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Sample records for surrogate endpoints frequently

  1. Surrogate Endpoint Evaluation: Principal Stratification Criteria and the Prentice Definition.

    Science.gov (United States)

    Gilbert, Peter B; Gabriel, Erin E; Huang, Ying; Chan, Ivan S F

    2015-09-01

    A common problem of interest within a randomized clinical trial is the evaluation of an inexpensive response endpoint as a valid surrogate endpoint for a clinical endpoint, where a chief purpose of a valid surrogate is to provide a way to make correct inferences on clinical treatment effects in future studies without needing to collect the clinical endpoint data. Within the principal stratification framework for addressing this problem based on data from a single randomized clinical efficacy trial, a variety of definitions and criteria for a good surrogate endpoint have been proposed, all based on or closely related to the "principal effects" or "causal effect predictiveness (CEP)" surface. We discuss CEP-based criteria for a useful surrogate endpoint, including (1) the meaning and relative importance of proposed criteria including average causal necessity (ACN), average causal sufficiency (ACS), and large clinical effect modification; (2) the relationship between these criteria and the Prentice definition of a valid surrogate endpoint; and (3) the relationship between these criteria and the consistency criterion (i.e., assurance against the "surrogate paradox"). This includes the result that ACN plus a strong version of ACS generally do not imply the Prentice definition nor the consistency criterion, but they do have these implications in special cases. Moreover, the converse does not hold except in a special case with a binary candidate surrogate. The results highlight that assumptions about the treatment effect on the clinical endpoint before the candidate surrogate is measured are influential for the ability to draw conclusions about the Prentice definition or consistency. In addition, we emphasize that in some scenarios that occur commonly in practice, the principal strata sub-populations for inference are identifiable from the observable data, in which cases the principal stratification framework has relatively high utility for the purpose of effect

  2. Surrogate Endpoint Evaluation: Principal Stratification Criteria and the Prentice Definition

    Science.gov (United States)

    Gilbert, Peter B.; Gabriel, Erin E.; Huang, Ying; Chan, Ivan S.F.

    2015-01-01

    A common problem of interest within a randomized clinical trial is the evaluation of an inexpensive response endpoint as a valid surrogate endpoint for a clinical endpoint, where a chief purpose of a valid surrogate is to provide a way to make correct inferences on clinical treatment effects in future studies without needing to collect the clinical endpoint data. Within the principal stratification framework for addressing this problem based on data from a single randomized clinical efficacy trial, a variety of definitions and criteria for a good surrogate endpoint have been proposed, all based on or closely related to the “principal effects” or “causal effect predictiveness (CEP)” surface. We discuss CEP-based criteria for a useful surrogate endpoint, including (1) the meaning and relative importance of proposed criteria including average causal necessity (ACN), average causal sufficiency (ACS), and large clinical effect modification; (2) the relationship between these criteria and the Prentice definition of a valid surrogate endpoint; and (3) the relationship between these criteria and the consistency criterion (i.e., assurance against the “surrogate paradox”). This includes the result that ACN plus a strong version of ACS generally do not imply the Prentice definition nor the consistency criterion, but they do have these implications in special cases. Moreover, the converse does not hold except in a special case with a binary candidate surrogate. The results highlight that assumptions about the treatment effect on the clinical endpoint before the candidate surrogate is measured are influential for the ability to draw conclusions about the Prentice definition or consistency. In addition, we emphasize that in some scenarios that occur commonly in practice, the principal strata sub-populations for inference are identifiable from the observable data, in which cases the principal stratification framework has relatively high utility for the purpose of

  3. Overview of Biomarkers and Surrogate Endpoints in Drug Development

    Directory of Open Access Journals (Sweden)

