail: kiyak@isikun.edu.tr; Polymeris, G.S. [Cultural and Educational Technology Institute, Archaeometry Laboratory, Tsimiski 58, 67100-Xanthi (Greece); Nuclear Physics Laboratory, Aristotle University of Thessaloniki, 54124-Thessaloniki (Greece); Kitis, G. [Nuclear Physics Laboratory, Aristotle University of Thessaloniki, 54124-Thessaloniki (Greece)

    2007-02-15

    The structure of the linearly modulated optically stimulated luminescence (LM-OSL) signal was studied for four sedimentary quartz samples, collected from different sites around Istanbul, Turkey. Applying a computerized deconvolution analysis to the LM-OSL curves, at least six individual components of first-order kinetics were identified and photoionization cross-section of each component was evaluated. The OSL dose-response curve of each component for each quartz sample was obtained, showing a remarkable differentiation from component to component. The behavior of a highly dosed sample to successive LM-OSL measurements was also studied showing a stable recuperation signal in the position of the 'slow' and 'medium' components and high resistance to OSL bleaching of the 'slow' component. The individual sensitivity of each component as a function of the activation temperature was obtained. The sensitivity of each component was normalized over the respective sensitivity of the glow-peak at 110 deg. C of quartz in order to investigate the ability of the 110 deg. C glow-peak to act as a correction factor for all components of the LM-OSL curves examined.

  18. Aldrin and dieldrin: a reevaluation of the cancer and noncancer dose-response assessments.

    Science.gov (United States)

    Hooker, Eric P; Fulcher, Keri G; Gibb, Herman J

    2014-05-01

    The dose-response analyses of cancer and noncancer health effects of aldrin and dieldrin were evaluated using current methodology, including benchmark dose analysis and the current U.S. Environmental Protection Agency (U.S. EPA) guidance on body weight scaling and uncertainty factors. A literature review was performed to determine the most appropriate adverse effect endpoints. Using current methodology and information, the estimated reference dose values were 0.0001 and 0.00008 mg/kg-day for aldrin and dieldrin, respectively. The estimated cancer slope factors for aldrin and dieldrin were 3.4 and 7.0 (mg/kg-day)(-1), respectively (i.e., about 5- and 2.3-fold lower risk than the 1987 U.S. EPA assessments). Because aldrin and dieldrin are no longer used as pesticides in the United States, they are presumed to be a low priority for additional review by the U.S. EPA. However, because they are persistent and still detected in environmental samples, quantitative risk assessments based on the best available methods are required. Recent epidemiologic studies do not demonstrate a causal association between aldrin and dieldrin and human cancer risk. The proposed reevaluations suggest that these two compounds pose a lower human health risk than currently reported by the U.S. EPA. © 2013 Society for Risk Analysis.

  19. Dose-response effect of ergocalciferol therapy on serum 25-hydroxyvitamin D concentration during critical illness.

    Science.gov (United States)

    Dickerson, Roland N; Berry, Scott C; Ziebarth, Jamie D; Swanson, Joseph M; Maish, George O; Minard, Gayle; Brown, Rex O

    2015-10-01

    The aim of this study was to evaluate the dose-response relationship between ergocalciferol therapy and serum 25-hydroxyvitamin D concentrations in enterally fed, critically ill patients with traumatic injuries. A retrospective cohort of critically ill patients with traumatic injuries and vitamin D deficiency (25-OH vitamin D vitamin D and ionized calcium concentrations were monitored weekly. Ergocalciferol therapy was stopped when the serum 25-OH vitamin D was >75 nmol/L, if the patient experienced hypercalcemia (ionized calcium >1.34 mmol/L), when the patient was discharged from the ICU, or if enteral nutrition was discontinued. Sixty-five patients (16, 18, and 31 per dosage group) were examined. One (6%), two (11%), and eight (26%) patients achieved normal 25-OH vitamin D concentrations after 2 to 4 wk of ergocalciferol therapy for each dosage group, respectively (P vitamin D concentrations improved from 36 ± 6, 40 ± 7, and 37 ± 6 nmol/L to 50 ± 15, 54 ± 21, and 62 ± 17 nmol/L, respectively, after 2 wk of ergocalciferol therapy (P vitamin D concentrations but was inadequate for consistently achieving normal serum concentrations of 25-OH vitamin D during critical illness. The trend in increasing appearance of mild hypercalcemia for the highest dosage group is concerning. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Dose-Response of High-Intensity Training (HIT) on Atheroprotective miRNA-126 Levels

    Science.gov (United States)

    Schmitz, Boris; Schelleckes, Katrin; Nedele, Johanna; Thorwesten, Lothar; Klose, Andreas; Lenders, Malte; Krüger, Michael; Brand, Eva; Brand, Stefan-Martin

    2017-01-01

    Aim: MicroRNA-126 (miR-126) exerts beneficial effects on vascular integrity, angiogenesis, and atherosclerotic plaque stability. The purpose of this investigation was to analyze the dose-response relationship of high-intensity interval training (HIIT) on miR-126-3p and -5p levels. Methods: Sixty-one moderately trained individuals (females = 31 [50.8%]; 22.0 ± 1.84 years) were consecutively recruited and allocated into three matched groups using exercise capacity. During a 4-week intervention a HIIT group performed three exercise sessions/week of 4 × 30 s at maximum speed (all-out), a progressive HIIT (proHIIT) group performed three exercise sessions/week of 4 × 30 s at maximum speed (all-out) with one extra session every week (up to 7 × 30 s) and a low-intensity training (LIT) control group performed three exercise sessions/week for 25 min HIIT groups (after 4 min of high-intensity running). After the intervention, the LIT group presented an increase in miR-126-3p, while in the HIIT group, miR-126-3p levels were still reduced (all p HIIT (−1.05 ± 2.6 units). Conclusions: LIT and proHIIT may be performed to increase individual miR-126 levels. HIIT without progression was less effective in increasing miR-126. PMID:28611681

  1. Support vector regression and least squares support vector regression for hormetic dose-response curves fitting.

    Science.gov (United States)

    Qin, Li-Tang; Liu, Shu-Shen; Liu, Hai-Ling; Zhang, Yong-Hong

    2010-01-01

    Accurate description of hormetic dose-response curves (DRC) is a key step for the determination of the efficacy and hazards of the pollutants with the hormetic phenomenon. This study tries to use support vector regression (SVR) and least squares support vector regression (LS-SVR) to address the problem of curve fitting existing in hormesis. The SVR and LS-SVR, which are entirely different from the non-linear fitting methods used to describe hormetic effects based on large sample, are at present only optimum methods based on small sample often encountered in the experimental toxicology. The tuning parameters (C and p1 for SVR, gam and sig2 for LS-SVR) determining SVR and LS-SVR models were obtained by both the internal and external validation of the models. The internal validation was performed by using leave-one-out (LOO) cross-validation and the external validation was performed by splitting the whole data set (12 data points) into the same size (six data points) of training set and test set. The results show that SVR and LS-SVR can accurately describe not only for the hermetic J-shaped DRC of seven water-soluble organic solvents consisting of acetonitrile, methanol, ethanol, acetone, ether, tetrahydrofuran, and isopropanol, but also for the classical sigmoid DRC of six pesticides including simetryn, prometon, bromacil, velpar, diquat-dibromide monohydrate, and dichlorvos. Copyright 2009 Elsevier Ltd. All rights reserved.

  2. The determination of effective antiviral doses using a computer program for sigmoid dose-response curves.

    Science.gov (United States)

    Taylor, J L; O'Brien, W J; Goldman, A I

    1984-05-01

    A computer program was designed to construct best fit sigmoid dose-response curves for determination of the dose required to reduce the yield of virus by 50%, effective antiviral dose (ED50). A single antiviral agent, 9-beta-D-arabinofuranosyladenine, was examined for effectiveness against four strains of herpes simplex virus type 1. The resulting ED50 values were compared with those obtained by probit analysis. The statistical parameters obtained from sigmoid curve fit program were utilized to evaluate statistical differences between ED50 values for resistant and sensitive virus strains and to evaluate the goodness-of-fit of the regression line to the data. In addition, using this analytical method, it was shown that a change in one experimental variable, i.e., multiplicity of infection, in the yield reduction assay significantly affected the apparent ED50 value. The computer program was easily utilized for analysis of data obtained from both plaque reduction and yield reduction assays and generated the parameters necessary for statistical comparison of relative antiviral activity of any antiviral agent.

  3. Effect of composition interactions on the dose response of an N-isopropylacrylamide gel dosimeter.

    Directory of Open Access Journals (Sweden)

    Yuan-Jen Chang

    Full Text Available In this study, a two-level full factorial design was used to identify the effects of the interactions between compositions in an N-isopropylacrylamide (NIPAM gel dosimeter involving the following variables: (A gelatin, (B NIPAM, (C the crosslinker N, N'-methylene-bis-acrylamide (Bis, and (D the antioxidant tetrakis (hydroxymethyl phosphonium chloride (THPC. The dose range was from 0 Gy to 5 Gy. Optical computed tomography was used to scan the polymer gel dosimeter. Each component was set to two levels for all four variables, including (A 4% and 6%, (B 4% and 6%, (C 2% and 4%, as well as (D 5 and 15 mM. Response surface methodology and a central composite design were adopted for the quantitative investigation of the respective interaction effects on the dose response curve of the gel. The results showed that the contributions of the interaction effects, i.e., AB (6.22%, AC (8.38%, AD (7.74%, BC (9.44%, ABC (18.24%, BCD (12.66%, and ABCD (13.4%, were greater than those of the four main effects, accounting for over 76.08% of the total variability. These results also indicated that the NIPAM gel recipe with the highest sensitivity was at 40%C (mass fraction of Bis.

  4. Estimation and uncertainty analysis of dose response in an inter-laboratory experiment

    Science.gov (United States)

    Toman, Blaza; Rösslein, Matthias; Elliott, John T.; Petersen, Elijah J.

    2016-02-01

    An inter-laboratory experiment for the evaluation of toxic effects of NH2-polystyrene nanoparticles on living human cancer cells was performed with five participating laboratories. Previously published results from nanocytoxicity assays are often contradictory, mostly due to challenges related to producing a reliable cytotoxicity assay protocol for use with nanomaterials. Specific challenges include reproducibility preparing nanoparticle dispersions, biological variability from testing living cell lines, and the potential for nano-related interference effects. In this experiment, such challenges were addressed by developing a detailed experimental protocol and using a specially designed 96-well plate layout which incorporated a range of control measurements to assess multiple factors such as nanomaterial interference, pipetting accuracy, cell seeding density, and instrument performance. Detailed data analysis of these control measurements showed that good control of the experiments was attained by all participants in most cases. The main measurement objective of the study was the estimation of a dose response relationship between concentration of the nanoparticles and metabolic activity of the living cells, under several experimental conditions. The dose curve estimation was achieved by imbedding a three parameter logistic curve in a three level Bayesian hierarchical model, accounting for uncertainty due to all known experimental conditions as well as between laboratory variability in a top-down manner. Computation was performed using Markov Chain Monte Carlo methods. The fit of the model was evaluated using Bayesian posterior predictive probabilities and found to be satisfactory.

  5. Overlapping dose responses of spermatogenic and extragonadal testosterone actions jeopardize the principle of hormonal male contraception.

    Science.gov (United States)

    Oduwole, Olayiwola O; Vydra, Natalia; Wood, Nicholas E M; Samanta, Luna; Owen, Laura; Keevil, Brian; Donaldson, Mandy; Naresh, Kikkeri; Huhtaniemi, Ilpo T

    2014-06-01

    Testosterone (T), alone or in combination with progestin, provides a promising approach to hormonal male contraception. Its principle relies on enhanced negative feedback of exogenous T to suppress gonadotropins, thereby blocking the testicular T production needed for spermatogenesis, while simultaneously maintaining the extragonadal androgen actions, such as potency and libido, to avoid hypogonadism. A serious drawback of the treatment is that a significant proportion of men do not reach azoospermia or severe oligozoospermia, commensurate with contraceptive efficacy. We tested here, using hypogonadal luteinizing hormone/choriongonadotropin receptor (LHCGR) knockout (LHR(-/-)) mice, the basic principle of the T-based male contraceptive method, that a specific T dose could maintain extragonadal androgen actions without simultaneously activating spermatogenesis. LHR(-/-) mice were treated with increasing T doses, and the responses of their spermatogenesis and extragonadal androgen actions (including gonadotropin suppression and sexual behavior) were assessed. Conspicuously, all dose responses to T were practically superimposable, and no dose of T could be defined that would maintain sexual function and suppress gonadotropins without simultaneously activating spermatogenesis. This finding, never addressed in clinical contraceptive trials, is not unexpected in light of the same androgen receptor mediating androgen actions in all organs. When extrapolated to humans, our findings may jeopardize the current approach to hormonal male contraception and call for more effective means of inhibiting intratesticular T production or action, to achieve consistent spermatogenic suppression. © FASEB.

  6. Analysis of dose-response effects on gene expression data with comparison of two microarray platforms.

    Science.gov (United States)

    Hu, Jianhua; Kapoor, Mini; Zhang, Wei; Hamilton, Stanley R; Coombes, Kevin R

    2005-09-01

    The problems of analyzing dose effects on gene expression are gaining attention in biomedical research. A specific challenge is to detect genes with expression levels that change according to dose levels in a non-random manner, but nonetheless may be considered as potential biomarkers. We are among the first to formally apply a tool that uses an isotonic (monotonic) regression approach to this area of study. We introduce a test statistic to select genes with significant dose-response expression in a monotonic fashion based on a permutation procedure. We then compare the results with those achieved from the application of a likelihood ratio-based test. We apply the isotonic regression approach to a study of gene expression in the RKO colon carcinoma cell line in response to varying dosage levels of the chemotherapeutic agent 5-fluorouracil. A feature of both Affymetrix and printed 75mer oligomer cDNA arrays produced from the same samples provides an opportunity to compare the two microarray platforms. Statistical software S-plus Code to implement the method is available from the authors. kcoombes@mdanderson.org

  7. Dose response of a new phytase on dry matter, calcium, and phosphorus digestibility in weaned piglets.

    Science.gov (United States)

    Bento, M H L; Pedersen, C; Plumstead, P W; Salmon, L; Nyachoti, C M; Bikker, P

    2012-12-01

    The present study evaluated the dose response of Buttiauxella phytase on apparent total tract digestibility (ATTD) of DM, Ca, and P in weaned pigs at 2 locations. Experimental diets fed to weaned pigs were a positive control (PC), a negative control (NC), and NC supplemented with increasing levels of Buttiauxella phytase. In Trial A, ATTD of P was 57.2% for PC, 32.5% for NC, and 59.4, 62.0, 63.8, 66.0, and 67.3% for 250, 500, 750, 1000, and 2000 phytase units (FTU) added to NC, respectively. In Trial B, ATTD of P was 45.2% for PC, 28.4% for NC, and 58.7, 64.1, 67.9, and 70.9% for 250, 500, 1000, and 2000 FTU added to NC, respectively. In both studies, the reduction in P in the NC diets reduced (P digestible P increase from Buttiauxella phytase (vs. the NC diet) was 1.3, 1.5, 1.6, and 1.7 g digestible P/kg feed for 250, 500, 1000, and 2000 FTU/kg, respectively.

  8. Monitoring aspirin therapy in children after interventional cardiac catheterization: laboratory measures, dose response, and clinical outcomes.

    Science.gov (United States)

    Schmugge, Markus; Speer, Oliver; Kroiss, Sabine; Knirsch, Walter; Kretschmar, Oliver; Rand, Margaret L; Albisetti, Manuela

    2015-07-01

    Very few studies have investigated dose response of aspirin and agreement of different platelet function assays in children. One hundred five children were studied at baseline and after interventional cardiac catheterization during aspirin treatment and, in cases of aspirin resistance (AR), after dose increase. Results from arachidonate-induced aggregation (AA) were compared with aggregation induced by ADP, PFA-100 closure times (CTs), urinary 11-dehydro-thromboxane B2 (urinary 11-dhTxB2) levels, and Impact-R % surface coverage. Aspirin at 2-5 mg/kg/day inhibited platelet function in a large majority. While 19 % showed bruising and mild epistaxis, no thrombotic complications were recorded. AR was detected by AA in seven children (6.7 %). After dose increase, the majority showed inhibition by aspirin. Infants had higher urinary 11-dhTxB2 baseline levels; this assay showed some correlation with AA. Both assays manifested high sensitivity and specificity for aspirin while inferior results were found for the other assays. With the PFA-100, 15.2 % of patients were found to have AR, but this corresponded to AR by AA in only one of seven children. While there was poor agreement among assays, AA and urinary 11-dhTxB2 show good specificity for the monitoring of aspirin therapy in children. Aspirin at 2-5 mg/kg inhibits platelet function; AR in children is rare and can be overcome by dose increase.

  9. Dose responses in a normoxic polymethacrylic acid gel dosimeter using optimal CT scanning parameters

    Science.gov (United States)

    Cho, K. H.; Cho, S. J.; Lee, S.; Lee, S. H.; Min, C. K.; Kim, Y. H.; Moon, S. K.; Kim, E. S.; Chang, A. R.; Kwon, S. I.

    2012-05-01

    The dosimetric characteristics of normoxic polymethacrylic acid gels are investigated using optimal CT scanning parameters and the possibility of their clinical application is also considered. The effects of CT scanning parameters (tube voltage, tube current, scan time, slick thickness, field of view, and reconstruction algorithm) are experimentally investigated to determine the optimal parameters for minimizing the amount of noise in images obtained using normoxic polymethacrylic acid gel. In addition, the dose sensitivity, dose response, accuracy, and reproducibility of the normoxic polymethacrylic acid gel are evaluated. CT images are obtained using a head phantom that is fabricated for clinical applications. In addition, IMRT treatment planning is performed using a Tomotherapy radiation treatment planning system. A program for analyzing the results is produced using Visual C. A comparison between the treatment planning and the CT images of irradiated gels is performed. The dose sensitivity is found to be 2.41±0.04 HGy-1. The accuracies of dose evaluation at doses of 2 Gy and 4 Gy are 3.0% and 2.6%, respectively, and their reproducibilities are 2.0% and 2.1%, respectively. In the comparison of gel and Tomotherpay planning, the pass rate of the γ-index, based on the reference values of a dose error of 3% and a DTA of 3 mm, is 93.7%.

  10. Alcohol consumption and site-specific cancer risk: a comprehensive dose-response meta-analysis.

    Science.gov (United States)

    Bagnardi, V; Rota, M; Botteri, E; Tramacere, I; Islami, F; Fedirko, V; Scotti, L; Jenab, M; Turati, F; Pasquali, E; Pelucchi, C; Galeone, C; Bellocco, R; Negri, E; Corrao, G; Boffetta, P; La Vecchia, C

    2015-02-03

    Alcohol is a risk factor for cancer of the oral cavity, pharynx, oesophagus, colorectum, liver, larynx and female breast, whereas its impact on other cancers remains controversial. We investigated the effect of alcohol on 23 cancer types through a meta-analytic approach. We used dose-response meta-regression models and investigated potential sources of heterogeneity. A total of 572 studies, including 486 538 cancer cases, were identified. Relative risks (RRs) for heavy drinkers compared with nondrinkers and occasional drinkers were 5.13 for oral and pharyngeal cancer, 4.95 for oesophageal squamous cell carcinoma, 1.44 for colorectal, 2.65 for laryngeal and 1.61 for breast cancer; for those neoplasms there was a clear dose-risk relationship. Heavy drinkers also had a significantly higher risk of cancer of the stomach (RR 1.21), liver (2.07), gallbladder (2.64), pancreas (1.19) and lung (1.15). There was indication of a positive association between alcohol consumption and risk of melanoma and prostate cancer. Alcohol consumption and risk of Hodgkin's and Non-Hodgkin's lymphomas were inversely associated. Alcohol increases risk of cancer of oral cavity and pharynx, oesophagus, colorectum, liver, larynx and female breast. There is accumulating evidence that alcohol drinking is associated with some other cancers such as pancreas and prostate cancer and melanoma.

  11. Dose-Response Effect of Sunlight on Vitamin D2 Production in Agaricus bisporus Mushrooms

    DEFF Research Database (Denmark)

    Urbain, Paul; Jakobsen, Jette

    2015-01-01

    The dose response effect of UV-B irradiation from sunlight on vitamin D2 content of sliced Agaricus bisporus (white button mushroom) during the process of sun-drying was investigated.Real-time UV-B and UV-A data were obtained using a high-performance spectroradiometer. During the first hour...... of sunlight exposure, the vitamin D2 content of the mushrooms increased in a linear manner, with concentrations increasing from 0.1 μg/g up to 3.9 ± 0.8 μg/g dry weight (DW). At the subsequent two measurements one and 3 h later, respectively, a plateau was reached. Two hours of additional exposure triggered...... a significant decline in vitamin D2 content. After just 15 min of sun exposure and an UV-B dose of 0.13 J/cm(2), the vitamin D2 content increased significantly to 2.2 ± 0.5 μg/g DW (P mushrooms and comparable to levels found...

  12. Severity of killer whale behavioral responses to ship noise: a dose-response study.

    Science.gov (United States)

    Williams, Rob; Erbe, Christine; Ashe, Erin; Beerman, Amber; Smith, Jodi

    2014-02-15

    Critical habitats of at-risk populations of northeast Pacific "resident" killer whales can be heavily trafficked by large ships, with transits occurring on average once every hour in busy shipping lanes. We modeled behavioral responses of killer whales to ship transits during 35 "natural experiments" as a dose-response function of estimated received noise levels in both broadband and audiogram-weighted terms. Interpreting effects is contingent on a subjective and seemingly arbitrary decision about severity threshold indicating a response. Subtle responses were observed around broadband received levels of 130 dB re 1 μPa (rms); more severe responses are hypothesized to occur at received levels beyond 150 dB re 1 μPa, where our study lacked data. Avoidance responses are expected to carry minor energetic costs in terms of increased energy expenditure, but future research must assess the potential for reduced prey acquisition, and potential population consequences, under these noise levels. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Is more better? Using metadata to explore dose-response relationships in stroke rehabilitation.

    Science.gov (United States)

    Lohse, Keith R; Lang, Catherine E; Boyd, Lara A

    2014-07-01

    Neurophysiological models of rehabilitation and recovery suggest that a large volume of specific practice is required to induce the neuroplastic changes that underlie behavioral recovery. The primary objective of this meta-analysis was to explore the relationship between time scheduled for therapy and improvement in motor therapy for adults after stroke by (1) comparing high doses to low doses and (2) using metaregression to quantify the dose-response relationship further. Databases were searched to find randomized controlled trials that were not dosage matched for total time scheduled for therapy. Regression models were used to predict improvement during therapy as a function of total time scheduled for therapy and years after stroke. Overall, treatment groups receiving more therapy improved beyond control groups that received less (g=0.35; 95% confidence interval, 0.26-0.45). Furthermore, increased time scheduled for therapy was a significant predictor of increased improvement by itself and when controlling for linear and quadratic effects of time after stroke. There is a positive relationship between the time scheduled for therapy and therapy outcomes. These data suggest that large doses of therapy lead to clinically meaningful improvements, controlling for time after stroke. Currently, trials report time scheduled for therapy as a measure of therapy dose. Preferable measures of dose would be active time in therapy or repetitions of an exercise. © 2014 American Heart Association, Inc.

  14. A review of dosimetry used in epidemiological studies considered to evaluate the linear no-threshold (LNT) dose-response model for radiation protection.

    Science.gov (United States)

    Till, John E; Beck, Harold L; Grogan, Helen A; Caffrey, Emily A

    2017-10-01

    Accurate dosimetry is key to deriving the dose response from radiation exposure in an epidemiological study. It becomes increasingly important to estimate dose as accurately as possible when evaluating low dose and low dose rate as the calculation of excess relative risk per Gray (ERR/Gy) is very sensitive to the number of excess cancers observed, and this can lead to significant errors if the dosimetry is of poor quality. By including an analysis of the dosimetry, we gain a far better appreciation of the robustness of the work from the standpoint of its value in supporting the shape of the dose response curve at low doses and low dose rates. This article summarizes a review of dosimetry supporting epidemiological studies currently being considered for a re-evaluation of the linear no-threshold assumption as a basis for radiation protection. The dosimetry for each study was evaluated based on important attributes from a dosimetry perspective. Our dosimetry review consisted of dosimetry supporting epidemiological studies published in the literature during the past 15 years. Based on our review, it is clear there is wide variation in the quality of the dosimetry underlying each study. Every study has strengths and weaknesses. The article describes the results of our review, explaining which studies clearly stand out for their strengths as well as common weaknesses among all investigations. To summarize a review of dosimetry used in epidemiological studies being considered by the National Council on Radiation Protection and Measurements (NCRP) in an evaluation of the linear no-threshold dose-response model that underpins the current framework of radiation protection. The authors evaluated each study using criteria considered important from a dosimetry perspective. The dosimetry analysis was divided into the following categories: (1) general study characteristics, (2) dose assignment, (3) uncertainty, (4) dose confounders (5) dose validation, and (6) strengths and

  15. Results and cost of meeting the National Service Framework for Coronary Heart Disease requirement for 12 month follow-up after acute coronary events.

    Science.gov (United States)

    Evans, Julie; Turner, Sally; Bethell, Hugh

    2004-06-01

    The National Service Framework (NSF) for Coronary Heart Disease (CHD) set standards, targets and milestones. In the case of acute myocardial infarction (AMI) or coronary revascularization, Milestone 3 of Standard 12 requires a 12 month audit of exercise and smoking habit and of body mass index (BMI) for patients who have attended cardiac rehabilitation (CR). The targets are that 50 per cent of patients should be exercising regularly, not smoking and have a BMI of <30 kg/m(2). The purpose of this study was to find out whether the targets are realistic and to measure the cost of retrieving the data. A postal questionnaire was used to follow up all the patients who attended our CR programme over a 12 month period. The project was costed. Four hundred and three CHD patients who had attended the programme between April 2001 and March 2002 were sent questionnaires 12 months after their index event. Their diagnoses were AMI in 147 (36.5 per cent), coronary artery surgery in 157 (39 per cent) and angioplasty in 99 (24.5 per cent). Completed questionnaires were received from 358 (89 per cent). Of the responders, 69 per cent were exercising regularly, 91.6 per cent were not smoking (73 per cent had been non-smokers before their index cardiac event) and 79 per cent had a BMI of <30 kg/m(2)(the figure at the start of rehabilitation had been 79 per cent). The cost of performing the audit was pounds sterling 1204. This audit is inexpensive. The targets for smoking and BMI set by the NSF were achieved by a very large margin before either the index cardiac event or starting CR.

  16. Low back pain in drivers exposed to whole body vibration: analysis of a dose-response pattern

    NARCIS (Netherlands)

    Tiemessen, I. J. H.; Hulshof, C. T. J.; Frings-Dresen, M. H. W.

    2008-01-01

    Analysis of a dose-response pattern between exposure to whole body vibration (WBV) and low back pain (LBP) in a group of drivers. This study assessed individual factors, work-related risk factors, various LBP outcome measures and LBP disability in a group of drivers (n = 571) approached at baseline

  17. Dose-Response Analysis of RNA-Seq Profiles in Archival Formalin-Fixed Paraffin-Embedded (FFPE) Samples.

    Science.gov (United States)

    Use of archival resources has been limited to date by inconsistent methods for genomic profiling of degraded RNA from formalin-fixed paraffin-embedded (FFPE) samples. RNA-sequencing offers a promising way to address this problem. Here we evaluated transcriptomic dose responses us...

  18. Pancreatic beta cell function increases in a linear dose-response manner following exercise training in adults with prediabetes

    DEFF Research Database (Denmark)

    Malin, Steven K; Solomon, Thomas; Blaszczak, Alecia

    2013-01-01

    While some studies suggest that a linear dose-response relationship exists between exercise and insulin sensitivity, the exercise dose required to enhance pancreatic beta-cell function is unknown. Thirty-five older, obese adults with prediabetes underwent a progressive 12-week supervised exercise...

  19. Introduction to methodology of dose-response meta-analysis for binary outcome: With application on software.

    Science.gov (United States)

    Zhang, Chao; Jia, Pengli; Yu, Liu; Xu, Chang

    2018-01-18

    Dose-response meta-analysis (DRMA) is widely applied to investigate the dose-specific relationship between independent and dependent variables. Such methods have been in use for over 30 years and are increasingly employed in healthcare and clinical decision-making. In this article, we give an overview of the methodology used in DRMA. We summarize the commonly used regression model and the pooled method in DRMA. We also use an example to illustrate how to employ a DRMA by these methods. Five regression models, linear regression, piecewise regression, natural polynomial regression, fractional polynomial regression, and restricted cubic spline regression, were illustrated in this article to fit the dose-response relationship. And two types of pooling approaches, that is, one-stage approach and two-stage approach are illustrated to pool the dose-response relationship across studies. The example showed similar results among these models. Several dose-response meta-analysis methods can be used for investigating the relationship between exposure level and the risk of an outcome. However the methodology of DRMA still needs to be improved. © 2018 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.

  20. Gadobenate dimeglumine-enhanced MRI of the breast : Analysis of dose response and comparison with gadopentetate dimeglumine

    NARCIS (Netherlands)

    Knopp, MV; Bourne, MW; Sardanelli, F; Wasser, MN; Bonomo, L; Boetes, C; Muller-Schimpfle, M; Hall-Craggs, MA; Hamm, B; Orlacchio, A; Bartolozzi, C; Kessler, M; Fischer, U; Schneider, G; Dudkerk, M; Teh, WL; Gehl, HB; Salerio, [No Value; Pirovano, G; La Noce, A; Kirchin, MA; Spinazzi, A

    OBJECTIVE. The purpose of this study was to evaluate the clinical efficacy and dose response relationship of three doses of gadobenate dimeglumine for MRI of the breast and to compare the results with those obtained after a dose of 0.1 mmol/kg of body weight of gadopentetate dimeglumine. SUBJECTS

  1. A meta-analysis on dose-response relationship between night shift work and the risk of breast cancer.

    Science.gov (United States)

    Wang, F; Yeung, K L; Chan, W C; Kwok, C C H; Leung, S L; Wu, C; Chan, E Y Y; Yu, I T S; Yang, X R; Tse, L A

    2013-11-01

    This study aimed to conduct a systematic review to sum up evidence of the associations between different aspects of night shift work and female breast cancer using a dose-response meta-analysis approach. We systematicly searched all cohort and case-control studies published in English on MEDLINE, Embase, PSYCInfo, APC Journal Club and Global Health, from January 1971 to May 2013. We extracted effect measures (relative risk, RR; odd ratio, OR; or hazard ratio, HR) from individual studies to generate pooled results using meta-analysis approaches. A log-linear dose-response regression model was used to evaluate the relationship between various indicators of exposure to night shift work and breast cancer risk. Downs and Black scale was applied to assess the methodological quality of included studies. Ten studies were included in the meta-analysis. A pooled adjusted relative risk for the association between 'ever exposed to night shift work' and breast cancer was 1.19 [95% confidence interval (CI) 1.05-1.35]. Further meta-analyses on dose-response relationship showed that every 5-year increase of exposure to night shift work would correspondingly enhance the risk of breast cancer of the female by 3% (pooled RR = 1.03, 95% CI 1.01-1.05; Pheterogeneity breast cancer risk. This systematic review updated the evidence that a positive dose-response relationship is likely to present for breast cancer with increasing years of employment and cumulative shifts involved in the work.

  2. Adult height in children with growth hormone deficiency: a randomized, controlled, growth hormone dose-response trial.

    NARCIS (Netherlands)

    Sas, T.C.J.; Ridder, M.A. de; Wit, J.M.; Rotteveel, J.J.; Oostdijk, W.; Reeser, H.M.; Otten, B.J.; Muinck Keizer-Schrama, S.M.P.F. de

    2010-01-01

    AIM: To investigate the effect of 2 growth hormone (GH) doses on adult height (AH) in GH deficiency (GHD). METHODS: A multicenter, randomized, controlled dose-response trial compared attained AH minus target height (TH) between children receiving 0.7 mg/m(2)/day biosynthetic GH (approx. 0.025

  3. Dose-response relationship in phase i clinical trials : a European Drug Development Network (EDDN) Collaboration Study

    NARCIS (Netherlands)

    Moreno García, Victor; Olmos, David; Gomez-Roca, Carlos; Cassier, Philippe A; Morales-Barrera, Rafael; Del Conte, Gianluca; Gallerani, Elisa; Brunetto, Andre T; Schöffski, Patrick; Marsoni, Silvia; Schellens, Jan H M|info:eu-repo/dai/nl/073926272; Penel, Nicolas; Voest, Emile; Evans, Jeffrey; Plummer, Ruth; Wilson, Richard H; Soria, Jean Charles; Tabernero, Josep; Verweij, Jaap; Kaye, Stan B

    2014-01-01

    INTRODUCTION: Because a dose-response relationship is characteristic of conventional chemotherapy, this concept is widely used for the development of novel cytotoxic (CTX) drugs. However, the need to reach the MTD to obtain optimal benefit with molecularly targeted agents (MTA) is controversial. In

  4. Dose-response and concentration-response relation of rocuronium infusion during propofol nitrous oxide and isoflurane nitrous oxide anaesthesia

    NARCIS (Netherlands)

    Kansanaho, M; Olkkola, KT; Wierda, JMKH

    The dose-response and concentration-response relation of rocuronium infusion was studied in 20 adult surgical patients during proporfol-nitrous oxide and isoflurane (1 MAC) -nitrous oxide anaesthesia. Neuromuscular block was kept constant, initially at 90% and then at 50% with a closed-loop feedback

  5. Adult Height in Children with Growth Hormone Deficiency: A Randomized, Controlled, Growth Hormone Dose-Response Trial

    NARCIS (Netherlands)

    Sas, T.C.J.; de Ridder, M.A.J.; Wit, J.M.; Rotteveel, J.; Oostdijk, W.; Reeser, H.M.; Otten, B.J.; Keizer-Schrama, S.M.P.F.

    2010-01-01

    Aim: To investigate the effect of 2 growth hormone (GH) doses on adult height (AH) in GH deficiency (GHD). Methods: A multicenter, randomized, controlled dose-response trial compared attained AH minus target height (TH) between children receiving 0.7 mg/m

  6. Low dose effects and non-monotonic dose responses for endocrine active chemicals: Science to practice workshop: Workshop summary

    DEFF Research Database (Denmark)

    Beausoleil, Claire; Ormsby, Jean-Nicolas; Gies, Andreas

    2013-01-01

    A workshop was held in Berlin September 12–14th 2012 to assess the state of the science of the data supporting low dose effects and non-monotonic dose responses (“low dose hypothesis”) for chemicals with endocrine activity (endocrine disrupting chemicals or EDCs). This workshop consisted...

  7. Dairy consumption is inversely associated with type 2 diabetes: dose-response meta-analysis of prospective cohort studies

    NARCIS (Netherlands)

    Gijsbers, L.; Geleijnse, J.M.; Soedamah-Muthu, S.S.

    2011-01-01

    Observational studies suggest an inverse association between dairy intake and incident type 2 diabetes, but the quantity of dairy is not known. Previous meta-analyses did not take into account the type of dairy product. Therefore, we examined dose-response associations between the intake of total

  8. Acute Effects of Classroom Exercise Breaks on Executive Function and Math Performance: A Dose-Response Study

    Science.gov (United States)

    Howie, Erin K.; Schatz, Jeffrey; Pate, Russell R.

    2015-01-01

    Purpose: The purpose of this study was to determine the acute dose-response relationship of classroom exercise breaks with executive function and math performance in 9- to 12-year-old children by comparing 5-min, 10-min, or 20-min classroom exercise breaks to 10 min of sedentary classroom activity. Method: This study used a within-subjects…

  9. Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose response (BBDR) Model***

    Science.gov (United States)

    A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (HPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the 1-IPT axis. Model calibrations, carried out by adjusting key model...

  10. Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose-response model

    Science.gov (United States)

    A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (BPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the HPT axis. Model calibrations, carried out by adjusting key model p...

  11. Dose-Response Relationships of Resistance Training in Healthy Old Adults : A Systematic Review and Meta-Analysis

    NARCIS (Netherlands)

    Borde, Ron; Hortobagyi, Tibor; Granacher, Urs

    2015-01-01

    Background Resistance training (RT) is an intervention frequently used to improve muscle strength and morphology in old age. However, evidence-based, dose-response relationships regarding specific RT variables (e.g., training period, frequency, intensity, volume) are unclear in healthy old adults.

  12. European Academy of Allergy and Clinical Immunology task force report on 'dose-response relationship in allergen-specific immunotherapy'

    DEFF Research Database (Denmark)

    Calderón, M A; Larenas, D; Kleine-Tebbe, J

    2011-01-01

    For a century, allergen-specific immunotherapy (SIT) has proven to be an effective treatment for allergic rhinitis, asthma, and insect sting allergy. However, as allergen doses are frequently adapted to the individual patient, there are few data on dose-response relationship in SIT. Allergen prod...

  13. Dose-response model of murine typhus (Rickettsia typhi: time post inoculation and host age dependency analysis

    Directory of Open Access Journals (Sweden)

    Tamrakar Sushil B

    2012-03-01

    Full Text Available Abstract Background Rickettsia typhi (R. mooseri is the causative agent of murine typhus. It is one of the most widely distributed flea-borne diseases with a relatively mild febrile initial illness with six to 14 days of incubation period. The bacterium is gram negative and an obligate intracellular pathogen. The disease is transmitted to humans and vertebrate host through fleabites or via contact with infected feces. This paper develops dose-response models of different routes of exposure for typhus in rodents. Methods Data from published articles were analyzed using parametric dose-response relationship models. Dose-response relationships were fit to data using the method of maximum likelihood estimation (MLE. Results Dose-response models quantifying the effects of different ages of rats and time post inoculation in BALB/c mice were analyzed in the study. Both the adult rats (inoculated intradermally and newborn rats (inoculated subcutaneously were best fit by exponential models and both distributions could be described by a single dose-response relationship. The BALB/C mice inoculated subcutaneously were best fit by Beta-Poisson models. The time post inoculation analysis showed that there was a definite time and response relationship existed in this case. Conclusions Intradermally or subcutaneously inoculated rats (adult and newborn models suggest that less than 1 plaque-forming unit (PFU (1.33 to 0.38 in 95% confidence limits of the pathogen is enough to seroconvert 50% of the exposed population on average. For the BALB/c mouse time post inoculation model, an average dose of 0.28 plaque-forming units (PFU (0.75 to 0.11 in 95% confidence limits will seroconvert 50% of the exposed mice.

  14. Dose-response relationship between tobacco or alcohol consumption and the development of diabetes mellitus in Japanese male workers.