    John A. Wagner

    2002-01-01

    Full Text Available There are numerous factors that recommend the use of biomarkers in drug development including the ability to provide a rational basis for selection of lead compounds, as an aid in determining or refining mechanism of action or pathophysiology, and the ability to work towards qualification and use of a biomarker as a surrogate endpoint. Examples of biomarkers come from many different means of clinical and laboratory measurement. Total cholesterol is an example of a clinically useful biomarker that was successfully qualified for use as a surrogate endpoint. Biomarkers require validation in most circumstances. Validation of biomarker assays is a necessary component to delivery of high-quality research data necessary for effective use of biomarkers. Qualification is necessary for use of a biomarker as a surrogate endpoint. Putative biomarkers are typically identified because of a relationship to known or hypothetical steps in a pathophysiologic cascade. Biomarker discovery can also be effected by expression profiling experiment using a variety of array technologies and related methods. For example, expression profiling experiments enabled the discovery of adipocyte related complement protein of 30 kD (Acrp30 or adiponectin as a biomarker for in vivo activation of peroxisome proliferator-activated receptors (PPAR γ activity.

  4. Sperm count as a surrogate endpoint for male fertility control.

    Science.gov (United States)

    Benda, Norbert; Gerlinger, Christoph

    2007-11-30

    When assessing the effectiveness of a hormonal method of fertility control in men, the classical approach used for the assessment of hormonal contraceptives in women, by estimating the pregnancy rate or using a life-table analysis for the time to pregnancy, is difficult to apply in a clinical development program. The main reasons are the dissociation of the treated unit, i.e. the man, and the observed unit, i.e. his female partner, the high variability in the frequency of male intercourse, the logistical cost and ethical concerns related to the monitoring of the trial. A reasonable surrogate endpoint of the definite endpoint time to pregnancy is sperm count. In addition to the avoidance of the mentioned problems, trials that compare different treatments are possible with reasonable sample sizes, and study duration can be shorter. However, current products do not suppress sperm production to 100 per cent in all men and the sperm count is only observed with measurement error. Complete azoospermia might not be necessary in order to achieve an acceptable failure rate compared with other forms of male fertility control. Therefore, the use of sperm count as a surrogate endpoint must rely on the results of a previous trial in which both the definitive- and surrogate-endpoint results were assessed. The paper discusses different estimation functions of the mean pregnancy rate (corresponding to the cumulative hazard) that are based on the results of sperm count trial and a previous trial in which both sperm count and time to pregnancy were assessed, as well as the underlying assumptions. Sample size estimations are given for pregnancy rate estimation with a given precision.

  5. Imaging biomarkers as surrogate endpoints for drug development

    International Nuclear Information System (INIS)

    Richter, Wolf S.

    2006-01-01

    The employment of biomarkers (including imaging biomarkers, especially PET) in drug development has gained increasing attention during recent years. This has been partly stimulated by the hope that the integration of biomarkers into drug development programmes may be a means to increase the efficiency and effectiveness of the drug development process by early identification of promising drug candidates - thereby counteracting the rising costs of drug development. More importantly, however, the interest in biomarkers for drug development is the logical consequence of recent advances in biosciences and medicine which are leading to target-specific treatments in the framework of ''personalised medicine''. A considerable proportion of target-specific drugs will show effects in subgroups of patients only. Biomarkers are a means to identify potential responders, or patient subgroups at risk for specific side-effects. Biomarkers are used in early drug development in the context of translational medicine to gain information about the drug's potential in different patient groups and disease states. The information obtained at this stage is mainly important for designing subsequent clinical trials and to identify promising drug candidates. Biomarkers in later phases of clinical development may - if properly validated - serve as surrogate endpoints for clinical outcomes. Regulatory agencies in the EU and the USA have facilitated the use of biomarkers early in the development process. The validation of biomarkers as surrogate endpoints is part of FDA's ''critical path initiative''. (orig.)

  6. Surrogate endpoints for overall survival in digestive oncology trials: which candidates? A questionnaires survey among clinicians and methodologists

    Directory of Open Access Journals (Sweden)

    Bonnetain Franck

    2010-06-01

    , were ranked first, with a frequency of more than 69% in 20 out of 22 settings. PFS was proposed in association with QoL in metastatic primary liver and stomach cancers (both 81%. This composite endpoint was ranked second in metastatic oesophageal (69%, colorectal (56% and anal (56% cancers, whereas QoL alone was also suggested in most metastatic situations. Other endpoints frequently suggested were R0 resection in the neoadjuvant settings (oesophagus (69%, stomach (56%, pancreas (75% and biliary tract (63% and response. An unexpected endpoint was metastatic PFS in non operable oesophageal (31% and pancreatic (44% cancers. Quality and results of surgical procedures like sphincter preservation were also cited as eligible surrogate endpoints in rectal (19% and anal (50% in case of localized disease cancers. Except for alpha-FP kinetic in hepatocellular carcinoma (13% and CA19-9 decline (6% in pancreas, few endpoints based on biological or tumour markers were proposed. Conclusion The overall results should help prioritise the endpoints to be statistically evaluated as surrogate for OS, so that trialists and clinicians can rely on endpoints that ensure relevant clinical benefit to the patient.

  7. Surrogate endpoints for overall survival in digestive oncology trials: which candidates? A questionnaires survey among clinicians and methodologists

    International Nuclear Information System (INIS)

    Methy, Nicolas; Bedenne, Laurent; Bonnetain, Franck

    2010-01-01

    69% in 20 out of 22 settings. PFS was proposed in association with QoL in metastatic primary liver and stomach cancers (both 81%). This composite endpoint was ranked second in metastatic oesophageal (69%), colorectal (56%) and anal (56%) cancers, whereas QoL alone was also suggested in most metastatic situations. Other endpoints frequently suggested were R0 resection in the neoadjuvant settings (oesophagus (69%), stomach (56%), pancreas (75%) and biliary tract (63%)) and response. An unexpected endpoint was metastatic PFS in non operable oesophageal (31%) and pancreatic (44%) cancers. Quality and results of surgical procedures like sphincter preservation were also cited as eligible surrogate endpoints in rectal (19%) and anal (50% in case of localized disease) cancers. Except for alpha-FP kinetic in hepatocellular carcinoma (13%) and CA19-9 decline (6%) in pancreas, few endpoints based on biological or tumour markers were proposed. The overall results should help prioritise the endpoints to be statistically evaluated as surrogate for OS, so that trialists and clinicians can rely on endpoints that ensure relevant clinical benefit to the patient

  8. Surrogate endpoints for overall survival in digestive oncology trials: which candidates? A questionnaires survey among clinicians and methodologists.

    Science.gov (United States)

    Methy, Nicolas; Bedenne, Laurent; Bonnetain, Franck

    2010-06-10

    % in 20 out of 22 settings. PFS was proposed in association with QoL in metastatic primary liver and stomach cancers (both 81%). This composite endpoint was ranked second in metastatic oesophageal (69%), colorectal (56%) and anal (56%) cancers, whereas QoL alone was also suggested in most metastatic situations.Other endpoints frequently suggested were R0 resection in the neoadjuvant settings (oesophagus (69%), stomach (56%), pancreas (75%) and biliary tract (63%)) and response. An unexpected endpoint was metastatic PFS in non operable oesophageal (31%) and pancreatic (44%) cancers. Quality and results of surgical procedures like sphincter preservation were also cited as eligible surrogate endpoints in rectal (19%) and anal (50% in case of localized disease) cancers. Except for alpha-FP kinetic in hepatocellular carcinoma (13%) and CA19-9 decline (6%) in pancreas, few endpoints based on biological or tumour markers were proposed. The overall results should help prioritise the endpoints to be statistically evaluated as surrogate for OS, so that trialists and clinicians can rely on endpoints that ensure relevant clinical benefit to the patient.

  9. Five criteria for using a surrogate endpoint to predict treatment effect based on data from multiple previous trials.

    Science.gov (United States)