    Science.gov (United States)

    Teratani, Toshiyasu; Morimoto, Hideki; Sakata, Kouichi; Oishi, Mitsuhiro; Tanaka, Kumihiko; Nakada, Satoru; Nogawa, Kazuhiro; Suwazono, Yasushi

    2012-10-01

    The aim of this study was to examine the dose-response relationships between tobacco or alcohol consumption and the development of diabetes mellitus. An 8-year prospective cohort study was conducted in 8423 male workers who received annual health check-ups between 2002 and 2010 at a Japanese steel company. The endpoints were defined as an HbA(lc)≥6.1% or taking any anti-diabetic medication. The dose-response relationships of tobacco or alcohol consumption were investigated using a proportional hazards regression with time-dependent covariates selected from baseline age, body mass index, mean arterial pressure, total serum cholesterol, aspartate aminotransferase, creatinine and uric acid, shift work or day work, and habitual exercise by stepwise selection method. A positive dose-response relationship between tobacco consumption and the development of diabetes mellitus was observed, with a significantly higher hazard ratio (HR) seen with higher tobacco consumption (11-20 cigarettes/day, HR 1.26 [95% confidence interval (CI), 1.00-1.59], ≥21 cigarettes/day, HR 1.54 [95%CI, 1.20-1.97]). In contrast, we observed a negative dose-response relationship between alcohol consumption and the development of diabetes mellitus, with a significantly lower HR with higher weekly alcohol consumption (7.0-13.9 gou/week [154-307 g/week], HR 0.73 [95% CI, 0.55-0.97], ≥14.0 gou/week [308 g/week], HR 0.75 [95% CI, 0.57-0.98]). The results indicated that decreasing tobacco consumption will achieve significant prevention of diabetes mellitus. On the other hand, we observed a significant, negative dose-response relationship between alcohol consumption and the development of diabetes mellitus, in contrast to previous studies that reported a positive relationship in the Japanese population. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  15. Effects of the pre-irradiation storage procedure on the dose response of a Fricke xylenol orange gel dosimeter

    Directory of Open Access Journals (Sweden)

    Liosi Giulia Maria

    2015-09-01

    Full Text Available The Fricke xylenol orange (FX gel system is a chemical dosimeter characterized by good sensitivity, linear dose response, tissue equivalence, no toxicity, easy preparation, reproducibility and low cost. Thanks to the presence of the gelatinous matrix, the system is particularly suitable to perform reliable 3D mapping of the absorbed dose spatial distribution via magnetic resonance imaging (MRI or optical techniques. The aim of this work is to study in a systematic way the influence of the pre-irradiation storage procedure upon sensitivity, dose response stability and lifetime of use of a FX gel system made with gelatin from porcine skin subjected to homogeneous irradiation. For this purpose, different pre-irradiation storage procedures, in terms of temperature and duration of each storage step, were investigated. In order to evaluate the dose response stability, the optical analyses of the samples were performed up to 6 hours after irradiation. Moreover, the samples were irradiated at time intervals of 24 hours for up to 7 days after preparation in order to evaluate the system lifetime of use. Regardless of their thermal and temporal life, the samples show linear dose responses in the investigated dose range (3-24 Gy and an increase of sensitivity with the time elapsed between preparation and irradiation. Among the three pre-irradiation storage procedures considered here, a procedure that provides the best dose response stability and lifetime of use was identified and recommended for further use. The analyzed dosimetric system possesses good properties that make it promising for medical application, particularly concerning the evaluation of pre-treatment plan quality assurance within the conformational external beam radiotherapy

  16. Dose Response of Retinol and Isotretinoin in the Prevention of Non-Melanoma Skin Cancer Recurrence

    Science.gov (United States)

    Clouser, Mary C.; Roe, Denise J.; Foote, Janet A.; Harris, Robin B.; Alberts, David S.

    2014-01-01

    Using data from a randomized, double blind, study of the efficacy of retinol or isotretinoin versus placebo on recurrence of non-melanoma skin cancer in high risk subjects, a reanalysis of the original intent to treat analysis was performed in a dose response format. Cox proportional hazards models describe the relationship between dose quartiles of isotretinoin and retinol use and time to first occurrence of squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) in crude and adjusted models. Neither the isotretinoin nor retinol models showed any significance at any quartile for reduction in first BCC or SCC occurrence. Crude and adjusted retinol models show a statistically significant increase in risk of developing an SCC in the first quartile, while only the crude model shows a statistically significant increase in risk in the first quartile of the isotretinoin model. For retinol and SCC hazard ratios for the first quartile were as follows; HR= 2.92, 95% CI 1.67–5.10 crude, HR= 1.95, 95% CI 1.00–3.80 adjusted. For isotretinoin and SCC hazard ratios for the first quartile were as follows; HR=2.38, 95% CI 1.35–4.19 crude, HR= 1.69, 95% CI 0.87–3.31 adjusted. Test for trend was not significant in any of the models. These analyses confirm the results of the original intent to treat analyses and raise an interesting question related to the potential for increased risk for patients in the first quartile of retinol dose. PMID:21058193

  17. Energy crop (Sida hermaphrodita) fertilization using digestate under marginal soil conditions: A dose-response experiment

    Science.gov (United States)

    Nabel, Moritz; Bueno Piaz Barbosa, Daniela; Horsch, David; Jablonowski, Nicolai David

    2014-05-01

    The global demand for energy security and the mitigation of climate change are the main drivers pushing energy-plant production in Germany. However, the cultivation of these plants can cause land use conflicts since agricultural soil is mostly used for plant production. A sustainable alternative to the conventional cultivation of food-based energy-crops is the cultivation of special adopted energy-plants on marginal lands. To further increase the sustainability of energy-plant cultivation systems the dependency on synthetic fertilizers needs to be reduced via closed nutrient loops. In the presented study the energy-plant Sida hermaphrodita (Malvaceae) will be used to evaluate the potential to grow this high potential energy-crop on a marginal sandy soil in combination with fertilization via digestate from biogas production. With this dose-response experiment we will further identify an optimum dose, which will be compared to equivalent doses of NPK-fertilizer. Further, lethal doses and deficiency doses will be observed. Two weeks old Sida seedlings were transplanted to 1L pots and fertilized with six doses of digestate (equivalent to a field application of 5, 10, 20, 40, 80, 160t/ha) and three equivalent doses of NPK-fertilizer. Control plants were left untreated. Sida plants will grow for 45 days under greenhouse conditions. We hypothesize that the nutrient status of the marginal soil can be increased and maintained by defined digestate applications, compared to control plants suffering of nutrient deficiency due to the low nutrient status in the marginal substrate. The dose of 40t/ha is expected to give a maximum biomass yield without causing toxicity symptoms. Results shall be used as basis for further experiments on the field scale in a field trial that was set up to investigate sustainable production systems for energy crop production under marginal soil conditions.

  18. Lead-induced anemia: Dose-response relationships and evidence for a threshold

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, J.; Landrigan, P.J.; Baker, E.L. Jr.; Orenstein, W.A.; von Lindern, I.H. (Environmental Protection Agency, Washington, DC (USA))

    1990-02-01

    We conducted a cross-sectional epidemiologic study to assess the association between blood lead level and hematocrit in 579 one to five year-old children living near a primary lead smelter in 1974. Blood lead levels ranged from 0.53 to 7.91 mumol/L (11 to 164 micrograms/dl). To predict hematocrit as a function of blood lead level and age, we derived non-linear regression models and fit percentile curves. We used logistic regression to predict the probability of hematocrit values less than 35 per cent. We found a strong non-linear, dose-response relationship between blood lead level and hematocrit. This relationship was influenced by age, but (in this age group) not by sex; the effect was strongest in youngest children. In one year-olds, the age group most severely affected, the risk of an hematocrit value below 35 percent was 2 percent above background at blood lead levels between 0.97 and 1.88 mumol/L (20 and 39 micrograms/dl), 18 percent above background at lead levels of 1.93 to 2.85 mumol/L (40 to 59 micrograms/dl), and 40 percent above background at lead levels of 2.9 mumol/L (60 micrograms/dl) and greater; background was defined as a blood lead level below 1.88 mumol/L (20 micrograms/dl). This effect appeared independent of iron deficiency. These findings suggest that blood lead levels close to the currently recommended limit value of 1.21 mumol/L (25 micrograms/dl) are associated with dose-related depression of hematocrit in young children.

  19. Early changes, attrition, and dose-response in low intensity psychological interventions.

    Science.gov (United States)

    Delgadillo, Jaime; McMillan, Dean; Lucock, Mike; Leach, Chris; Ali, Shehzad; Gilbody, Simon

    2014-03-01

    To investigate if early symptom changes in brief low intensity psychological interventions (guided self-help and psycho-education using cognitive behavioural therapy principles) are predictive of final treatment outcome. Retrospective cohort data analysis. Clinical records for 1,850 patients who screened positive for depression and/or an anxiety disorder were analysed. Reliable and clinically significant improvement (RCSI) on depression (Patient Health Questionnaire-9: PHQ-9) or anxiety (generalized anxiety disorder-7: GAD-7) outcome measures after treatment was the primary outcome. Change scores ≥6 on PHQ-9 and ≥5 on GAD-7 were taken as indicative of reliable improvement (RI). The model assumed that RI in the earliest treatment sessions would be predictive of RCSI post-treatment. Predictive accuracy was assessed by calculating the area under the curve (AUC), as well as positive and negative predictive values. Diagnostic odds ratios were also estimated, adjusting for confounders such as baseline severity, use of medication, and pre-treatment symptom change. The AUC estimates for session-to-session change scores ranged between .62 and .88, indicative of modest to high predictive reliability. Predictive accuracy was higher for patients who had four or more treatment sessions, with more than 70% of patients with RCSI being accurately identified as early as sessions 1-3. Attrition rates were significantly associated with poor outcomes. Results suggest that at least four therapy sessions are necessary to achieve more than 50% RCSI rates, and the dose-response effect appears to decline in treatments longer than six sessions. Patients showing RI early in treatment were at least twice as likely to fully recover compared to those without early RI. © 2013 The British Psychological Society.

  20. Dose-response effects of atropine and HI-6 treatment of organophosphorus poisoning in guinea pigs

    Energy Technology Data Exchange (ETDEWEB)

    Koplovitz, I.; Menton, R.; Matthews, C.; Shutz, M.; Nalls, C.

    1995-12-31

    H1-6 (1-2-hydrnxyiminomethyl-1 pyridino-3-(4-carbameyl- 1--pyddino)-2- oxaprnpane dichioride) has been evaluated as an oxime alternative to pralidoxime, and toxogonin in the treatment of organophosphorus (OP) poisoning. The dose response effects of atropine (ATR) and HI-6 were investigated to more fully explore the interaction of these compounds in the treatment of OP poisoning. ATR, HI-6 and various combinations of the two drugs were evaluated against lethal poisoning by soman (GD) and tabun (GA) in guinea pigs. The effect of adjunctive diazepam treatment on the efficacy of atropine and HI-6 against soman was also investigated. Animals of either sex were challenged s.c. with OP and treated i.m. 1 min later with ATR and/or HI-6. When used, diazepam was injected immediately after ATR+HI6. LD50s of each treatment were calculated from probit models based on 24-hour survival against 5 levels of nerve agent and 6 animals per challenge level. A protective index (PI) was calculated by dividing the nerve agent LD50 in the presence of treatment by the LD50 in the absence of treatment. Treatment with HI-6 alone had little effect on the toxicity of either OP. Treatment with ATR alone was more effective than HI-6 alone and was significantly more effective against soman than against tabun. When used in combination atropine and HI-6 had a strong synergistic effect against both agents. The dose of atropine used with HI-6 was critical in determining the efficacy of HI-6 against either agent. The slopes of the dose-lethality curves were minimally affected by the dose of ATR or HI-6. Adjunctive treatment with diazepam enhanced the efficacy of HI-6 and atropine against soman.

  1. Alcohol consumption and dementia risk: a dose-response meta-analysis of prospective studies.

    Science.gov (United States)

    Xu, Wei; Wang, Huifu; Wan, Yu; Tan, Chenchen; Li, Jieqiong; Tan, Lan; Yu, Jin-Tai

    2017-01-01

    It is widely believed that light-to-moderate alcohol intake may protect against dementia while excessive drinking may instead increase the risk. Nonetheless, these findings need cautious interpretations due to varying methodologies and lack of standard definition, which hindered our transferring into preventative practice. The objective of this study is to investigate the potential dose-response association between alcohol consumption and risk of dementia. A systematic search was conducted in electronic databases to identify relevant studies. Risk estimates were combined using a random-effect model. Eleven studies with 73,330 participants and 4586 cases for all-cause dementia (ACD), five studies with 52,715 participants and 1267 cases for Alzheimer's dementia (AD) and four studies with 49,535 participants and 542 cases for vascular dementia were included. We observed a nonlinear association between alcohol consumption and ACD risk (p nonlinearity alcohol dose associated with lower risk of dementia was confined to at most 12.5 g/day, with the risk hitting bottom (RR ≈ 0.9) at roughly 6 g/day. Of note, the ACD risk seemed to be elevated (≈10%) when the dose surpasses certain levels: 23 drinks/week or 38 g/day. For the alcohol type, recommendation for wine is prioritized. The subgroup analysis further indicated that the effect of alcohol may be greater in younger adults (alcohol consumption (≤12.5 g/day) is associated with a reduced risk of dementia with 6 g/day of alcohol conferring a lower risk than other levels while excessive drinking (≥38 g/day) may instead elevate the risk.

  2. Dose-response relationship between sports activity and musculoskeletal pain in adolescents.

    Science.gov (United States)

    Kamada, Masamitsu; Abe, Takafumi; Kitayuguchi, Jun; Imamura, Fumiaki; Lee, I-Min; Kadowaki, Masaru; Sawada, Susumu S; Miyachi, Motohiko; Matsui, Yuzuru; Uchio, Yuji

    2016-06-01

    Physical activity has multiple health benefits but may also increase the risk of developing musculoskeletal pain (MSP). However, the relationship between physical activity and MSP has not been well characterized. This study examined the dose-response relationship between sports activity and MSP among adolescents. Two school-based serial surveys were conducted 1 year apart in adolescents aged 12 to 18 years in Unnan, Japan. Self-administered questionnaires were completed by 2403 students. Associations between time spent in organized sports activity and MSP were analyzed cross-sectionally (n = 2403) and longitudinally (n = 374, students free of pain and in seventh or 10th grade at baseline) with repeated-measures Poisson regression and restricted cubic splines, with adjustment for potential confounders. The prevalence of overall pain, defined as having pain recently at least several times a week in at least one part of the body, was 27.4%. In the cross-sectional analysis, sports activity was significantly associated with pain prevalence. Each additional 1 h/wk of sports activity was associated with a 3% higher probability of having pain (prevalence ratio = 1.03, 95% confidence interval = 1.02-1.04). Similar trends were found across causes (traumatic and nontraumatic pain) and anatomic locations (upper limbs, lower back, and lower limbs). In longitudinal analysis, the risk ratio for developing pain at 1-year follow-up per 1 h/wk increase in baseline sports activity was 1.03 (95% confidence interval = 1.02-1.05). Spline models indicated a linear association (P sports, the more likely they were to have and develop pain.

  3. Sludge reduction by ozone: Insights and modeling of the dose-response effects.

    Science.gov (United States)

    Fall, C; Silva-Hernández, B C; Hooijmans, C M; Lopez-Vazquez, C M; Esparza-Soto, M; Lucero-Chávez, M; van Loosdrecht, M C M

    2018-01-15

    Applying ozone to the return flow in an activated sludge (AS) process is a way for reducing the residual solids production. To be able to extend the activated sludge models to the ozone-AS process, adequate prediction of the tri-atoms effects on the particulate COD fractions is needed. In this study, the biomass inactivation, COD mineralization, and solids dissolution were quantified in batch tests and dose-response models were developed as a function of the reacted ozone doses (ROD). Three kinds of model-sludge were used. S1 was a lab-cultivated synthetic sludge with two components (heterotrophs XH and XP). S2 was a digestate of S1 almost made by the endogenous residues, XP. S3 was from a municipal activated sludge plant. The specific ozone uptake rate (SO3UR, mgO3/gCOD.h) was determined as a tool for characterizing the reactivity of the sludges. SO3UR increased with the XH fraction and decreased with more XP. Biomass inactivation was exponential (e-β.ROD) as a function of the ROD doses. The percentage of solids reduction was predictable through a linear model (CMiner + Ysol ROD), with a fixed part due to mineralization (CMiner) and a variable part from the solubilization process. The parameters of the models, i.e. the inactivation and the dissolution yields (β, 0.008-0.029 (mgO3/mgCODini)-1 vs Ysol, 0.5-2.8 mg CODsol/mgO3) varied in magnitude, depending on the intensity of the scavenging reactions and potentially the compactness of the flocs for each sludge. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Dose-response of EBT3 radiochromic films to proton and carbon ion clinical beams.

    Science.gov (United States)

    Castriconi, Roberta; Ciocca, Mario; Mirandola, Alfredo; Sini, Carla; Broggi, Sara; Schwarz, Marco; Fracchiolla, Francesco; Martišíková, Mária; Aricò, Giulia; Mettivier, Giovanni; Russo, Paolo

    2017-01-21

    We investigated the dose-response of the external beam therapy 3 (EBT3) films for proton and carbon ion clinical beams, in comparison with conventional radiotherapy beams; we also measured the film response along the energy deposition-curve in water. We performed measurements at three hadrontherapy centres by delivering monoenergetic pencil beams (protons: 63-230 MeV; carbon ions: 115-400 MeV/u), at 0.4-20 Gy dose to water, in the plateau of the depth-dose curve. We also irradiated the films to clinical MV-photon and electron beams. We placed the EBT3 films in water along the whole depth-dose curve for 148.8 MeV protons and 398.9 MeV/u carbon ions, in comparison with measurements provided by a plane-parallel ionization chamber. For protons, the response of EBT3 in the plateau of the depth-dose curve is not different from that of photons, within experimental uncertainties. For carbon ions, we observed an energy dependent under-response of EBT3 film, from 16% to 29% with respect to photon beams. Moreover, we observed an under-response in the Bragg peak region of about 10% for 148.8 MeV protons and of about 42% for 398.9 MeV/u carbon ions. For proton and carbon ion clinical beams, an under-response occurs at the Bragg peak. For carbon ions, we also observed an under-response of the EBT3 in the plateau of the depth-dose curve. This effect is the highest at the lowest initial energy of the clinical beams, a phenomenon related to the corresponding higher LET in the film sensitive layer. This behavior should be properly modeled when using EBT3 films for accurate 3D dosimetry.

  5. Dose-response relationship of octylphenol and radiation evaluated by tradescantia-micronucleus assay

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J. K.; Cheon, K. J.; Lee, B. H. [KAERI, Taejon (Korea, Republic of); Shin, H. S.; Lee, J. H. [Chungnam National Univ., Taejon (Korea, Republic of)

    2002-05-01

    Many kinds of synthetic chemicals have been being used for various purposes. Some of them are called 'Endocrine Disruptor's because they can disturb the endocrine system of organisms. Presently no technique is established for the quantitative assessment of biological risk of the environmental hormones. The pollen mother cells (PMC) of Tradescantia are very sensitive to chemical toxicants or ionizing radiation, and thus can be used as a biological end-point assessing their effect. Micronucleus frequencies in PMC showed a good dose- and concentration-response relationship for radiation, bisphenol A and octylphenol. A parallel series of experiment using five increasing doses of gamma-ray at 10, 20, 30, 40 and 50 cGy was conducted. The MCN frequencies of 12.0, 25.2, 41.7, 76 and 83 MCN/100 tetrads were observed from each of the increasing gamma-ray dosage groups, respectively. Lenear regression analysis of the gamma-ray data MCN frequencies yielded a correlation coefficient of 0.95. the MCN frequencies in pollen mother cells treated with bisphenol a and octylphenol showed dose-response relationship in a concentration of 0, 1, 2, 4 {mu}M and 0, 4, 10, 20 {mu}M. the MCN frequency for the bisphenol a and octylphenol group yields 2.33, 8.06, 12.7 and 19.6 MCN/100 tetrads for the bisphenol a and 2.33, 2.33, 11.47, 17.6 MCN/100 tetrads for the octylphenol. The MCN frequency of the control was 2.33 MCN/100 tetrads. It is known from the result that Trad-MCN assay can be an excellent tool for detection of biological risk due to environmental toxicants or synthetic chemicals.

  6. Effect of dietary fat level on dose response relationships during aflatoxicosis in young chickens.

    Science.gov (United States)

    Richardson, K E; Nelson, L A; Hamilton, P B

    1987-09-01

    The effect of aflatoxin in poultry is greater on birds fed a low fat diet, but it is not known whether this effect is associated with a lower apparent minimum effective dose (MED), altered slope of the response curve, or both. Aflatoxin at 16 dosages ranging from 0 to 3.797 micrograms/g of feed was fed to six groups of 15 young chickens per treatment ingesting a 2 or 4% fat diet for 3 wk. The weights of the body, liver, bursa of Fabricius, and spleen and the total lipid content of the liver were measured. Mathematical models were fitted to the data and dose-response curves were predicted as continuous functions of aflatoxin concentration. Quadratic polynomials fit body weight and spleen weight whereas plateau-linear models fit liver weight and liver lipid content in both 2 and 4% fat diets. The weight of the bursa of Fabricius was fit equally well by quadratic and linear plateau models. Dietary fat had negligible effects on the apparent MED (micrograms of aflatoxin per gram of feed) for body, liver and spleen weights, which were calculated from the modeling approach to be 1.37 and 1.41, 1.68 and 1.69, and 1.49 and 1.46 on 2 and 4% fat diets, respectively. The apparent MED for liver lipid content was appreciably lower for birds fed the 2% fat diet than those fed the 4% fat diet (.88 and 1.62, respectively). Similarly, the apparent MED for the bursa was 1.48 and 1.74 for birds fed the 2 and 4% fat diets, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Interaction of dietary protein level on dose response relationships during aflatoxicosis in young chickens.

    Science.gov (United States)

    Richardson, K E; Nelson, L A; Hamilton, P B

    1987-06-01

    It is well known that the effect of aflatoxin is enhanced by a low protein diet, but whether this is associated with a lower apparent minimum effective dose, increased slope of response curves, or both has not been investigated previously. Aflatoxin at 12 dosages ranging from 0 to 2.34 micrograms/g of feed was fed to eight groups of 10 young chickens per treatment consuming a 10.00 or 12.75% protein diet for 3 weeks. The body weights, liver weights relative to body weights, and total lipid content of the livers were determined. Mathematical models were fitted to the data and from the appropriate equations the dose-response curves were predicted as continuous functions of aflatoxin concentration. A quadratic polynomial fit body weight data on the 12.75% protein diet whereas a plateau-linear model fit body weight data on the 10.00% protein diet. This implies that in a low protein diet aflatoxin affects only one of the factors controlling growth. Plateau-linear models fit liver relative weight and liver lipid content data on both 10.00 and 12.75% diets. For both variables the lower protein diet decreased the apparent minimum effective dose and increased the positive slope of the linear response. The apparent minimum effective doses (micrograms of aflatoxin per gram of feed) in this experimental system were calculated from the modeling approach to be 1.21 and 2.00 for body weight, 1.08 and 1.65 for liver lipids, and 1.45 and 2.34 for liver relative weight in 10.00 and 12.75% protein diets, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Determining the optimal whole-body vibration dose-response relationship for muscle performance.

    Science.gov (United States)

    Da Silva-Grigoletto, Marzo E; De Hoyo, Moisés; Sañudo, Borja; Carrasco, Luis; García-Manso, Juan M

    2011-12-01

    Da Silva-Grigoletto, ME, de Hoyo, M, Sañudo, B, Corrales, L, and García-Manso, JM. Determining the optimal whole-body vibration dose-response relationship for muscle performance. J Strength Cond Res 25(12): 3326-3333, 2011-The aim of this investigation was twofold: first, to determine the optimal duration of a single whole-body vibration (WBV) exposure (phase 1) and second to find out the ideal number of sets per intervention to maximize muscle performance (phase 2). All participants were young (age: 19.4 ± 1.6 years), healthy, physically active men. In both studies, a 30-Hz frequency and a 4-mm peak-to-peak displacement were used. In phase 1, subjects (n = 30) underwent 3 sets of different durations (30, 60, and 90 seconds), whereas in phase 2, subjects (n = 27) underwent 3 interventions where the duration remained fixed at 60 seconds, and the number of sets performed (3, 6, or 9) was modified. The recovery time between sets was set at 2 minutes. In all interventions, each set consisted of 1 isometric repetition in a squat position with knees flexed at 100°. Before and after each session, jump height (countermovement jump [CMJ] and squat jump [SJ]) and power output in half squat (90° knee flexion) were assessed. In phase 1, an improvement in jump ability and power output was observed after the 30- and 60-second intervention (p effect for the program of 6 sets (p < 0.05). In conclusion, a WBV intervention consisting of six 60-second sets produces improved muscle performance measured by SJ, CMJ, and power output.

  9. Gadobenate dimeglumine-enhanced MRI of the breast: analysis of dose response and comparison with gadopentetate dimeglumine.

    Science.gov (United States)

    Knopp, Michael V; Bourne, Michael W; Sardanelli, Francesco; Wasser, Martin N; Bonomo, Lorenzo; Boetes, Carla; Müller-Schimpfle, Markus; Hall-Craggs, Margaret A; Hamm, Bernd; Orlacchio, Antonio; Bartolozzi, Carlo; Kessler, Mareike; Fischer, Uwe; Schneider, Günther; Oudkerk, Matthijs; Teh, William L; Gehl, Hans-Björn; Salerio, Isabella; Pirovano, Gianpaolo; La Noce, Anna; Kirchin, Miles A; Spinazzi, Alberto

    2003-09-01

    The purpose of this study was to evaluate the clinical efficacy and dose response relationship of three doses of gadobenate dimeglumine for MRI of the breast and to compare the results with those obtained after a dose of 0.1 mmol/kg of body weight of gadopentetate dimeglumine. SUBJECTS AND METHODS. Gadobenate dimeglumine at 0.05, 0.1, or 0.2 mmol/kg of body weight or gadopentetate dimeglumine at 0.1 mmol/kg of body weight was administered by IV bolus injection to 189 patients with known or suspected breast cancer. Coronal three-dimensional T1-weighted gradient-echo images were acquired before and at 0, 2, 4, 6, and 8 min after the administration of the dose. Images were evaluated for lesion presence, location, size, morphology, enhancement pattern, conspicuity, and type. Lesion signal intensity-time curves were acquired, and lesion matching with on-site final diagnosis was performed. A determination of global lesion detection from unenhanced to contrast-enhanced and combined images was performed, and evaluations were made of the diagnostic accuracy for lesion detection and characterization. A full safety evaluation was conducted. Significant dose-related increases in global lesion detection were noted for patients who received gadobenate dimeglumine (p dimeglumine, and specificity was highest with the 0.1 mmol/kg dose. Higher detection scores and higher sensitivity values for lesion characterization were found for 0.1 mmol/kg of gadobenate dimeglumine compared with 0.1 mmol/kg of gadopentetate dimeglumine, although more variable specificity values were obtained. No differences in safety were observed, and no serious adverse events were reported. Gadobenate dimeglumine is a capable diagnostic agent for MRI of the breast. Although preliminary, our results suggest that 0.1 mmol/kg of gadobenate dimeglumine may offer advantages over doses of 0.05 and 0.2 mmol/kg of gadobenate dimeglumine and 0.1 mmol/kg of gadopentetate dimeglumine for breast lesion detection and

  10. Dose response of umeclidinium administered once or twice daily in patients with COPD: a randomised cross-over study.

    Science.gov (United States)

    Church, Alison; Beerahee, Misba; Brooks, Jean; Mehta, Rashmi; Shah, Palvi

    2014-01-06

    Umeclidinium bromide (UMEC) is an inhaled long-acting muscarinic antagonist in development for chronic obstructive pulmonary disease (COPD). This was a multicentre, randomised, double-blind, placebo-controlled, three-way cross-over, incomplete block study to evaluate UMEC 15.6, 31.25, 62.5, and 125 μg administered once daily (QD), and UMEC 15.6 μg and 31.25 μg administered twice daily (BID), over 7 days in patients with COPD. Tiotropium was included as an open-label treatment arm. The primary efficacy endpoint was trough forced expiratory volume in 1 second (FEV1) on Day 8. Secondary efficacy endpoints included weighted mean FEV1 over 0-24 hours after morning dosing on Day 7, and serial FEV1 at each time point over 24 hours after morning dosing on Day 7. Safety and pharmacokinetics were also examined. One hundred and sixty-three patients (mean age 59.5 years, 52% female) were randomised. Based on the population dose-response model of trough FEV1 data, the geometric mean potency (ED50) of UMEC was 37 μg (95% confidence interval [CI]: 18, 57) with a predicted maximum intrinsic efficacy (Emax) at trough of 0.185 L (95% CI: 0.153, 0.218) after QD dosing. UMEC 125 μg QD demonstrated the greatest improvements in measure of lung function compared with doses of 62.5 μg and below. UMEC 125 μg QD exhibited more consistent increases in FEV1 from baseline across serial time points over 24 hours compared with other UMEC doses and tiotropium. Increases in FEV1 over 0-12 hours were similar to those observed over 12-24 hours after the second dose of UMEC was administered. UMEC was rapidly absorbed following inhaled dosing and eliminated from plasma. Adverse events, generally mild, were highest with UMEC 125 μg QD (18%) compared with placebo (8%), tiotropium (4%) and other UMEC doses (5-12%). UMEC is a potent QD bronchodilator with geometric mean ED50 of 37 μg. A dose ordering over the range of UMEC 15.6-125 μg QD doses was observed, with UMEC 125 μg showing the greatest

  11. Relative risk of injury from acute alcohol consumption: modeling the dose-response relationship in emergency department data from 18 countries.

    Science.gov (United States)

    Cherpitel, Cheryl J; Ye, Yu; Bond, Jason; Borges, Guilherme; Monteiro, Maristela

    2015-02-01

    To update and extend analysis of the dose-response relationship of injury and drinking by demographic and injury subgroups and country-level drinking pattern, and examine the validity and efficiency of the fractional polynomial approach to modeling this relationship. Pair-matched case-cross-over analysis of drinking prior to injury, using categorical step-function and fractional polynomial analysis. Thirty-seven emergency departments (EDs) across 18 countries. A total of 13 119 injured drinkers arriving at the ED within 6 hours of the event. The dose-response relationship was analyzed by gender, age, cause of injury (traffic, violence, fall, other) and country detrimental drinking pattern (DDP). Estimated risks were similar between the two analytical methods, with injury risk doubling at one drink [odds ratio (OR) = 2.3-2.7] and peaking at about 30 drinks. Although risk was similar for males and females up to three drinks (OR = 4.6), it appeared to increase more rapidly for females and was significantly higher starting from 20 drinks [female OR = 28.6; confidence interval (CI) = 16.8, 48.9; male OR = 12.8; CI = 10.1, 16.3]. No significant differences were found across age groups. Risk was significantly higher for violence-related injury than for other causes across the volume range. Risk was also higher at all volumes for DDP-3 compared with DDP-2 countries. There is an increasing risk relationship between alcohol and injury but risk is not uniform across gender, cause of injury or country drinking pattern. The fractional polynomial approach is a valid and efficient approach for modeling the alcohol injury risk relationship. © 2014 Society for the Study of Addiction.

  12. Caudate neuronal recording in freely behaving animals following acute and chronic dose response methylphenidate exposure.

    Science.gov (United States)

    Claussen, Catherine M; Dafny, Nachum

    2015-09-01

    The misuse and abuse of the psychostimulant, methylphenidate (MPD) the drug of choice in the treatment of attention deficit hyperactivity disorder (ADHD) has seen a sharp uprising in recent years among both youth and adults for its cognitive enhancing effects and for recreational purposes. This uprise in illicit use has lead to many questions concerning the long-term consequences of MPD exposure. The objective of this study was to record animal behavior concomitantly with the caudate nucleus (CN) neuronal activity following acute and repetitive (chronic) dose response exposure to methylphenidate (MPD). A saline control and three MPD dose (0.6, 2.5, and 10.0mg/kg) groups were used. Behaviorally, the same MPD dose in some animals following chronic MPD exposure elicited behavioral sensitization and other animals elicited behavioral tolerance. Based on this finding, the CN neuronal population recorded from animals expressing behavioral sensitization was also evaluated separately from CN neurons recorded from animals expressing behavioral tolerance to chronic MPD exposure, respectively. Significant differences in CN neuronal population responses between the behaviorally sensitized and the behaviorally tolerant animals were observed for the 2.5 and 10.0mg/kg MPD exposed groups. For 2.5mg/kg MPD, behaviorally sensitized animals responded by decreasing their firing rates while behaviorally tolerant animals showed mainly an increase in their firing rates. The CN neuronal responses recorded from the behaviorally sensitized animals following 10.0mg/kg MPD responded by increasing their firing rates whereas the CN neuronal recordings from the behaviorally tolerant animals showed that approximately half decreased their firing rates in response to 10.0mg/kg MPD exposure. The comparison of percentage change in neuronal firing rates showed that the behaviorally tolerant animals trended to exhibit increases in their neuronal firing rates at ED1 following initial MPD exposure and

  13. Dose-Response of High-Intensity Training (HIT on Atheroprotective miRNA-126 Levels

    Directory of Open Access Journals (Sweden)

    Boris Schmitz

    2017-05-01

    Full Text Available Aim: MicroRNA-126 (miR-126 exerts beneficial effects on vascular integrity, angiogenesis, and atherosclerotic plaque stability. The purpose of this investigation was to analyze the dose-response relationship of high-intensity interval training (HIIT on miR-126-3p and -5p levels.Methods: Sixty-one moderately trained individuals (females = 31 [50.8%]; 22.0 ± 1.84 years were consecutively recruited and allocated into three matched groups using exercise capacity. During a 4-week intervention a HIIT group performed three exercise sessions/week of 4 × 30 s at maximum speed (all-out, a progressive HIIT (proHIIT group performed three exercise sessions/week of 4 × 30 s at maximum speed (all-out with one extra session every week (up to 7 × 30 s and a low-intensity training (LIT control group performed three exercise sessions/week for 25 min <75% of maximum heart rate. Exercise miR-126-3p/-5p plasma levels were determined using capillary blood from earlobes.Results: No exercise-induced increase in miR-126 levels was detected at baseline, neither in the LIT (after 25 min low-intensity running nor the HIIT groups (after 4 min of high-intensity running. After the intervention, the LIT group presented an increase in miR-126-3p, while in the HIIT group, miR-126-3p levels were still reduced (all p < 0.05. An increase for both, miR-126-3p and -5p levels (all p < 0.05, pre- vs. during and post-exercise was detected in the proHIIT group. Between group analysis revealed that miR-126-3p levels after LIT and proHIIT increased by 2.12 ± 2.55 and 1.24 ± 2.46 units (all p < 0.01, respectively, compared to HIIT (−1.05 ± 2.6 units.Conclusions: LIT and proHIIT may be performed to increase individual miR-126 levels. HIIT without progression was less effective in increasing miR-126.

  14. Is There a Dose-Response Relationship for Heart Disease With Low-Dose Radiation Therapy?

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Eugene [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Corbett, James R. [Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Moran, Jean M. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Griffith, Kent A. [Department of Biostatistics, University of Michigan, Ann Arbor, Michigan (United States); Marsh, Robin B.; Feng, Mary; Jagsi, Reshma; Kessler, Marc L. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Ficaro, Edward C. [Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Pierce, Lori J., E-mail: ljpierce@umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)

    2013-03-15

    Purpose: To quantify cardiac radiation therapy (RT) exposure using sensitive measures of cardiac dysfunction; and to correlate dysfunction with heart doses, in the setting of adjuvant RT for left-sided breast cancer. Methods and Materials: On a randomized trial, 32 women with node-positive left-sided breast cancer underwent pre-RT stress single photon emission computed tomography (SPECT-CT) myocardial perfusion scans. Patients received RT to the breast/chest wall and regional lymph nodes to doses of 50 to 52.2 Gy. Repeat SPECT-CT scans were performed 1 year after RT. Perfusion defects (PD), summed stress defects scores (SSS), and ejection fractions (EF) were evaluated. Doses to the heart and coronary arteries were quantified. Results: The mean difference in pre- and post-RT PD was −0.38% ± 3.20% (P=.68), with no clinically significant defects. To assess for subclinical effects, PD were also examined using a 1.5-SD below the normal mean threshold, with a mean difference of 2.53% ± 12.57% (P=.38). The mean differences in SSS and EF before and after RT were 0.78% ± 2.50% (P=.08) and 1.75% ± 7.29% (P=.39), respectively. The average heart Dmean and D95 were 2.82 Gy (range, 1.11-6.06 Gy) and 0.90 Gy (range, 0.13-2.17 Gy), respectively. The average Dmean and D95 to the left anterior descending artery were 7.22 Gy (range, 2.58-18.05 Gy) and 3.22 Gy (range, 1.23-6.86 Gy), respectively. No correlations were found between cardiac doses and changes in PD, SSS, and EF. Conclusions: Using sensitive measures of cardiac function, no clinically significant defects were found after RT, with the average heart Dmean <5 Gy. Although a dose response may exist for measures of cardiac dysfunction at higher doses, no correlation was found in the present study for low doses delivered to cardiac structures and perfusion, SSS, or EF.

  15. Neurobehavioral dynamics following chronic sleep restriction: dose-response effects of one night for recovery.

    Science.gov (United States)

    Banks, Siobhan; Van Dongen, Hans P A; Maislin, Greg; Dinges, David F

    2010-08-01

    Establish the dose-response relationship between increasing sleep durations in a single night and recovery of neurobehavioral functions following chronic sleep restriction. Intent-to-treat design in which subjects were randomized to 1 of 6 recovery sleep doses (0, 2, 4, 6, 8, or 10 h TIB) for 1 night following 5 nights of sleep restriction to 4 h TIB. Twelve consecutive days in a controlled laboratory environment. N = 159 healthy adults (aged 22-45 y), median = 29 y). Following a week of home monitoring with actigraphy and 2 baseline nights of 10 h TIB, subjects were randomized to either sleep restriction to 4 h TIB per night for 5 nights followed by randomization to 1 of 6 nocturnal acute recovery sleep conditions (N = 142), or to a control condition involving 10 h TIB on all nights (N = 17). Primary neurobehavioral outcomes included lapses on the Psychomotor Vigilance Test (PVT), subjective sleepiness from the Karolinska Sleepiness Scale (KSS), and physiological sleepiness from a modified Maintenance of Wakefulness Test (MWT). Secondary outcomes included psychomotor and cognitive speed as measured by PVT fastest RTs and number correct on the Digit Symbol Substitution Task (DSST), respectively, and subjective fatigue from the Profile of Mood States (POMS). The dynamics of neurobehavioral outcomes following acute recovery sleep were statistically modeled across the 0 h-10 h recovery sleep doses. While TST, stage 2, REM sleep and NREM slow wave energy (SWE) increased linearly across recovery sleep doses, best-fitting neurobehavioral recovery functions were exponential across recovery sleep doses for PVT and KSS outcomes, and linear for the MWT. Analyses based on return to baseline and on estimated intersection with control condition means revealed recovery was incomplete at the 10 h TIB (8.96 h TST) for PVT performance, KSS sleepiness, and POMS fatigue. Both TST and SWE were elevated above baseline at the maximum recovery dose of 10 h TIB. Neurobehavioral deficits

  16. Calcium intake and colorectal cancer risk: dose-response meta-analysis of prospective observational studies.

    Science.gov (United States)

    Keum, NaNa; Aune, Dagfinn; Greenwood, Darren C; Ju, Woong; Giovannucci, Edward L

    2014-10-15

    Mechanistic and epidemiologic studies provide considerable evidence for a protective association between calcium intake and incident colorectal cancer (CRC). While the relationship has not been substantiated by short-duration randomized controlled trials (RCTs) of CRC, trials do show a benefit on adenomas, a precursor to CRC. To address some of this inconsistency, we conducted dose-response meta-analyses by sources of calcium intake, based on prospective observational studies published up to December 2013 identified from PubMed, Embase, and BIOSIS. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. For total calcium intake, each 300 mg/day increase was associated with an approximately 8% reduced risk of CRC (summary RR = 0.92, 95% CI = 0.89-0.95, I(2)  = 47%, 15 studies with 12,305 cases, intake = 250-1,900 mg/day, follow-up = 3.3-16 years). While the risk decreased less steeply in higher range of total calcium intake (P(non-linearity)  = 0.04), the degree of curvature was mild and statistical significance of non-linearity was sensitive to one study. For supplementary calcium, each 300 mg/day increase was associated with an approximately 9% reduced risk of CRC (summary RR = 0.91, 95% CI = 0.86-0.98, I(2)  = 67%, six studies with 8,839 cases, intake = 0-1,150 mg/day, follow-up = 5-10 years). The test for non-linearity was not statistically significant (P(non-linearity)  = 0.11). In conclusion, both dietary and supplementary calcium intake may continue to decrease CRC risk beyond 1,000 mg/day. Calcium supplements and non-dairy products fortified with calcium may serve as additional targets in the prevention of CRC. RCTs of calcium supplements with at least 10 years of follow-up are warranted to confirm a benefit of calcium supplements on CRC risk. © 2014 UICC.

  17. [Dose-response relationship of ropivacaine for epidural block in early herpes zoster guided by CT].

    Science.gov (United States)

    Xie, K Y; Ma, J B; Xu, Q; Huang, B; Yao, M; Ni, H D; Deng, J J; Chen, G D

    2017-12-26

    Objective: To determine the dose-response relationship of ropivacaine for epidural block in early herpes zoster by CT guided. Methods: From January 2015 to February 2017, according to the principle of completely random digital table, 80 patients with early herpes zoster who were prepared for epidural block were divided into 4 groups(each group 20 patients): in group A the concentration of ropivacaine was 0.08%, in group B was 0.10%, in group C was 0.12% and in group D was 0.14%.Under CT guidance, epidural puncture was performed in the relevant section, mixing liquid 5.0 ml (with 10% iodohydrin)were injected into epidural gap.CT scan showed that the mixing liquid covered the relevant spinal nerve segmental.The numeric rating scale(NRS) values before treatment and at 30 minutes, the incidence of adverse reactions were recorded, and the treatment were evaluated. The response to ropivacaine for epidural block in early herpes zoster was defined as positive when the NRS values was less than or equal to one.The ED(50), ED(95) and 95% confidence interval ( CI ) of ropivacaine for epidural block in early herpes zoster guided by CT were calculated by probit analysis. Results: The NRS values before treatment were 5.00(4.00, 6.00), 5.00(4.25, 6.00), 5.50(5.00, 6.00) and 5.00(4.00, 6.00), the difference was no significant( Z =2.576, P =0.462). The NRS values at 30 minutes decreased and the effective rate of the treatment increased(χ(2)=8.371, P =0.004), following ropivacaine dose gradient increasing, they were 1.50(1.00, 2.00), 1.00(1.00, 2.00), 0.50(0.00, 1.00) and 0.00(0.00, 1.00), the difference was statistically significant ( Z =17.421, P =0.001). There was one case in group C and four cases in group D were hypoesthesia, others were no significant adverse reactions occurred. The ED(50) and ED(95) (95% CI ) of ropivacaine for epidural block in early herpes zoster guided by CT were 0.078%(0.015%-0.095%)and 0.157%(0.133%-0.271%), respectively. Conclusion: Ropivacaine for

  18. Sigmoid model versus median-effect analysis for obtaining dose-response curves for in vitro chemosensitivity testing.

    Science.gov (United States)

    Pöch, G; Vychodil-Kahr, S; Petru, E

    1999-04-01

    The aim of this study was to determine how the in vitro dose-response effects of chemotherapeutic agents should be analyzed and reported. We arbitrarily evaluated the effects of mitomycin-C and 4-OH-cyclophosphamide on the human ovarian cancer cell line CAOV-3. Dose-response curves (DRCs) were calculated by non-linear (sigmoid model: SigmaPlot) and linear curve fitting (median-effect analysis: CalcuSyn). In theory and practice, the sigmoid model provided better curve fits and graphical presentation than the median-effect analysis. Thus, this model should preferably be used as a basis for selection of anti-cancer drugs for clinical use.

  19. The dose-response relationship between the patch test and ROAT and the potential use for regulatory purposes

    DEFF Research Database (Denmark)

    Fischer, Louise Arup; Voelund, Aage; Andersen, Klaus Ejner

    2009-01-01

    . OBJECTIVES: The aim was to develop an equation that could predict the response to an allergen in a ROAT based on the dose-response curve derived by patch testing. MATERIALS/METHODS: Results from two human experimental elicitation studies with non-volatile allergens, nickel and the preservative methyldibromo...... glutaronitrile (MDBGN), were analysed by logistic dose-response statistics. The relation for volatile compounds was investigated using the results from experiments with the fragrance chemicals hydroxyisohexyl 3-cyclohexene carboxaldehyde and isoeugenol. RESULTS: For non-volatile compounds, the outcome of a ROAT...... can be estimated from the patch test by: ED(xx)(ROAT) = 0.0296 ED(xx)(patch test). For volatile compounds, the equation predicts that the response in the ROAT is more severe than the patch test response, but it overestimates the response. CONCLUSIONS: This equation may be used for non...

  20. Fundamental investigations of natural and laboratory generated SAR dose response curves for quartz OSL in the high dose range

    DEFF Research Database (Denmark)

    Timar-Gabor, Alida; Constantin, Daniela; Buylaert, Jan-Pieter

    2015-01-01

    saturation much earlier. Analysis of time resolved spectra indicated similar luminescence lifetimes for both fine and coarse quartz grains, and natural and laboratory generated OSL signals seem to use the same non-dosedependent recombination pathways. The natural signals of a sample with an expected......SAR-OSL investigations on quartz from Romanian loess resulted in non concordant fine and coarse-grain ages for equivalent doses higher than ~100 Gy. The laboratory dose response for both grain sizes is well represented by a sum of two saturating exponential functions, fine and coarse grains...... equivalent dose of 2000e2500 Gy were found to be below the saturation level of the laboratory dose response curve for both grain sizes; this also applied to the luminescence signals measured after >5000 Gy given on top of natural doses. © 2015 Elsevier Ltd. All rights reserved....

  1. The role of target and bystander cells in dose-response relationship of radiation-induced bystander effects in two cell lines

    National Research Council Canada - National Science Library

    Soleymanifard, Shokouhozaman; Bahreyni Toossi, Mohammad Taghi; Sazgarnia, Ameneh; Mohebbi, Shokoufe

    2013-01-01

    ...). Published data on dose-response relationship of RIBE is controversial. In the present study the role of targeted and bystander cells in RIBE dose-response relationship of two cell lines have been investigated. Two cell lines (QU-DB and MRC5...

  2. Dose-Response Association Between Physical Activity and Incident Hypertension: A Systematic Review and Meta-Analysis of Cohort Studies.

    Science.gov (United States)

    Liu, Xuejiao; Zhang, Dongdong; Liu, Yu; Sun, Xizhuo; Han, Chengyi; Wang, Bingyuan; Ren, Yongcheng; Zhou, Junmei; Zhao, Yang; Shi, Yuanyuan; Hu, Dongsheng; Zhang, Ming

    2017-05-01

    Despite the inverse association between physical activity (PA) and incident hypertension, a comprehensive assessment of the quantitative dose-response association between PA and hypertension has not been reported. We performed a meta-analysis, including dose-response analysis, to quantitatively evaluate this association. We searched PubMed and Embase databases for articles published up to November 1, 2016. Random effects generalized least squares regression models were used to assess the quantitative association between PA and hypertension risk across studies. Restricted cubic splines were used to model the dose-response association. We identified 22 articles (29 studies) investigating the risk of hypertension with leisure-time PA or total PA, including 330 222 individuals and 67 698 incident cases of hypertension. The risk of hypertension was reduced by 6% (relative risk, 0.94; 95% confidence interval, 0.92-0.96) with each 10 metabolic equivalent of task h/wk increment of leisure-time PA. We found no evidence of a nonlinear dose-response association of PA and hypertension (Pnonlinearity=0.094 for leisure-time PA and 0.771 for total PA). With the linear cubic spline model, when compared with inactive individuals, for those who met the guidelines recommended minimum level of moderate PA (10 metabolic equivalent of task h/wk), the risk of hypertension was reduced by 6% (relative risk, 0.94; 95% confidence interval, 0.92-0.97). This meta-analysis suggests that additional benefits for hypertension prevention occur as the amount of PA increases. © 2017 American Heart Association, Inc.

  3. Developing guidelines for economic evaluation of environmental impacts in EIAs. Part II: Case studies and dose-response literature

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-07-01

    This Part II of the report contains full versions of the case studies for air, water and land (Chapters 2-4), which were only summarised in Part I. In addition, during the work the research team has collected a large amount of literature and information on dose response relationships for air and water pollution relevant to China. This information is included as Chapters 5 and 6.

  4. Light exposure at night, sleep duration, melatonin, and breast cancer: a dose-response analysis of observational studies.

    Science.gov (United States)

    Yang, Wan-Shui; Deng, Qin; Fan, Wen-Yan; Wang, Wei-Ye; Wang, Xin

    2014-07-01

    Evidence from observational studies on light at night (LAN) exposure, sleep duration, endogenous melatonin levels, and risk for breast cancer in women is conflicting. This led us to conduct a dose-response analysis of published observational data. Pertinent studies were identified by searching Medline, Web of Science, and EMBASE through April 2013. The dose-response relationship between sleep duration, urinary 6-sulphatoxymelatonin levels, and breast cancer was assessed using the restricted cubic spline model and by multivariate random-effects metaregression. A separate meta-analysis was also carried out to calculate the relative risks (RRs) with 95% confidence intervals (CIs) for breast cancer for the comparable categories or highest levels of exposure versus the lowest levels. Twelve case-control and four cohort studies were included in the analysis. High artificial LAN exposure is associated with an increased risk for breast cancer (RR=1.17, 95% CI: 1.11-1.23), but not ambient LAN exposure (RR=0.91, 95% CI: 0.78-1.07). The summary RR for breast cancer is 1.00 (95% CI: 0.995-1.01) for an increment of 1 h of sleep per night. No significant dose-response relationship between sleep duration and breast cancer was found either for the linearity test (Ptrend=0.725) or for the nonlinearity (Ptrend=0.091) test. An increasein of 15 ng/mg creatinine in urinary 6-sulphatoxymelatonin is associated with a 14% reduced risk for breast cancer (RR=0.86, 95% CI: 0.78-0.95), with a linear dose-response trend (Ptrend=0.003). There was no evidence of substantial heterogeneity or publication bias in the analysis. Our study adds to the evidence of LAN breast cancer theory. Further research in this area is warranted.

  5. DOE program--developing a scientific basis for responses to low-dose exposures: impact on dose-response relationships.

    Science.gov (United States)

    Brooks, Antone L; Couch, Lezlie

    2006-09-23

    The DOE Low Dose Radiation Research Program focuses on biological mechanisms involved in response to low doses of both low and high-LET radiation (merger enables observation of radiation-induced cellular and molecular changes previously undetectable. These low-dose responses define mechanisms of interaction of radiation with living systems, and characterize the shape of dose-response. The research from this program suggests radiation paradigms regarding the involvement of radiation in the carcinogenic process. New biological phenomena observed at low doses include initial radiation-induced DNA damage and repair, changes in gene expression, adaptive responses and bystander effects. However, information from this cellular-molecular level cannot be directly extrapolated to risks in human populations. Links must be carefully developed between dose-response relationships at the cell and tissue levels and risk to human populations. The challenge and the ultimate goal of the Program is to determine if basic scientific data can be combined with more traditional epidemiological methods to improve the estimation of radiation risk from low level radiation exposures.

  6. In situ protocol for the determination of dose-response effect of low-fluoride dentifrices on enamel remineralization

    Directory of Open Access Journals (Sweden)

    Rebeca Lima AFONSO

    2013-12-01

    Full Text Available No in situ protocol has assessed the dose-response effects of fluoride dentifrices involving low-fluoride formulations. Objective: To assess the ability of an in situ remineralization model in determining dose-response effects of dentifrices containing low fluoride concentrations ([F] on bovine enamel. Material and Methods: Volunteers wore palatal appliances containing demineralized enamel blocks and brushed their teeth and devices with the dentifrices supplied (double-blind, crossover protocol separately for 3 and 7 days. Surface hardness (SH, integrated subsurface hardness (ΔKHN and [F] in enamel were determined. Data were analyzed by ANOVA, Tukey's test and Pearson's correlation (p<0.05. Results: Dose-response relationships were verified between [F] in dentifrices and SH, ΔKHN and enamel [F]. Higher correlation coefficients between enamel [F] and SH and ΔKHN were obtained for the 3-day period. Significant differences in SH and ΔKHN were observed among all groups for the 3-day period, but not between 0-275, 275-550, and 550-1,100 µg F/g dentifrices for the 7-day period, nor between 3- and 7-day periods for the 1,100 µg F/g groups. Conclusions: Considering that the peak remineralization capacity of the conventional dentifrice (1,100 µg F/g was achieved in 3 days, this experimental period could be used in future studies assessing new dentifrice formulations, especially at low-fluoride concentrations.

  7. Characterization of the bronchodilatory dose response to indacaterol in patients with chronic obstructive pulmonary disease using model-based approaches

    Directory of Open Access Journals (Sweden)

    Lawrence David

    2011-04-01

    Full Text Available Abstract Background Indacaterol is a once-daily long-acting inhaled β2-agonist indicated for maintenance treatment of moderate-to-severe chronic obstructive pulmonary disease (COPD. The large inter-patient and inter-study variability in forced expiratory volume in 1 second (FEV1 with bronchodilators makes determination of optimal doses difficult in conventional dose-ranging studies. We considered alternative methods of analysis. Methods We utilized a novel modelling approach to provide a robust analysis of the bronchodilatory dose response to indacaterol. This involved pooled analysis of study-level data to characterize the bronchodilatory dose response, and nonlinear mixed-effects analysis of patient-level data to characterize the impact of baseline covariates. Results The study-level analysis pooled summary statistics for each steady-state visit in 11 placebo-controlled studies. These study-level summaries encompassed data from 7476 patients at indacaterol doses of 18.75-600 μg once daily, and showed that doses of 75 μg and above achieved clinically important improvements in predicted trough FEV1 response. Indacaterol 75 μg achieved 74% of the maximum effect on trough FEV1, and exceeded the midpoint of the 100-140 mL range that represents the minimal clinically important difference (MCID; ≥120 mL vs placebo, with a 90% probability that the mean improvement vs placebo exceeded the MCID. Indacaterol 150 μg achieved 85% of the model-predicted maximum effect on trough FEV1 and was numerically superior to all comparators (99.9% probability of exceeding MCID. Indacaterol 300 μg was the lowest dose that achieved the model-predicted maximum trough response. The patient-level analysis included data from 1835 patients from two dose-ranging studies of indacaterol 18.75-600 μg once daily. This analysis provided a characterization of dose response consistent with the study-level analysis, and demonstrated that disease severity, as captured by

  8. Hydrometeorological multi-model ensemble simulations of the 4 November 2011 flash-flood event in Genoa, Italy, in the framework of the DRIHM project

    Science.gov (United States)

    Hally, A.; Caumont, O.; Garrote, L.; Richard, E.; Weerts, A.; Delogu, F.; Fiori, E.; Rebora, N.; Parodi, A.; Mihalović, A.; Ivković, M.; Dekić, L.; van Verseveld, W.; Nuissier, O.; Ducrocq, V.; D'Agostino, D.; Galizia, A.; Danovaro, E.; Clematis, A.

    2014-11-01

    The e-Science environment developed in the framework of the EU-funded DRIHM project was used to demonstrate its capability to provide relevant, meaningful hydrometeorological forecasts. This was illustrated for the tragic case of 4 November 2011, when Genoa, Italy, was flooded as the result of heavy, convective precipitation that inundated the Bisagno catchment. The Meteorological Model Bridge (MMB), an innovative software component developped within the DRIHM project for the interoperability of meteorological and hydrological models, is a key component of the DRIHM e-Science environment. The MMB allowed three different rainfall-discharge models (DRiFt, RIBS, and HBV) to be driven by four mesoscale limited-area atmospheric models (WRF-NMM, WRF-ARW, Meso-NH, and AROME) and a downscaling algorithm (RainFARM) in a seamless fashion. In addition to this multi-model configuration, some of the models were run in probabilistic mode, thus allowing a comprehensive account of modelling errors and a very large amount of likely hydrometeorological scenarios (>1500). The multi-model approach proved to be necessary because, whilst various aspects of the event were successfully simulated by different models, none of the models reproduced all of these aspects correctly. It was shown that the resulting set of simulations helped identify key atmospheric processes responsible for the large rainfall accumulations over the Bisagno basin. The DRIHM e-Science environment facilitated an evaluation of the sensitivity to atmospheric and hydrological modelling errors. This showed that both had a significant impact on predicted discharges, the former being larger than the latter. Finally, the usefulness of the set of hydrometeorological simulations was assessed from a flash-flood early-warning perspective.

  9. Hydrometeorological multi-model ensemble simulations of the 4 November 2011 flash flood event in Genoa, Italy, in the framework of the DRIHM project

    Science.gov (United States)

    Hally, A.; Caumont, O.; Garrote, L.; Richard, E.; Weerts, A.; Delogu, F.; Fiori, E.; Rebora, N.; Parodi, A.; Mihalović, A.; Ivković, M.; Dekić, L.; van Verseveld, W.; Nuissier, O.; Ducrocq, V.; D'Agostino, D.; Galizia, A.; Danovaro, E.; Clematis, A.

    2015-03-01

    The e-Science environment developed in the framework of the EU-funded DRIHM project was used to demonstrate its ability to provide relevant, meaningful hydrometeorological forecasts. This was illustrated for the tragic case of 4 November 2011, when Genoa, Italy, was flooded as the result of heavy, convective precipitation that inundated the Bisagno catchment. The Meteorological Model Bridge (MMB), an innovative software component developed within the DRIHM project for the interoperability of meteorological and hydrological models, is a key component of the DRIHM e-Science environment. The MMB allowed three different rainfall-discharge models (DRiFt, RIBS and HBV) to be driven by four mesoscale limited-area atmospheric models (WRF-NMM, WRF-ARW, Meso-NH and AROME) and a downscaling algorithm (RainFARM) in a seamless fashion. In addition to this multi-model configuration, some of the models were run in probabilistic mode, thus giving a comprehensive account of modelling errors and a very large amount of likely hydrometeorological scenarios (> 1500). The multi-model approach proved to be necessary because, whilst various aspects of the event were successfully simulated by different models, none of the models reproduced all of these aspects correctly. It was shown that the resulting set of simulations helped identify key atmospheric processes responsible for the large rainfall accumulations over the Bisagno basin. The DRIHM e-Science environment facilitated an evaluation of the sensitivity to atmospheric and hydrological modelling errors. This showed that both had a significant impact on predicted discharges, the former being larger than the latter. Finally, the usefulness of the set of hydrometeorological simulations was assessed from a flash flood early-warning perspective.

  10. Hydrometeorological multi-model ensemble simulations of the 4 November 2011 flash flood event in Genoa, Italy, in the framework of the DRIHM project

    Directory of Open Access Journals (Sweden)

    A. Hally

    2015-03-01

    Full Text Available The e-Science environment developed in the framework of the EU-funded DRIHM project was used to demonstrate its ability to provide relevant, meaningful hydrometeorological forecasts. This was illustrated for the tragic case of 4 November 2011, when Genoa, Italy, was flooded as the result of heavy, convective precipitation that inundated the Bisagno catchment. The Meteorological Model Bridge (MMB, an innovative software component developed within the DRIHM project for the interoperability of meteorological and hydrological models, is a key component of the DRIHM e-Science environment. The MMB allowed three different rainfall-discharge models (DRiFt, RIBS and HBV to be driven by four mesoscale limited-area atmospheric models (WRF-NMM, WRF-ARW, Meso-NH and AROME and a downscaling algorithm (RainFARM in a seamless fashion. In addition to this multi-model configuration, some of the models were run in probabilistic mode, thus giving a comprehensive account of modelling errors and a very large amount of likely hydrometeorological scenarios (> 1500. The multi-model approach proved to be necessary because, whilst various aspects of the event were successfully simulated by different models, none of the models reproduced all of these aspects correctly. It was shown that the resulting set of simulations helped identify key atmospheric processes responsible for the large rainfall accumulations over the Bisagno basin. The DRIHM e-Science environment facilitated an evaluation of the sensitivity to atmospheric and hydrological modelling errors. This showed that both had a significant impact on predicted discharges, the former being larger than the latter. Finally, the usefulness of the set of hydrometeorological simulations was assessed from a flash flood early-warning perspective.

  11. Receptor-agonist interactions in service-theoretic perspective, effects of molecular timing on the shape of dose-response curves.

    Science.gov (United States)

    Kühl, Peter W; Jobmann, Manfred

    2006-01-01

    Service-theoretic concepts and methods, widely used in other fields (e.g., telecommunication and operations research), are useful also in a biochemical setting because the treatment of biocatalysts (enzymes, receptors) as servers and their ligands as customers, based on the established formal methods of service or queuing theory, may lead to insights and results unobtainable by conventional, mass-action-law-based theories. In this article, we apply the service-theoretic approach to receptor-agonist systems and show how by changing the stochastic time pattern of "operationally relevant" point events (e.g., instants of agonist arrival, instants of post-climax agonist departure) a great variety of dose-response curves may be generated, even in very simple reaction schemes, which, according to mass action kinetics, invariably lead to hyperbolic r(A) curves (r and A stand for response and agonist concentration, respectively). The molecular timing inherent to a hyperbolic response system is not optimal: for instance, at the agonist concentration A(50), half of the agonist molecules are rejected ("lost") because of unfortunate timing of the arrival events. The fraction of lost arrivers can be diminished considerably if the arrivals are better timed: "sub-Poisson" arrivals improve the timing and, thus, convert hyperbolic r(A) curves into "lifted" nonhyperbolic ones. Conversely, "super-Poisson" arrivals make the non-optimal timing in hyperbolic response systems even worse and, thus, convert hyperbolic r(A) curves into "depressed" nonhyperbolic ones. Furthermore, under special timing conditions, nonhyperbolic r(A) curves can be generated, which are partly lifted, partly depressed relative to the reference hyperbola, and which resemble in shape well-known nonhyperbolic forms of enzyme and receptor kinetics (negatively cooperative, positively cooperative, and sigmoidal kinetics). In addition unusual (undulatory and sawtooth-like) r(A) curves can be generated solely by changing

  12. Serum Uric Acid Levels and Risk of Metabolic Syndrome: A Dose-Response Meta-Analysis of Prospective Studies.

    Science.gov (United States)

    Yuan, Huiping; Yu, Chenglong; Li, Xinghui; Sun, Liang; Zhu, Xiaoquan; Zhao, Chengxiao; Zhang, Zheng; Yang, Ze

    2015-11-01

    An excess circulating uric acid level, even within the normal range, is always comorbid with metabolic syndrome (MS), several of its components, and nonalcoholic fatty liver disease (NAFLD), which was regarded as hepatic manifestation of MS; however, these associations remain controversial. This study aimed to quantitatively assess the relationship between the serum uric acid (SUA) levels and the MS/NAFLD risk. We searched for related prospective cohort studies including SUA as an exposure and MS/NAFLD as a result in MEDLINE (PubMed) and EMBASE databases up to January 31, 2015 and July 28, 2015, respectively. Pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) were extracted. A random-effects model was used to evaluate dose-response relationships. On the basis of 11 studies (54 970 participants and 8719 MS cases), a combined RR of 1.72 (95% CI, 1.45-2.03; P < .0001) was observed for the highest SUA level category compared with the lowest SUA level category. Furthermore, based on nine studies (51 249 participants and 8265 MS cases), dose-response analysis suggested that each 1 mg/dL SUA increment was roughly linearly associated with the MS risk (RR, 1.30; 95% CI, 1.22-1.38; P < .0001). Beyond that, SUA level increased NAFLD risk (RR, 1.46; 95% CI, 1.31-1.63). Each 1 mg/dL SUA level increment led to 21% increase in the NAFLD risk. This meta-analysis suggests that higher SUA levels led to an increased risk of MS regardless of the study characteristics, and were consistent with a linear dose-response relationship. In addition, SUA was also a causal factor for the NAFLD risk.

  13. Fruit and vegetables consumption and incident hypertension: dose-response meta-analysis of prospective cohort studies.

    Science.gov (United States)

    Wu, L; Sun, D; He, Y

    2016-10-01

    The role of dietary factors on chronic diseases seems essential in the potentially adverse or preventive effects. However, no evidence of dose-response meta-analysis of prospective cohort studies has verified the association between the intake of fruit and/or vegetables and the risk of developing hypertension. The PubMed and Embase were searched for prospective cohort studies. A generic inverse-variance method with random effects model was used to calculate the pooled relative risks (RRs) and 95% confidence intervals (CIs). Generalized least squares trend estimation model was used to calculate the study-specific slopes for the dose-response analyses. Seven articles comprised nine cohorts involving 185 676 participants were assessed. The highest intake of fruit or vegetables separately, and total fruit and vegetables were inversely associated with the incident risk of hypertension compared with the lowest level, and the pooled RRs and 95% CIs were 0.87 (0.79, 0.95), 0.88 (0.79, 0.99) and 0.90 (0.84, 0.98), respectively. We also found an inverse dose-response relation between the risk of developing hypertension and fruit intake, and total fruit and vegetables consumption. The incident risk of hypertension was decreased by 1.9% for each serving per day of fruit consumption, and decreased by 1.2% for each serving per day of total fruit and vegetables consumption. Our results support the recommendation to increase the consumption of fruit and vegetables with respect to preventing the risk of developing hypertension. However, further large prospective studies and long-term high-quality randomized controlled trials are still needed to confirm the observed association.

  14. Comparison of Dose Response Models for Predicting Normal Tissue Complications from Cancer Radiotherapy: Application in Rat Spinal Cord

    Directory of Open Access Journals (Sweden)

    Magdalena Adamus-Górka

    2011-05-01

    Full Text Available Seven different radiobiological dose-response models have been compared with regard to their ability to describe experimental data. The first four models, namely the critical volume, the relative seriality, the inverse tumor and the critical element models are mainly based on cell survival biology. The other three models: the Lyman (Gaussian distribution, the parallel architecture and the Weibull distribution models are semi-empirical and rather based on statistical distributions. The maximum likelihood estimation was used to fit the models to experimental data and the χ2-distribution, AIC criterion and F-test were applied to compare the goodness-of-fit of the models. The comparison was performed using experimental data for rat spinal cord injury. Both the shape of the dose-response curve and the ability of handling the volume dependence were separately compared for each model. All the models were found to be acceptable in describing the present experimental dataset (p > 0.05. For the white matter necrosis dataset, the Weibull and Lyman models were clearly superior to the other models, whereas for the vascular damage case, the Relative Seriality model seems to have the best performance although the Critical volume, Inverse tumor, Critical element and Parallel architecture models gave similar results. Although the differences between many of the investigated models are rather small, they still may be of importance in indicating the advantages and limitations of each particular model. It appears that most of the models have favorable properties for describing dose-response data, which indicates that they may be suitable to be used in biologically optimized intensity modulated radiation therapy planning, provided a proper estimation of their radiobiological parameters had been performed for every tissue and clinical endpoint.

  15. An apparent threshold dose response in ferrous xylenol-orange gel dosimeters when scanned with a yellow light source

    Science.gov (United States)

    Babic, Steven; Battista, Jerry; Jordan, Kevin

    2008-03-01

    Freshly prepared radiochromic ferrous xylenol-orange (FX) gels optically scanned with a light source exhibit a threshold dose response that is thermally and wavelength dependent. Correction for this threshold dose leads to accurate dose calibration and better reproducibility in multiple fraction radiation exposures. The objective of this study was to determine the cause of the threshold dose effect and to control it through improved dose calibration procedures. The results of a systematic investigation into the chemical cause revealed that impurities within the various FX gel constituents (i.e. xylenol-orange, gelatin, sulfuric acid and ferrous ammonium sulfate) were not directly responsible for the threshold dose. Rather, it was determined that the threshold dose response stems from a spectral sensitivity to different chemical complexes that are formed at different dose levels in FX gels between ferric (Fe(III)) ions and xylenol-orange (XO), i.e. Fe(III)i:XOj. A double Fe(III)2:XO1 complex preferentially absorbs at longer wavelengths (i.e. yellow), while at shorter wavelengths (i.e. green) the sensitivity is biased toward the single Fe(III)1:XO1 complex. As a result, when scanning with yellow light, freshly prepared FX gels require a minimum concentration of Fe(III) ions to shift the equilibrium concentration to favor the predominant production of the double Fe(III)2:XO1 complex at low doses. This can be accomplished via pre-irradiation of freshly prepared gels to a priming dose of ~0.5 Gy or allowing auto-oxidation to generate the startup concentration of Fe(III) ions required to negate the apparent threshold dose response.

  16. A Linear Dose-Response Relationship between Fasting Plasma Glucose and Colorectal Cancer Risk: Systematic Review and Meta-analysis.

    Science.gov (United States)

    Shi, Jianguo; Xiong, Lijuan; Li, Jiaoyuan; Cao, Heng; Jiang, Wen; Liu, Bo; Chen, Xueqin; Liu, Cheng; Liu, Ke; Wang, Guobin; Cai, Kailin

    2015-12-01

    For many years, the question of whether hyperglycaemia, a manifestation of prediabetes, diabetes mellitus and metabolic syndrome, is a risk factor for colorectal cancer has been intensely studied. In fact, even after the conclusion of several prospective studies, the topic is still controversial. We conducted a systematic review and meta-analysis to investigate the dose-response relationship between blood glucose concentration and the incidence of colorectal cancer. A linear (P = 0.303 for non-linearity) dose-response relationship was observed between fasting plasma glucose (FPG) and colorectal cancer risk without significant heterogeneity. The relative risk (RR) for colorectal cancer per 20 mg/dL increase in FPG was 1.015 (95% CI: 1.012-1.019, P = 0.000). In subgroup analyses, the pooled RRs for colon cancer (CC) and rectal cancer (RC) studies were 1.035 (95% CI 1.008-1.062, P = 0.011) and 1.031 (95% CI: 0.189-5.628, P = 0.972), respectively; in the analysis comparing men and women, the pooled RRs were 1.016 (95% CI: 1.012-1.020, P = 0.000) and 1.011 (95% CI: 0.995-1.027, P = 0.164), respectively. Sensitivity analyses using two methods showed similar results. In conclusion, there is a significant linear dose-response relationship between FPG and the incidence risk of colorectal cancer. For people with diabetes or prediabetes, controlling blood glucose might be useful to prevent colorectal cancer.

  17. Comparison of Dose Response Models for Predicting Normal Tissue Complications from Cancer Radiotherapy: Application in Rat Spinal Cord

    Energy Technology Data Exchange (ETDEWEB)

    Adamus-Górka, Magdalena; Mavroidis, Panayiotis, E-mail: panayiotis.mavroidis@ki.se; Lind, Bengt K.; Brahme, Anders [Department of Medical Radiation Physics, Karolinska Institutet and Stockholm University, Stockholm S-17176 (Sweden)

    2011-05-18

    Seven different radiobiological dose-response models have been compared with regard to their ability to describe experimental data. The first four models, namely the critical volume, the relative seriality, the inverse tumor and the critical element models are mainly based on cell survival biology. The other three models: the Lyman (Gaussian distribution), the parallel architecture and the Weibull distribution models are semi-empirical and rather based on statistical distributions. The maximum likelihood estimation was used to fit the models to experimental data and the χ{sup 2}-distribution, AIC criterion and F-test were applied to compare the goodness-of-fit of the models. The comparison was performed using experimental data for rat spinal cord injury. Both the shape of the dose-response curve and the ability of handling the volume dependence were separately compared for each model. All the models were found to be acceptable in describing the present experimental dataset (p > 0.05). For the white matter necrosis dataset, the Weibull and Lyman models were clearly superior to the other models, whereas for the vascular damage case, the Relative Seriality model seems to have the best performance although the Critical volume, Inverse tumor, Critical element and Parallel architecture models gave similar results. Although the differences between many of the investigated models are rather small, they still may be of importance in indicating the advantages and limitations of each particular model. It appears that most of the models have favorable properties for describing dose-response data, which indicates that they may be suitable to be used in biologically optimized intensity modulated radiation therapy planning, provided a proper estimation of their radiobiological parameters had been performed for every tissue and clinical endpoint.

  18. Post-Injury Treatment with NIM811 Promotes Recovery of Function in Adult Female Rats after Spinal Cord Contusion: A Dose-Response Study.

    Science.gov (United States)

    Springer, Joe E; Visavadiya, Nishant P; Sullivan, Patrick G; Hall, Edward D

    2018-02-01

    Mitochondrial homeostasis is essential for maintaining cellular function and survival in the central nervous system (CNS). Mitochondrial function is significantly compromised after spinal cord injury (SCI) and is associated with accumulation of high levels of calcium, increased production of free radicals, oxidative damage, and eventually mitochondrial permeability transition (mPT). The formation of the mPT pore (mPTP) and subsequent mPT state are considered to be end stage events in the decline of mitochondrial integrity, and strategies that inhibit mPT can limit mitochondrial demise. Cyclosporine A (CsA) is thought to inhibit mPT by binding to cyclophilin D and has been shown to be effective in models of CNS injury. CsA, however, also inhibits calcineurin, which is responsible for its immunosuppressive properties. In the present study, we conducted a dose-response examination of NIM811, a nonimmunosuppressive CsA analog, on recovery of function and tissue sparing in a rat model of moderate to severe SCI. The results of our experiments revealed that NIM811 (10 mg/kg) significantly improved open field locomotor performance, while the two higher doses tested (20 and 40 mg/kg) significantly improved return of reflexive bladder control and significantly decreased the rostral-caudal extent of the lesion. Taken together, these results demonstrate the ability of NIM811 to improve recovery of function in SCI and support the role of protecting mitochondrial function as a potential therapeutic target.

  19. Modified Maxium Likelihood Estimation Method for Completely Separated and Quasi-Completely Separated Data for a Dose-Response Model

    Science.gov (United States)

    2015-08-01

    by ANSI Std. Z39.18 ii Blank iii EXECUTIVE SUMMARY Applying a generalized linear model (GLM) with a logit or probit link is a routine...4 log log 1 log 1 log (2) The canonical link derived for logit from eq 2 is expressed as log 1 (3) The logit model fits to the Ɵ for a...FOR A DOSE-RESPONSE MODEL ECBC-TN-068 Kyong H. Park Steven J. Lagan RESEARCH AND TECHNOLOGY DIRECTORATE August 2015 Approved for public release

  20. Unveiling time in dose-response models to infer host susceptibility to pathogens.

    Directory of Open Access Journals (Sweden)

    Delphine Pessoa

    2014-08-01

    Full Text Available The biological effects of interventions to control infectious diseases typically depend on the intensity of pathogen challenge. As much as the levels of natural pathogen circulation vary over time and geographical location, the development of invariant efficacy measures is of major importance, even if only indirectly inferrable. Here a method is introduced to assess host susceptibility to pathogens, and applied to a detailed dataset generated by challenging groups of insect hosts (Drosophila melanogaster with a range of pathogen (Drosophila C Virus doses and recording survival over time. The experiment was replicated for flies carrying the Wolbachia symbiont, which is known to reduce host susceptibility to viral infections. The entire dataset is fitted by a novel quantitative framework that significantly extends classical methods for microbial risk assessment and provides accurate distributions of symbiont-induced protection. More generally, our data-driven modeling procedure provides novel insights for study design and analyses to assess interventions.

  1. Occupational Exposure to Diesel Motor Exhaust and Lung Cancer: A Dose-Response Relationship Hidden by Asbestos Exposure Adjustment? The ICARE Study

    Science.gov (United States)

    Matrat, Mireille; Guida, Florence; Cénée, Sylvie; Févotte, Joelle; Carton, Matthieu; Cyr, Diane; Menvielle, Gwenn; Paget-Bailly, Sophie; Radoï, Loredana; Schmaus, Annie; Bara, Simona; Velten, Michel; Luce, Danièle; Stücker, Isabelle; The Icare Study Group

    2015-01-01

    Background. In a French large population-based case-control study we investigated the dose-response relationship between lung cancer and occupational exposure to diesel motor exhaust (DME), taking into account asbestos exposure. Methods. Exposure to DME was assessed by questionnaire. Asbestos was taken into account through a global indicator of exposure to occupational carcinogens or by a specific JEM. Results. We found a crude dose response relationship with most of the indicators of DME exposure, including with the cumulative exposure index. All results were affected by adjustment for asbestos exposure. The dose response relationships between DME and lung cancer were observed among subjects never exposed to asbestos. Conclusions. Exposure to DME and to asbestos is frequently found among the same subjects, which may explain why dose-response relationships in previous studies that adjusted for asbestos exposure were inconsistent. PMID:26425123

  2. Dose-response effects of aerobic exercise on body composition among colon cancer survivors: a randomised controlled trial.

    Science.gov (United States)

    Brown, Justin C; Zemel, Babette S; Troxel, Andrea B; Rickels, Michael R; Damjanov, Nevena; Ky, Bonnie; Rhim, Andrew D; Rustgi, Anil K; Courneya, Kerry S; Schmitz, Kathryn H

    2017-11-21

    Physical activity is associated with a lower risk of disease recurrence among colon cancer survivors. Excess visceral adipose tissue is associated with a higher risk of disease recurrence among colon cancer survivors. The pathways through which physical activity may alter disease outcomes are unknown, but may be mediated by changes in visceral adipose tissue. Thirty-nine stage I-III colon cancer survivors were randomised to one of three groups: usual-care control, 150 min wk -1 of aerobic exercise (low dose) and 300 min wk -1 of aerobic exercise (high dose) for 6 months. The prespecified key body composition outcome was visceral adipose tissue quantified using dual energy X-ray absorptiometry. Exercise reduced visceral adipose tissue in dose-response fashion (P trend =0.008). Compared with the control group, the low- and high-dose exercise groups lost 9.5 cm 2 (95% CI: -22.4, 3.5) and 13.6 cm 2 (95% CI: -27.0, -0.1) in visceral adipose tissue, respectively. Each 60 min wk -1 increase in exercise predicted a 2.7 cm 2 (95% CI: -5.4, -0.1) reduction in visceral adipose tissue. Aerobic exercise reduces visceral adipose tissue in dose-response fashion among patients with stage I-III colon cancer. Visceral adipose tissue may be a mechanism through which exercise reduces the risk of disease recurrence among colon cancer survivors.

  3. Dietary Magnesium Intake and Metabolic Syndrome in the Adult Population: Dose-Response Meta-Analysis and Meta-Regression

    Science.gov (United States)

    Ju, Sang-Yhun; Choi, Whan-Seok; Ock, Sun-Myeong; Kim, Chul-Min; Kim, Do-Hoon

    2014-01-01

    Increasing evidence has suggested an association between dietary magnesium intake and metabolic syndrome. However, previous research examining dietary magnesium intake and metabolic syndrome has produced mixed results. Our objective was to determine the relationship between dietary magnesium intake and metabolic syndrome in the adult population using a dose-response meta-analysis. We searched the PubMed, Embase and the Cochrane Library databases from August, 1965, to May, 2014. Observational studies reporting risk ratios with 95% confidence intervals (CIs) for metabolic syndrome in ≥3 categories of dietary magnesium intake levels were selected. The data extraction was performed independently by two authors, and the quality of the studies was evaluated using the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS). Based on eight cross-sectional studies and two prospective cohort studies, the pooled relative risks of metabolic syndrome per 150 mg/day increment in magnesium intake was 0.88 (95% CI, 0.84–0.93; I2 = 36.3%). The meta-regression model showed a generally linear, inverse relationship between magnesium intake (mg/day) and metabolic syndrome. This dose-response meta-analysis indicates that dietary magnesium intake is significantly and inversely associated with the risk of metabolic syndrome. However, randomized clinical trials will be necessary to address the issue of causality and to determine whether magnesium supplementation is effective for the prevention of metabolic syndrome. PMID:25533010

  4. Coffee consumption and mortality from all causes, cardiovascular disease, and cancer: a dose-response meta-analysis.

    Science.gov (United States)

    Crippa, Alessio; Discacciati, Andrea; Larsson, Susanna C; Wolk, Alicja; Orsini, Nicola

    2014-10-15

    Several studies have analyzed the relationship between coffee consumption and mortality, but the shape of the association remains unclear. We conducted a dose-response meta-analysis of prospective studies to examine the dose-response associations between coffee consumption and mortality from all causes, cardiovascular disease (CVD), and all cancers. Pertinent studies, published between 1966 and 2013, were identified by searching PubMed and by reviewing the reference lists of the selected articles. Prospective studies in which investigators reported relative risks of mortality from all causes, CVD, and all cancers for 3 or more categories of coffee consumption were eligible. Results from individual studies were pooled using a random-effects model. Twenty-one prospective studies, with 121,915 deaths and 997,464 participants, met the inclusion criteria. There was strong evidence of nonlinear associations between coffee consumption and mortality for all causes and CVD (P for nonlinearity Coffee consumption was not associated with cancer mortality. Findings from this meta-analysis indicate that coffee consumption is inversely associated with all-cause and CVD mortality. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Red and processed meat consumption and mortality: dose-response meta-analysis of prospective cohort studies.