    Baker, Stuart G

    2018-02-20

    A surrogate endpoint in a randomized clinical trial is an endpoint that occurs after randomization and before the true, clinically meaningful, endpoint that yields conclusions about the effect of treatment on true endpoint. A surrogate endpoint can accelerate the evaluation of new treatments but at the risk of misleading conclusions. Therefore, criteria are needed for deciding whether to use a surrogate endpoint in a new trial. For the meta-analytic setting of multiple previous trials, each with the same pair of surrogate and true endpoints, this article formulates 5 criteria for using a surrogate endpoint in a new trial to predict the effect of treatment on the true endpoint in the new trial. The first 2 criteria, which are easily computed from a zero-intercept linear random effects model, involve statistical considerations: an acceptable sample size multiplier and an acceptable prediction separation score. The remaining 3 criteria involve clinical and biological considerations: similarity of biological mechanisms of treatments between the new trial and previous trials, similarity of secondary treatments following the surrogate endpoint between the new trial and previous trials, and a negligible risk of harmful side effects arising after the observation of the surrogate endpoint in the new trial. These 5 criteria constitute an appropriately high bar for using a surrogate endpoint to make a definitive treatment recommendation. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  10. Comparing and combining biomarkers as principle surrogates for time-to-event clinical endpoints.

    Science.gov (United States)

    Gabriel, Erin E; Sachs, Michael C; Gilbert, Peter B

    2015-02-10

    Principal surrogate endpoints are useful as targets for phase I and II trials. In many recent trials, multiple post-randomization biomarkers are measured. However, few statistical methods exist for comparison of or combination of biomarkers as principal surrogates, and none of these methods to our knowledge utilize time-to-event clinical endpoint information. We propose a Weibull model extension of the semi-parametric estimated maximum likelihood method that allows for the inclusion of multiple biomarkers in the same risk model as multivariate candidate principal surrogates. We propose several methods for comparing candidate principal surrogates and evaluating multivariate principal surrogates. These include the time-dependent and surrogate-dependent true and false positive fraction, the time-dependent and the integrated standardized total gain, and the cumulative distribution function of the risk difference. We illustrate the operating characteristics of our proposed methods in simulations and outline how these statistics can be used to evaluate and compare candidate principal surrogates. We use these methods to investigate candidate surrogates in the Diabetes Control and Complications Trial. Copyright © 2014 John Wiley & Sons, Ltd.

  11. Surrogate endpoints for overall survival in digestive oncology trials: which candidates? A questionnaires survey among clinicians and methodologists

    OpenAIRE

    Bonnetain Franck; Bedenne Laurent; Methy Nicolas

    2010-01-01

    Abstract Background Overall survival (OS) is the gold standard for the demonstration of a clinical benefit in cancer trials. Replacement of OS by a surrogate endpoint allows to reduce trial duration. To date, few surrogate endpoints have been validated in digestive oncology. The aim of this study was to draw up an ordered list of potential surrogate endpoints for OS in digestive cancer trials, by way of a survey among clinicians and methodologists. Secondary objective was to obtain their opin...

  12. Serum urate as surrogate endpoint for flares in people with gout

    DEFF Research Database (Denmark)

    Stamp, Lisa K; Birger Morillon, Melanie; Taylor, William J

    2018-01-01

    Objectives The primary efficacy outcome in trials of urate lowering therapy (ULT) for gout is serum urate (SU). The aim of this study was to examine the strength of the relationship between SU and patient-important outcomes to determine whether SU is an adequate surrogate endpoint for clinical tr...

  13. 21 CFR 314.510 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

    Science.gov (United States)

    2010-04-01

    ... Serious or Life-Threatening Illnesses § 314.510 Approval based on a surrogate endpoint or on an effect on... well-controlled. The applicant shall carry out any such studies with due diligence. ...

  14. Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema.

    Science.gov (United States)

    Lassere, Marissa N; Johnson, Kent R; Boers, Maarten; Tugwell, Peter; Brooks, Peter; Simon, Lee; Strand, Vibeke; Conaghan, Philip G; Ostergaard, Mikkel; Maksymowych, Walter P; Landewe, Robert; Bresnihan, Barry; Tak, Paul-Peter; Wakefield, Richard; Mease, Philip; Bingham, Clifton O; Hughes, Michael; Altman, Doug; Buyse, Marc; Galbraith, Sally; Wells, George