    Science.gov (United States)

    Wang, Xia; Lin, Xinying; Ouyang, Ying Y; Liu, Jun; Zhao, Gang; Pan, An; Hu, Frank B

    2016-04-01

    To examine and quantify the potential dose-response relationship between red and processed meat consumption and risk of all-cause, cardiovascular and cancer mortality. We searched MEDLINE, Embase, ISI Web of Knowledge, CINHAL, Scopus, the Cochrane library and reference lists of retrieved articles up to 30 November 2014 without language restrictions. We retrieved prospective cohort studies that reported risk estimates for all-cause, cardiovascular and cancer mortality by red and/or processed meat intake levels. The dose-response relationships were estimated using data from red and processed meat intake categories in each study. Random-effects models were used to calculate pooled relative risks and 95 % confidence intervals and to incorporate between-study variations. Nine articles with seventeen prospective cohorts were eligible in this meta-analysis, including a total of 150 328 deaths. There was evidence of a non-linear association between processed meat consumption and risk of all-cause and cardiovascular mortality, but not for cancer mortality. For processed meat, the pooled relative risk with an increase of one serving per day was 1·15 (95 % CI 1·11, 1·19) for all-cause mortality (five studies; Pmeat intake. The association between unprocessed red meat consumption and mortality risk was found in the US populations, but not in European or Asian populations. The present meta-analysis indicates that higher consumption of total red meat and processed meat is associated with an increased risk of total, cardiovascular and cancer mortality.

  6. Dose-response in direct comparisons of different doses of aspirin, ibuprofen and paracetamol (acetaminophen) in analgesic studies.

    Science.gov (United States)

    McQuay, Henry J; Moore, R Andrew

    2007-03-01

    Establishing the dose-response relationship for clinically useful doses of aspirin, ibuprofen and paracetamol has been difficult. Indirect comparison from meta-analysis is compromised by too little information at some doses. A systematic review of randomized, double-blind trials in acute pain comparing different doses of aspirin, ibuprofen and paracetamol was therefore undertaken. Fifty trials were found. Numerical superiority of higher over lower dose was found by the original authors in 37/50 trials (74%) and statistical superiority in 11/50 (22%). Twenty-eight trials had design, quality and data reporting characteristics to allow pooling of common doses; in 3/28 (11%) of the individual trials our calculations showed statistical superiority of higher over lower dose. Pooled comparison of 1000/1200 mg aspirin over 500/600 mg was statistically superior, with a number-needed-to-treat (NNT) for higher over lower dose of 16 (8 to > 100). Pooled comparison of 400 mg ibuprofen over 200 mg was statistically superior, with an NNT for higher over lower dose of 10 (6-23). Pooled comparison of 1000 mg paracetamol over 500 mg was statistically superior, with an NNT for higher over lower dose of 9 (6-20). Use of trials making direct comparison of two different doses of target drugs revealed the underlying dose-response curve for clinical analgesia.

  7. Benchmarking B-cell epitope prediction with quantitative dose-response data on antipeptide antibodies: towards novel pharmaceutical product development.

    Science.gov (United States)

    Caoili, Salvador Eugenio C

    2014-01-01

    B-cell epitope prediction can enable novel pharmaceutical product development. However, a mechanistically framed consensus has yet to emerge on benchmarking such prediction, thus presenting an opportunity to establish standards of practice that circumvent epistemic inconsistencies of casting the epitope prediction task as a binary-classification problem. As an alternative to conventional dichotomous qualitative benchmark data, quantitative dose-response data on antibody-mediated biological effects are more meaningful from an information-theoretic perspective in the sense that such effects may be expressed as probabilities (e.g., of functional inhibition by antibody) for which the Shannon information entropy (SIE) can be evaluated as a measure of informativeness. Accordingly, half-maximal biological effects (e.g., at median inhibitory concentrations of antibody) correspond to maximally informative data while undetectable and maximal biological effects correspond to minimally informative data. This applies to benchmarking B-cell epitope prediction for the design of peptide-based immunogens that elicit antipeptide antibodies with functionally relevant cross-reactivity. Presently, the Immune Epitope Database (IEDB) contains relatively few quantitative dose-response data on such cross-reactivity. Only a small fraction of these IEDB data is maximally informative, and many more of them are minimally informative (i.e., with zero SIE). Nevertheless, the numerous qualitative data in IEDB suggest how to overcome the paucity of informative benchmark data.

  8. Dose-response association between leisure time physical activity and work ability: Cross-sectional study among 3000 workers.

    Science.gov (United States)

    Calatayud, Joaquin; Jakobsen, Markus D; Sundstrup, Emil; Casaña, Jose; Andersen, Lars L

    2015-12-01

    Regular physical activity is important for longevity and health, but knowledge about the optimal dose of physical activity for maintaining good work ability is unknown. This study investigates the association between intensity and duration of physical activity during leisure time and work ability in relation to physical demands of the job. From the 2010 round of the Danish Work Environment Cohort Study, currently employed wage earners with physically demanding work (n = 2952) replied to questions about work, lifestyle and health. Excellent (100 points), very good (75 points), good (50 points), fair (25 points) and poor (0 points) work ability in relation to the physical demands of the job was experienced by 18%, 40%, 30%, 10% and 2% of the respondents, respectively. General linear models that controlled for gender, age, physical and psychosocial work factors, lifestyle and chronic disease showed that the duration of high-intensity physical activity during leisure was positively associated with work ability, in a dose-response fashion (p activity per week had on average 8 points higher work ability than those not performing such activities. The duration of low-intensity leisure-time physical activity was not associated with work ability (p = 0.5668). The duration of high-intensity physical activity during leisure time is associated in a dose-response fashion with work ability, in workers with physically demanding jobs. © 2015 the Nordic Societies of Public Health.

  9. An in vitro dynamic microcosm biofilm model for caries lesion development and antimicrobial dose-response studies.

    Science.gov (United States)

    Maske, T T; Brauner, K V; Nakanishi, L; Arthur, R A; van de Sande, F H; Cenci, M S

    2016-01-01

    Some dynamic biofilm models for dental caries development are limited as they require multiple experiments and do not allow independent biofilm growth units, making them expensive and time-consuming. This study aimed to develop and test an in vitro dynamic microcosm biofilm model for caries lesion development and for dose-response to chlorhexidine. Microcosm biofilms were grown under two different protocols from saliva on bovine enamel discs for up to 21 days. The study outcomes were as follows: the percentage of enamel surface hardness change, integrated hardness loss, and the CFU counts from the biofilms formed. The measured outcomes, mineral loss and CFU counts showed dose-response effects as a result of the treatment with chlorhexidine. Overall, the findings suggest that biofilm growth for seven days with 0.06 ml min(-1) salivary flow under exposure to 5% sucrose (3 × daily, 0.25 ml min(-1), 6 min) was suitable as a pre-clinical model for enamel demineralization and antimicrobial studies.

  10. Coffee, tea, caffeine and risk of depression: A systematic review and dose-response meta-analysis of observational studies.

    Science.gov (United States)

    Grosso, Giuseppe; Micek, Agnieszka; Castellano, Sabrina; Pajak, Andzrej; Galvano, Fabio

    2016-01-01

    The aim of the study was to systematically review and analyze results from observational studies on coffee, caffeine, and tea consumption and association or risk of depression. Embase and PubMed databases were searched from inception to June 2015 for observational studies reporting the odds ratios or relative risks (RRs) and 95% confidence intervals (CI) of depression by coffee/tea/caffeine consumption. Random effects models, subgroup analyses, and dose-response analyses were performed. Twelve studies with 23 datasets were included in the meta-analysis, accounting for a total of 346 913 individuals and 8146 cases of depression. Compared to individuals with lower coffee consumption, those with higher intakes had pooled RR of depression of 0.76 (95% CI: 0.64, 0.91). Dose-response effect suggests a nonlinear J-shaped relation between coffee consumption and risk of depression with a peak of protective effect for 400 mL/day. A borderline nonsignificant association between tea consumption and risk of depression was found (RR 0.70, 95% CI: 0.48, 1.01), while significant results were found only for analysis of prospective studies regarding caffeine consumption (RR = 0.84, 95% CI: 0.75, 0.93). This study suggests a protective effect of coffee and, partially, of tea and caffeine on risk of depression. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Dose-response effects of customised foot orthoses on lower limb muscle activity and plantar pressures in pronated foot type.

    Science.gov (United States)

    Telfer, Scott; Abbott, Mandy; Steultjens, Martijn; Rafferty, Daniel; Woodburn, James

    2013-07-01

    Customised foot orthoses (FOs) featuring extrinsic rearfoot posting are commonly prescribed for individuals with a symptomatic pronated foot type. By altering the angle of the posting it is purported that a controlled dose-response effect during the stance phase of gait can be achieved, however these biomechanical changes have yet to be characterised. Customised FOs were administered to participant groups with symptomatic pronated foot types and asymptomatic normal foot types. The electromyographic (EMG) and plantar pressure effects of varying the dose were measured. Dose was varied by changing the angle of posting from 6° lateral to 10° medial in 2° steps on customised devices produced using computer aided orthoses design software. No effects due to posting level were found for EMG variables. Significant group effects were seen with customised FOs reducing above knee muscle activity in pronated foot types compared to normal foot types (biceps femoris p=0.022; vastus lateralis pcustomised FOs can provide a dose response effect for selected plantar pressure variables, but no such effect could be identified for muscle activity. Foot type may play an important role in the effect of customised orthoses on activity of muscles above the knee. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Dose-response effects of customised foot orthoses on lower limb kinematics and kinetics in pronated foot type.

    Science.gov (United States)

    Telfer, Scott; Abbott, Mandy; Steultjens, Martijn P M; Woodburn, James

    2013-05-31

    Despite the widespread use of customised foot orthoses (FOs) for the pronated foot type there is a lack of reliable information on the dose-response effect on lower limb mechanics. This study investigated these effects in subjects with normal and pronated foot types. Customised FOs were administered to 12 participants with symptomatic pronated foot type and 12 age and gender matched controls. A computer-aided design (CAD) software was used to design nine FOs per participant with dose incrementally changed by varying only the rearfoot post angle. This was done in 2° increments from 6° lateral to 10° medial posting. A 3D printing method was used to manufacture the FOs. Quantification of the dose-response effect was performed using three-dimensional gait analyses for selected rearfoot and knee kinematics and kinetics. Under these experimental conditions, significant and linear effects of posting were seen for the peak (pcustomised FOs used to treat pronated foot type. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Dose-response analysis of bromate-induced DNA damage and mutagenicity is consistent with low-dose linear, nonthreshold processes.

    Science.gov (United States)

    Spassova, Maria A; Miller, David J; Eastmond, David A; Nikolova, Nadejda S; Vulimiri, Suryanarayana V; Caldwell, Jane; Chen, Chao; White, Paul D

    2013-01-01

    Mutagenic agents have long been inferred to act through low-dose linear, nonthreshold processes. However, there is debate about this assumption, with various studies interpreting datasets as showing thresholds for DNA damage and mutation. We have applied rigorous statistical analyses to investigate the shape of dose-response relationships for a series of in vitro and in vivo genotoxicity studies using potassium bromate (KBrO(3) ), a water ozonation byproduct that is bioactivated to a reactive species causing oxidative damage to DNA. We analyzed studies of KBrO(3) genotoxicity where no-effect/threshold levels were reported as well as other representative datasets. In all cases, the data were consistent with low-dose linear models. In the majority of cases, the data were fit either by a linear (straight line) model or a model which was linear at low doses and showed a saturation-like downward curvature at high doses. Other datasets with apparent upward curvature were still adequately represented by models that were linear at low dose. Sensitivity analysis of datasets showing upward curvature revealed that both low-dose linear and nonlinear models provide adequate fits. Additionally, a simple biochemical model of selected key processes in bromate-induced DNA damage was developed and illustrated a situation where response for early primary events suggested an apparent threshold while downstream events were linear. Overall, the statistical analyses of DNA damage and mutations induced by KBrO(3) are consistent with a low-dose linear response and do not provide convincing evidence for the presence of a threshold. Copyright © 2012 Wiley Periodicals, Inc.

  14. Hybrid Architectural Framework for C4ISR and Discrete-Event Simulation (DES) to Support Sensor-Driven Model Synthesis in Real-World Scenarios

    Science.gov (United States)

    2013-09-01

    the time/event/process driven approach by Galluscio and time-step/discrete-event/time-parallel architecture by Marquez , they can all be included in...Clive Wood, Patricio Jiménez López, Heliodoro Ruipérez Garcia , & Jan van Geest. (2008). Developing a federation to demonstrate the NATO live, virtual

  15. A model of cytotoxic dose-response nonlinearities arising from adaptive cell inventory management in tissues.

    Science.gov (United States)

    Cox, Louis Anthony Tony

    2006-05-22

    Why do low-level exposures to environmental toxins often elicit over-compensating responses that reduce risk to an organism? Conversely, if these responses improve health, why wait for an environmental challenge to trigger them? This paper presents a mathematical modeling framework that addresses both questions using the principle that evolution favors tissues that hedge their bets against uncertain environmental challenges. We consider a tissue composed of differentiated cells performing essential functions (e.g., lung tissue, bone marrow, etc.). The tissue seeks to maintain adequate supplies of these cells, but many of them may occasionally be killed relatively quickly by cytotoxic challenges. The tissue can "order replacements" (e.g., via cytokine network signaling) from a deeper compartment of proliferative stem cells, but there is a delivery lag because these cells must undergo maturation, amplification via successive divisions, and terminal differentiation before they can replace the killed functional cells. Therefore, a "rational" tissue maintains an inventory of relatively mature cells (e.g., the bone marrow reserve for blood cells) for quick release when needed. This reservoir is replenished by stimulating proliferation in the stem cell compartment. Normally, stem cells have a very low risk of unrepaired carcinogenic (or other) damage, due to extensive checking and repair. But when production is rushed to meet extreme demands, error rates increase. We use a mathematical model of cell inventory management to show that decision rules that effectively manage the inventory of mature cells to maintain tissue function across a wide range of unpredictable cytotoxic challenges imply that increases in average levels of cytotoxic challenges can increase average inventory levels and reduce the average error rate in stem cell production. Thus, hormesis and related nonlinearities can emerge as a natural result of cell-inventory risk management by tissues.

  16. Building a Human Health Risk Assessment Ontology (RsO): A Proposed Framework.

    Science.gov (United States)

    McKone, Thomas E; Feng, Lydia

    2015-11-01

    Over the last decade the health and environmental research communities have made significant progress in collecting and improving access to genomic, toxicology, exposure, health, and disease data useful to health risk assessment. One of the barriers to applying these growing volumes of information in fields such as risk assessment is the lack of informatics tools to organize, curate, and evaluate thousands of journal publications and hundreds of databases to provide new insights on relationships among exposure, hazard, and disease burden. Many fields are developing ontologies as a way of organizing and analyzing large amounts of complex information from multiple scientific disciplines. Ontologies include a vocabulary of terms and concepts with defined logical relationships to each other. Building from the recently published exposure ontology and other relevant health and environmental ontologies, this article proposes an ontology for health risk assessment (RsO) that provides a structural framework for organizing risk assessment information and methods. The RsO is anchored by eight major concepts that were either identified by exploratory curations of the risk literature or the exposure-ontology working group as key for describing the risk assessment domain. These concepts are: (1) stressor, (2) receptor, (3) outcome, (4) exposure event, (5) dose-response approach, (6) dose-response metric, (7) uncertainty, and (8) measure of risk. We illustrate the utility of these concepts for the RsO with example curations of published risk assessments for ionizing radiation, arsenic in drinking water, and persistent pollutants in salmon. © 2015 Society for Risk Analysis.

  17. The Dose-Response Association between Nitrogen Dioxide Exposure and Serum Interleukin-6 Concentrations.

    Science.gov (United States)

    Perret, Jennifer L; Bowatte, Gayan; Lodge, Caroline J; Knibbs, Luke D; Gurrin, Lyle C; Kandane-Rathnayake, Rangi; Johns, David P; Lowe, Adrian J; Burgess, John A; Thompson, Bruce R; Thomas, Paul S; Wood-Baker, Richard; Morrison, Stephen; Giles, Graham G; Marks, Guy; Markos, James; Tang, Mimi L K; Abramson, Michael J; Walters, E Haydn; Matheson, Melanie C; Dharmage, Shyamali C

    2017-05-08

    Systemic inflammation is an integral part of chronic obstructive pulmonary disease (COPD), and air pollution is associated with cardiorespiratory mortality, yet the interrelationships are not fully defined. We examined associations between nitrogen dioxide (NO₂) exposure (as a marker of traffic-related air pollution) and pro-inflammatory cytokines, and investigated effect modification and mediation by post-bronchodilator airflow obstruction (post-BD-AO) and cardiovascular risk. Data from middle-aged participants in the Tasmanian Longitudinal Health Study (TAHS, n = 1389) were analyzed by multivariable logistic regression, using serum interleukin (IL)-6, IL-8 and tumor necrosis factor-α (TNF-α) as the outcome. Mean annual NO₂ exposure was estimated at residential addresses using a validated satellite-based land-use regression model. Post-BD-AO was defined by post-BD forced expiratory ratio (FEV₁/FVC) < lower limit of normal, and cardiovascular risk by a history of either cerebrovascular or ischaemic heart disease. We found a positive association with increasing serum IL-6 concentration (geometric mean 1.20 (95% CI: 1.1 to 1.3, p = 0.001) per quartile increase in NO₂). This was predominantly a direct relationship, with little evidence for either effect modification or mediation via post-BD-AO, or for the small subgroup who reported cardiovascular events. However, there was some evidence consistent with serum IL-6 being on the causal pathway between NO₂ and cardiovascular risk. These findings raise the possibility that the interplay between air pollution and systemic inflammation may differ between post-BD airflow obstruction and cardiovascular diseases.

  18. Leisure-time physical activity and endometrial cancer risk: dose-response meta-analysis of epidemiological studies.

    Science.gov (United States)

    Keum, NaNa; Ju, Woong; Lee, Dong Hoon; Ding, Eric L; Hsieh, Chung C; Goodman, Julie E; Giovannucci, Edward L

    2014-08-01

    Although considerable evidence suggests that leisure-time physical activity is associated with a reduced risk of endometrial cancer (EC), the shape of dose-response relationship has not been investigated and previous meta-analyses have not accounted for differences in measures of physical activity. To address such issues, we conducted linear and nonlinear dose-response meta-analyses by metabolic equivalent of task (MET)-hour/week and hour/week, respectively, based on observational studies published up to September 2013 identified from PubMed and Embase databases. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. In the linear dose-response analysis, an increase in leisure-time physical activity by 3 MET-hour/week was associated with an ∼2% reduced risk of EC (summary RR = 0.98, p = 0.02, 95% CI = 0.95-1.00, I(2)  = 53%, p(heterogeneity)  = 0.06, three case-control studies and three cohort studies, 3,460 cases, range of activity = 0-50 MET-hour/week) and an increase by an hour/week was associated with an ∼5% reduced risk of EC (summary RR = 0.95, p response meta-analysis suggested that the curve may plateau at 10 MET-hour/week (p(change) in slope  = 0.04) but this statistical significance was sensitive to one study. No evidence of a nonlinear association was indicated by hour/week (p(change) in slope  > 0.69). In conclusion, an increase in leisure-time physical activity may continue to decrease EC risk, within the range of 0-50 MET-hour/week or 0-15 hour/week. Future studies should evaluate possible independent role of intensity of physical activity and effect modification by obesity. © 2013 UICC.

  19. Establishing a dose-response relationship between acute resistance-exercise and the immune system: Protocol for a systematic review.

    Science.gov (United States)

    Szlezak, Adam Michael; Szlezak, Siri Lauluten; Keane, James; Tajouri, Lotti; Minahan, Clare

    2016-12-01

    Exercise immunology research has traditionally focussed on aerobic-exercise, however it has become apparent in more recent years that resistance-exercise can also considerably affect host immunobiology. To date however, no systematic process has been used to establish a dose-response relationship between resistance-exercise and the immune system. The present systematic review was thus conducted to determine the dose-response effects of a bout of resistance-exercise on acute leukocyte counts. In accordance with the PRISMA guidelines, a systematic literature search was conducted in the electronic databases, PubMed, Web of Science, and Google Scholar, over the date range of 1989-2016. Following the PICO elements, eligibility criteria included: i) participants: healthy humans aged 18-40; ii) intervention: a single bout of resistance-exercise; iii) comparator: at least one comparator group; iv) outcome: acute measures of circulating leukocyte counts. Specific exclusion criteria were also applied. Risk of bias and quality of evidence was assessed using the PEDro scale. Due to the individual designs of the admitted studies, a qualitative analysis (systematic narrative synthesis) was employed in the present review. The results of the present review demonstrate that a single bout of resistance-exercise induces an acute monocytosis, neutrophilia, and lymphocytosis. It became apparent that the reviewed literature either does not consistently specify, or does not describe with sufficient detail, the time-course between the onset of exercise and the collection of blood. We recommend that researchers consider addressing this in future studies, and also collect blood measures during exercise to aid with comparison of temporal effects. Regarding the determination of a dose-response relationship, an acute neutrophilia, monocytosis and lymphocytosis appears to occur more rapidly and to a greater magnitude following a single bout of high-dose vs low-dose resistance

  20. Extent of exposure to environmental tobacco smoke (ETS and its dose-response relation to respiratory health among adults

    Directory of Open Access Journals (Sweden)

    Ward Kenneth D

    2005-02-01

    Full Text Available Abstract Background There is a dearth of standardized studies examining exposure to environmental tobacco smoke (ETS and its relationship to respiratory health among adults in developing countries. Methods In 2004, the Syrian Center for Tobacco Studies (SCTS conducted a population-based survey using stratified cluster sampling to look at issues related to environmental health of adults aged 18–65 years in Aleppo (2,500,000 inhabitants. Exposure to ETS was assessed from multiple self-reported indices combined into a composite score (maximum 22, while outcomes included both self-report (symptoms/diagnosis of asthma, bronchitis, and hay fever, and objective indices (spirometric assessment of FEV1 and FVC. Logistic and linear regression analyses were conducted to study the relation between ETS score and studied outcomes, whereby categorical (tertiles and continuous scores were used respectively, to evaluate the association between ETS exposure and respiratory health, and explore the dose-response relationship of the association. Results Of 2038 participants, 1118 were current non-smokers with breath CO levels ≤ 10 ppm (27.1% men, mean age 34.7 years and were included in the current analysis. The vast majority of study participants were exposed to ETS, whereby only 3.6% had ETS score levels ≤ 2. In general, there was a significant dose-response pattern in the relationship of ETS score with symptoms of asthma, hay fever, and bronchitis, but not with diagnoses of these outcomes. The magnitude of the effect was in the range of twofold increases in the frequency of symptoms reported in the high exposure group compared to the low exposure group. Severity of specific respiratory problems, as indicated by frequency of symptoms and health care utilization for respiratory problems, was not associated with ETS exposure. Exposure to ETS was associated with impaired lung function, indicative of airflow limitation, among women only. Conclusions This study

  1. Food Groups and Risk of Hypertension: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies.

    Science.gov (United States)

    Schwingshackl, Lukas; Schwedhelm, Carolina; Hoffmann, Georg; Knüppel, Sven; Iqbal, Khalid; Andriolo, Violetta; Bechthold, Angela; Schlesinger, Sabrina; Boeing, Heiner

    2017-11-01

    The aim of this systematic review and meta-analysis was to summarize the evidence on the relation of the intakes of 12 major food groups, including whole grains, refined grains, vegetables, fruits, nuts, legumes, eggs, dairy, fish, red meat, processed meat, and sugar-sweetened beverages (SSBs) with the risk of hypertension. PubMed, Scopus, and Web of Science were searched systematically until June 2017 for prospective studies having quantitatively investigated the above-mentioned foods. We conducted meta-analysis on the highest compared with the lowest intake categories and linear and nonlinear dose-response meta-analyses to analyze the association. Summary RRs and 95% CIs were estimated by using a random-effects model. Overall, 28 reports were included in the meta-analysis. An inverse association for the risk of hypertension was observed for 30 g whole grains/d (RR: 0.92; 95% CI: 0.87, 0.98), 100 g fruits/d (RR: 0.97; 95% CI: 0.96, 0.99), 28 g nuts/d (RR: 0.70; 95% CI: 0.45, 1.08), and 200 g dairy/d (RR: 0.95; 95% CI: 0.94, 0.97), whereas a positive association for 100 g red meat/d (RR: 1.14; 95% CI: 1.02, 1.28), 50 g processed meat/d (RR: 1.12; 95% CI: 1.00, 1.26), and 250 mL SSB/d (RR: 1.07; 95% CI: 1.04, 1.10) was seen in the linear dose-response meta-analysis. Indication for nonlinear relations of the intakes of whole grains, fruits, fish, and processed meats with the risk of hypertension was detected. In summary, this comprehensive dose-response meta-analysis of 28 reports identified optimal intakes of whole grains, fruits, nuts, legumes, dairy, red and processed meats, and SSBs related to the risk of hypertension. These findings need to be seen under the light of very-low to low quality of meta-evidence. However, the findings support the current dietary guidelines in the prevention of hypertension. © 2017 American Society for Nutrition.

  2. Alcohol consumption as a preventive factor for developing rheumatoid arthritis: a dose-response meta-analysis of prospective studies.

    Science.gov (United States)

    Jin, Zhichao; Xiang, Chun; Cai, Qing; Wei, Xin; He, Jia

    2014-11-01

    To summarise the evidence regarding the dose-response association between alcohol consumption and risk of rheumatoid arthritis (RA). Studies were identified from search of MEDLINE, Embase and Web of Science databases between 1 January 1946 and 10 April 2013, and from review of the conference abstracts and the reference lists of retrieved articles. Prospective studies that reported relative risks (RRs) with 95% CIs for the association between alcohol consumption and the risk of RA were included. Results from individual studies were pooled using a dose-response meta-analysis. Up to 10 April 2013, 8 prospective studies contained 195 029 participants and 1878 RA cases were included. The results indicated that low to moderate alcohol consumption yielded a preventive effect on RA development (RR: 0.86; 95% CI 0.78 to 0.94), and provided some evidence of a non-linear relationship between alcohol consumption and risk of RA. Dose-response meta-analysis of the study data revealed that compared with that for no alcohol consumption, the adjusted RR was 0.93 (95% CI 0.88 to 0.98) for 3 g/day of alcohol consumption, 0.86 (95% CI 0.76 to 0.97) for 9 g/day, 0.88 (95% CI 0.78 to 0.99) for 12 g/day, 0.91 (95% CI 0.81 to 1.03) for 15 g/day, and 1.28 (95% CI 0.94 to 1.73) for 30 g/day. Subgroup analysis indicated that women who had low to moderate alcohol consumption had a 19% reduction in RA risk. Regardless of sex, a consistent low to moderate alcohol consumption for a period of at least 10 years was found to have a 17% reduction in RA risk. Low to moderate alcohol consumption inversely associated with the development of RA in a manner that appears to be dose-dependent, time-dependent and sex-dependent. Large prospective studies that investigate gene-environment interactions are required to further clarify the aetiology of RA. 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.

  3. Non-linear dose-response of aluminium hydroxide adjuvant particles: Selective low dose neurotoxicity.

    Science.gov (United States)

    Crépeaux, Guillemette; Eidi, Housam; David, Marie-Odile; Baba-Amer, Yasmine; Tzavara, Eleni; Giros, Bruno; Authier, François-Jérôme; Exley, Christopher; Shaw, Christopher A; Cadusseau, Josette; Gherardi, Romain K

    2017-01-15

    , but not to the highest doses, exclusively contained small agglomerates in the bacteria-size range known to favour capture and, presumably, transportation by monocyte-lineage cells. In any event, the view that Alhydrogel(®) neurotoxicity obeys "the dose makes the poison" rule of classical chemical toxicity appears overly simplistic. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Development, analysis, and evaluation of a commercial software framework for the study of Extremely Low Probability of Rupture (xLPR) events at nuclear power plants.

    Energy Technology Data Exchange (ETDEWEB)

    Kalinich, Donald A.; Helton, Jon Craig; Sallaberry, Cedric M.; Mattie, Patrick D.

    2010-12-01

    Sandia National Laboratories (SNL) participated in a Pilot Study to examine the process and requirements to create a software system to assess the extremely low probability of pipe rupture (xLPR) in nuclear power plants. This project was tasked to develop a prototype xLPR model leveraging existing fracture mechanics models and codes coupled with a commercial software framework to determine the framework, model, and architecture requirements appropriate for building a modular-based code. The xLPR pilot study was conducted to demonstrate the feasibility of the proposed developmental process and framework for a probabilistic code to address degradation mechanisms in piping system safety assessments. The pilot study includes a demonstration problem to assess the probability of rupture of DM pressurizer surge nozzle welds degraded by primary water stress-corrosion cracking (PWSCC). The pilot study was designed to define and develop the framework and model; then construct a prototype software system based on the proposed model. The second phase of the project will be a longer term program and code development effort focusing on the generic, primary piping integrity issues (xLPR code). The results and recommendations presented in this report will be used to help the U.S. Nuclear Regulatory Commission (NRC) define the requirements for the longer term program.

  5. Hydrometeorological multi-model ensemble simulations of the 4 November 2011 flash flood event in Genoa, Italy, in the framework of the DRIHM Project

    NARCIS (Netherlands)

    Hally, A.; Caumont, O.; Garrote, L.; Richard, E.; Weerts, A.H.; Delogu, F.; Fiori, E.; Rebora, N.; Parodi, A.; Mihalovic, A.; Ivkovic, M.; Dekic, L.; Verseveld, W.J.; Nuissier, O.; Ducrocq, V.P.; Agostino, d' D.; Galizia, A.; Danovaro, E.; Clematis, A.

    2015-01-01

    The e-Science environment developed in the framework of the EU-funded DRIHM project was used to demonstrate its ability to provide relevant, meaningful hydrometeorological forecasts. This was illustrated for the tragic case of 4 November 2011, when Genoa, Italy, was flooded as the result of heavy,

  6. Harnessing the theoretical foundations of the exponential and beta-Poisson dose-response models to quantify parameter uncertainty using Markov Chain Monte Carlo.

    Science.gov (United States)

    Schmidt, Philip J; Pintar, Katarina D M; Fazil, Aamir M; Topp, Edward

    2013-09-01

    Dose-response models are the essential link between exposure assessment and computed risk values in quantitative microbial risk assessment, yet the uncertainty that is inherent to computed risks because the dose-response model parameters are estimated using limited epidemiological data is rarely quantified. Second-order risk characterization approaches incorporating uncertainty in dose-response model parameters can provide more complete information to decisionmakers by separating variability and uncertainty to quantify the uncertainty in computed risks. Therefore, the objective of this work is to develop procedures to sample from posterior distributions describing uncertainty in the parameters of exponential and beta-Poisson dose-response models using Bayes's theorem and Markov Chain Monte Carlo (in OpenBUGS). The theoretical origins of the beta-Poisson dose-response model are used to identify a decomposed version of the model that enables Bayesian analysis without the need to evaluate Kummer confluent hypergeometric functions. Herein, it is also established that the beta distribution in the beta-Poisson dose-response model cannot address variation among individual pathogens, criteria to validate use of the conventional approximation to the beta-Poisson model are proposed, and simple algorithms to evaluate actual beta-Poisson probabilities of infection are investigated. The developed MCMC procedures are applied to analysis of a case study data set, and it is demonstrated that an important region of the posterior distribution of the beta-Poisson dose-response model parameters is attributable to the absence of low-dose data. This region includes beta-Poisson models for which the conventional approximation is especially invalid and in which many beta distributions have an extreme shape with questionable plausibility. © Her Majesty the Queen in Right of Canada 2013. Reproduced with the permission of the Minister of the Public Health Agency of Canada.

  7. Evaluation of the Comet Assay for Assessing the Dose-Response Relationship of DNA Damage Induced by Ionizing Radiation

    Science.gov (United States)

    Wang, Yan; Xu, Chang; Du, Li Qing; Cao, Jia; Liu, Jian Xiang; Su, Xu; Zhao, Hui; Fan, Fei-Yue; Wang, Bing; Katsube, Takanori; Fan, Sai Jun; Liu, Qiang

    2013-01-01

    Dose- and time-response curves were combined to assess the potential of the comet assay in radiation biodosimetry. The neutral comet assay was used to detect DNA double-strand breaks in lymphocytes caused by γ-ray irradiation. A clear dose-response relationship with DNA double-strand breaks using the comet assay was found at different times after irradiation (p < 0.001). A time-response relationship was also found within 72 h after irradiation (p < 0.001). The curves for DNA double-strand breaks and DNA repair in vitro of human lymphocytes presented a nice model, and a smooth, three-dimensional plane model was obtained when the two curves were combined. PMID:24240807

  8. Accumulative dose response of CdZnTe detectors to 14.1 MeV neutrons

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Xiang, E-mail: chenxiang@nint.ac.cn; Han, He-tong; Li, Gang; Lu, Yi

    2017-03-01

    The accumulative dose response of CdZnTe (CZT) detectors to 14.1 MeV neutrons is discussed experimentally in this paper. The Cockcroft–Walton Accelerator is used to obtain a steady neutron beam of 14.1 MeV neutrons. A pulsed X-ray source is used to test the response parameters of the neutron-exposed CZT detectors under the pulse mode. The irradiation time (hours) is shorter relative to the time scales (years) where annealing effects occur. Time and linearity response is analyzed to evaluate the maximum dose rate of the CZT detectors and the pulse shape. The result shows that the experimental CZT detectors maintain stable response behaviors, while the maximum dose rate and the total accumulative dose are less than 10{sup 6} neutrons/(cm{sup 2}·s) and 10{sup 10} neutrons/cm{sup 2}, respectively.

  9. Implementation of the New Approach for the Dose-Response Functions Development for the Case of Athens and Greece

    Science.gov (United States)

    Christodoulakis, J.; Tzanis, C. G.; Varotsos, C. A.; Kouremadas, G.

    2016-08-01

    Dose-response functions (DRFs) are functions used for estimating corrosion and/or soiling levels of materials used in constructions and cultural monuments. In order to achieve this, DRFs lean on ground-based measurements of specific air pollution and climatic parameters like nitrogen oxides, ozone, temperature and others. In DRAGON 3 2015 Symposium we presented a new approach which proposed a technique for using satellite-based data for the necessary parameters instead of ground-based expanding in this way: a) the usage of DRFs in cases/areas where there is no availability of in situ measurements, b) the applicability of satellite-based data. In this work we present mapping results of deterioration levels (corrosion and soiling) for the case of Athens, Greece but also for the whole Greece country.

  10. Phase II dose-response trials: A simulation study to compare analysis method performance under design considerations.

    Science.gov (United States)

    Rekowski, Jan; Köllmann, Claudia; Bornkamp, Björn; Ickstadt, Katja; Scherag, André

    2017-02-21

    Phase II trials are intended to provide information about the dose-response relationship and to support the choice of doses for a pivotal phase III trial. Recently, new analysis methods have been proposed to address these objectives, and guidance is needed to select the most appropriate analysis method in specific situations. We set up a simulation study to evaluate multiple performance measures of one traditional and three more recent dose-finding approaches under four design options and illustrate the investigated analysis methods with an example from clinical practice. Our results reveal no general recommendation for a particular analysis method across all design options and performance measures. However, we also demonstrate that the new analysis methods are worth the effort compared to the traditional ANOVA-based approach.

  11. Psychophysical and Vasomotor Responses of the Oral Tissues: A Nicotine Dose-Response and Menthol Interaction Study.

    Science.gov (United States)

    Arendt Nielsen, Thomas; Nielsen, Bruno Provstgaard; Wang, Kelun; Arendt-Nielsen, Lars; Boudreau, Shellie A

    2016-05-01

    This study implemented an intra-oral test-platform to assess the sensory, psychophysical, and vasomotor responses to nicotine and menthol, alone or in combination. Two double-blinded, placebo-controlled, randomized, cross-over studies, including healthy nonsmoking participants were performed. Study I: A dose-response relationship (N = 20) between 0, 2, and 4 mg nicotine gum. Study II: An interaction response (N = 22) to 30 mg menthol and 4 mg nicotine alone or in combination. Heart rate, blood pressure, tactile and thermosensory thresholds, intra-oral blood flow and temperature, pain/irritation intensities/locations, McGill Pain Questionnaire, and taste experience were assessed before, during or after the completion of a standardized chewing regime. A dose-response elevation in heart rate was attenuated when nicotine was combined with menthol. Blood flow, temperature, and warm-detection thresholds, as assessed on the tongue, similarly increased for all gums. Pain intensity and taste experiences were similar between nicotine doses. Nicotine attenuated the sweet, cooling, and freshening sensation of menthol. Within the first 4 minutes, menthol reduced the intensity but not the area of nicotine-induced pain and irritation. The 4-mg nicotine dose led to a continued increase in the intensity and area of irritation in the throat post-chewing. Moreover, one-half of participants responded to menthol as an irritant, and these individuals demonstrated larger areas of nicotine-induced irritation in the throat post-chewing. The intra-oral test platform provides a basis to optimize the assessment of nicotine-related taste and sensory experiences and can be used in future studies for profiling nicotine gum. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Dose response of micronuclei induced by combination radiation of α-particles and γ-rays in human lymphoblast cells

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Ruiping; He, Mingyuan; Dong, Chen; Xie, Yuexia; Ye, Shuang; Yuan, Dexiao [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China); Shao, Chunlin, E-mail: clshao@shmu.edu.cn [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China)

    2013-01-15

    Highlights: ► α-Particle induced MN had a biphasic dose–response followed by a bystander model. ► MN dose–response of α- and γ-combination IR was similar to that of α-particle. ► α-Particles followed by γ-rays yielded a synergistic effect on MN induction. ► Low dose γ-rays triggered antagonistic and adaptive responses against α-particle. - Abstract: Combination radiation is a real situation of both nuclear accident exposure and space radiation environment, but its biological dosimetry is still not established. This study investigated the dose–response of micronuclei (MN) induction in lymphocyte by irradiating HMy2.CIR lymphoblast cells with α-particles, γ-rays, and their combinations. Results showed that the dose–response of MN induced by γ-rays was well-fitted with the linear-quadratic model. But for α-particle irradiation, the MN induction had a biphasic phenomenon containing a low dose hypersensitivity characteristic and its dose response could be well-stimulated with a state vector model where radiation-induced bystander effect (RIBE) was involved. For the combination exposure, the dose response of MN was similar to that of α-irradiation. However, the yield of MN was closely related to the sequence of irradiations. When the cells were irradiated with α-particles at first and then γ-rays, a synergistic effect of MN induction was observed. But when the cells were irradiated with γ-rays followed by α-particles, an antagonistic effect of MN was observed in the low dose range although this combination radiation also yielded a synergistic effect at high doses. When the interval between two irradiations was extended to 4 h, a cross-adaptive response against the other irradiation was induced by a low dose of γ-rays but not α-particles.

  13. Dairy products consumption and risk of type 2 diabetes: systematic review and dose-response meta-analysis.

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    Dengfeng Gao

    Full Text Available BACKGROUND: The consumption of dairy products may influence the risk of type 2 diabetes mellitus (T2DM, but inconsistent findings have been reported. Moreover, large variation in the types of dairy intake has not yet been fully explored. METHODS AND RESULTS: We conducted a systematic review and meta-analysis to clarify the dose-response association of dairy products intake and T2DM risk. We searched PubMed, EMBASE and Scopus for studies of dairy products intake and T2DM risk published up to the end of October 2012. Random-effects models were used to estimate summary relative risk (RR statistics. Dose-response relations were evaluated using data from different dairy products in each study. We included 14 articles of cohort studies that reported RR estimates and 95% confidence intervals (95% CIs of T2DM with dairy products intake. We found an inverse linear association of consumption of total dairy products (13 studies, low-fat dairy products (8 studies, cheese (7 studies and yogurt (7 studies and risk of T2DM. The pooled RRs were 0.94 (95% CI 0.91-0.97 and 0.88 (0.84-0.93 for 200 g/day total and low-fat dairy consumption, respectively. The pooled RRs were 0.80 (0.69-0.93 and 0.91 (0.82-1.00 for 30 g/d cheese and 50 g/d yogurt consumption, respectively. We also found a nonlinear association of total and low-fat dairy intake and T2DM risk, and the inverse association appeared to be strongest within 200 g/d intake. CONCLUSION: A modest increase in daily intake of dairy products such as low fat dairy, cheese and yogurt may contribute to the prevention of T2DM, which needs confirmation in randomized controlled trials.

  14. The effect of recent vaccination on the dose-response to experimental Dermatophilus congolensis infection in rabbits.

    Science.gov (United States)

    How, S J; Lloyd, D H

    1990-02-01

    Dermatophilus congolensis infection of rabbits was used to investigate the effects of active immunity on epidermal challenge following vaccination. Rabbits (three groups of four) were vaccinated intradermally with live whole-cell preparations of D. congolensis strains SS18C and FD11 (groups SSVAC and FDVAC respectively); a third group (UNVAC) remained as unvaccinated controls. Two weeks after vaccination, separate 1.5-cm2 clipped and ether-swabbed skin sites were inoculated with a 10-fold dilution range (10(7) to 10(1) zoospores per cm2 of skin) of SS18C or FD11. Lesion scores at each site were calculated from the sum of individual scores (0 to 4+) for erythema, oedema and scab formation multiplied by the percentage of the inoculated area affected. A clear dose-response relationship between the size of inoculum and the severity of lesions was seen for both D. congolensis stains in the control group (UNVAC). In the SSVAC and FDVAC groups the lesions were less severe and developed more quickly. The number of zoospores required to cause infection in the vaccinated animals was up to 10,000-fold higher for homologous inoculated sites and 100-fold for heterologous sites. Serological analysis was carried out with an ELISA system. Vaccination and challenge resulted in increases in specific antibody against D. congolensis antigens. Cross-reacting antibody to the heterologous strain of D. congolensis used was demonstrated in both vaccinated groups but did not correlate with equal protection to homologous or heterologous challenge. The dose-response relationship demonstrated by this model enabled semi-quantitative analysis of the effects of vaccination on D. congolensis infective dose and severity of infection.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Dairy products consumption and risk of type 2 diabetes: systematic review and dose-response meta-analysis.

    Science.gov (United States)

    Gao, Dengfeng; Ning, Ning; Wang, Congxia; Wang, Yuhuan; Li, Qing; Meng, Zhe; Liu, Yang; Li, Qiang

    2013-01-01

    The consumption of dairy products may influence the risk of type 2 diabetes mellitus (T2DM), but inconsistent findings have been reported. Moreover, large variation in the types of dairy intake has not yet been fully explored. We conducted a systematic review and meta-analysis to clarify the dose-response association of dairy products intake and T2DM risk. We searched PubMed, EMBASE and Scopus for studies of dairy products intake and T2DM risk published up to the end of October 2012. Random-effects models were used to estimate summary relative risk (RR) statistics. Dose-response relations were evaluated using data from different dairy products in each study. We included 14 articles of cohort studies that reported RR estimates and 95% confidence intervals (95% CIs) of T2DM with dairy products intake. We found an inverse linear association of consumption of total dairy products (13 studies), low-fat dairy products (8 studies), cheese (7 studies) and yogurt (7 studies) and risk of T2DM. The pooled RRs were 0.94 (95% CI 0.91-0.97) and 0.88 (0.84-0.93) for 200 g/day total and low-fat dairy consumption, respectively. The pooled RRs were 0.80 (0.69-0.93) and 0.91 (0.82-1.00) for 30 g/d cheese and 50 g/d yogurt consumption, respectively. We also found a nonlinear association of total and low-fat dairy intake and T2DM risk, and the inverse association appeared to be strongest within 200 g/d intake. A modest increase in daily intake of dairy products such as low fat dairy, cheese and yogurt may contribute to the prevention of T2DM, which needs confirmation in randomized controlled trials.

  16. Dose-response meta-analysis on coffee, tea and caffeine consumption with risk of Parkinson's disease.

    Science.gov (United States)

    Qi, Hui; Li, Shixue

    2014-04-01

    A dose-response meta-analysis was carried out between Parkinson's disease (PD) risk, and coffee, tea and caffeine consumption. A comprehensive search was carried out to identify eligible studies. The fixed or random effect model was used based on heterogeneity test. The dose-response relationship was assessed by restricted cubic spline. A total of 13 articles involving 901 764 participants for coffee, eight articles involving 344 895 participants for tea and seven articles involving 492 724 participants for caffeine were included. A non-linear relationship was found between coffee consumption and PD risk overall, and the strength of protection reached the maximum at approximately 3 cups/day (smoking-adjusted relative risk: 0.72, 95% confidence interval 0.65-0.81). A linear relationship was found between tea and caffeine consumption, and PD risk overall, and the smoking-adjusted risk of PD decreased by 26% and 17% for every two cups/day and 200 mg/day increments, respectively. The association of coffee and tea consumption with PD risk was stronger for men than that for women, and the association of caffeine consumption with PD risk was stronger for ever users of hormones than that for never users of hormones among postmenopausal women. The aforementioned associations were weaker for USA relative to Europe or Asia. A linear dose-relationship for decreased PD risk with tea and caffeine consumption was found, whereas the strength of protection reached a maximum at approximately 3 cups/day for coffee consumption overall. Further studies are required to confirm the findings. © 2013 Japan Geriatrics Society.

  17. Association between dietary vitamin C intake and risk of esophageal cancer: A dose-response meta-analysis.

    Science.gov (United States)

    Bo, Yacong; Lu, Yan; Zhao, Yan; Zhao, Erjiang; Yuan, Ling; Lu, Weiquan; Cui, Lingling; Lu, Quanjun

    2016-04-15

    While several epidemiological studies have investigated the association between vitamin C and risk of esophageal cancer, the results remain inconsistent. In the present study, a meta-analysis was conducted to assess the impact of dietary vitamin C intake on esophageal cancer risk. Online databases were searched up to March 29, 2015, for studies on the association between dietary vitamin C intake and esophageal cancer risk. Pooled risk ratios (RRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Dose-response analyses were performed using the method of restricted cubic splines with four knots at percentiles of 5, 35, 65 and 95% of the distribution. Publication bias was estimated using Egger's tests and funnel plots. In all, 15 articles were included in this meta-analysis, including 20 studies, containing 7063 controls and 3955 cases of esophageal cancer. By comparing the highest vs. the lowest categories of vitamin C intake, we found that vitamin C was inversely associated with the risk of esophageal cancer [overall OR = 0.58, 95% CI = 0.49-0.68, I(2) = 56%]. A linear dose-response relationship was found. With an increase in dietary vitamin C intake of 50 mg/day, the risk of esophageal cancer statistically decreased by 13% (OR = 0.87, 95% CI = 0.80-0.93, p(linearity) = 0.0002). In conclusion, our analysis suggested that the higher intake of dietary vitamin C might have a protective effect against esophageal cancer. © 2015 UICC.

  18. Determining the behavioural dose-response relationship of marine mammals to air gun noise and source proximity.

    Science.gov (United States)

    Dunlop, Rebecca A; Noad, Michael J; McCauley, Robert D; Scott-Hayward, Lindsay; Kniest, Eric; Slade, Robert; Paton, David; Cato, Douglas H

    2017-08-15

    The effect of various anthropogenic sources of noise (e.g. sonar, seismic surveys) on the behaviour of marine mammals is sometimes quantified as a dose-response relationship, where the probability of an animal behaviourally 'responding' (e.g. avoiding the source) increases with 'dose' (or received level of noise). To do this, however, requires a definition of a 'significant' response (avoidance), which can be difficult to quantify. There is also the potential that the animal 'avoids' not only the source of noise but also the vessel operating the source, complicating the relationship. The proximity of the source is an important variable to consider in the response, yet difficult to account for given that received level and proximity are highly correlated. This study used the behavioural response of humpback whales to noise from two different air gun arrays (20 and 140 cubic inch air gun array) to determine whether a dose-response relationship existed. To do this, a measure of avoidance of the source was developed, and the magnitude (rather than probability) of this response was tested against dose. The proximity to the source, and the vessel itself, was included within the one-analysis model. Humpback whales were more likely to avoid the air gun arrays (but not the controls) within 3 km of the source at levels over 140 re. 1 µPa 2  s -1 , meaning that both the proximity and the received level were important factors and the relationship between dose (received level) and response is not a simple one. © 2017. Published by The Company of Biologists Ltd.

  19. Soy food intake and risk of gastric cancer: A dose-response meta-analysis of prospective studies.

    Science.gov (United States)

    Weng, Ke-Gui; Yuan, Ya-Ling

    2017-08-01

    Epidemiological studies were inconsistent on the association between soy food intake and risk of gastric cancer (GC). This study aimed to determine the role of soy food intake in the development of GC.A systematic search was conducted in PubMed and Web of Science to identify all relevant studies. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were pooled using a random-effects model, and the dose-response relationship between soy food intake and GC risk was also assessed.Thirteen prospective studies were identified with a total of 517,106 participants and 5800 cases. Among 11 types of soy food, high intake of total soy food (the highest vs the lowest category: RR: 0.78, 95% CI: 0.62-0.98) and nonfermented soy food (RR: 0.63, 95% CI: 0.50-0.79) were inversely associated with GC risk, while high intake of miso soup was associated with the risk in male (RR: 1.17, 95% CI: 1.02-1.36). In dose-response meta-analysis, total soy food intake (0-150 g/day) showed no significant association with GC risk, while high intake of nonfermented soy food was inversely related, especially an intake of more than 100 g/day. In male, miso soup intake (1-5 cups/day) was significantly associated with GC risk.High intake of nonfermented soy food might reduce the risk of GC, while miso soup intake might increase the risk in male.

  20. Dose-Response Relationships of Resistance Training in Healthy Old Adults: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Borde, Ron; Hortobágyi, Tibor; Granacher, Urs

    2015-12-01

    Resistance training (RT) is an intervention frequently used to improve muscle strength and morphology in old age. However, evidence-based, dose-response relationships regarding specific RT variables (e.g., training period, frequency, intensity, volume) are unclear in healthy old adults. The aims of this systematic review and meta-analysis were to determine the general effects of RT on measures of muscle strength and morphology and to provide dose-response relationships of RT variables through an analysis of randomized controlled trials (RCTs) that could improve muscle strength and morphology in healthy old adults. A computerized, systematic literature search was performed in the electronic databases PubMed, Web of Science, and The Cochrane Library from January 1984 up to June 2015 to identify all RCTs related to RT in healthy old adults. The initial search identified 506 studies, with a final yield of 25 studies. Only RCTs that examined the effects of RT in adults with a mean age of 65 and older were included. The 25 studies quantified at least one measure of muscle strength or morphology and sufficiently described training variables (e.g., training period, frequency, volume, intensity). We quantified the overall effects of RT on measures of muscle strength and morphology by computing weighted between-subject standardized mean differences (SMDbs) between intervention and control groups. We analyzed the data for the main outcomes of one-repetition maximum (1RM), maximum voluntary contraction under isometric conditions (MVC), and muscle morphology (i.e., cross-sectional area or volume or thickness of muscles) and assessed the methodological study quality by Physiotherapy Evidence Database (PEDro) scale. Heterogeneity between studies was assessed using I2 and χ2 statistics. A random effects meta-regression was calculated to explain the influence of key training variables on the effectiveness of RT in terms of muscle strength and morphology. For meta

  1. Daytime Napping and the Risk of Cardiovascular Disease and All-Cause Mortality: A Prospective Study and Dose-Response Meta-Analysis.

    Science.gov (United States)

    Yamada, Tomohide; Hara, Kazuo; Shojima, Nobuhiro; Yamauchi, Toshimasa; Kadowaki, Takashi

    2015-12-01

    To summarize evidence about the association between daytime napping and the risk of cardiovascular disease and all-cause mortality, and to quantify the potential dose-response relation. Meta-analysis of prospective cohort studies. Electronic databases were searched for articles published up to December 2014 using the terms nap, cardiovascular disease, and all-cause mortality. We selected well-adjusted prospective cohort studies reporting risk estimates for cardiovascular disease and all-cause mortality related to napping. Eleven prospective cohort studies were identified with 151,588 participants (1,625,012 person-years) and a mean follow-up period of 11 years (60% women, 5,276 cardiovascular events, and 18,966 all-cause deaths). Pooled analysis showed that a long daytime nap (≥ 60 min/day) was associated with a higher risk of cardiovascular disease (rate ratio [RR]: 1.82 [1.22-2.71], P = 0.003, I(2) = 37%) compared with not napping. All-cause mortality was associated with napping for ≥ 60 min/day (RR: 1.27 [1.11-1.45], P napping. In contrast, napping for nap time and cardiovascular disease (P for nonlinearity = 0.01). The RR initially decreased from 0 to 30 min/day. Then it increased slightly until about 45 min/day, followed by a sharp increase at longer nap times. There was also a positive linear relation between nap time and all-cause mortality (P for non-linearity = 0.97). Nap time and cardiovascular disease may be associated via a J-curve relation. Further studies are needed to confirm the efficacy of a short nap. © 2015 Associated Professional Sleep Societies, LLC.

  2. Gender difference in efficacy and dose response in Japanese patients with nocturia treated with four different doses of desmopressin orally disintegrating tablet in a randomized, placebo-controlled trial.

    Science.gov (United States)

    Yamaguchi, Osamu; Nishizawa, Osamu; Juul, Kristian Vinter; Nørgaard, Jens Peter

    2013-03-01

    WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Desmopressin orally disintegrating tablet (ODT) 60-240 μg has proved an effective and well-tolerated antidiuretic treatment in male and female patients with nocturia. The main adverse event is hyponatraemia. Recent studies suggest that female patients are more sensitive to desmopressin ODT, achieving the same efficacy at lower doses than male patients. The study demonstrates the efficacy of desmopressin ODT in male and female Japanese patients with nocturia. It provides further evidence that the optimum desmopressin dose for the treatment of nocturia is lower in females than in males. Tailoring the dose according to gender provides an improved therapeutic window with the benefits of a decreased risk of hyponatraemia without compromising efficacy. To establish the dose-response efficacy of desmopressin in a Japanese patient population for the treatment of nocturia. To explore gender differences in sensitivity to desmopressin in Japanese patients with nocturia. A phase II multicentre, randomized, placebo-controlled, double-blind, parallel-group, comparative clinical trial was conducted. Subjects aged 55-75 years, with a mean of ≥2 voids per night, were included and randomized to receive placebo or one of four doses of desmopressin orally disintegrating tablet (ODT): 10 μg, 25 μg, 50 μg or 100 μg. The dose-response relationship of pharmacodynamic variables measured after a single dose of desmopressin administered to water-loaded subjects (treatment period 1) was compared with the primary clinical endpoint of change from baseline in mean number of nocturnal voids, after 28 days of desmopressin treatment (treatment period 2). A total of 116 patients were treated in treatment period 1 of whom 113 qualified for treatment period 2, and 111 completed the study. In treatment period 1 a dose-response relationship was observed, both overall and in each gender group. Overall, the duration of

  3. Dose-Response Relationship between Dietary Magnesium Intake and Risk of Type 2 Diabetes Mellitus: A Systematic Review and Meta-Regression Analysis of Prospective Cohort Studies.

    Science.gov (United States)

    Fang, Xin; Han, Hedong; Li, Mei; Liang, Chun; Fan, Zhongjie; Aaseth, Jan; He, Jia; Montgomery, Scott; Cao, Yang

    2016-11-19

    The epidemiological evidence for a dose-response relationship between magnesium intake and risk of type 2 diabetes mellitus (T2D) is sparse. The aim of the study was to summarize the evidence for the association of dietary magnesium intake with risk of T2D and evaluate the dose-response relationship. We conducted a systematic review and meta-analysis of prospective cohort studies that reported dietary magnesium intake and risk of incident T2D. We identified relevant studies by searching major scientific literature databases and grey literature resources from their inception to February 2016. We included cohort studies that provided risk ratios, i.e., relative risks (RRs), odds ratios (ORs) or hazard ratios (HRs), for T2D. Linear dose-response relationships were assessed using random-effects meta-regression. Potential nonlinear associations were evaluated using restricted cubic splines. A total of 25 studies met the eligibility criteria. These studies comprised 637,922 individuals including 26,828 with a T2D diagnosis. Compared with the lowest magnesium consumption group in the population, the risk of T2D was reduced by 17% across all the studies; 19% in women and 16% in men. A statistically significant linear dose-response relationship was found between incremental magnesium intake and T2D risk. After adjusting for age and body mass index, the risk of T2D incidence was reduced by 8%-13% for per 100 mg/day increment in dietary magnesium intake. There was no evidence to support a nonlinear dose-response relationship between dietary magnesium intake and T2D risk. The combined data supports a role for magnesium in reducing risk of T2D, with a statistically significant linear dose-response pattern within the reference dose range of dietary intake among Asian and US populations. The evidence from Europe and black people is limited and more prospective studies are needed for the two subgroups.

  4. Dose-response relationship between dietary magnesium intake and cardiovascular mortality: A systematic review and dose-based meta-regression analysis of prospective studies.

    Science.gov (United States)

    Fang, Xin; Liang, Chun; Li, Mei; Montgomery, Scott; Fall, Katja; Aaseth, Jan; Cao, Yang

    2016-12-01

    Although epidemiology studies have reported the relationship, including a dose-response relationship, between dietary magnesium intake and risk of cardiovascular disease (CVD), the risk for CVD mortality is inconclusive and the evidence for a dose-response relationship has not been summarized. We conducted a systematic review and meta-analysis of prospective studies to summarize the evidence regarding the association of dietary magnesium intake with risk of CVD mortality and describe their dose-response relationship. We identified relevant studies by searching major scientific literature databases and grey literature resources from their inception to August 2015, and reviewed references lists of retrieved articles. We included population-based studies that reported mortality risks, i.e. relative risks (RRs), odds ratios (ORs) or hazard ratios (HRs) of CVD mortality or cause-specific CVD death. Linear dose-response relationships were assessed using random-effects meta-regression. Potential nonlinear associations were evaluated using restricted cubic splines. Out of 3002 articles, 9 articles from 8 independent studies met the eligibility criteria. These studies comprised 449,748 individuals and 10,313 CVD deaths. Compared with the lowest dietary magnesium consumption group in the population, the risk of CVD mortality was reduced by 16% in women and 8% in men. No significant linear dose-response relationship was found between increment in dietary magnesium intake and CVD mortality across all the studies. After adjusting for age and BMI, the risk of CVD mortality was reduced by 24-25% per 100mg/d increment in dietary magnesium intake in women of all the participants and in all the US participants. Although the combined data confirm the role of dietary magnesium intake in reducing CVD mortality, the dose-response relationship was only found among women and in US population. Copyright © 2016 Elsevier GmbH. All rights reserved.

  5. The efficacy and safety of Tanacetum parthenium (feverfew) in migraine prophylaxis--a double-blind, multicentre, randomized placebo-controlled dose-response study.

    Science.gov (United States)

    Pfaffenrath, V; Diener, H C; Fischer, M; Friede, M; Henneicke-von Zepelin, H H

    2002-09-01

    placebo (-0.3 +/- 1.9; P = 0.02). Overall, 52 of 147 (35%) patients reported at least one adverse event (AE). The incidence of AEs in the active treatment groups was similar to that in the placebo group, and no dose-related effect was observed in any safety parameter. MIG-99 failed to show a significant migraine prophylactic effect in general. Accordingly, in the ITT analysis a dose-response relationship could not be observed. MIG-99 was shown to be effective only in a small predefined subgroup of patients with at least four attacks during the 28-day baseline period where the most favourable benefit-risk ratio was observed with a dosage of three capsules of 6.25 mg MIG-99 extract per day. Because of the low number of patients, these findings need to be verified in a larger sample. The incidence of AEs was similar for all treatment groups.

  6. SU-E-T-122: Dose Response Analysis of Radiochromic Films in Regions of Low Dose Using Separation Color Components.

    Science.gov (United States)

    Marini, G; Nicolucci, P

    2012-06-01

    To evaluate the dose response of EBT2 films in regions of low dose using the decomposition of the image's color channels (RGB, Red, Green and Blue). Doses ranging from 1 Gy to 60 Gy were used to calibrate the dose response of Gafchromic ® EBT2 films irradiated in 6MV photons beams. Segments of film with dimensions of 8.5 cm × 8.5 cm were used. Another segment of film with dimensions 8.5 cm × 20.25 cm was also irradiated with a maximum dose of 4Gy to determine the percentage depth dose (PDD). The films were digitized by a LaserJet M1132 MFP - HP ® scanner in standard resolution of 150dpi and analyzed by a routine created in MatLab to convert the image to gray levels as well as assess the desired color components from the image. The green component presented the higher sensitivity (17.8 a.u./Gy) when the separated color channels and the shades of gray analysis are compared. The red component presented the highest signal to noise ratio in the low dose range (63% at 1Gy). The blue component presented low sensitivity (0.66 a.u./Gy) in the entire dose range. A linear fitting (r=0.998) was used to the green and gray components until a dose of 4 Gy. The red component presented a non-linear behavior in the entire dose range. The useful dose range found was from 1 Gy to 15 Gy. The maximum differences between the reference PDD, measured with ionization chamber in a water phantom, and the PDDs determined with film were 6%, 9% and 14% for the green, gray and red components, respectively. This work results show that the use of radiochromic films on planning verification procedures in low dose ranges can be benefit from the analysis of the image's separated color components. © 2012 American Association of Physicists in Medicine.

  7. Egg consumption and risk of coronary heart disease and stroke: dose-response meta-analysis of prospective cohort studies.

    Science.gov (United States)

    Rong, Ying; Chen, Li; Zhu, Tingting; Song, Yadong; Yu, Miao; Shan, Zhilei; Sands, Amanda; Hu, Frank B; Liu, Liegang

    2013-01-07

    To investigate and quantify the potential dose-response association between egg consumption and risk of coronary heart disease and stroke. Dose-response meta-analysis of prospective cohort studies. PubMed and Embase prior to June 2012 and references of relevant original papers and review articles. Prospective cohort studies with relative risks and 95% confidence intervals of coronary heart disease or stroke for three or more categories of egg consumption. Eight articles with 17 reports (nine for coronary heart disease, eight for stroke) were eligible for inclusion in the meta-analysis (3,081,269 person years and 5847 incident cases for coronary heart disease, and 4,148,095 person years and 7579 incident cases for stroke). No evidence of a curve linear association was seen between egg consumption and risk of coronary heart disease or stroke (P=0.67 and P=0.27 for non-linearity, respectively). The summary relative risk of coronary heart disease for an increase of one egg consumed per day was 0.99 (95% confidence interval 0.85 to 1.15; P=0.88 for linear trend) without heterogeneity among studies (P=0.97, I(2)=0%). For stroke, the combined relative risk for an increase of one egg consumed per day was 0.91 (0.81 to 1.02; P=0.10 for linear trend) without heterogeneity among studies (P=0.46, I(2)=0%). In a subgroup analysis of diabetic populations, the relative risk of coronary heart disease comparing the highest with the lowest egg consumption was 1.54 (1.14 to 2.09; P=0.01). In addition, people with higher egg consumption had a 25% (0.57 to 0.99; P=0.04) lower risk of developing hemorrhagic stroke. Higher consumption of eggs (up to one egg per day) is not associated with increased risk of coronary heart disease or stroke. The increased risk of coronary heart disease among diabetic patients and reduced risk of hemorrhagic stroke associated with higher egg consumption in subgroup analyses warrant further studies.

  8. Fat intake and risk of ulcerative colitis: Systematic review and dose-response meta-analysis of epidemiological studies.

    Science.gov (United States)

    Wang, Fan; Lin, Xue; Zhao, Qiu; Li, Jin

    2017-01-01

    Fat intake is generally thought as a risk factor for onset of ulcerative colitis (UC), while epidemiological data had been controversial. This study aimed to evaluate the role of fat intake in the development of UC. Comprehensive search in PubMed and Embase was conducted to identify all relevant studies, and the role of fat intake in the development of UC was quantitatively assessed by dose-response meta-analysis. Nine studies (four case-control and five prospective cohort) were indentified with a total of 966 UC cases and 171 589 controls. No evidence of a nonlinear dose-response association was found between fat intake and UC risk. Overall, the summary relative risks (RR) for per 30 g increment/day were 1.023 (95%confidence interval [CI]: 0.963-1.087; I2  = 24%; n = 6) for total fat intake, 1.063 (95%CI: 0.845-1.337; I2  = 44.5%; n = 4) for saturated fat intake, 1.214 (95%CI: 0.911-1.618; I2  = 63.1%; n = 4) for monounsaturated fat (MUFA) intake, and 1.247 (95%CI: 0.948-1.640; I2  = 25.4%; n = 4) for polyunsaturated fat (PUFA) intake, respectively. Subgroup and sensitivity analyses showed inconsistent results on PUFA intake, which was significantly related with UC risk after adjusting for smoking (RR: 1.617, 95%CI: 1.045-2.502; I2  = 0%; n = 3). For PUFA and MUFA subtypes, no subtypes were significantly associated with UC risk (P > 0.05), and only docosahexaenoic acid showed a potential protective effect in the development of UC (RR for the highest versus lowest intake level: 0.642, 95%CI: 0.403-1.024; I2  = 34.4%; n = 3) CONCLUSIONS: This meta-analysis suggested a lack of association between fat intake and UC risk, and large-scale prospective designed studies are warranted to confirm our findings. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  9. Consumption of dairy foods and diabetes incidence: a dose-response meta-analysis of observational studies.

    Science.gov (United States)

    Gijsbers, Lieke; Ding, Eric L; Malik, Vasanti S; de Goede, Janette; Geleijnse, Johanna M; Soedamah-Muthu, Sabita S

    2016-04-01

    A growing number of cohort studies suggest a potential role of dairy consumption in type 2 diabetes (T2D) prevention. The strength of this association and the amount of dairy needed is not clear. We performed a meta-analysis to quantify the associations of incident T2D with dairy foods at different levels of intake. A systematic literature search of the PubMed, Scopus, and Embase databases (from inception to 14 April 2015) was supplemented by hand searches of reference lists and correspondence with authors of prior studies. Included were prospective cohort studies that examined the association between dairy and incident T2D in healthy adults. Data were extracted with the use of a predefined protocol, with double data-entry and study quality assessments. Random-effects meta-analyses with summarized dose-response data were performed for total, low-fat, and high-fat dairy, (types of) milk, (types of) fermented dairy, cream, ice cream, and sherbet. Nonlinear associations were investigated, with data modeled with the use of spline knots and visualized via spaghetti plots. The analysis included 22 cohort studies comprised of 579,832 individuals and 43,118 T2D cases. Total dairy was inversely associated with T2D risk (RR: 0.97 per 200-g/d increment; 95% CI: 0.95, 1.00;P= 0.04;I(2)= 66%), with a suggestive but similar linear inverse association noted for low-fat dairy (RR: 0.96 per 200 g/d; 95% CI: 0.92, 1.00;P= 0.072;I(2)= 68%). Nonlinear inverse associations were found for yogurt intake (at 80 g/d, RR: 0.86 compared with 0 g/d; 95% CI: 0.83, 0.90;Pbenefits were found at a higher intake. Other dairy types were not associated with T2D risk. This dose-response meta-analysis of observational studies suggests a possible role for dairy foods, particularly yogurt, in the prevention of T2D. Results should be considered in the context of the observed heterogeneity. © 2016 American Society for Nutrition.

  10. The dose response relation for rat spinal cord paralysis analyzed in terms of the effective size of the functional subunit

    Science.gov (United States)

    Adamus-Górka, Magdalena; Mavroidis, Panayiotis; Brahme, Anders; Lind, Bengt K.

    2008-11-01

    Radiobiological models for estimating normal tissue complication probability (NTCP) are increasingly used in order to quantify or optimize the clinical outcome of radiation therapy. A good NTCP model should fulfill at least the following two requirements: (a) it should predict the sigmoid shape of the corresponding dose-response curve and (b) it should accurately describe the probability of a specified response for arbitrary non-uniform dose delivery for a given endpoint as accurately as possible, i.e. predict the volume dependence. In recent studies of the volume effect of a rat spinal cord after irradiation with narrow and broad proton beams the authors claim that none of the existing NTCP models is able to describe their results. Published experimental data have been used here to try to quantify the change in the effective dose (D50) causing 50% response for different field sizes. The present study was initiated to describe the induction of white matter necrosis in a rat spinal cord after irradiation with narrow proton beams in terms of the mean dose to the effective volume of the functional subunit (FSU). The physically delivered dose distribution was convolved with a function describing the effective size or, more accurately, the sensitivity distribution of the FSU to obtain the effective mean dose deposited in it. This procedure allows the determination of the mean D50 value of the FSUs of a certain size which is of interest for example if the cell nucleus of the oligodendrocyte is the sensitive target. Using the least-squares method to compare the effective doses for different sizes of the functional subunits with the experimental data the best fit was obtained with a length of about 9 mm. For the non-uniform dose distributions an effective FSU length of 8 mm gave the optimal fit with the probit dose-response model. The method could also be used to interpret the so-called bath and shower experiments where the heterogeneous dose delivery was used in the

  11. Breakdown of lung framework and an increase in pores of Kohn as initial events of emphysema and a cause of reduction in diffusing capacity.

    Science.gov (United States)

    Yoshikawa, Akira; Sato, Shuntaro; Tanaka, Tomonori; Hashisako, Mikiko; Kashima, Yukio; Tsuchiya, Tomoshi; Yamasaki, Naoya; Nagayasu, Takeshi; Yamamoto, Hiroshi; Fukuoka, Junya

    2016-01-01

    Pulmonary emphysema is the pathological prototype of chronic obstructive pulmonary disease and is also associated with other lung diseases. We considered that observation with different approaches may provide new insights for the pathogenesis of emphysema. We reviewed tissue blocks of the lungs of 25 cases with/without emphysema and applied a three-dimensional observation method to the blocks. Based on the three-dimensional characteristics of the alveolar structure, we considered one face of the alveolar polyhedron as a structural unit of alveoli and called it a framework unit (FU). We categorized FUs based on their morphological characteristics and counted their number to evaluate the destructive changes in alveoli. We also evaluated the number and the area of pores of Kohn in FUs. We performed linear regression analysis to estimate the effect of these data on pulmonary function tests. In multivariable regression analysis, a decrease in the number of FUs without an alveolar wall led to a significant decrease in the diffusing capacity of the lung for carbon monoxide (DLCO) and DLCO per unit alveolar volume, and an increase in the area of pores of Kohn had a significant effect on an increase in residual capacity. A breakdown in the lung framework and an increase in pores of Kohn are associated with a decrease in DLCO and DLCO per unit alveolar volume with/without emphysema.

  12. Prediction of effect-site concentration of sufentanil by dose-response target controlled infusion of sufentanil and propofol for analgesic and sedation maintenance in burn dressing changes.

    Science.gov (United States)

    Chen, Lingyang; Wang, Mingcang; Xiang, Haifei; Lin, Xianju; Cao, Donghang; Ye, Liyue

    2014-05-01

    This study was to investigate the feasibility and efficiency of by target-controlled infusion (TCI) for analgesia and sedation during burn dressing change, and to predict the effect-site concentration of sufentanil. Eighty burn patients were randomly and evenly divided into four groups according to target sufentanil effect-site concentration (0.2, 0.3, 0.4 and 0.5 ng/ml). The sufentanil-propofol TCI was carried out during dressing changes. The effect-site concentration of propofol was maintained at 1.2 μg/ml. The dose-response relationships of sufentanil for providing adequate analgesia were evaluated by visual analog scales and Ramsay sedation scores. The effect-site concentration of sufentanil was calculated by Probit regression analysis. Incidence of respiratory depression, doctors and patients' satisfaction and adverse events were assessed. The EC50 and EC95 of sufentanil to maintain anesthesia for uncovering the inner layer dressings during TCI were 0.278 ng/ml (95% CI 0.231-0.318 ng/ml) and 0.394 ng/ml (95% CI 0.366-0.530 ng/ml), respectively, while the EC50 and EC95 of sufentanil to maintain anesthesia for wound management were 0.349 ng/ml (95% CI 0.299-0.366 ng/ml) and 0.465 ng/ml (95% CI 0.430-0.563 ng/ml), respectively. Doctors and patients' satisfaction were significantly higher in the 0.4 and 0.5 ng/ml groups than the 0.2 ng/ml group. One and three patients had respiratory depression in the 0.4 and 0.5 ng/ml groups, respectively. No adverse events occurred after operations. In conclusion, low dose sufentanil-propofol TCI for anesthesia and sedation maintenance in burn dressing changes is feasible and effective, and wound management requires higher effect-site concentrations of sufentanil than disclosing inner layer dressings. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

  13. Dose response relationship of disturbed migration of Purkinje cells in the cerebellum due to X-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Darmanto, W.; Inouye, Minoru; Hayasaka, Shizu; Takagishi, Yoshiko; Aolad, H.; Murata, Yoshiharu [Nagoya Univ. (Japan). Research Inst. of Environmental Medicine

    1998-10-01

    Pregnant rats were exposed to 2.0, 2.25 or 2.5 Gy X-irradiation on gestation day 21. Pups were sacrificed 12 hr after exposure, and on postnatal day 5 (P5), P7 and P9. Their cerebella were observed immunohistochemically using anti-inositol 1,4,5 triphosphate (IP3) receptor antibody to identify Purkinje cells. These cells were disturbed to migrate and remained in the internal granular layer and white matter of the cerebellum. They had short dendrites, and some showed an abnormal direction of dendrites in rats exposed to 2.25 or 2.5 Gy. Alignment of Purkinje cells was also disturbed when examined either on P5, P7 or P9 especially by doses of 2.25 and 2.5 Gy. There was a relationship between X-ray doses and the number of cells piling up in the Purkinje cell layer of the cerebellum. The dose-response relationship with the number of ectopic Purkinje cells was noted in the anterior lobes of the cerebellum. (author)

  14. The relationship between the IC(50), toxic threshold, and the magnitude of stimulatory response in biphasic (hormetic) dose-responses.

    Science.gov (United States)

    Nascarella, Marc A; Calabrese, Edward J

    2009-08-01

    Hormesis is a dose-response relationship characterized by a biphasic (U- or inverted U-shaped) response. We present the results of a study designed to assess the relationship between toxic potency (as measured by the IC(50)) and the magnitude of the hormesis stimulation. To facilitate this, we describe a new parameter (Delta(X)), which we define as the difference between the concentration (or dose) that inhibits 50% of the growth of the organism under study (IC(50)), and the concentration (or dose) of the respective toxicological threshold (either the benchmark dose (BMD) or zero equivalent point (ZEP)). Our analysis includes a subset of data from a previously published report describing a National Cancer Institute study that exposed yeast to putative anticancer agents in a high throughput assay. The toxic threshold used in this paper was the BMD(5). Thus, the Delta(X) in this paper is defined as: Delta(X)=IC(50)-BMD(5). We have found that the Delta(X) and the magnitude of stimulation above the control response are inversely related. These findings describe the first known relationship between toxic potency and the magnitude of hormetic response and warrant further inquiry.

  15. Association between water fluoride and the level of children's intelligence: a dose-response meta-analysis.

    Science.gov (United States)

    Duan, Q; Jiao, J; Chen, X; Wang, X

    2018-01-01

    Higher fluoride concentrations in water have inconsistently been associated with the levels of intelligence in children. The following study summarizes the available evidence regarding the strength of association between fluoridated water and children's intelligence. Meta-analysis. PubMed, Embase, and Cochrane Library databases were systematically analyzed from November 2016. Observational studies that have reported on intelligence levels in relation to high and low water fluoride contents, with 95% confidence intervals (CIs) were included. Further, the results were pooled using inverse variance methods. The correlation between water fluoride concentration and intelligence level was assessed by a dose-response meta-analysis. Twenty-six studies reporting data on 7258 children were included. The summary results indicated that high water fluoride exposure was associated with lower intelligence levels (standardized mean difference : -0.52; 95% CI: -0.62 to -0.42; P intelligence (P intelligence levels. Greater exposure to high levels of fluoride in water was significantly associated with reduced levels of intelligence in children. Therefore, water quality and exposure to fluoride in water should be controlled in areas with high fluoride levels in water. Copyright © 2017. Published by Elsevier Ltd.

  16. Efficacy of metformin in type II diabetes: results of a double-blind, placebo-controlled, dose-response trial.

    Science.gov (United States)

    Garber, A J; Duncan, T G; Goodman, A M; Mills, D J; Rohlf, J L

    1997-12-01

    To study the efficacy and safety of various dosages of metformin as compared with placebo in patients with type II diabetes mellitus. A 14-week, multicenter, double-blind, dose-response study was conducted. After a 3-week, single-blind, placebo-controlled washout, 451 patients with fasting plasma glucose levels of at least 180 mg/dL were randomized to receive an 11-week course of placebo or metformin given at 500, 1000, 1500, 2000, or 2500 mg daily. Metformin improved glucose variables as compared with placebo. The adjusted mean changes in fasting plasma glucose from baseline associated with each metformin group at week 7, 11, or at endpoint exceeded those associated with placebo by 19 to 84 mg/dL at dosages of 500 to 2000 mg daily, respectively. The corresponding between-group differences in glycated hemoglobin (HbA1c) ranged from 0.6% to 2.0% at dosages of 500 to 2000 mg daily, respectively. All between-group differences were significant (P limits of the recommended daily dosage. All dosages were well tolerated. Metformin appears to be a useful therapeutic option for physicians who wish to titrate drug therapy to achieve target glucose concentrations.

  17. A dose-response relationship between fish consumption and human milk DHA content among Filipino women in Cebu City, Philippines.

    Science.gov (United States)

    Quinn, E A; Kuzawa, C W

    2012-10-01

      Human milk is the primary source of docosahexaenoic acid (DHA) for most infants, an important fatty acid for neurological development. Milk DHA is largely incorporated from the maternal diet. Little is known about whether milk DHA varies within populations with differences in maternal fish consumption. Here, we investigate this association in a sample of marginally nourished Filipino women.   Milk samples were collected during in-home interviews with 117 lactating Filipino mothers from Cebu City, Philippines, nursing infants composition using gas chromatography. Multivariate regression was used to test the association between fish consumption and milk DHA.   Milk DHA showed a positive, dose-response relationship with maternal fish consumption (p Milk DHA was also positively related to protein intake, likely reflecting the association between fish and protein intake (p milk DHA (p = 0.03).   Increasing fish consumption during lactation may be a cost-effective means of maximizing DHA delivery to infants particularly in populations with marginal energy intakes during lactation. However, this must be weighed against the potential dangers of increasing exposure to fish-based pollutants. © 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.