    2007-03-01

    There are clear advantages to using biomarkers and surrogate endpoints, but concerns about clinical and statistical validity and systematic methods to evaluate these aspects hinder their efficient application. Our objective was to review the literature on biomarkers and surrogates to develop a hierarchical schema that systematically evaluates and ranks the surrogacy status of biomarkers and surrogates; and to obtain feedback from stakeholders. After a systematic search of Medline and Embase on biomarkers, surrogate (outcomes, endpoints, markers, indicators), intermediate endpoints, and leading indicators, a quantitative surrogate validation schema was developed and subsequently evaluated at a stakeholder workshop. The search identified several classification schema and definitions. Components of these were incorporated into a new quantitative surrogate validation level of evidence schema that evaluates biomarkers along 4 domains: Target, Study Design, Statistical Strength, and Penalties. Scores derived from 3 domains the Target that the marker is being substituted for, the Design of the (best) evidence, and the Statistical strength are additive. Penalties are then applied if there is serious counterevidence. A total score (0 to 15) determines the level of evidence, with Level 1 the strongest and Level 5 the weakest. It was proposed that the term "surrogate" be restricted to markers attaining Levels 1 or 2 only. Most stakeholders agreed that this operationalization of the National Institutes of Health definitions of biomarker, surrogate endpoint, and clinical endpoint was useful. Further development and application of this schema provides incentives and guidance for effective biomarker and surrogate endpoint research, and more efficient drug discovery, development, and approval.

  15. Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema

    DEFF Research Database (Denmark)

    Lassere, Marissa N; Johnson, Kent R; Boers, Maarten

    2007-01-01

    endpoints, and leading indicators, a quantitative surrogate validation schema was developed and subsequently evaluated at a stakeholder workshop. RESULTS: The search identified several classification schema and definitions. Components of these were incorporated into a new quantitative surrogate validation...... of the National Institutes of Health definitions of biomarker, surrogate endpoint, and clinical endpoint was useful. CONCLUSION: Further development and application of this schema provides incentives and guidance for effective biomarker and surrogate endpoint research, and more efficient drug discovery...... are then applied if there is serious counterevidence. A total score (0 to 15) determines the level of evidence, with Level 1 the strongest and Level 5 the weakest. It was proposed that the term "surrogate" be restricted to markers attaining Levels 1 or 2 only. Most stakeholders agreed that this operationalization...

  16. Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema

    DEFF Research Database (Denmark)

    Lassere, Marissa N; Johnson, Kent R; Boers, Maarten

    2007-01-01

    endpoints, and leading indicators, a quantitative surrogate validation schema was developed and subsequently evaluated at a stakeholder workshop. RESULTS: The search identified several classification schema and definitions. Components of these were incorporated into a new quantitative surrogate validation...... level of evidence schema that evaluates biomarkers along 4 domains: Target, Study Design, Statistical Strength, and Penalties. Scores derived from 3 domains the Target that the marker is being substituted for, the Design of the (best) evidence, and the Statistical strength are additive. Penalties...... of the National Institutes of Health definitions of biomarker, surrogate endpoint, and clinical endpoint was useful. CONCLUSION: Further development and application of this schema provides incentives and guidance for effective biomarker and surrogate endpoint research, and more efficient drug discovery...

  17. Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema

    NARCIS (Netherlands)

    Lassere, Marissa N.; Johnson, Kent R.; Boers, Maarten; Tugwell, Peter; Brooks, Peter; Simon, Lee; Strand, Vibeke; Conaghan, Philip G.; Ostergaard, Mikkel; Maksymowych, Walter P.; Landewe, Robert; Bresnihan, Barry; Tak, Paul-Peter; Wakefield, Richard; Mease, Philip; Bingham, Clifton O.; Hughes, Michael; Altman, Doug; Buyse, Marc; Galbraith, Sally; Wells, George

    2007-01-01

    OBJECTIVE: There are clear advantages to using biomarkers and surrogate endpoints, but concerns about clinical and statistical validity and systematic methods to evaluate these aspects hinder their efficient application. Our objective was to review the literature on biomarkers and surrogates to

  18. Impact of copula directional specification on multi-trial evaluation of surrogate endpoints

    Science.gov (United States)

    Renfro, Lindsay A.; Shang, Hongwei; Sargent, Daniel J.