  18. Deriving ozone dose-response of photosynthesis in adult forest trees from branch-level cuvette gas exchange assessment

    Energy Technology Data Exchange (ETDEWEB)

    Then, C. [Unit of Alpine Timberline Ecophysiology, Federal Office and Research Centre for Forests, Rennweg 1, A-6020 Innsbruck (Austria); Ecophysiology of Plants, Department of Ecology, Technische Universitaet Muenchen, Life Science Center Weihenstephan, Am Hochanger 13, D-85354 Freising (Germany)], E-mail: christiane.then@uibk.ac.at; Loew, M.; Matyssek, R. [Ecophysiology of Plants, Department of Ecology, Technische Universitaet Muenchen, Life Science Center Weihenstephan, Am Hochanger 13, D-85354 Freising (Germany); Wieser, G. [Unit of Alpine Timberline Ecophysiology, Federal Office and Research Centre for Forests, Rennweg 1, A-6020 Innsbruck (Austria)

    2008-06-15

    Branch-level gas exchange provided the basis for assessing ozone flux in order to derive the dose-response relationship between cumulative O{sub 3} uptake (COU) and carbon gain in the upper sun crown of adult Fagus sylvatica. Fluxes of ozone, CO{sub 2} and water vapour were monitored simultaneously by climatized branch cuvettes. The cuvettes allowed branch exposure to an ambient or twice-ambient O{sub 3} regime, while tree crowns were exposed to the same O{sub 3} regimes (twice-ambient generated by a free-air canopy O{sub 3} exposure system). COU levels higher than 20 mmol m{sup -2} led to a pronounced decline in carbon gain under elevated O{sub 3}. The limiting COU range is consistent with findings on neighbouring branches exposed to twice-ambient O{sub 3} through free-air fumigation. The cuvette approach allows to estimate O{sub 3} flux at peripheral crown positions, where boundary layers are low, yielding a meso-scale within-crown resolution of photosynthetic foliage sensitivity under whole-tree free-air O{sub 3} fumigation. - Branch-level O{sub 3} dose dependence of photosynthesis derived from cuvette assessment yields sun-crown foliage sensitivity under whole-tree free-air O{sub 3} fumigation.

  19. Acute Effects of Classroom Exercise Breaks on Executive Function and Math Performance: A Dose-Response Study.

    Science.gov (United States)

    Howie, Erin K; Schatz, Jeffrey; Pate, Russell R

    2015-01-01

    The purpose of this study was to determine the acute dose-response relationship of classroom exercise breaks with executive function and math performance in 9- to 12-year-old children by comparing 5-min, 10-min, or 20-min classroom exercise breaks to 10 min of sedentary classroom activity. This study used a within-subjects experimental design conducted in the spring of 2012. Ninety-six 4th- and 5th-grade students in 5 classrooms in South Carolina were randomized to receive each of 4 treatments: 5-min, 10-min, or 20-min exercise breaks or 10 min of a sedentary lesson led by research staff. Students completed the Trail-Making Test, an Operational Digit Recall test, and a math fluency test immediately before and after each condition. Planned linear contrasts were used to compare posttest scores between conditions using a repeated-measures mixed model, adjusted for gender, classroom, and the time-varying pretest scores. Potential effect modifiers were added as interaction terms. Math scores were higher after the 10-min and 20-min exercise breaks compared with the sedentary condition (d = 0.24, p = .04, and d = 0.27, p = .02, respectively), and an interaction was observed with gender, IQ, aerobic fitness, and lower engagement in some of the conditions. There were no improvements in executive function tasks. A 10-min and 20-min classroom exercise break moderately improved math performance in students compared with a seated classroom lesson.

  20. Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts after Exposure to Very Low Doses of High LET Radiation

    Science.gov (United States)

    Hada, M.; George, Kerry; Cucinotta, Francis A.

    2011-01-01

    The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivors with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (1-20 cGy) of 170 MeV/u Si-28- ions or 600 MeV/u Fe-56-ions. Chromosomes were analyzed using the whole chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving greater than 2 breaks in 2 or more chromosomes). The curves for doses above 10 cGy were fitted with linear or linear-quadratic functions. For Si-28- ions no dose response was observed in the 2-10 cGy dose range, suggesting a non-target effect in this range.

  1. Statins intake and risk of liver cancer: A dose-response meta analysis of prospective cohort studies.

    Science.gov (United States)

    Yi, Changhong; Song, Zhenggui; Wan, Maolin; Chen, Ya; Cheng, Xiang

    2017-07-01

    Previous studies have indicated that statins intake was associated with liver cancer risk, but presented controversial results.Studies in PubMed and EMBASE were searched update to February 2017 to identify and quantify the potential dose-response association between statins intake and liver cancer.Six eligible studies involving a total of 11,8961 participants with 9530 incident cases were included in this meta-analysis. Statistically significant association was observed between increasing statins intake and liver cancer risk reduction (OR = 0.46, 95%CI: 0.24-0.68, P risk of liver cancer for an increase of 50 cumulative defined daily dose per year was 0.86 (95%CI: 0.81-0.90, P risk was found (P for nonlinearity analysis indicated that statins intake was associated with a significantly risk of liver cancer risk reduction in Asia (OR = 0.44, 95%CI: 0.11-0.77, P risk reduction.

  2. The road less traveled: new views of steroid receptor action from the path of dose-response curves

    Science.gov (United States)

    Simons, S. Stoney; Chow, Carson C.

    2011-01-01

    Conventional studies of steroid hormone action proceed via quantitation of the maximal activity for gene induction at saturating concentrations of agonist steroid (i.e., Amax). Less frequently analyzed parameters of receptor-mediated gene expression are EC50 and PAA. The EC50 is the concentration of steroid required for half-maximal agonist activity and is readily determined from the dose-response curve. The PAA is the partial agonist activity of an antagonist steroid, expressed as percent of Amax under the same conditions. Recent results demonstrate that new and otherwise inaccessible mechanistic information is obtained when the EC50 and/or PAA are examined in addition to the Amax. Specifically, Amax, EC50, and PAA can be independently regulated, which suggests that novel pathways and factors may preferentially modify the EC50 and/or PAA with little effect on Amax. Other approaches indicate that the activity of receptor-bound factors can be altered without changing the binding of factors to receptor. Finally, a new theoretical model of steroid hormone action not only permits a mechanistically based definition of factor activity but also allows the positioning of when a factor acts, as opposed to binds, relative to a kinetically defined step. These advances illustrate some of the benefits of expanding the mechanistic studies of steroid hormone action to routinely include EC50 and PAA. PMID:21664235

  3. Enhancement of Dose Response and Nuclear Magnetic Resonance Image of PAGAT Polymer Gel Dosimeter by Adding Silver Nanoparticles.

    Directory of Open Access Journals (Sweden)

    Rahim Sabbaghizadeh

    Full Text Available In the present study, the normoxic polyacrylamide gelatin and tetrakis hydroxy methyl phosphoniun chloride (PAGAT polymer gel dosimeters were synthesized with and without the presence of silver (Ag nanoparticles. The amount of Ag nanoparticles varied from 1 to 3 ml with concentration 3.14 g/l, thus forming two types of PAGAT polymer gel dosimeters before irradiating them with 6 to 25 Gy produced by 1.25-MeV 60Co gamma rays. In this range, the predominant gamma ray interaction with matter is by Compton scattering effect, as the photoelectric absorption effect diminishes. MRI was employed when evaluating the polymerization of the dosimeters and the gray scale of the MRI film was determined via an optical densitometer. Subsequent analyses of optical densities revealed that the extent of polymerization increased with the increase in the absorbed dose, while the increase of penetration depth within the dosimeters has a reverse effect. Moreover, a significant increase in the optical density-dose response (11.82% was noted for dosimeters containing 2 ml Ag nanoparticles.

  4. EMS in Viracept--initial ('traditional') assessment of risk to patients based on linear dose response relations.

    Science.gov (United States)

    Gocke, Elmar; Müller, Lutz; Pfister, Thomas

    2009-11-12

    Prior to having performed in depth toxicological, genotoxicological and DMPK studies on ethyl methanesulfonate (EMS) providing solid evidence for a thresholded dose response relationship, we had prepared and shared with regulatory authorities a preliminary risk estimate based on standard linear dose-effect projections. We estimated that maximal lifetime cancer risk was in the order of 10(-3) (for lifetime ingestion of the maximally contaminated tablets) or 10(-4) for the exposure lasting for 3 months. This estimate was based on a lifetime cancer study with methyl methanesulfonate (MMS; as insufficient data were available for EMS) in rodents and default linear back extrapolation. Analogous estimates were made specifically for breast cancer based on short term tumorigenicity studies with EMS in rats, for the induction of heritable mutations based on specific locus and dominant lethal tests in mice and for the induction of birth defects based on teratogenicity studies in mice. We concluded that even under worst case assumptions of linear dose relations the chance of experiencing these adverse effects would be very small, comprising at most a minute additional burden among the background incidence of the patients.

  5. A novel method of estimating dose responses for polymer gels using texture analysis of scanning electron microscopy images.

    Directory of Open Access Journals (Sweden)

    Cheng-Ting Shih

    Full Text Available Polymer gels are regarded as a potential dosimeter for independent validation of absorbed doses in clinical radiotherapy. Several imaging modalities have been used to convert radiation-induced polymerization to absorbed doses from a macro-scale viewpoint. This study developed a novel dose conversion mechanism by texture analysis of scanning electron microscopy (SEM images. The modified N-isopropyl-acrylamide (NIPAM gels were prepared under normoxic conditions, and were administered radiation doses from 5 to 20 Gy. After freeze drying, the gel samples were sliced for SEM scanning with 50×, 500×, and 3500× magnifications. Four texture indices were calculated based on the gray level co-occurrence matrix (GLCM. The results showed that entropy and homogeneity were more suitable than contrast and energy as dose indices for higher linearity and sensitivity of the dose response curves. After parameter optimization, an R (2 value of 0.993 can be achieved for homogeneity using 500× magnified SEM images with 27 pixel offsets and no outlier exclusion. For dose verification, the percentage errors between the prescribed dose and the measured dose for 5, 10, 15, and 20 Gy were -7.60%, 5.80%, 2.53%, and -0.95%, respectively. We conclude that texture analysis can be applied to the SEM images of gel dosimeters to accurately convert micro-scale structural features to absorbed doses. The proposed method may extend the feasibility of applying gel dosimeters in the fields of diagnostic radiology and radiation protection.

  6. Cytogenetic dose-response in vitro for biological dosimetry after exposure to high doses of gamma-rays.

    Science.gov (United States)

    Vinnikov, Volodymyr A; Maznyk, Nataliya A

    2013-04-01

    The dose response for dicentrics plus centric rings and total unstable chromosome-type aberrations was studied in the first mitoses of cultured human peripheral blood lymphocytes irradiated in vitro to doses of ∼2, 4, 6, 8, 10, 16 and 20 Gy of acute (60)Со gamma-rays. A dose-dependent increase of aberration yield was accompanied by a tendency to the underdispersion of dicentrics and centric rings among cells distributions compared with Poisson statistics at doses ≥6 Gy. The formal fitting of the data to a linear-quadratic model resulted in an equation with the linear and quadratic coefficients ranged 0.098-0.129×cell(-1)×Gy(-1) and 0.039-0.034×cell(-1)×Gy(-2), respectively, depending on the fitting method. The actual radiation-induced aberration yield was markedly lower than expected from a calibration curve, generated earlier within a lower dose range. Interlaboratory variations in reported dicentric yields induced by medium-to-high radiation doses in vitro are discussed.

  7. NITRO MUSK ADDUCTS OF RAINBOW TROUT HEMOGLOBIN: DOSE-RESPONSE AND TOXICOKINETICS DETERMINATION BY GC-NICI-MS FOR A SENTINEL SPECIES

    Science.gov (United States)

    Rainbow trout and other fish species can serve as 'sentinel' species for the assessment of ecological status and the presence of certain environmental contaminants. As such they act as bioindicators of exposure. Here we present seminal data regarding dose-response and toxicokinet...

  8. DOSE-RESPONSE RELATION, NEUROMUSCULAR BLOCKING ACTION, INTUBATION CONDITIONS, AND CARDIOVASCULAR EFFECTS OF ORG-9273, A NEW NEUROMUSCULAR BLOCKING-AGENT

    NARCIS (Netherlands)

    VANDENBROEK, L; LAMBALK, LM; RICHARDSON, FJ; WIERDA, JMKH

    The ED50 and the ED90, the time-course of the neuromuscular block, the intubation conditions, and the cardiovascular effects of Org 9273, a new steroidal nondepolarizing neuromuscular blocking agent, have been evaluated in 41 anesthetized patients. From cumulative dose-response curves the ED50 and

  9. TIME COURSE AND DOSE RESPONSE ASSESSMENT OF CHOLINESTERASE (CHE) INHIBITION IN ADULT RATS TREATED ACUTELY WITH CARBARYL, METHOMYL, METHIOCARB, OXAMYL, OR PROPOXUR.

    Science.gov (United States)

    To compare the toxicity of 5 N-methyl carbamates, the time course and dose response profiles for ChE inhibition were established for each. For the time course comparison, adult male Long Evans rats (n=5 dose group) were dosed orally with either carbaryl (CB; 30 mg/kg in corn oi...

  10. The dose-response relationship between the amount of straw provided on the floor and gastric ulceration of pars oesophagea in growing pigs

    DEFF Research Database (Denmark)

    Jensen, Karin Hjelholt; Jørgensen, Lisbeth; Haugegaard, Svend

    2017-01-01

    The aim of the present study was (1) to determine the dose-response relationship between the amount of straw provided on the floor and oesophageal ulceration in pigs kept under typical Danish production conditions (18 pigs/pen, 0.7 m2/pig, partly slatted floor, ad libitum access to feed), (2) to ...

  11. Dose-response relationship between selective serotonin re-uptake inhibitors and injurious falls: A study in nursing home residents with dementia

    NARCIS (Netherlands)

    C.S. Sterke (Carolyn); G. Ziere; E.F. van Beeck (Ed); C.W.N. Looman (Caspar); T.J.M. van der Cammen (Tischa)

    2012-01-01

    textabstractAim: The contribution of selective serotonin re-uptake inhibitors (SSRIs) to injurious fall risk in patients with dementia has not been quantified precisely until now. Our objective was to determine whether a dose-response relationship exists for the use of SSRIs and injurious falls in a

  12. Systematic review using meta-analyses to estimate dose-response relationships between iodine intake and biomarkers of iodine status in different population groups

    NARCIS (Netherlands)

    Ristic-Medic, D.; Dullemeijer, C.; Tepsic, J.; Petrovic-Oggiano, G.; Popovic, Z.; Arsic, A.; Glibetic, M.; Souverein, O.W.; Collings, R.; Cavelaars, A.J.E.M.; Groot, de C.P.G.M.; Veer, van 't P.; Gurinovic, M.

    2014-01-01

    The objective of this systematic review was to identify studies investigating iodine intake and biomarkers of iodine status, to assess the data of the selected studies, and to estimate dose-response relationships using meta-analysis. All randomized controlled trials, prospective cohort studies,

  13. A tiered approach for integrating exposure and dosimetry with in vitro dose-response data in the modern risk assessment paradigm

    Science.gov (United States)

    High-throughput (HT) risk screening approaches apply in vitro dose-response data to estimate potential health risks that arise from exposure to chemicals. However, much uncertainty is inherent in relating bioactivities observed in an in vitro system to the perturbations of biolog...

  14. A randomized controlled dose-response pilot study of addition of hCG to recombinant FSH during controlled ovarian stimulation for in vitro fertilization

    DEFF Research Database (Denmark)

    Loft, A; Egeberg, Anne Noes; Smitz, J

    2012-01-01

    of hCG up to 150 IU are compatible with good live birth rates. A ceiling level of estradiol (E(2)) was reached with hCG doses above 100 IU/day. A positive dose-response was seen for pre-ovulatory progesterone, but concentrations remained below values for which an impairment of endometrial receptivity...

  15. Dose-response and time-course of neurotoxicity and tissue concentrations of carbaryl in Brown Norway rats from preweaning to senescence.

    Science.gov (United States)

    Factors impacting sensitivity to chemicals across life stages include toxicokinetic and toxicodynamic changes. We systematically compared the dose-response (3, 7.5, 15,22.5 mg/kg) and time-course (3 or 15 mg/kg at 30, 60, 120, 240 min) of acute effects of carbaryl (oral gavage) i...

  16. Cytogenetics dosimetry: dose-response curve for low doses of X-ray; Dosimetria citogenetica: curva dosis-respuesta para bajas dosis de rayos-X

    Energy Technology Data Exchange (ETDEWEB)

    Lara, Virginia E. Noval; Pineda Bolivar, William R.; Riano, Victor M. Pabon, E-mail: venovall.15@hotmail.com, E-mail: wrpineda@misena.edu.co, E-mail: vmpabonr@udistrital.edu.co [Universidad Distrital Francisco Jose de Caldas (UD), Bogota (Colombia). Grupo de Investigacion en Ciencia y Tecnologia Nuclear; Ureana, Cecilia Crane, E-mail: cecicrane@yahoo.com [Instituto Nacional de Salud (INS), Bogota (Colombia). Laboratorio de Genetica

    2013-07-01

    The purpose of this study was to conduct a preliminary study for the standardization in the future, the dose-response curve for low doses of X-rays, through the analysis of in vitro cultures of peripheral blood samples of 3 men and 3 women occupationally not exposed to artificial sources of ionizing radiation, age 18-40 years, where possible nonsmokers.

  17. Bell-shaped and ultrasensitive dose-response in phosphorylation-dephosphorylation cycles: the role of kinase-phosphatase complex formation

    Directory of Open Access Journals (Sweden)

    Szomolay Barbara

    2012-04-01

    Full Text Available Abstract Background Phosphorylation-dephosphorylation cycles (PDCs mediated by kinases and phosphatases are common in cellular signalling. Kinetic modelling of PDCs has shown that these systems can exhibit a variety of input-output (dose-response behaviors including graded response, ultrasensitivity and bistability. In addition to proteins, there are a class of lipids known as phosphoinositides (PIs that can be phosphorylated. Experimental studies have revealed the formation of an antagonistic kinase-phosphatase complex in regulation of phosphorylation of PIs. However, the functional significance of this type of complex formation is not clear. Results We first revisit the basic PDC and show that partial asymptotic phosphorylation of substrate limits ultrasensitivity. Also, substrate levels are changed one can obtain non-monotonic bell-shaped dose-response curves over a narrow range of parameters. Then we extend the PDC to include kinase-phosphatase complex formation. We report the possibility of robust bell-shaped dose-response for a specific class of the model with complex formation. Also, we show that complex formation can produce ultrasensitivity outside the Goldbeter-Koshland zero-order ultrasensitivity regime through a mechanism similar to competitive inhibition between an enzyme and its inhibitor. Conclusions We conclude that the novel PDC module studied here exhibits new dose-response behaviour. In particular, we show that the bell-shaped response could result in transient phosphorylation of substrate. We discuss the relevance of this result in the context of experimental observations on PI regulation in endosomal trafficking.

  18. Breakdown of lung framework and an increase in pores of Kohn as initial events of emphysema and a cause of reduction in diffusing capacity

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    Yoshikawa A

    2016-09-01

    Full Text Available Akira Yoshikawa,1 Shuntaro Sato,2,3 Tomonori Tanaka,1 Mikiko Hashisako,1,4 Yukio Kashima,5,6 Tomoshi Tsuchiya,7 Naoya Yamasaki,7 Takeshi Nagayasu,7 Hiroshi Yamamoto,2 Junya Fukuoka1,6 1Nagasaki Educational and Diagnostic Center of Pathology (NEDCP, Department of Pathology, 2Clinical Research Center, Nagasaki University Hospital, Nagasaki, 3Division of Biostatistics, Kurume University School of Medicine, Fukuoka, 4Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 5Department of Pathology, Hyogo Prefectural Awaji Medical Center, Sumoto, 6Department of Pathology, 7Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan Purpose: Pulmonary emphysema is the pathological prototype of chronic obstructive pulmonary disease and is also associated with other lung diseases. We considered that observation with different approaches may provide new insights for the pathogenesis of emphysema. Patients and methods: We reviewed tissue blocks of the lungs of 25 cases with/without emphysema and applied a three-dimensional observation method to the blocks. Based on the three-dimensional characteristics of the alveolar structure, we considered one face of the alveolar polyhedron as a structural unit of alveoli and called it a framework unit (FU. We categorized FUs based on their morphological characteristics and counted their number to evaluate the destructive changes in alveoli. We also evaluated the number and the area of pores of Kohn in FUs. We performed linear regression analysis to estimate the effect of these data on pulmonary function tests. Results: In multivariable regression analysis, a decrease in the number of FUs without an alveolar wall led to a significant decrease in the diffusing capacity of the lung for carbon monoxide (DLCO and DLCO per unit alveolar volume, and an increase in the area of

  19. Dose-response analysis of testosterone replacement therapy in patients with female to male gender identity disorder.

    Science.gov (United States)

    Nakamura, Aya; Watanabe, Masami; Sugimoto, Morito; Sako, Tomoko; Mahmood, Sabina; Kaku, Haruki; Nasu, Yasutomo; Ishii, Kazushi; Nagai, Atsushi; Kumon, Hiromi

    2013-01-01

    Gender identity disorder (GID) is a conflict between a person's actual physical gender and the one they identify him or herself with. Testosterone is the key agent in the medical treatment of female to male GID patients. We conducted a dose-response analysis of testosterone replacement therapy (TRT) in 138 patients to determine the onset of the therapeutic effects. The TRT consisted of intramuscular injection of testosterone enanthate and patients were divided into three groups; 250 mg every two weeks, 250 mg every three weeks and 125 mg every two weeks. The onset of deepening of voice, increase in facial hair and cessation of menses was evaluated in each group. At one month after the start of TRT, the onset of these physical changes was more prevalent in the group receiving the higher dose of testosterone, and there were dose-dependent effects observed between the three treatment groups. On the other hand, at six months after the start of TRT, most of the patients had achieved treatment responses and there were no dose-dependent effects with regard to the percentage of patients with therapeutic effects. No significant side effects were observed in any of the treatment groups. We demonstrated that the early onset of the treatment effects of TRT is dose-dependent, but within six months of starting TRT, all three doses were highly effective. Current study provides useful information to determine the initial dose of TRT and to suggest possible changes that should be made in the continuous dosage for long term TRT.

  20. Dose-response relationships between physical activity, social participation, and health-related quality of life in colorectal cancer survivors.

    Science.gov (United States)

    Thraen-Borowski, Keith M; Trentham-Dietz, Amy; Edwards, Dorothy Farrar; Koltyn, Kelli F; Colbert, Lisa H

    2013-09-01

    The purpose of this study was to examine the relationships between physical activity (PA), social participation, and health-related quality of life (HQOL) in older, long-term colorectal cancer survivors. Male and female colorectal cancer survivors (n = 1,768), aged ≥65 and ≥5 years post-diagnosis, completed surveys on their current PA, social participation, HQOL, health history, and relevant covariates. Analysis of covariance was used to evaluate the cross-sectional relationship between PA and social participation with the SF-36 subscales, as well as the physical component summary score (PCS) and mental health component summary score (MCS). The final analytic sample (n = 832) was 81.5 ± 5.8 years and 8.2 ± 1.7 years post-diagnosis (mean ± SD). Meeting the current recommendation of 150 min/week of PA was associated with higher PCS (p social participation, vs. none, was associated with MCS (p = 0.003), but not PCS (p = 0.13). There was a dose-response relationship between moderate-vigorous-intensity PA and PCS (p trend 0.05), but in survivors performing no higher-intensity PA, it was associated with both (p social participation had higher PCS and MCS (p trendphysical health, while social participation is predominantly related to their mental health. Older colorectal cancer survivors who participate socially and are engaged in PA, even non-exercise and light-intensity activities, have higher levels of physical and mental health.

  1. Has the sensitivity of soybean cultivars to ozone pollution increased with time? An analysis of published dose-response data.

    Science.gov (United States)

    Osborne, Stephanie A; Mills, Gina; Hayes, Felicity; Ainsworth, Elizabeth A; Büker, Patrick; Emberson, Lisa

    2016-09-01

    The rising trend in concentrations of ground-level ozone (O3 ) - a common air pollutant and phytotoxin - currently being experienced in some world regions represents a threat to agricultural yield. Soybean (Glycine max (L.) Merr.) is an O3 -sensitive crop species and is experiencing increasing global demand as a dietary protein source and constituent of livestock feed. In this study, we collate O3 exposure-yield data for 49 soybean cultivars, from 28 experimental studies published between 1982 and 2014, to produce an updated dose-response function for soybean. Different cultivars were seen to vary considerably in their sensitivity to O3 , with estimated yield loss due to O3 ranging from 13.3% for the least sensitive cultivar to 37.9% for the most sensitive, at a 7-h mean O3 concentration (M7) of 55 ppb - a level frequently observed in regions of the USA, India and China in recent years. The year of cultivar release, country of data collection and type of O3 exposure used were all important explanatory variables in a multivariate regression model describing soybean yield response to O3 . The data show that the O3 sensitivity of soybean cultivars increased by an average of 32.5% between 1960 and 2000, suggesting that selective breeding strategies targeting high yield and high stomatal conductance may have inadvertently selected for greater O3 sensitivity over time. Higher sensitivity was observed in data from India and China compared to the USA, although it is difficult to determine whether this effect is the result of differential cultivar physiology, or related to local environmental factors such as co-occurring pollutants. Gaining further understanding of the underlying mechanisms that govern the sensitivity of soybean cultivars to O3 will be important in shaping future strategies for breeding O3 -tolerant cultivars. © 2016 The Authors. Global Change Biology Published by John Wiley & Sons Ltd.

  2. Steroid therapy and the risk of osteonecrosis in SARS patients: a dose-response meta-analysis.

    Science.gov (United States)

    Zhao, R; Wang, H; Wang, X; Feng, F

    2017-03-01

    This meta-analysis synthesized current evidence from 10 trials to evaluate the association between steroid therapy and osteonecrosis incidence in patients with severe acute respiratory syndrome (SARS). Our results suggest that higher cumulative doses and longer treatment durations of steroids are more likely to lead to the development of osteonecrosis in SARS patients. The link between steroid treatment and the risk of osteonecrosis in SARS patients remains unknown. The present meta-analysis aimed to examine the dose-response association between steroid therapy and osteonecrosis incidence in SARS patients. The sex differences in the development of steroid-induced osteonecrosis were also examined. We searched PubMed, Web of Science, CNKI, and WANFANG for studies that involved steroid therapy and reported osteonecrosis data in SARS patients. Two authors independently extracted the data from the individual studies, and the rate ratio (RR) of osteonecrosis was calculated using random-effect models. Ten studies with 1137 recovered SARS patients met the inclusion criteria. Close relationships between osteonecrosis incidence and both the cumulative dose and treatment duration of steroids were observed. The summary RR of osteonecrosis was 1.57 (95% confidence interval (CI) 1.30-1.89, p SARS patients who received higher cumulative doses and longer treatment durations of steroids were more likely to develop osteonecrosis, and there were no sex differences in this dose-dependent side effect. Our findings suggest that it is important to reduce osteonecrosis risk by modifying the cumulative dose and the treatment duration of steroids in SARS patients.

  3. Dietary Protein Sources and Incidence of Breast Cancer: A Dose-Response Meta-Analysis of Prospective Studies

    Directory of Open Access Journals (Sweden)

    Jing Wu

    2016-11-01

    Full Text Available Protein is important to the human body, and different sources of protein may have different effects on the risk of breast cancer. Thus, we conducted a meta-analysis to investigate the association between different dietary protein sources and breast cancer risk. PubMed and several databases were searched until December 2015. Relevant articles were retrieved according to specific searching criteria. Forty-six prospective studies were included. The summary relative risk (RR for highest versus lowest intake was 1.07 (95% confidence interval (CI 1.01–1.14, I2 = 34.6% for processed meat, 0.92 (95% CI 0.84–1.00, I2 = 0% for soy food, 0.93 (95% CI 0.85–1.00, I2 = 40.1% for skim milk, and 0.90 (95% CI 0.82–1.00, I2 = 0% for yogurt. Similar conclusions were obtained in dose-response association for each serving increase: total red meat (RR: 1.07; 95% CI 1.01–1.14, I2 = 7.1%, fresh red meat (RR: 1.13; 95% CI 1.01–1.26, I2 = 56.4%, processed meat (RR: 1.09; 95% CI 1.02–1.17, I2 = 11.8%, soy food (RR: 0.91; 95% CI 0.84–1.00, I2 = 0%, and skim milk (RR: 0.96; 95% CI 0.92–1.00, I2 = 11.9%. There was a null association between poultry, fish, egg, nuts, total milk, and whole milk intake and breast cancer risk. Higher total red meat, fresh red meat, and processed meat intake may be risk factors for breast cancer, whereas higher soy food and skim milk intake may reduce the risk of breast cancer.

  4. Red and processed meat consumption and risk of bladder cancer: a dose-response meta-analysis of epidemiological studies.

    Science.gov (United States)

    Crippa, Alessio; Larsson, Susanna C; Discacciati, Andrea; Wolk, Alicja; Orsini, Nicola

    2016-12-22

    Several epidemiological studies have analyzed the associations between red and processed meat and bladder cancer risk but the shape and strength of the associations are still unclear. Therefore, we conducted a dose-response meta-analysis to quantify the potential association between red and processed meat and bladder cancer risk. Relevant studies were identified by searching the PubMed database through January 2016 and reviewing the reference lists of the retrieved articles. Results were combined using random-effects models. Five cohort studies with 3262 cases and 1,038,787 participants and 8 cases-control studies with 7009 cases and 27,240 participants met the inclusion criteria. Red meat was linearly associated with bladder cancer risk in case-control studies, with a pooled RR of 1.51 (95% confidence interval (CI) 1.13, 2.02) for every 100 g increase per day, while no association was observed among cohort studies (P heterogeneity across study design = 0.02). Based on both case-control and cohort studies, the pooled relative risk (RR) for every 50 g increase of processed meat per day was 1.20 (95% CI 1.06, 1.37) (P heterogeneity across study design = 0.22). This meta-analysis suggests that processed meat may be positively associated with bladder cancer risk. A positive association between red meat and risk of bladder cancer was observed only in case-control studies, while no association was observe in prospective studies.

  5. Evolution of Hemodynamic and Functional Human Kidney Graft Dose Response to Dopamine Using an Implantable Doppler Device.

    Science.gov (United States)

    Bataille, Aurélien; Payen, Didier; Villiers, Stéphane; Chazalet, Jean-Jacques; Jacob, Laurent

    2016-04-01

    The relation between dopamine infusion and renal hemodynamics and function has not been studied in renal allografts during early recovery. We analyzed the dose response of dopamine infusion on renal blood flow and function in human kidney transplant recipients at reperfusion and during early graft recovery. Phasic and mean renal blood flow was measured by the pulsed Doppler technique using implantable Doppler microprobes in contact with the graft artery. Systemic and renal parameters were recorded on dopamine infusion (0, 3, 5, and 10 μg·kg⁻¹·min⁻¹) immediately after transplant (day 0) in 13 patients and at day 6 in 7/13 patients with early graft recovery. Results are expressed as median and interquartile range between the 25th and 75th percentiles. At day 0, 3 μg·kg⁻¹·min⁻¹) dopamine did not increase mean renal blood flow over baseline (580 mL/min [219-663 mL/min] vs 542 mL/min [207-686 mL/min]; P = .84). There was an absence of effect with higher dopamine doses, whereas cardiac output, heart rate, and systolic and mean arterial pressure were significantly increased. Urinary sodium excretion, creatinine clearance, and urine output increased dose dependently, with a positive correlation between the increase in urine output and mean arterial pressure (r = 0.48, P < .001). At day 6, 3 μg·kg⁻¹·min⁻¹ dopamine increased mean renal blood flow over baseline (318 mL/min [234-897 mL/min] vs 191 mL/min [173-706 mL/min]; P = .016), with no further increase at higher doses. Immediately after transplant, kidney grafts with ischemic-reperfusion injury are fully dilated and do not respond to dopamine. The specific renal effects observed are due to systemic hemodynamic status. Vascular responsiveness to a "renal dopamine dose" returns on graft recovery.

  6. Mycoprotein represents a bioavailable and insulinotropic non-animal-derived dietary protein source: a dose-response study.

    Science.gov (United States)

    Dunlop, Mandy V; Kilroe, Sean P; Bowtell, Joanna L; Finnigan, Tim J A; Salmon, Deborah L; Wall, Benjamin T

    2017-11-01

    The anabolic potential of a dietary protein is determined by its ability to elicit postprandial rises in circulating essential amino acids and insulin. Minimal data exist regarding the bioavailability and insulinotropic effects of non-animal-derived protein sources. Mycoprotein is a sustainable and rich source of non-animal-derived dietary protein. We investigated the impact of mycoprotein ingestion, in a dose-response manner, on acute postprandial hyperaminoacidaemia and hyperinsulinaemia. In all, twelve healthy young men completed five experimental trials in a randomised, single-blind, cross-over design. During each trial, volunteers consumed a test drink containing either 20 g milk protein (MLK20) or a mass matched (not protein matched due to the fibre content) bolus of mycoprotein (20 g; MYC20), a protein matched bolus of mycoprotein (40 g; MYC40), 60 g (MYC60) or 80 g (MYC80) mycoprotein. Circulating amino acid, insulin and uric acid concentrations, and clinical chemistry profiles, were assessed in arterialised venous blood samples during a 4-h postprandial period. Mycoprotein ingestion resulted in slower but more sustained hyperinsulinaemia and hyperaminoacidaemia compared with milk when protein matched, with overall bioavailability equivalent between conditions (P>0·05). Increasing the dose of mycoprotein amplified these effects, with some evidence of a plateau at 60-80 g. Peak postprandial leucine concentrations were 201 (sem 24) (30 min), 118 (sem 10) (90 min), 150 (sem 14) (90 min), 173 (sem 23) (45 min) and 201 (sem 21 (90 min) µmol/l for MLK20, MYC20, MYC40, MYC60 and MYC80, respectively. Mycoprotein represents a bioavailable and insulinotropic dietary protein source. Consequently, mycoprotein may be a useful source of dietary protein to stimulate muscle protein synthesis rates.

  7. Intake of fruit and vegetables and risk of bladder cancer: a dose-response meta-analysis of observational studies.

    Science.gov (United States)

    Yao, Baodong; Yan, Yujie; Ye, Xianwu; Fang, Hong; Xu, Huilin; Liu, Yinan; Li, Sheran; Zhao, Yanping

    2014-12-01

    Observational studies suggest an association between fruit and vegetables intake and risk of bladder cancer, but the results are controversial. We therefore summarized the evidence from observational studies in categorical, linear, and nonlinear, dose-response meta-analysis. Pertinent studies were identified by searching EMBASE and PubMed from their inception to August 2013. Thirty-one observational studies involving 12,610 cases and 1,121,649 participants were included. The combined rate ratio (RR, 95 % CI) of bladder cancer for the highest versus lowest intake was 0.83 (0.69-0.99) for total fruit and vegetables, 0.81 (0.70-0.93) for total vegetables, 0.77 (0.69-0.87) for total fruit, 0.84 (0.77-0.91) for cruciferous vegetables, 0.79 (0.68-0.91) for citrus fruits, and 0.74 (0.66-0.84) for yellow-orange vegetables. Subgroup analysis showed study design and gender as possible sources of heterogeneity. A nonlinear relationship was found of citrus fruits intake with risk of bladder cancer (P for nonlinearity = 0.018), and the RRs (95 % CI) of bladder cancer were 0.87 (0.78-0.96), 0.80 (0.67-0.94), 0.79 (0.66-0.94), 0.79 (0.65-0.96), and 0.79 (0.64-0.99) for 30, 60, 90, 120, and 150 g/day. A nonlinear relationship was also found of yellow-orange vegetable intake with risk of bladder cancer risk (P for nonlinearity = 0.033). Some evidence of publication bias was observed for fruit, citrus fruits, and yellow-orange vegetables. This meta-analysis supports the hypothesis that intakes of fruit and vegetables may reduce the risk of bladder cancer. Future well-designed studies are required to confirm this finding.

  8. Dose-responsiveness and persistence of microRNA expression alterations induced by cigarette smoke in mouse lung

    Energy Technology Data Exchange (ETDEWEB)

    Izzotti, Alberto; Larghero, Patrizia; Longobardi, Mariagrazia; Cartiglia, Cristina; Camoirano, Anna [Department of Health Sciences, University of Genoa, Genoa (Italy); Steele, Vernon E. [National Cancer Institute (NCI), Rockville, MD (United States); De Flora, Silvio, E-mail: sdf@unige.it [Department of Health Sciences, University of Genoa, Genoa (Italy)

    2011-12-01

    Our previous studies demonstrated that exposure to cigarette smoke (CS), either mainstream or environmental, results in a remarkable downregulation of microRNA expression in the lung of both mice and rats. The goals of the present study were to evaluate the dose responsiveness to CS and the persistence of microRNA alterations after smoking cessation. ICR (CD-1) neonatal mice were exposed whole-body to mainstream CS, at the doses of 119, 292, 438, and 631 mg/m{sup 3} of total particulate matter. Exposure started within 12 h after birth and continued daily for 4 weeks. The levels of bulky DNA adducts and 8-oxo-7,8-dihydro-2 Prime -deoxyguanosine (8-oxodGuo) were measured by {sup 32}P postlabeling procedures, and the expression of 697 mouse microRNAs was analyzed by microarray. The highest CS dose was lethal. Exposure to CS caused a dose-dependent increase of DNA alterations. DNA adducts and, even more sharply, 8-oxodGuo were reverted 1 and 4 weeks after smoking cessation. Exposure to CS resulted in an evident dysregulation of microRNA expression profiles, mainly in the sense of downregulation. The two lowest doses were not particularly effective, while the highest nonlethal dose produced extensive microRNA alterations. The expression of most downregulated microRNAs, including among others 7 members of the let-7 family, was restored one week after smoking cessation. However, the recovery was incomplete for a limited array of microRNAs, including mir-34b, mir-345, mir-421, mir-450b, mir-466, and mir-469. Thus, it appears that microRNAs mainly behave as biomarkers of effect and that exposure to high-dose, lasting for an adequate period of time, is needed to trigger the CS-related carcinogenesis process in the experimental animal model used.

  9. Restoration of cardiac tissue thyroid hormone status in experimental hypothyroidism: a dose-response study in female rats.

    Science.gov (United States)

    Weltman, Nathan Y; Ojamaa, Kaie; Savinova, Olga V; Chen, Yue-Feng; Schlenker, Evelyn H; Zucchi, Riccardo; Saba, Alessandro; Colligiani, Daria; Pol, Christine J; Gerdes, A Martin

    2013-07-01

    Thyroid hormones (THs) play a pivotal role in regulating cardiovascular homeostasis. To provide a better understanding of the coordinated processes that govern cardiac TH bioavailability, this study investigated the influence of serum and cardiac TH status on the expression of TH transporters and cytosolic binding proteins in the myocardium. In addition, we sought to determine whether the administration of T(3) (instead of T(4)) improves the relationship between THs in serum and cardiac tissue and cardiac function over a short-term treatment period. Adult female Sprague Dawley rats were made hypothyroid by 7 weeks treatment with the antithyroid drug 6-n-propyl-2-thiouracil (PTU). After establishing hypothyroidism, rats were assigned to 1 of 5 graded T(3) dosages plus PTU for a 2-week dose-response experiment. Untreated, age-matched rats served as euthyroid controls. PTU was associated with depressed serum and cardiac tissue T(3) and T(4) levels, arteriolar atrophy, altered TH transporter and cytosolic TH binding protein expression, fetal gene reexpression, and cardiac dysfunction. Short-term administration of T(3) led to a mismatch between serum and cardiac tissue TH levels. Normalization of serum T(3) levels was not associated with restoration of cardiac tissue T(3) levels or cardiac function. In fact, a 3-fold higher T(3) dosage was necessary to normalize cardiac tissue T(3) levels and cardiac function. Importantly, this study provides the first comprehensive data on the relationship between altered TH status (serum and cardiac tissue), cardiac function, and the coordinated in vivo changes in cardiac TH membrane transporters and cytosolic TH binding proteins in altered TH states.