    2014-01-01

    Evaluation of surrogate endpoints using patient-level data from multiple trials is the gold standard, where multi-trial copula models are used to quantify both patient-level and trial-level surrogacy. While limited consideration has been given in the literature to copula choice (e.g., Clayton), no prior consideration has been given to direction of implementation (via survival versus distribution functions). We demonstrate that evenwith the “correct” copula family, directional misspecification leads to biased estimates of patient-level and trial-level surrogacy. We illustrate with a simulation study and a re-analysis of disease-free survival as a surrogate for overall survival in early stage colon cancer. PMID:24905465

  19. Correlates of protection for inactivated enterovirus 71 vaccine: the analysis of immunological surrogate endpoints.

    Science.gov (United States)

    Zhu, Wenbo; Jin, Pengfei; Li, Jing-Xin; Zhu, Feng-Cai; Liu, Pei

    2017-09-01

    Inactivated Enterovirus 71 (EV71) vaccines showed significant efficacy against the diseases associated with EV71 and a neutralizing antibody (NTAb) titer of 1:16-1:32 was suggested as the correlates of the vaccine protection. This paper aims to further estimate the immunological surrogate endpoints for the protection of inactivated EV71 vaccines and the effect factors. Pre-vaccination NTAb against EV71 at baseline (day 0), post-vaccination NTAb against EV71 at day 56, and the occurrence of laboratory-confirmed EV71-associated diseases during a 24-months follow-up period were collected from a phase 3 efficacy trial of an inactivated EV71 vaccine. We used the mixed-scaled logit model and the absolute sigmoid function by some extensions in continuous models to estimate the immunological surrogate endpoint for the EV71 vaccine protection, respectively. For children with a negative baseline of EV71 NTAb titers, an antibody level of 26.6 U/ml (1:30) was estimated to provide at least a 50% protection for 12 months, and an antibody level of 36.2 U/ml (1:42) may be needed to achieve a 50% protective level of the population for 24 months. Both the pre-vaccination NTAb level and the vaccine protective period could affect the estimation of the immunological surrogate for EV71 vaccine. A post-vaccination NTAb titer of 1:42 or more may be needed for long-term protection. NCT01508247.

  20. An evaluation of culture results during treatment for tuberculosis as surrogate endpoints for treatment failure and relapse.

    Directory of Open Access Journals (Sweden)

    Patrick P J Phillips

    Full Text Available It is widely acknowledged that new regimens are urgently needed for the treatment of tuberculosis. The primary endpoint in the Phase III trials is a composite outcome of failure at the end of treatment or relapse after stopping treatment. Such trials are usually both long and expensive. Valid surrogate endpoints measured during or at the end of treatment could dramatically reduce both the time and cost of assessing the effectiveness of new regimens. The objective of this study was to evaluate sputum culture results on solid media during treatment as surrogate endpoints for poor outcome. Data were obtained from twelve randomised controlled trials conducted by the British Medical Research Council in the 1970s and 80s in East Africa and East Asia, consisting of 6974 participants and 49 different treatment regimens. The month two culture result was shown to be a poor surrogate in East Africa but a good surrogate in Hong Kong. In contrast, the month three culture was a good surrogate in trials conducted in East Africa but not in Hong Kong. As well as differences in location, ethnicity and probable strain of Mycobacteria tuberculosis, Hong Kong trials more often evaluated regimens with rifampicin throughout and intermittent regimens, and patients in East African trials more often presented with extensive cavitation and were slower to convert to culture negative during treatment. An endpoint that is a summary measure of the longitudinal profile of culture results over time or that is able to detect the presence of M. tuberculosis later in treatment is more likely to be a better endpoint for a phase II trial than a culture result at a single time point and may prove to be an acceptable surrogate. More data are needed before any endpoint can be used as a surrogate in a confirmatory phase III trial.

  1. Center-Within-Trial Versus Trial-Level Evaluation of Surrogate Endpoints

    Science.gov (United States)

    Renfro, Lindsay A.; Shi, Qian; Xue, Yuan; Li, Junlong; Shang, Hongwei; Sargent, Daniel J.