  10. Dose-response relationship of total and leisure time physical activity to risk of heart failure: a prospective cohort study.

    Science.gov (United States)

    Andersen, Kasper; Mariosa, Daniela; Adami, Hans-Olov; Held, Claes; Ingelsson, Erik; Lagerros, Ylva Trolle; Nyrén, Olof; Ye, Weimin; Bellocco, Rino; Sundström, Johan

    2014-09-01

    The nature of the association between levels of physical activity and risk of heart failure is little known. We investigated nonlinear associations of total and leisure time physical activity with risk of heart failure. In 1997, 39 805 persons without heart failure completed a questionnaire of lifestyle factors and medical history. We used Cox regression models to investigate total (adjusting for education and previous myocardial infarction) and direct (multivariable-adjusted) effects of self-reported total and leisure time physical activity on risk of heart failure of any cause and heart failure of nonischemic origin. Heart failure diagnoses were obtained until December 31, 2010. Higher leisure time physical activity was associated with lower risk of heart failure of any cause; hazard ratio of the total effect of leisure time physical activity was for fifth versus first quintile 0.54; 95% confidence interval was 0.44 to 0.66. The direct effect was similar. High total daily physical activity level was associated with lower risk of heart failure, although the effect was less pronounced than for leisure time physical activity (total effect hazard ratio, 0.81; 95% confidence interval, 0.69-0.95; fifth versus first quintile). A similar direct effect observed. Leisure time physical activity was inversely related to risk of developing heart failure in a dose-response fashion. This was reflected in a similar but less pronounced association of total physical activity with risk of heart failure. Only part of the effects appeared to be mediated by traditional risk factors. © 2014 American Heart Association, Inc.

  11. Dietary Flavonoid and Lignan Intake and Mortality in Prospective Cohort Studies: Systematic Review and Dose-Response Meta-Analysis.

    Science.gov (United States)

    Grosso, Giuseppe; Micek, Agnieszka; Godos, Justyna; Pajak, Andrzej; Sciacca, Salvatore; Galvano, Fabio; Giovannucci, Edward L

    2017-06-15

    Recent evidence has suggested that flavonoid and lignan intake may be associated with decreased risk of chronic and degenerative diseases. The aim of this meta-analysis was to assess the association between dietary flavonoid and lignan intake and all-cause and cardiovascular disease (CVD) mortality in prospective cohort studies. A systematic search was conducted in electronic databases to identify studies published from January 1996 to December 2015 that satisfied inclusion/exclusion criteria. Risk ratios and 95% confidence intervals were extracted and analyzed using a random-effects model. Nonlinear dose-response analysis was modeled by using restricted cubic splines. The inclusion criteria were met by 22 prospective studies exploring various flavonoid and lignan classes. Compared with lower intake, high consumption of total flavonoids was associated with decreased risk of all-cause mortality (risk ratio = 0.74, 95% confidence intervals: 0.55, 0.99), while a 100-mg/day increment in intake led to a (linear) decreased risk of 6% and 4% of all-cause and CVD mortality, respectively. Among flavonoid classes, significant results were obtained for intakes of flavonols, flavones, flavanones, anthocyanidins, and proanthocyanidins. Only limited evidence was available on flavonoid classes and lignans and all-cause mortality. Findings from this meta-analysis indicated that dietary flavonoids are associated with decreased risk of all-cause and CVD mortality. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts After Exposure to Very Low Dose of High Let Radiation

    Science.gov (United States)

    Hada, M.; George, K.; Chappell, L.; Cucinotta, F. A.

    2011-01-01

    The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivor with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (0.01 - 0.20 Gy) of 170 MeV/u Si-28 ions or 600 MeV/u Fe-56 ions, including doses where on average less than one direct ion traversal per cell nucleus occurs. Chromosomes were analyzed using the whole-chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). The responses for doses above 0.1 Gy (more than one ion traverses a cell) showed linear dose responses. However, for doses less than 0.1 Gy, both Si-28 ions and Fe-56 ions showed a dose independent response above background chromosome aberrations frequencies. Possible explanations for our results are non-targeted effects due to aberrant cell signaling [1], or delta-ray dose fluctuations [2] where a fraction of cells receive significant delta-ray doses due to the contributions of multiple ion tracks that do not directly traverse cell nuclei where chromosome aberrations are scored.

  13. Dietary Protein Sources and Incidence of Breast Cancer: A Dose-Response Meta-Analysis of Prospective Studies.

    Science.gov (United States)

    Wu, Jing; Zeng, Rong; Huang, Junpeng; Li, Xufeng; Zhang, Jiren; Ho, James Chung-Man; Zheng, Yanfang

    2016-11-17

    Protein is important to the human body, and different sources of protein may have different effects on the risk of breast cancer. Thus, we conducted a meta-analysis to investigate the association between different dietary protein sources and breast cancer risk. PubMed and several databases were searched until December 2015. Relevant articles were retrieved according to specific searching criteria. Forty-six prospective studies were included. The summary relative risk (RR) for highest versus lowest intake was 1.07 (95% confidence interval (CI) 1.01-1.14, I² = 34.6%) for processed meat, 0.92 (95% CI 0.84-1.00, I² = 0%) for soy food, 0.93 (95% CI 0.85-1.00, I² = 40.1%) for skim milk, and 0.90 (95% CI 0.82-1.00, I² = 0%) for yogurt. Similar conclusions were obtained in dose-response association for each serving increase: total red meat (RR: 1.07; 95% CI 1.01-1.14, I² = 7.1%), fresh red meat (RR: 1.13; 95% CI 1.01-1.26, I² = 56.4%), processed meat (RR: 1.09; 95% CI 1.02-1.17, I² = 11.8%), soy food (RR: 0.91; 95% CI 0.84-1.00, I² = 0%), and skim milk (RR: 0.96; 95% CI 0.92-1.00, I² = 11.9%). There was a null association between poultry, fish, egg, nuts, total milk, and whole milk intake and breast cancer risk. Higher total red meat, fresh red meat, and processed meat intake may be risk factors for breast cancer, whereas higher soy food and skim milk intake may reduce the risk of breast cancer.

  14. Dose-response relationship between alcohol use and blood pressure among drivers of commercial vehicles in Calabar, Southern Nigeria

    Directory of Open Access Journals (Sweden)

    Segun Bello

    2010-08-01

    Full Text Available Alcohol is a sedative/hypnotic with effects similar to those of barbiturates.1 The type of alcoholic beverages consumed depends on the social context and financial capability. Alcoholic beverages may be in form of beer, wine, dry gin. Drinking alcohol is an activity that many people enjoy; taking a few drinks occasionally is generally harmless. Most people do not have problems as a result of drinking alcohol in this manner, although this may predispose to heavy use. Heavy alcohol consumption has been shown in observational studies to have a strong positive association with elevated blood pressure.2-4 Further evidence have been shown by clinical trials5,6 that have demonstrated that reduction in alcohol intake among individuals who drink heavily (i.e. three or more drinks per day can lower blood pressure in normotensive and hypertensive men. Some studies have recorded a linear dose-response relationship sometimes starting with a consumption threshold of three drinks per day (30 g of ethanol.7-13 In others, the relationship has been non-linear especially in women, and some authors have speculated that ingestion of small quantities may reduce blood pressure.14-22 These discrepancies may reflect differences in investigational design, methods and populations.23 Many studies have been done in this area in developed countries like the United States, United Kingdom and Australia. This is however, not a commonly researched area in this part of the world. The aim of this study was to assess the relationship between alcohol consumption and blood pressure of drivers of commercial vehicles.

  15. Dietary fiber intake and risk of type 2 diabetes: a dose-response analysis of prospective studies.

    Science.gov (United States)

    Yao, Baodong; Fang, Hong; Xu, Wanghong; Yan, Yujie; Xu, Huilin; Liu, Yinan; Mo, Miao; Zhang, Hua; Zhao, Yanping

    2014-02-01

    Observational studies suggest an association between dietary fiber intake and risk of type 2 diabetes, but the results are inconclusive. We conducted a meta-analysis of prospective studies evaluating the associations of dietary fiber intake and risk of type 2 diabetes. Relevant studies were identified by searching EMBASE (from 1974 to April 2013) and PubMed (from 1966 to April 2013). The fixed or random-effect model was selected based on the homogeneity test among studies. In addition, a 2-stage random-effects dose-response meta-analysis was performed. We identified 17 prospective cohort studies of dietary fiber intake and risk of type 2 diabetes involving 19,033 cases and 488,293 participants. The combined RR (95 % CI) of type 2 diabetes for intake of total dietary fiber, cereal fiber, fruit fiber and insoluble fiber was 0.81 (0.73-0.90), 0.77 (0.69-0.85), 0.94 (0.88-0.99) and 0.75 (0.63-0.89), respectively. A nonlinear relationship was found of total dietary fiber intake with risk of type 2 diabetes (P for nonlinearity diabetes were 0.98 (0.90-1.06), 0.97 (0.87-1.07), 0.89 (0.80-0.99), 0.76 (0.65-0.88), and 0.66 (0.53-0.82) for 15, 20, 25, 30, and 35 g/day. The departure from nonlinear relationship was not significant (P for nonlinearity = 0.72), and the risk of type 2 diabetes decreased by 6 % (RR 0.94, 95 % CI 0.93-0.96) for 2 g/day increment in cereal fiber intake. Findings from this meta-analysis indicate that the intakes of dietary fiber may be inversely associated with risk of type 2 diabetes.

  16. SU-F-T-130: [18F]-FDG Uptake Dose Response in Lung Correlates Linearly with Proton Therapy Dose

    Energy Technology Data Exchange (ETDEWEB)

    Kim, D; Titt, U; Mirkovic, D [University of Texas M.D. Anderson Cancer Center, Houston, TX (United States)

    2016-06-15

    Purpose: Analysis of clinical outcomes in lung cancer patients treated with protons using 18F-FDG uptake in lung as a measure of dose response. Methods: A test case lung cancer patient was selected in an unbiased way. The test patient’s treatment planning and post treatment positron emission tomography (PET) were collected from picture archiving and communication system at the UT M.D. Anderson Cancer Center. Average computerized tomography scan was registered with post PET/CT through both rigid and deformable registrations for selected region of interest (ROI) via VelocityAI imaging informatics software. For the voxels in the ROI, a system that extracts the Standard Uptake Value (SUV) from PET was developed, and the corresponding relative biological effectiveness (RBE) weighted (both variable and constant) dose was computed using the Monte Carlo (MC) methods. The treatment planning system (TPS) dose was also obtained. Using histogram analysis, the voxel average normalized SUV vs. 3 different doses was obtained and linear regression fit was performed. Results: From the registration process, there were some regions that showed significant artifacts near the diaphragm and heart region, which yielded poor r-squared values when the linear regression fit was performed on normalized SUV vs. dose. Excluding these values, TPS fit yielded mean r-squared value of 0.79 (range 0.61–0.95), constant RBE fit yielded 0.79 (range 0.52–0.94), and variable RBE fit yielded 0.80 (range 0.52–0.94). Conclusion: A system that extracts SUV from PET to correlate between normalized SUV and various dose calculations was developed. A linear relation between normalized SUV and all three different doses was found.

  17. SnET2 for the treatment of vascular disease: dose/response study in New Zealand white (NZW) rabbits

    Science.gov (United States)

    Narciso, Hugh L., Jr.; Anderson, Steven C.; DeHoratius, Sandra L.; Guerrero, Jan; Wang, T.; Spears, J. Richard

    1995-05-01

    Tin ethyl etiopurpurin, SnET2, is presently undergoing clinical trials for the treatment of cutaneous cancers and AIDS related Kaposi's sarcoma. Extensive pre-clinical work has been performed investigating the uptake, localization, and retention of SnET2 in catheter induced atheromatous plaques in New Zealand White (NZW) rabbits and juvenile female swine. The ultimate goal is to employ SnET2 for the prevention of intimal hyperplasia following various forms of angioplasty, thus enabling the prevention of a significant cause of restenosis. To that end, a dose/response study was undertaken to investigate the effect of varying total light dose (200, 100, and 50 J/cm2) and light dose rate (637, 318, 159 mW/cm2) during SnET2-Photodynamic Therapy, SnET2-PDT, of catheter induced plaque in a NZW rabbit iliac artery model. The SnET2 dose was held constant at 1.0 mg/kg b.w. and light was delivered intraluminally via a guidewire compatible light diffusing balloon catheter. The greatest light dose of those tested without inducing thermal damage was found to be 318 mW/cm2 while the total light dose of 50 J/cm2 produced PDT effect which was limited to the neo-intima. A relatively substantial total light dose of 200 J/cm2 was shown to produce a transmural PDT effect. This study demonstrated that the depth of PDT effect can be modulated by varying the total light dose.

  18. Temporal consistency of lidar observations during aerosol transport events in the framework of the ChArMEx/ADRIMED campaign at Minorca in June 2013

    Directory of Open Access Journals (Sweden)

    P. Chazette

    2016-03-01

    Full Text Available We performed synergetic daytime and nighttime active and passive remote-sensing observations at Minorca (Balearic Islands, Spain, over more than 3 weeks during the Chemistry-Aerosol Mediterranean Experiment/Aerosol Direct Radiative Effect in the Mediterranean (ChArMEx/ADRIMED special observation period (SOP 1a, June–July 2013. We characterized the aerosol optical properties and type in the low and middle troposphere using an automated procedure combining Rayleigh–Mie–Raman lidar (355, 387 and 407 nm with depolarization (355 nm and AERONET Cimel® sun-photometer data. Results show a high variability due to varying dynamical forcing. The mean column-averaged lidar backscatter-to-extinction ratio (BER was close to 0.024 sr−1 (lidar ratio of  ∼ 41.7 sr, with a large dispersion of ±33 % over the whole observation period due to changing atmospheric transport regimes and aerosol sources. The ground-based remote-sensing measurements, coupled with satellite observations, allowed the documentation of (i dust particles up to 5 km (above sea level in altitude originating from Morocco and Algeria from 15 to 18 June with a peak in aerosol optical thickness (AOT of 0.25 ± 0.05 at 355 nm, (ii a long-range transport of biomass burning aerosol (AOT  =  0.18 ± 0.16 related to North American forest fires detected from 26 to 28 June 2013 by the lidar between 2 and 7 km and (iii mixture of local sources including marine aerosol particles and pollution from Spain. During the biomass burning event, the high value of the particle depolarization ratio (8–14 % may imply the presence of dust-like particles mixed with the biomass burning aerosols in the mid-troposphere. For the field campaign period, we also show linearity with SEVIRI retrievals of the aerosol optical thickness despite 35 % relative bias, which is discussed as a function of aerosol type.

  19. A Statistical Framework for Microbial Source Attribution: Measuring Uncertainty in Host Transmission Events Inferred from Genetic Data (Part 2 of a 2 Part Report)

    Energy Technology Data Exchange (ETDEWEB)

    Allen, J; Velsko, S

    2009-11-16

    outbreak or the availability of only partial rather than whole genome sequencing, indel information was shown to have the potential to improve performance but only for select outbreak conditions. In examined HIV transmission cases, extended evolution proved to be the limiting factor in assigning high confidence to transmission links, however, the potential to correct for extended evolution not associated with transmission events is demonstrated. Outbreak specific conditions such as selective pressure (in the form of varying mutation rate), are shown to impact the strength of inference made and a Monte Carlo simulation tool is introduced, which is used to provide upper and lower bounds on the confidence values associated with a forensic hypothesis.

  20. A Reanalysis of Curvature in the Dose Response for Cancer and Modifications by Age at Exposure Following Radiation Therapy for Benign Disease

    Energy Technology Data Exchange (ETDEWEB)

    Little, Mark P., E-mail: mark.little@nih.gov [Radiation Epidemiology Branch, National Cancer Institute, Rockville, Maryland (United States); Stovall, Marilyn; Smith, Susan A. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Kleinerman, Ruth A. [Radiation Epidemiology Branch, National Cancer Institute, Rockville, Maryland (United States)

    2013-02-01

    Purpose: To assess the shape of the dose response for various cancer endpoints and modifiers by age and time. Methods and Materials: Reanalysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by cancer endpoint (stomach, pancreas, lung, leukemia, all other). Results: There are statistically significant (P<.05) excess risks for all cancer and for lung cancer and borderline statistically significant risks for stomach cancer (P=.07), and leukemia (P=.06), with excess relative risks Gy{sup -1} of 0.024 (95% confidence interval [CI] 0.011, 0.039), 0.559 (95% CI 0.221, 1.021), 0.042 (95% CI -0.002, 0.119), and 1.087 (95% CI -0.018, 4.925), respectively. There is statistically significant (P=.007) excess risk of pancreatic cancer when adjusted for dose-response curvature. General downward curvature is apparent in the dose response, statistically significant (P<.05) for all cancers, pancreatic cancer, and all other cancers (ie, other than stomach, pancreas, lung, leukemia). There are indications of reduction in relative risk with increasing age at exposure (for all cancers, pancreatic cancer), but no evidence for quadratic variations in relative risk with age at exposure. If a linear-exponential dose response is used, there is no significant heterogeneity in the dose response among the 5 endpoints considered or in the speed of variation of relative risk with age at exposure. The risks are generally consistent with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers. Conclusions: There are excess risks for various malignancies in this data set. Generally there is a marked downward curvature in the dose response and significant reduction in relative risk with increasing age at exposure. The consistency of risks with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.

  1. Dose-Response Relationship between Dietary Magnesium Intake and Risk of Type 2 Diabetes Mellitus: A Systematic Review and Meta-Regression Analysis of Prospective Cohort Studies

    Directory of Open Access Journals (Sweden)

    Xin Fang

    2016-11-01

    Full Text Available The epidemiological evidence for a dose-response relationship between magnesium intake and risk of type 2 diabetes mellitus (T2D is sparse. The aim of the study was to summarize the evidence for the association of dietary magnesium intake with risk of T2D and evaluate the dose-response relationship. We conducted a systematic review and meta-analysis of prospective cohort studies that reported dietary magnesium intake and risk of incident T2D. We identified relevant studies by searching major scientific literature databases and grey literature resources from their inception to February 2016. We included cohort studies that provided risk ratios, i.e., relative risks (RRs, odds ratios (ORs or hazard ratios (HRs, for T2D. Linear dose-response relationships were assessed using random-effects meta-regression. Potential nonlinear associations were evaluated using restricted cubic splines. A total of 25 studies met the eligibility criteria. These studies comprised 637,922 individuals including 26,828 with a T2D diagnosis. Compared with the lowest magnesium consumption group in the population, the risk of T2D was reduced by 17% across all the studies; 19% in women and 16% in men. A statistically significant linear dose-response relationship was found between incremental magnesium intake and T2D risk. After adjusting for age and body mass index, the risk of T2D incidence was reduced by 8%–13% for per 100 mg/day increment in dietary magnesium intake. There was no evidence to support a nonlinear dose-response relationship between dietary magnesium intake and T2D risk. The combined data supports a role for magnesium in reducing risk of T2D, with a statistically significant linear dose-response pattern within the reference dose range of dietary intake among Asian and US populations. The evidence from Europe and black people is limited and more prospective studies are needed for the two subgroups.

  2. TH-E-BRF-03: A Multivariate Interaction Model for Assessment of Hippocampal Vascular Dose-Response and Early Prediction of Radiation-Induced Neurocognitive Dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Farjam, R; Pramanik, P; Srinivasan, A; Chapman, C; Tsien, C; Lawrence, T; Cao, Y [University of Michigan, Ann Arbor, MI (United States)

    2014-06-15

    Purpose: Vascular injury could be a cause of hippocampal dysfunction leading to late neurocognitive decline in patients receiving brain radiotherapy (RT). Hence, our aim was to develop a multivariate interaction model for characterization of hippocampal vascular dose-response and early prediction of radiation-induced late neurocognitive impairments. Methods: 27 patients (17 males and 10 females, age 31–80 years) were enrolled in an IRB-approved prospective longitudinal study. All patients were diagnosed with a low-grade glioma or benign tumor and treated by 3-D conformal or intensity-modulated RT with a median dose of 54 Gy (50.4–59.4 Gy in 1.8− Gy fractions). Six DCE-MRI scans were performed from pre-RT to 18 months post-RT. DCE data were fitted to the modified Toft model to obtain the transfer constant of gadolinium influx from the intravascular space into the extravascular extracellular space, Ktrans, and the fraction of blood plasma volume, Vp. The hippocampus vascular property alterations after starting RT were characterized by changes in the hippocampal mean values of, μh(Ktrans)τ and μh(Vp)τ. The dose-response, Δμh(Ktrans/Vp)pre->τ, was modeled using a multivariate linear regression considering integrations of doses with age, sex, hippocampal laterality and presence of tumor/edema near a hippocampus. Finally, the early vascular dose-response in hippocampus was correlated with neurocognitive decline 6 and 18 months post-RT. Results: The μh(Ktrans) increased significantly from pre-RT to 1 month post-RT (p<0.0004). The multivariate model showed that the dose effect on Δμh(Ktrans)pre->1M post-RT was interacted with sex (p<0.0007) and age (p<0.00004), with the dose-response more pronounced in older females. Also, the vascular dose-response in the left hippocampus of females was significantly correlated with memory function decline at 6 (r = − 0.95, p<0.0006) and 18 (r = −0.88, p<0.02) months post-RT. Conclusion: The hippocampal vascular

  3. Accuracy requirements for head and neck intensity-modulated radiation therapy based on observed dose response of the major salivary glands.

    Science.gov (United States)

    Kapanen, Mika; Collan, Juhani; Saarilahti, Kauko; Heikkonen, Jorma; Kairemo, Kalevi; Tenhunen, Mikko

    2009-10-01

    We estimated accuracy requirements for dose and position of the major salivary glands in head and neck intensity-modulated radiotherapy (IMRT) based on the dose response characteristics of the glands obtained by using the sigmoidal dose response model. Dose response of the parotid and submandibular salivary glands was determined for 25 head and neck cancer patients treated by IMRT. Individual salivary gland functions were assessed by scintigraphy before and 6months after radiotherapy. Accuracy requirements were estimated by using the maximal slope of the fitted dose response model and average value of the dose gradients within the glands. In addition, systematic and random set-up errors were estimated for each patient by at least weekly portal imaging. We investigated the changes in the salivary gland mean doses (D(mean)) that would have occurred without correction of patient positioning. This was done by shifting the planned isocenter according to the obtained systematic set-up error and by recalculating the dose distribution in treatment planning system (TPS). The maximal slope and D(50) values of the dose response model were -0.0411/Gy and 30.4Gy, respectively. The results suggested that spared fraction of individual salivary gland function can be estimated with an accuracy of +/-10%, if actual D(mean) of the gland is within +/-2.4Gy with the planned value. On the average, this was achieved with maximal systematic positional 3D shift of 3.0mm for the parotid glands and 2.7mm for the submandibular glands. The magnitude of systematic 1D set-up errors was 1.7+/-1.3mm (mean+/-SD) while that of systematic 3D errors was 3.4+/-1.6mm. The SD of random set-up errors was 1.5mm. The magnitude of D(mean) shifts due to set-up errors was 1.5+/-1.4Gy. The steepness of dose gradients within the glands was 0.8+/-0.5Gy/mm in the most critical direction (toward the glands). When substantial part of salivary gland function is intended to be spared in head and neck IMRT, narrow

  4. Dose response effects of a caffeine-containing energy drink on muscle performance: a repeated measures design.

    Science.gov (United States)

    Del Coso, Juan; Salinero, Juan José; González-Millán, Cristina; Abián-Vicén, Javier; Pérez-González, Benito

    2012-05-08

    Energy drinks have become the most used caffeine-containing beverages in the sport setting. The aim of this study was to determine the effects of two doses of a caffeine-containing energy drink on muscle performance during upper- and lower-body power-load tests. In a randomized order, twelve active participants ingested 1 and 3 mg of caffeine per kg of body weight using a commercially available energy drink (Fure®, ProEnergetics) or the same drink without caffeine (placebo; 0 mg/kg). After sixty minutes, resting metabolic rate, heart rate and blood pressure were determined. Then, half-squat and bench-press power production with loads from 10 to 100% of 1 repetition maximum was determined using a rotator encoder. In comparison to the placebo, the ingestion of the caffeinated drink increased mean arterial pressure (82 ± 7 < 88 ± 8 ≈ 90 ± 6 mmHg for 0 mg/kg, 1 mg/kg, 3 mg/kg of caffeine, respectively; P < 0.05) and heart rate (57 ± 7 < 59 ± 8 < 62 ± 8 beats/min, respectively; P < 0.05) at rest in a dose response manner, though it did not affect resting metabolic rate. While the ingestion of 1 mg/kg of caffeine did not affect maximal power during the power-load tests with respect to the placebo, 3 mg/kg increased maximal power in the half-squat (2554 ± 167 ≈ 2549 ± 161 < 2726 ± 167 W, respectively; P < 0.05) and bench-press actions (349 ± 34 ≈ 358 ± 35 < 375 ± 33 W, respectively; P < 0.05). A caffeine dose of at least 3 mg/kg in the form of an energy drink is necessary to significantly improve half-squat and bench-press maximal muscle power.

  5. Dietary vitamin C intake and the risk of hip fracture: a dose-response meta-analysis.

    Science.gov (United States)

    Sun, Y; Liu, C; Bo, Y; You, J; Zhu, Y; Duan, D; Cui, H; Lu, Q

    2017-11-03

    The meta-analysis suggested that dietary vitamin C was statistically inversely associated with the risk of hip fracture (overall OR = 0.73, 95% CI = 0.55-0.97, I (2) = 69.1%) and with the increase of 50 mg/day vitamin C intake, the risk of hip fracture will reduce by 5% (OR = 0.95, 95% CI 0.91-1.00, P = 0.05). Previous studies had inconsistent findings regarding the association between vitamin C intake and the risk of hip fracture. Therefore, we conducted a meta-analysis to evaluate the association of dietary vitamin C intake and the risk of hip fracture. Relevant studies were identified by searching PubMed, Embase, and Web of Science up to December 2016. Additional articles were identified from reviewing the reference lists of relevant articles. The summary relative risks (RRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by random effects model. Funnel plot and Egger's test were used to test publication bias. The total six articles containing 7908 controls and 2899 cases of hip fracture were included in this meta-analysis. By comparing the highest versus the lowest categories of vitamin C intake, we found that dietary vitamin C was statistically correlated with the risk of hip fracture [overall OR = 0.73, 95% CI = 0.55-0.97, I (2) = 69.1%]. A linear dose-response association showed that the increase with vitamin C intake of 50 mg/day statistically reduced by 5% (OR = 0.95, 95% CI 0.91-1.00, P = 0.05) the risk of hip fracture. In conclusion, the results of current meta-analysis strongly support that increasing dietary vitamin C intake can decrease the risk of hip fracture. In order to verify the association of vitamin C intake and hip fracture risk, further well-designed largely randomized controlled trials (RCTs) are needed.

  6. Hypertonic Saline in Conjunction with High-Dose Furosemide Improves Dose-Response Curves in Worsening Refractory Congestive Heart Failure.

    Science.gov (United States)

    Paterna, Salvatore; Di Gaudio, Francesca; La Rocca, Vincenzo; Balistreri, Fabio; Greco, Massimiliano; Torres, Daniele; Lupo, Umberto; Rizzo, Giuseppina; di Pasquale, Pietro; Indelicato, Sergio; Cuttitta, Francesco; Butler, Javed; Parrinello, Gaspare

    2015-10-01

    14% for urine output; 29, 24, and 16% for total sodium excretion; 45, 34, and 20% for urinary osmolarity; and 27, 36, and 32% for total furosemide excretion in groups 1, 2, and 3, respectively. These findings were translated in an improvement in the furosemide dose-response curves in these patients. These results may serve as new pathophysiological basis for HSS use in the treatment of refractory CHF.

  7. Accelerometer-measured dose-response for physical activity, sedentary time, and mortality in US adults123

    Science.gov (United States)

    Matthews, Charles E; Keadle, Sarah Kozey; Troiano, Richard P; Kahle, Lisa; Koster, Annemarie; Brychta, Robert; Van Domelen, Dane; Caserotti, Paolo; Chen, Kong Y; Harris, Tamara B; Berrigan, David

    2016-01-01

    Background: Moderate-to-vigorous–intensity physical activity is recommended to maintain and improve health, but the mortality benefits of light activity and risk for sedentary time remain uncertain. Objectives: Using accelerometer-based measures, we 1) described the mortality dose-response for sedentary time and light- and moderate-to-vigorous–intensity activity using restricted cubic splines, and 2) estimated the mortality benefits associated with replacing sedentary time with physical activity, accounting for total activity. Design: US adults (n = 4840) from NHANES (2003–2006) wore an accelerometer for ≤7 d and were followed prospectively for mortality. Proportional hazards models were used to estimate adjusted HRs and 95% CIs for mortality associations with time spent sedentary and in light- and moderate-to-vigorous–intensity physical activity. Splines were used to graphically present behavior-mortality relation. Isotemporal models estimated replacement associations for sedentary time, and separate models were fit for low- (<5.8 h total activity/d) and high-active participants to account for nonlinear associations. Results: Over a mean of 6.6 y, 700 deaths occurred. Compared with less-sedentary adults (6 sedentary h/d), those who spent 10 sedentary h/d had 29% greater risk (HR: 1.29; 95% CI: 1.1, 1.5). Compared with those who did less light activity (3 h/d), those who did 5 h of light activity/d had 23% lower risk (HR: 0.77; 95% CI: 0.6, 1.0). There was no association with mortality for sedentary time or light or moderate-to-vigorous activity in highly active adults. In less-active adults, replacing 1 h of sedentary time with either light- or moderate-to-vigorous–intensity activity was associated with 18% and 42% lower mortality, respectively. Conclusions: Health promotion efforts for physical activity have mostly focused on moderate-to-vigorous activity. However, our findings derived from accelerometer-based measurements suggest that increasing

  8. Fat Intake Is Not Linked to Prostate Cancer: A Systematic Review and Dose-Response Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Chang Xu

    Full Text Available Since the late 1960s, the average global supply of fat has increased by 20 g per capita per day. While fat intake has been considered a potential risk factor for prostate cancer (Pca, the hypothesis from previous epidemiologic studies remained equivocal.Relevant cohort studies were identified through a literature search in PubMed, ScienceDirect and Wiley Online Library up to March 1, 2015. A systematic review and dose-response meta-analysis were used to assess the relationship between fat intake and the risk for Pca.We identified 14 cohort studies, which included 37,349 cases and a total of 751,030 participants. We found no evidence of a non-linear association between fat intake and the risk for Pca. Overall, the summarized relative risks for every 28.35 g increment a day was 0.99 (95%CI: 0.98, 1.01; P=0.94; n=13 for total fat intake, 1.00 (95%CI: 1.00, 1.00; P=0.72; n=9 for saturated fat, 0.99 (95%CI: 0.95, 1.03; P=0.55; n=7 for polyunsaturated fat, and 1.00 (95%CI: 0.95, 1.04; P=0.85; n=8 for monounsaturated fat. Additionally, there was no link to the risk for advanced stage Pca regarding total fat intake (RR=1.02, 95%CI: 0.96, 1.08; P=0.63; n=5, saturated fat (RR=0.96, 95%CI: 0.84, 1.11; P=0.61; n=6, polyunsaturated fat (RR=0.96, 95%CI: 0.79, 1.17; P=0.68; n=6, or monounsaturated fat (RR=0.96, 95%CI: 0.86, 1.07; P=0.42; n=6. Subgroup and sensitively analyses showed consistent results.Little evidence from published cohort studies supports the statement that total fat, saturated fat or unsaturated fat intake increases the risk for Pca or advanced stage Pca.

  9. Dissolution and subsequent re-crystallization as zeroing mechanism, thermal properties and component resolved dose response of salt (NaCl) for retrospective dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Polymeris, George S., E-mail: polymers@auth.gr [Faculty of Science and Arts, Physics Department, ISIK University, 34980-Sile, Istanbul (Turkey); Kitis, George [Aristotle University of Thessaloniki, Nuclear Physics Laboratory, 54124-Thessaloniki (Greece); Kiyak, Nafiye G. [Faculty of Science and Arts, Physics Department, ISIK University, 34980-Sile, Istanbul (Turkey); Sfamba, Ioanna; Subedi, Bhagawan [Aristotle University of Thessaloniki, Nuclear Physics Laboratory, 54124-Thessaloniki (Greece); Pagonis, Vasilis [Physics Department, McDaniel College, Westminster, MD 21157 (United States)

    2011-09-15

    In the present study we report dosimetric properties of iodized salt aiming at using it as an accidental luminescent dosimeter. It was found that the very good sensitivity of its main dosimetric peak is strongly affected by thermal treatments. This is also the case for OSL emission. The sensitivity loss due to heating implies that caution should be exercised while applying single aliquot protocols for dose evaluation. The sequence of dissolution and subsequent re-crystallization was established to be an extremely effective zeroing mechanism for the TL signal. The linearity in the dose response was also monitored in the case of dissolved and subsequently re-crystallized salt. In the case of naturally occurring salt, zeroing of the TL signal due to dissolution as well as the linearity of dose response up to doses as large as 100 Gy were found to be very promising features for dating applications.

  10. The six year report: Acidification of surface water in Europe and North America. Dose/response relationships and long-term trends

    Energy Technology Data Exchange (ETDEWEB)

    Skjelkvaale, B.L.; Newell, A.D.; Raddum, G.; Johannessen, M.; Hovind, H.; Tjomsland, T.; Wathne, B.M.

    1994-12-31

    This report discusses The International Cooperative Programme on Assessment and Monitoring of Acidification of Rivers and Lakes, which is designed to (1) establish degree and extent of acidification of surface waters, (2) evaluate dose/response relationships and (3) define long-term trends and variations in aquatic chemistry and biota attributable to atmospheric pollution. Data from 200 sites in 14 countries of Europe and North America are available. Dose/response relationships show that the fauna is adapted to different water qualities in different regions, and that critical limits for the fauna must be calculated according to data for the specific region. Long-term trends of water chemistry show decreases in SO{sub 4}{sup 2-} and Ca{sup 2+} at many sites. Nitrate shows no consistent trends. 66 refs., 26 figs., 16 tabs.

  11. The incidence of radioepidermitis and the dose-response relationship in parotid gland cancer patients treated with 125I seed brachytherapy. Incidence of radioepidermitis and the dose-response relationship

    Energy Technology Data Exchange (ETDEWEB)

    Mao, Ming-Hui; Zheng, Lei; Gao, Hong; Zhang, Jie; Liu, Shu-ming; Huang, Ming-wei; Shi, Yan [Peking University School and Hospital of Stomatology, Department of Oral and Maxillofacial Surgery, Beijing (China); Zhang, Jian-Guo [Peking University School and Hospital of Stomatology, Department of Oral and Maxillofacial Surgery, Beijing (China); Fujian Provincial Hospital, Fujian (China)

    2014-09-09

    We studied the incidence and dose-response relationship of radioepidermitis in parotid gland carcinoma patients treated with [{sup 125}I] seed brachytherapy in the hopes of designing an optimized pre-implant treatment plan that would reduce the incidence and severity of radioepidermitis in patients receiving this therapy. Between January 2007 and May 2010, 100 parotid gland cancer patients were treated postoperatively with [{sup 125}I] seed brachytherapy. The matched peripheral dose (MPD) was 80-140 Gy, and [{sup 125}I] seed activity was 0.7-0.8 mCi. The mean dose delivered to the skin was calculated in the post-implant CT on day 0 following implantation. Grades of acute and late dermatitis were evaluated at 2, 6, 12, and 18 months post-implantation. Most patients experienced grade 0-2 acute and late skin side effects (86 and 97 %, respectively), though a small subset developed severe complications. Most grade 1-3 effects resolved within 6 months of implantation, though some grade 1-3 effects and all grade 4 effects remained unchanged throughout the 18-month follow-up period. Grade 3 and 4 effects were most prominent (75 and 25 %, respectively) with doses of 110-140 Gy; doses higher than 140 Gy produced only grade 4 effects. [{sup 125}I] seed brachytherapy produced acceptable levels of acute and late radioepidermitis with a good clinical outcome. A mean dose under 100 Gy delivered to the skin was safe, though doses of 110-140 Gy should be given with caution and extra monitoring; doses greater than 140 Gy are dangerous and likely to produce grade 4-5 effects. (orig.) [German] Wir untersuchten die Inzidenz und die Dosis-Wirkung-Beziehung bei Patienten mit Ohrspeicheldruesenkrebs, die mit [{sup 125}I]-Seed-Brachytherapie behandelt wurden, in der Hoffnung, eine optimierte praeimplantologische Behandlung zu entwickeln, welche die Inzidenz und Schwere der Radioepidermitis bei Patienten, die diese Therapie erhalten haben, reduziert. Zwischen Januar 2007 und Mai 2010

  12. Adult height after long-term, continuous growth hormone (GH) treatment in short children born small for gestational age: results of a randomized, double-blind, dose-response GH trial

    NARCIS (Netherlands)

    Y. van Pareren; M. Houdijk; M. Jansen (Maarten); M. Reeser; P.G.H. Mulder (Paul); A.C.S. Hokken-Koelega (Anita)

    2003-01-01

    textabstractThe GH dose-response effect of long-term continuous GH treatment on adult height (AH) was evaluated in 54 short children born small for gestational age (SGA) who were participating in a randomized, double-blind, dose-response trial. Patients were randomly and blindly

  13. Frameworks in CS1

    DEFF Research Database (Denmark)

    Christensen, Henrik Bærbak; Caspersen, Michael Edelgaard

    2002-01-01

    In this paper we argue that introducing object-oriented frameworks as subject already in the CS1 curriculum is important if we are to train the programmers of tomorrow to become just as much software reusers as software producers. We present a simple, graphical, framework that we have successfully...... used to introduce the principles of object-oriented frameworks to students at the introductory programming level. Our framework, while simple, introduces central abstractions such as inversion of control, event-driven programming, and variability points/hot-spots. This has provided a good starting...... point for introducing graphical user interface frameworks such as Java Swing and AWT as the students are not overwhelmed by all the details of such frameworks right away but given a conceptual road-map and practical experience that allow them to cope with the complexity....

  14. Physical activity and the risk of gestational diabetes mellitus: a systematic review and dose?response meta-analysis of epidemiological studies

    OpenAIRE

    Aune, D; Sen, A; Henriksen, T; Saugstad, OD; Tonstad, S.

    2016-01-01

    Physical activity has been inconsistently associated with risk of gestational diabetes mellitus in epidemiological studies, and questions remain about the strength and shape of the dose?response relationship between the two. We therefore conducted a systematic review and meta-analysis of cohort studies and randomized trials?on physical activity and gestational diabetes mellitus. PubMed, Embase and Ovid databases were searched for cohort studies, and randomized controlled trials of physical ac...

  15. The Role of Target and Bystander Cells in Dose-Response Relationship of Radiation-Induced Bystander Effects in Two Cell Lines

    Science.gov (United States)

    Soleymanifard, Shokouhozaman; Bahreyni Toossi, Mohammad Taghi; Sazgarnia, Ameneh; Mohebbi, Shokoufe

    2013-01-01

    Objective(s): Radiation effect induced in nonirradiated cells which are adjacent or far from irradiated cells is termed radiation-induced bystander effect (RIBE). Published data on dose-response relationship of RIBE is controversial. In the present study the role of targeted and bystander cells in RIBE dose-response relationship of two cell lines have been investigated. Materials and Methods: Two cell lines (QU-DB and MRC5) which had previously exhibited different dose-response relationship were selected. In the previous study the two cell lines received medium from autologous irradiated cells and the results showed that the magnitude of damages induced in QU-DB cells was dependent on dose unlike MRC5 cells. In the present study, the same cells irradiated with 0.5, 2 and 4 Gy gamma rays and their conditioned media were transferred to nonautologous bystander cells; such that the bystander effects due to cross-interaction between them were studied. Micronucleus assay was performed to measure the magnitude of damages induced in bystander cells (RIBE level). Results: QU-DB cells exhibited a dose-dependent response. RIBE level in MRC5 cells which received medium from 0.5 and 2 Gy QU-DB irradiated cells was not statistically different, but surprisingly when they received medium from 4Gy irradiated QU-DB cells, RIBE was abrogated. Conclusion: Results pertaining to QU-DB and MRC5 cells indicated that both target and bystander cells determined the outcome. Triggering the bystander effect depended on the radiation dose and the target cell-type, but when RIBE was triggered, dose-response relationship was predominantly determined by the bystander cell type. PMID:24298387

  16. The role of target and bystander cells in dose-response relationship of radiation-induced bystander effects in two cell lines.

    Science.gov (United States)

    Soleymanifard, Shokouhozaman; Bahreyni Toossi, Mohammad Taghi; Sazgarnia, Ameneh; Mohebbi, Shokoufe

    2013-02-01

    Radiation effect induced in nonirradiated cells which are adjacent or far from irradiated cells is termed radiation-induced bystander effect (RIBE). Published data on dose-response relationship of RIBE is controversial. In the present study the role of targeted and bystander cells in RIBE dose-response relationship of two cell lines have been investigated. Two cell lines (QU-DB and MRC5) which had previously exhibited different dose-response relationship were selected. In the previous study the two cell lines received medium from autologous irradiated cells and the results showed that the magnitude of damages induced in QU-DB cells was dependent on dose unlike MRC5 cells. In the present study, the same cells irradiated with 0.5, 2 and 4 Gy gamma rays and their conditioned media were transferred to nonautologous bystander cells; such that the bystander effects due to cross-interaction between them were studied. Micronucleus assay was performed to measure the magnitude of damages induced in bystander cells (RIBE level). QU-DB cells exhibited a dose-dependent response. RIBE level in MRC5 cells which received medium from 0.5 and 2 Gy QU-DB irradiated cells was not statistically different, but surprisingly when they received medium from 4Gy irradiated QU-DB cells, RIBE was abrogated. RESULTS pertaining to QU-DB and MRC5 cells indicated that both target and bystander cells determined the outcome. Triggering the bystander effect depended on the radiation dose and the target cell-type, but when RIBE was triggered, dose-response relationship was predominantly determined by the bystander cell type.

  17. Influence of strength training variables on strength gains in adults over 55 years-old: a meta-analysis of dose-response relationships.

    Science.gov (United States)

    Silva, Nádia L; Oliveira, Ricardo B; Fleck, Steven J; Leon, Antonio C M P; Farinatti, Paulo

    2014-05-01

    The importance of strength training to elderly individuals is well established. However, the dose-response relationship of the benefits of strength training in this population is unclear. The purpose of the study was to use meta-analysis to investigate the dose-response of the effects of strength training in elderly individuals. Fifteen studies with a total of 84 effect-sizes were included. The analyses examined the dose-response relationships of the following training variables 'intensity', 'number of sets', 'weekly frequency', and 'training duration' on strength improvement. The studies selected met the following inclusion criteria: (a) randomized controlled trials; (b) trained healthy subjects of both genders; (c) trained subjects aged 55 years or older; (d) strength increases were determined pre- and post-training; (e) use of similar strength evaluation techniques (strength determined by a repetition maximum test) and training routine (dynamic concentric-eccentric knee extension exercise to train the quadriceps muscle group). The effect-sizes were calculated using fixed and random effect models with the main effects determined by meta-regression. Many combinations of training variables resulted in strength increases. However meta-regression indicated only "training duration" had a significant dose-response relationship to strength gains (p=0.001). Over durations of 8-52 weeks, longer training durations had a greater effect on strength gains compared to shorter duration protocols. Resistive training causes strength gains in elderly individuals, provided the training duration is sufficiently long, regardless of the combination of other training variables. Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  18. A randomized, dose-response study of sugammadex given for the reversal of deep rocuronium- or vecuronium-induced neuromuscular blockade under sevoflurane anesthesia

    DEFF Research Database (Denmark)

    Duvaldestin, Philippe; Kuizenga, Karel; Saldien, Vera

    2010-01-01

    Sugammadex is the first of a new class of selective muscle relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade induced by rocuronium and vecuronium. Many studies have demonstrated a dose-response relationship with sugammadex for reversal of neuromuscular...... blockade in patients induced and maintained under propofol anesthesia. However, sevoflurane anesthesia, unlike propofol, can prolong the effect of neuromuscular blocking drugs (NMBDs) such as rocuronium and vecuronium....

  19. Systematic review using meta-analyses to estimate dose-response relationships between iodine intake and biomarkers of iodine status in different population groups.

    Science.gov (United States)

    Ristić-Medić, Danijela; Dullemeijer, Carla; Tepsić, Jasna; Petrović-Oggiano, Gordana; Popović, Tamara; Arsić, Aleksandra; Glibetić, Marija; Souverein, Olga W; Collings, Rachel; Cavelaars, Adriënne; de Groot, Lisette; van't Veer, Pieter; Gurinović, Mirjana

    2014-03-01

    The objective of this systematic review was to identify studies investigating iodine intake and biomarkers of iodine status, to assess the data of the selected studies, and to estimate dose-response relationships using meta-analysis. All randomized controlled trials, prospective cohort studies, nested case-control studies, and cross-sectional studies that supplied or measured dietary iodine and measured iodine biomarkers were included. The overall pooled regression coefficient (β) and the standard error of β were calculated by random-effects meta-analysis on a double-log scale, using the calculated intake-status regression coefficient (β) for each individual study. The results of pooled randomized controlled trials indicated that the doubling of dietary iodine intake increased urinary iodine concentrations by 14% in children and adolescents, by 57% in adults and the elderly, and by 81% in pregnant women. The dose-response relationship between iodine intake and biomarkers of iodine status indicated a 12% decrease in thyroid-stimulating hormone and a 31% decrease in thyroglobulin in pregnant women. The model of dose-response quantification used to describe the relationship between iodine intake and biomarkers of iodine status may be useful for providing complementary evidence to support recommendations for iodine intake in different population groups.

  20. Cumulative childhood maltreatment and its dose-response relation with adult symptomatology: Findings in a sample of adult survivors of sexual abuse.

    Science.gov (United States)

    Steine, Iris M; Winje, Dagfinn; Krystal, John H; Bjorvatn, Bjørn; Milde, Anne Marita; Grønli, Janne; Nordhus, Inger Hilde; Pallesen, Ståle

    2017-03-01

    In the present study, we examined the role of cumulative childhood maltreatment experiences for several health related outcomes in adulthood, including symptoms of psychological distress as well as perceived social support and hardiness. The sample comprised adult survivors of sexual abuse (N=278, 95.3% women, mean age at first abusive incident=6.4 years). One-way ANOVAs revealed a statistically significant dose-response relation between cumulative childhood maltreatment scores and self-reported symptoms of posttraumatic stress (PTSS), anxiety, depression, eating disorders, dissociation, insomnia, nightmare related distress, physical pain, emotional pain, relational problems, self-harm behaviors as well as on a measure of symptom complexity. Cumulative childhood maltreatment was also associated with lower levels of work functioning. An inverse dose-response relation was found for perceived social support and hardiness. Using a Bonferroni corrected alpha level, cumulative childhood maltreatment remained significantly associated with all outcome measures with the exception of eating disorder symptoms after controlling for abuse-related independent variables in hierarchical regression analyses. Results add to previous literature by showing that dose-response relation between cumulative childhood adversities and adult symptom outcomes could also be identified in a sample characterized by high exposure to adversities, and lends support to the notion put forth by previous authors that cumulative childhood adversities seem to be related to the severity of adult health outcomes in a rule-governed way. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Dose-response relationship of physical activity to premature and total all-cause and cardiovascular disease mortality in walkers.

    Directory of Open Access Journals (Sweden)

    Paul T Williams

    Full Text Available PURPOSE: To assess the dose-response relationships between cause-specific mortality and exercise energy expenditure in a prospective epidemiological cohort of walkers. METHODS: The sample consisted of the 8,436 male and 33,586 female participants of the National Walkers' Health Study. Walking energy expenditure was calculated in metabolic equivalents (METs, 1 MET = 3.5 ml O2/kg/min, which were used to divide the cohort into four exercise categories: category 1 (≤ 1.07 MET-hours/d, category 2 (1.07 to 1.8 MET-hours/d, category 3 (1.8 to 3.6 MET-hours/d, and category 4 (≥ 3.6 MET-hours/d. Competing risk regression analyses were use to calculate the risk of mortality for categories 2, 3 and 4 relative to category 1. RESULTS: 22.9% of the subjects were in category 1, 16.1% in category 2, 33.3% in category 3, and 27.7% in category 4. There were 2,448 deaths during the 9.6 average years of follow-up. Total mortality was 11.2% lower in category 2 (P = 0.04, 32.4% lower in category 3 (P<10(-12 and 32.9% lower in category 4 (P = 10(-11 than in category 1. For underlying causes of death, the respective risk reductions for categories 2, 3 and 4 were 23.6% (P = 0.008, 35.2% (P<10(-5, and 34.9% (P = 0.0001 for cardiovascular disease mortality; 27.8% (P = 0.18, 20.6% (P = 0.07, and 31.4% (P = 0.009 for ischemic heart disease mortality; and 39.4% (P = 0.18, 63.8% (P = 0.005, and 90.6% (P = 0.002 for diabetes mortality when compared to category 1. For all related mortality (i.e., underlying and contributing causes of death combined, the respective risk reductions for categories 2, 3 and 4 were 18.7% (P = 0.22, 42.5% (P = 0.001, and 57.5% (P = 0.0001 for heart failure; 9.4% (P = 0.56, 44.3% (P = 0.0004, and 33.5% (P = 0.02 for hypertensive diseases; 11.5% (P = 0.38, 41.0% (P<10(-4, and 35.5% (P = 0.001 for dysrhythmias: and 23.2% (P = 0.13, 45.8% (P = 0.0002, and 41.1% (P

  2. Site-specific dose-response relationships for cancer induction from the combined Japanese A-bomb and Hodgkin cohorts for doses relevant to radiotherapy

    Directory of Open Access Journals (Sweden)

    Sumila Marcin

    2011-07-01

    Full Text Available Abstract Background and Purpose Most information on the dose-response of radiation-induced cancer is derived from data on the A-bomb survivors. Since, for radiation protection purposes, the dose span of main interest is between zero and one Gy, the analysis of the A-bomb survivors is usually focused on this range. However, estimates of cancer risk for doses larger than one Gy are becoming more important for radiotherapy patients. Therefore in this work, emphasis is placed on doses relevant for radiotherapy with respect to radiation induced solid cancer. Materials and methods For various organs and tissues the analysis of cancer induction was extended by an attempted combination of the linear-no-threshold model from the A-bomb survivors in the low dose range and the cancer risk data of patients receiving radiotherapy for Hodgkin's disease in the high dose range. The data were fitted using organ equivalent dose (OED calculated for a group of different dose-response models including a linear model, a model including fractionation, a bell-shaped model and a plateau-dose-response relationship. Results The quality of the applied fits shows that the linear model fits best colon, cervix and skin. All other organs are best fitted by the model including fractionation indicating that the repopulation/repair ability of tissue is neither 0 nor 100% but somewhere in between. Bone and soft tissue sarcoma were fitted well by all the models. In the low dose range beyond 1 Gy sarcoma risk is negligible. For increasing dose, sarcoma risk increases rapidly and reaches a plateau at around 30 Gy. Conclusions In this work OED for various organs was calculated for a linear, a bell-shaped, a plateau and a mixture between a bell-shaped and plateau dose-response relationship for typical treatment plans of Hodgkin's disease patients. The model parameters (α and R were obtained by a fit of the dose-response relationships to these OED data and to the A-bomb survivors. For

  3. Site-specific dose-response relationships for cancer induction from the combined Japanese A-bomb and Hodgkin cohorts for doses relevant to radiotherapy.

    Science.gov (United States)

    Schneider, Uwe; Sumila, Marcin; Robotka, Judith

    2011-07-26

    Most information on the dose-response of radiation-induced cancer is derived from data on the A-bomb survivors. Since, for radiation protection purposes, the dose span of main interest is between zero and one Gy, the analysis of the A-bomb survivors is usually focused on this range. However, estimates of cancer risk for doses larger than one Gy are becoming more important for radiotherapy patients. Therefore in this work, emphasis is placed on doses relevant for radiotherapy with respect to radiation induced solid cancer. For various organs and tissues the analysis of cancer induction was extended by an attempted combination of the linear-no-threshold model from the A-bomb survivors in the low dose range and the cancer risk data of patients receiving radiotherapy for Hodgkin's disease in the high dose range. The data were fitted using organ equivalent dose (OED) calculated for a group of different dose-response models including a linear model, a model including fractionation, a bell-shaped model and a plateau-dose-response relationship. The quality of the applied fits shows that the linear model fits best colon, cervix and skin. All other organs are best fitted by the model including fractionation indicating that the repopulation/repair ability of tissue is neither 0 nor 100% but somewhere in between. Bone and soft tissue sarcoma were fitted well by all the models. In the low dose range beyond 1 Gy sarcoma risk is negligible. For increasing dose, sarcoma risk increases rapidly and reaches a plateau at around 30 Gy. In this work OED for various organs was calculated for a linear, a bell-shaped, a plateau and a mixture between a bell-shaped and plateau dose-response relationship for typical treatment plans of Hodgkin's disease patients. The model parameters (α and R) were obtained by a fit of the dose-response relationships to these OED data and to the A-bomb survivors. For any three-dimensional inhomogenous dose distribution, cancer risk can be compared by

  4. Th Application of Dose-Response Models to Determine the Median Effctive Adsorbent Bone Char Dose to Remove Fluoride From Drinking Aqueous Solutions

    Directory of Open Access Journals (Sweden)

    S.Zebarjadi

    2016-11-01

    Full Text Available Introduction: In studies of the adsorption of pollutants onto diffrent adsorbents, determining the adsorbent dose of the most important characteristics must be considered. Th aim of the study was the determination and modeling of dose-response bone char floride removal from aqueous solutions and comparison of the adsorption isotherm models with dose-response models from the perspective of adsorption. Methods: In this experimental study, bone char was prepared by using an electric furnace at 450˚C in two hours. Sorting the adsorbent was conducted by standard sieve ASTM in the range of 35-18 meshes and its characteristics were determined with conventional methods. Th concentration of floride was measured according to the recommendation of manufacturer HACH( with Dr5000- of regent floride. Dose-response models were fi to the data and parameters were estimated. Based on the quality of finess indicators, the adsorption isotherm models were compared with dose-response models. Analysis of the data in this study was performed using the R softare version 3.1.2 and stats package. Results: Fit indexes AIC and R2( showed that the most appropriate model for the data in pH= 10, concentration = 10 and pH = 7, concentration = 20 was the Emax model and in pH = 7, concentration = 10 and pH = 7, concentration = 15 the quadratic model. According to these models, the median of effctive dose on bone char at removal of floride was determined 0.11 g in concentration of 10 mg/L and pH = 10. Th maximum effctive dose was determined 1.25 g in concentration of 20 mg/L and pH = 7. Th index AIC( showed that quadratic dose-response models bettr fi to adsorption data than adsorption isotherm models. Conclusions: Th median and maximum effctive doses of bone char at removal of floride were estimated by statistical models more accurately. In addition, determining the goal dose was performed using modeling method, which was more economic than repeated testing, and the performance

  5. Characterization of Saharan dust ageing over the western Mediterranean Basin during a multi-intrusion event in June 2013 in the framework of the ADRIMED/ChArMEx campaign

    Science.gov (United States)

    Barragan, Ruben; Sicard, Michaël; Totems, Julien; François Léon, Jean; Baptiste Renard, Jean; Dulac, François; Mallet, Marc; Pelon, Jacques; Alados-Arboledas, Lucas; Amodeo, Aldo; José Granados-Muñoz, María; Boselli, Antonella; Bravo-Aranda, Juan Antonio; Muñoz-Porcar, Constantino; Chazette, Patrick; Comerón, Adolfo; D'Amico, Giuseppe; Wang, Xuan; Mona, Lucia; Pappalardo, Gelsomina

    2015-04-01

    In the framework of the ChArMEx (Chemistry-Aerosol Mediterranean Experiment, http://charmex.lsce.ipsl.fr/) initiative, a field campaign took place in the western Mediterranean Basin between 10 June and 5 July 2013 within the ADRIMED (Aerosol Direct Radiative Impact on the regional climate in the MEDiterranean region) project. The scientific objectives of the campaign were the characterization of the different aerosol types found over the Mediterranean Sea and the calculation of their direct radiative forcing (column closure and regional scale). Two super-sites (Ersa, Corsica Island, France, and Lampedusa Island, Italy) were equipped with a complete set of instruments to measure in-situ aerosol physical, chemical and optical properties, as well as aerosol mixing state and vertical distribution and radiative fluxes. Four secondary sites were operated in Granada (Spain), Menorca Island (Spain), Rome (Italy) and Lecce (Italy). All sites were equipped with AERONET sunphotometers. The ground observations were supported by airborne measurements including 2 SAFIRE aircraft (ATR-42 equipped with in situ measurements (10 June - 5 July) and Falcon-20 (17 June - 5 July) with the LNG aerosol lidar) and sounding and drifting balloons launched by CNES from Menorca Island and carrying the LOAC particle counter/sizer (16 June - 4 July). Satellite products from MODIS, MSG/SEVIRI and CALIOP provided additional observations. In several occasions corresponding to aerosol loads of different types, the aircraft flew near EARLINET/ACTRIS (European Aerosol Research Lidar Network / Aerosols, Clouds, and Trace gases Research InfraStructure Network, http://www.actris.net/) lidar stations. This work is focused on a moderate multi-intrusion Saharan dust event occurred over the western Mediterranean Basin (WMB) during the period 14 - 27 June. The dust plumes were detected by the EARLINET stations of Granada, Barcelona, Naples, Potenza, Lecce and Serra la Nave (Sicily) and by the ChArMEx lidar

  6. Dose response of Gabapentin Enacarbil versus placebo in subjects with moderate-to-severe primary restless legs syndrome: an integrated analysis of three 12-week studies.

    Science.gov (United States)

    VanMeter, Susan A; Kavanagh, Sarah T; Warren, Samantha; Barrett, Ronald W

    2012-09-01

    .0001). A significantly higher proportion of subjects was rated as responders on the investigator-rated CGI-I scale with gabapentin enacarbil 600 mg compared with placebo (70.2% vs 42.2%; adjusted odds ratio 3.1; 95% CI 1.96, 4.89; p < 0.0001). Similar treatment benefits were seen with both efficacy endpoints for the three higher doses. The AEs reported most frequently were somnolence and dizziness; there was a dose-response relationship to these AEs. No new or unexpected safety issues were identified by this integrated analysis. The lowest dose of gabapentin enacarbil evaluated (600 mg) significantly improved RLS symptoms compared with placebo. The safety profile was consistent with that described previously in the literature.

  7. Magnetic field influences on the lateral dose response functions of photon-beam detectors: MC study of wall-less water-filled detectors with various densities

    Science.gov (United States)

    Khee Looe, Hui; Delfs, Björn; Poppinga, Daniela; Harder, Dietrich; Poppe, Björn

    2017-06-01

    The distortion of detector reading profiles across photon beams in the presence of magnetic fields is a developing subject of clinical photon-beam dosimetry. The underlying modification by the Lorentz force of a detector’s lateral dose response function—the convolution kernel transforming the true cross-beam dose profile in water into the detector reading profile—is here studied for the first time. The three basic convolution kernels, the photon fluence response function, the dose deposition kernel, and the lateral dose response function, of wall-less cylindrical detectors filled with water of low, normal and enhanced density are shown by Monte Carlo simulation to be distorted in the prevailing direction of the Lorentz force. The asymmetric shape changes of these convolution kernels in a water medium and in magnetic fields of up to 1.5 T are confined to the lower millimetre range, and they depend on the photon beam quality, the magnetic flux density and the detector’s density. The impact of this distortion on detector reading profiles is demonstrated using a narrow photon beam profile. For clinical applications it appears as favourable that the magnetic flux density dependent distortion of the lateral dose response function, as far as secondary electron transport is concerned, vanishes in the case of water-equivalent detectors of normal water density. By means of secondary electron history backtracing, the spatial distribution of the photon interactions giving rise either directly to secondary electrons or to scattered photons further downstream producing secondary electrons which contribute to the detector’s signal, and their lateral shift due to the Lorentz force is elucidated. Electron history backtracing also serves to illustrate the correct treatment of the influences of the Lorentz force in the EGSnrc Monte Carlo code applied in this study.

  8. A gradient Markov chain Monte Carlo algorithm for computing multivariate maximum likelihood estimates and posterior distributions: mixture dose-response assessment.

    Science.gov (United States)

    Li, Ruochen; Englehardt, James D; Li, Xiaoguang

    2012-02-01

    Multivariate probability distributions, such as may be used for mixture dose-response assessment, are typically highly parameterized and difficult to fit to available data. However, such distributions may be useful in analyzing the large electronic data sets becoming available, such as dose-response biomarker and genetic information. In this article, a new two-stage computational approach is introduced for estimating multivariate distributions and addressing parameter uncertainty. The proposed first stage comprises a gradient Markov chain Monte Carlo (GMCMC) technique to find Bayesian posterior mode estimates (PMEs) of parameters, equivalent to maximum likelihood estimates (MLEs) in the absence of subjective information. In the second stage, these estimates are used to initialize a Markov chain Monte Carlo (MCMC) simulation, replacing the conventional burn-in period to allow convergent simulation of the full joint Bayesian posterior distribution and the corresponding unconditional multivariate distribution (not conditional on uncertain parameter values). When the distribution of parameter uncertainty is such a Bayesian posterior, the unconditional distribution is termed predictive. The method is demonstrated by finding conditional and unconditional versions of the recently proposed emergent dose-response function (DRF). Results are shown for the five-parameter common-mode and seven-parameter dissimilar-mode models, based on published data for eight benzene-toluene dose pairs. The common mode conditional DRF is obtained with a 21-fold reduction in data requirement versus MCMC. Example common-mode unconditional DRFs are then found using synthetic data, showing a 71% reduction in required data. The approach is further demonstrated for a PCB 126-PCB 153 mixture. Applicability is analyzed and discussed. Matlab(®) computer programs are provided. © 2012 Society for Risk Analysis. All rights reserved.

  9. SU-D-16A-03: A Radiation Pneumonitis Dose-Response Model Incorporating Non- Local Radiation-Induced Bystander Effect

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, J; Snyder, K; Zhong, H; Chetty, I [Henry Ford Health System, Dept. Radiation Oncology, Detroit, MI (United States)

    2014-06-01

    Purpose: Dose-response models that can reliably predict radiation pneumonitis (RP) to guide radiation therapy (RT) for lung cancer presently do not exist. A model is proposed that incorporates non-local radiationinduced bystander effect (RIBE). Methods: A single sigmoid response function, derived from published data for whole lung irradiation, relates RP probability to cumulative lung damage, regardless of fractionation scheme. Lung damage is assumed to be caused by direct local radiation damage, quantified via the linear-quadratic (LQ) model, and RIBE. Based on published data, RIBE is assumed to be activated when per-fraction dose rises above ∼0.6 Gy, but is constant with dose above that threshold. Integral RIBE damage is assumed proportional to lung volume irradiated above ∼0.6 Gy per fraction. Key model parameters include LQ α and β, and two RIBE parameters: the single-fraction probability δ of damage, and a proportionality parameter κ that relates the potential for RIBE damage to irradiated lung volume. All parameters are tentatively fitted from published data, the RIBE parameters from published RP rates for conventionally fractionated RT (CFRT) and stereotactic body RT (SBRT). Results: The model predicts dose-response curves that are consistent with clinical experience. It provides a tentative explanation for why V20 (33 fractions), V13 (20 fractions) and V5 (<10 fractions) are observed to be correlated with RP. It also provides a plausible explanation for the success of SBRT — RIBE damage increases with the number of fractions, so penalizes CFRT relative to SBRT. Conclusion: The proposed model is relatively simple, extrapolates from published data, plausibly explains several clinical observations, and produces dose-response curves that are consistent with clinical experience. While capable of elaboration, its ability to explain doseresponse experience with different fractionation schemes using a small number of assumptions and parameters is an

  10. Dose-Response Analysis of Chemotactic Signaling Response in Salmonella typhimurium LT2 upon Exposure to Cysteine/Cystine Redox Pair.

    Directory of Open Access Journals (Sweden)

    Bob T Rosier

    Full Text Available The chemotaxis system enables motile bacteria to search for an optimum level of environmental factors. Salmonella typhimurium senses the amino acid cysteine as an attractant and its oxidized dimeric form, cystine, as a repellent. We investigated the dose-response dependence of changes in chemotactic signaling activity upon exposure to cysteine and cystine of S. typhimurium LT2 using in vivo fluorescence resonance energy transfer (FRET measurements. The dose-response curve of the attractant response to cysteine had a sigmoidal shape, typical for receptor-ligand interactions. However, in a knockout strain of the chemoreceptor genes tsr and tar, we detected a repellent response to cysteine solutions, scaling linearly with the logarithm of the cysteine concentration. Interestingly, the magnitude of the repellent response to cystine also showed linear dependence to the logarithm of the cystine concentration. This linear dependence was observed over more than four orders of magnitude, where detection started at nanomolar concentrations. Notably, low concentrations of another oxidized compound, benzoquinone, triggered similar responses. In contrast to S. typhimurium 14028, where no response to cystine was observed in a knockout strain of chemoreceptor genes mcpB and mcpC, here we showed that McpB/McpC-independent responses to cystine existed in the strain S. typhimurium LT2 even at nanomolar concentrations. Additionally, knocking out mcpB and mcpC did not affect the linear dose-response dependence, whereas enhanced responses were only observed to solutions that where not pH neutral (>100 μM cystine in the case of McpC overexpression. We discuss that the linear dependence of the response on the logarithm of cystine concentrations could be a result of a McpB/C-independent redox-sensing pathway that exists in S. typhimurium LT2. We supported this hypothesis with experiments with defined cysteine/cystine mixed solutions, where a transition from repellent

  11. Glycemic index, glycemic load, carbohydrates, and type 2 diabetes: systematic review and dose-response meta-analysis of prospective studies.

    Science.gov (United States)

    Greenwood, Darren C; Threapleton, Diane E; Evans, Charlotte E L; Cleghorn, Christine L; Nykjaer, Camilla; Woodhead, Charlotte; Burley, Victoria J

    2013-12-01

    Diets with high glycemic index (GI), with high glycemic load (GL), or high in all carbohydrates may predispose to higher blood glucose and insulin concentrations, glucose intolerance, and risk of type 2 diabetes. We aimed to conduct a systematic literature review and dose-response meta-analysis of evidence from prospective cohorts. We searched the Cochrane Library, MEDLINE, MEDLINE in-process, Embase, CAB Abstracts, ISI Web of Science, and BIOSIS for prospective studies of GI, GL, and total carbohydrates in relation to risk of type 2 diabetes up to 17 July 2012. Data were extracted from 24 publications on 21 cohort studies. Studies using different exposure categories were combined on the same scale using linear and nonlinear dose-response trends. Summary relative risks (RRs) were estimated using random-effects meta-analysis. The summary RR was 1.08 per 5 GI units (95% CI 1.02-1.15; P = 0.01), 1.03 per 20 GL units (95% CI 1.00-1.05; P = 0.02), and 0.97 per 50 g/day of carbohydrate (95% CI 0.90-1.06; P = 0.5). Dose-response trends were linear for GI and GL but more complex for total carbohydrate intake. Heterogeneity was high for all exposures (I(2) >50%), partly accounted for by different covariate adjustment and length of follow-up. Included studies were observational and should be interpreted cautiously. However, our findings are consistent with protective effects of low dietary GI and GL, quantifying the range of intakes associated with lower risk. Future research could focus on the type of sugars and other carbohydrates associated with greatest risk.

  12. Dose response of gamma rays and iron nuclei for induction of chromosomal aberrations in normal and repair-deficient cell lines.

    Science.gov (United States)

    George, Kerry A; Hada, Megumi; Jackson, Lori J; Elliott, Todd; Kawata, Tetsuya; Pluth, Janice M; Cucinotta, Francis A

    2009-06-01

    We studied the effects of DNA double-strand break (DSB) repair deficiencies on chromosomal aberration frequency using low doses (gamma rays and high-energy iron ions (LET = 151 keV/microm). Chromosomal aberrations were measured using the fluorescence whole-chromosome painting technique. The cell lines included fibroblasts deficient in ATM (product of the gene that is mutated in ataxia telangiectasia patients) or NBS (product of the gene mutated in the Nijmegen breakage syndrome) and gliomablastoma cells proficient in or lacking DNA-dependent protein kinase (DNA-PK) activity. The yields of both simple and complex chromosomal aberrations were increased in DSB repair-defective cells compared to normal cells; the increase was more than twofold higher for gamma rays compared to iron nuclei. For gamma-ray-induced aberrations, the ATM- and NBS-defective lines were found to have significantly larger quadratic components compared to normal fibroblasts for both simple and complex aberrations, while the linear dose-response term was significantly higher only for the NBS cells. For simple and complex aberrations induced by iron nuclei, regression models preferred purely linear and quadratic dose responses, respectively, for each cell line studied. RBEs were reduced relative to normal cells for all of the DSB repair-defective lines, with the DNA-PK-deficient cells found to have RBEs near unity. The large increase in the quadratic dose-response terms in the DSB repair-deficient cell lines points to the importance of the functions of ATM and NBS in chromatin modifications to facilitate correct DSB repair and to minimize aberration formation. The differences found between AT and NBS cells at lower doses suggest important questions about the applicability of observations of radiation sensitivity at high doses to low-dose exposures.

  13. Dose-Response Effects of Aerobic Exercise on Quality of Life in Postmenopausal Women: Results from the Breast Cancer and Exercise Trial in Alberta (BETA).

    Science.gov (United States)

    Courneya, Kerry S; McNeil, Jessica; O'Reilly, Rachel; Morielli, Andria R; Friedenreich, Christine M

    2017-06-01

    Exercise generally improves quality of life (QoL) and psychosocial functioning in adult populations but few randomized trials have examined dose-response effects. The purpose of the present study was to report the QoL and psychosocial outcomes from the Breast Cancer and Exercise Trial in Alberta (BETA). Healthy but inactive postmenopausal women at risk for breast cancer were randomized to a year-long aerobic exercise intervention consisting of either 150 min/week (moderate volume group, n = 200) or 300 min/week (high volume group, n = 200). QoL was assessed at baseline and 1 year using the short form-36 health survey. Sleep quality, depression, anxiety, stress, self-esteem, and happiness were also assessed. Participant preference for group assignment (i.e., exercise volume) was assessed at baseline and tested as a moderator. There were no statistically significant dose-response effects of aerobic exercise on any QoL, sleep quality, or psychosocial outcome. Participant preference for group assignment did not moderate any QoL, sleep quality, or psychosocial responses. Marital status was a significant moderator (p for interaction = 0.01) and obesity showed a trend towards being a moderator (p for interaction = 0.08) of the dose-response effects of aerobic exercise on global sleep quality such that unmarried and obese women improved sleep quality with the higher volume of aerobic exercise. A higher volume of aerobic exercise, approximately double the minimum public health guideline, did not provide additional QoL or psychosocial benefits compared to the minimum public health guideline in inactive postmenopausal women, even for women who preferred the higher volume of exercise at baseline. Trial Registration clinicaltrials.gov identifier: NCT1435005.

  14. Dose response of saccharin in induction of urinary bladder hyperplasias in Fischer 344 rats pretreated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

    Science.gov (United States)

    Nakanishi, K; Hagiwara, A; Shibata, M; Imaida, K; Tatematsu, M; Ito, N

    1980-11-01

    Studies were made on the dose response of saccharin in the induction of bladder lesions. Inbred F344 rats of both sexes were pretreated with 100 ppm N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in the drinking water for 4 weeks. Sodium saccharin was given at 50,000, 10,000, 2,000, and 400 ppm in the diet for 32 weeks after BBN administration, and surviving rats were killed at the end of week 36 of the experiment. No increase in incidence of papilloma or cancer was noted in either sex at any dose of saccharin after BBN as compared to levels induced by BBN alone. The incidences of two types of hyperplasia and average number of papillary or nodular hyperplasias per 10 cm of basement membrane were significantly increased in the group receiving 50,000 ppm saccharin as compared to the group given BBN only. None of the incidences or numbers of these lesions were significantly different in any of the other saccharin-treated groups when compared to the group treated with BBN alone except for the incidences of two types of hyperplasias in the female rats dosed with 10,000 ppm saccharin. Dose-response curves showed enhanced hyperplastic responses in both sexes given 2,000--50,000 ppm saccharin. Administration of various doses of saccharin without BBN did not cause any changes in the urinary bladders of rats of either sex. These results show that saccharin enhances the induction of early-stage bladder lesions and that the biologic response demonstrates a dose-response effect.

  15. Magnetic field influences on the lateral dose response functions of photon-beam detectors: MC study of wall-less water-filled detectors with various densities.

    Science.gov (United States)

    Looe, Hui Khee; Delfs, Björn; Poppinga, Daniela; Harder, Dietrich; Poppe, Björn

    2017-06-21

    The distortion of detector reading profiles across photon beams in the presence of magnetic fields is a developing subject of clinical photon-beam dosimetry. The underlying modification by the Lorentz force of a detector's lateral dose response function-the convolution kernel transforming the true cross-beam dose profile in water into the detector reading profile-is here studied for the first time. The three basic convolution kernels, the photon fluence response function, the dose deposition kernel, and the lateral dose response function, of wall-less cylindrical detectors filled with water of low, normal and enhanced density are shown by Monte Carlo simulation to be distorted in the prevailing direction of the Lorentz force. The asymmetric shape changes of these convolution kernels in a water medium and in magnetic fields of up to 1.5 T are confined to the lower millimetre range, and they depend on the photon beam quality, the magnetic flux density and the detector's density. The impact of this distortion on detector reading profiles is demonstrated using a narrow photon beam profile. For clinical applications it appears as favourable that the magnetic flux density dependent distortion of the lateral dose response function, as far as secondary electron transport is concerned, vanishes in the case of water-equivalent detectors of normal water density. By means of secondary electron history backtracing, the spatial distribution of the photon interactions giving rise either directly to secondary electrons or to scattered photons further downstream producing secondary electrons which contribute to the detector's signal, and their lateral shift due to the Lorentz force is elucidated. Electron history backtracing also serves to illustrate the correct treatment of the influences of the Lorentz force in the EGSnrc Monte Carlo code applied in this study.

  16. A Randomized, Double-Blind, Parallel Study to Evaluate the Dose-Response of Three Different Vitamin D Treatment Schemes on the 25-Hydroxyvitamin D Serum Concentration in Patients with Vitamin D Deficiency

    Directory of Open Access Journals (Sweden)

    Marie-Louise Schleck

    2015-07-01

    Full Text Available Many people worldwide are vitamin D (VTD deficient or insufficient, and there is still no consensus on the dose of VTD that should be administered to achieve a 25(OHD concentration of 20 or 30 ng/mL. In this study, we aimed to determine an adapted supplementation of VTD able to quickly and safely increase the vitamin D status of healthy adults with low 25(OHD. One hundred and fifty (150 subjects were randomized into three groups, each to receive, orally, a loading dose of 50,000, 100,000 or 200,000 IU of VTD3 at Week 0, followed by 25,000, 50,000 or 100,000 IU at Week 4 and Week 8. Whereas 25(OHD baseline values were not different between groups (p = 0.42, a significant increase was observed at Week 12 (p < 0.0001 with a mean change from baseline of 7.72 ± 5.08, 13.3 ± 5.88 and 20.12 ± 7.79 ng/mL. A plateau was reached after eight weeks. No related adverse event was recorded. This study demonstrated a linear dose-response relationship with an increase in 25(OHD levels proportional to the dose administered. In conclusion, a loading dose of 200,000 IU VTD3 followed by a monthly dose of 100,000 IU is the best dosing schedule to quickly and safely correct the VTD status.

  17. Dose-response relationship between arsenic exposure and the serum enzymes for liver function tests in the individuals exposed to arsenic: a cross sectional study in Bangladesh.

    Science.gov (United States)

    Islam, Khairul; Haque, Abedul; Karim, Rezaul; Fajol, Abul; Hossain, Ekhtear; Salam, Kazi Abdus; Ali, Nurshad; Saud, Zahangir Alam; Rahman, Matiar; Rahman, Mashiur; Karim, Rezaul; Sultana, Papia; Hossain, Mostaque; Akhand, Anwarul Azim; Mandal, Abul; Miyataka, Hideki; Himeno, Seiichiro; Hossain, Khaled

    2011-07-08

    Chronic arsenic exposure has been shown to cause liver damage. However, serum hepatic enzyme activity as recognized on liver function tests (LFTs) showing a dose-response relationship with arsenic exposure has not yet been clearly documented. The aim of our study was to investigate the dose-response relationship between arsenic exposure and major serum enzyme marker activity associated with LFTs in the population living in arsenic-endemic areas in Bangladesh. A total of 200 residents living in arsenic-endemic areas in Bangladesh were selected as study subjects. Arsenic concentrations in the drinking water, hair and nails were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). The study subjects were stratified into quartile groups as follows, based on concentrations of arsenic in the drinking water, as well as in subjects' hair and nails: lowest, low, medium and high. The serum hepatic enzyme activities of alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine transaminase (ALT) were then assayed. Arsenic concentrations in the subjects' hair and nails were positively correlated with arsenic levels in the drinking water. As regards the exposure-response relationship with arsenic in the drinking water, the respective activities of ALP, AST and ALT were found to be significantly increased in the high-exposure groups compared to the lowest-exposure groups before and after adjustments were made for different covariates. With internal exposure markers (arsenic in hair and nails), the ALP, AST and ALT activity profiles assumed a similar shape of dose-response relationship, with very few differences seen in the higher groups compared to the lowest group, most likely due to the temporalities of exposure metrics. The present study demonstrated that arsenic concentrations in the drinking water were strongly correlated with arsenic concentrations in the subjects' hair and nails. Further, this study revealed a novel exposure- and dose- response

  18. Wrappers, Aspects, Quantification and Events

    Science.gov (United States)

    Filman, Robert E.

    2005-01-01

    Talk overview: Object infrastructure framework (OIF). A system development to simplify building distributed applications by allowing independent implementation of multiple concern. Essence and state of AOP. Trinity. Quantification over events. Current work on a generalized AOP technology.

  19. PHP frameworks

    OpenAIRE

    SRŠA, ALJAŽ

    2016-01-01

    The thesis presents one of the four most popular PHP web frameworks: Laravel, Symfony, CodeIgniter and CakePHP. These frameworks are compared with each other according to the four criteria, which can help with the selection of a framework. These criteria are size of the community, quality of official support, comprehensibility of framework’s documentation and implementation of functionalities in individual frameworks, which are automatic code generation, routing, object-relational mapping and...

  20. Framework Nette

    OpenAIRE

    Tölg, Jan

    2012-01-01

    This thesis deals with an interesting Czech PHP framework called Nette. The first part of the thesis introduces the reader to general ideas, design patterns used in Nette and also describes the main properties of the framework. Goal of the second part is focused on real-life application demonstration of the framework while developing a web application. This thesis is not an instructional material, but helps to explain the main advantages of the framework and can thus offer a more detailed des...

  1. Distributed web framework

    OpenAIRE

    Bondari, Serghei

    2009-01-01

    Develop a distributed component based web framework built upon the PHP5 programming language that allows independent component development, deployment and active component re-usage. A component of the work will recommend and implement a component interface definition schema and effective middleware layer that facilitates events, messaging and data exchange between various components.

  2. Dose-Response Relationship between Cumulati