    2014-01-01

    Evaluation of candidate surrogate endpoints using individual patient data from multiple clinical trials is considered the gold standard approach to validate surrogates at both patient and trial levels. However, this approach assumes the availability of patient-level data from a relatively large collection of similar trials, which may not be possible to achieve for a given disease application. One common solution to the problem of too few similar trials involves performing trial-level surrogacy analyses on trial sub-units (e.g., centers within trials), thereby artificially increasing the trial-level sample size for feasibility of the multi-trial analysis. To date, the practical impact of treating trial sub-units (centers) identically to trials in multi-trial surrogacy analyses remains unexplored, and conditions under which this ad hoc solution may in fact be reasonable have not been identified. We perform a simulation study to identify such conditions, and demonstrate practical implications using a multi-trial dataset of patients with early stage colon cancer. PMID:25061255

  2. Relative Biological Effectiveness of HZE Particles for Chromosomal Exchanges and Other Surrogate Cancer Risk Endpoints.

    Directory of Open Access Journals (Sweden)

    Eliedonna Cacao

    Full Text Available The biological effects of high charge and energy (HZE particle exposures are of interest in space radiation protection of astronauts and cosmonauts, and estimating secondary cancer risks for patients undergoing Hadron therapy for primary cancers. The large number of particles types and energies that makeup primary or secondary radiation in HZE particle exposures precludes tumor induction studies in animal models for all but a few particle types and energies, thus leading to the use of surrogate endpoints to investigate the details of the radiation quality dependence of relative biological effectiveness (RBE factors. In this report we make detailed RBE predictions of the charge number and energy dependence of RBE's using a parametric track structure model to represent experimental results for the low dose response for chromosomal exchanges in normal human lymphocyte and fibroblast cells with comparison to published data for neoplastic transformation and gene mutation. RBE's are evaluated against acute doses of γ-rays for doses near 1 Gy. Models that assume linear or non-targeted effects at low dose are considered. Modest values of RBE (10 are predicted at low doses <0.1 Gy. The radiation quality dependence of RBE's against the effects of acute doses γ-rays found for neoplastic transformation and gene mutation studies are similar to those found for simple exchanges if a linear response is assumed at low HZE particle doses. Comparisons of the resulting model parameters to those used in the NASA radiation quality factor function are discussed.

  3. Predicting treatment effect from surrogate endpoints and historical trials: an extrapolation involving probabilities of a binary outcome or survival to a specific time.

    Science.gov (United States)

    Baker, Stuart G; Sargent, Daniel J; Buyse, Marc; Burzykowski, Tomasz

    2012-03-01

    Using multiple historical trials with surrogate and true endpoints, we consider various models to predict the effect of treatment on a true endpoint in a target trial in which only a surrogate endpoint is observed. This predicted result is computed using (1) a prediction model (mixture, linear, or principal stratification) estimated from historical trials and the surrogate endpoint of the target trial and (2) a random extrapolation error estimated from successively leaving out each trial among the historical trials. The method applies to either binary outcomes or survival to a particular time that is computed from censored survival data. We compute a 95% confidence interval for the predicted result and validate its coverage using simulation. To summarize the additional uncertainty from using a predicted instead of true result for the estimated treatment effect, we compute its multiplier of standard error. Software is available for download. © 2011, The International Biometric Society No claim to original US government works.

  4. The Biomarker-Surrogacy Evaluation Schema: a review of the biomarker-surrogate literature and a proposal for a criterion-based, quantitative, multidimensional hierarchical levels of evidence schema for evaluating the status of biomarkers as surrogate endpoints.

    Science.gov (United States)

    Lassere, Marissa N

    2008-06-01

    There are clear advantages to using biomarkers and surrogate endpoints, but concerns about clinical and statistical validity and systematic methods to evaluate these aspects hinder their efficient application. Section 2 is a systematic, historical review of the biomarker-surrogate endpoint literature with special reference to the nomenclature, the systems of classification and statistical methods developed for their evaluation. In Section 3 an explicit, criterion-based, quantitative, multidimensional hierarchical levels of evidence schema - Biomarker-Surrogacy Evaluation Schema - is proposed to evaluate and co-ordinate the multiple dimensions (biological, epidemiological, statistical, clinical trial and risk-benefit evidence) of the biomarker clinical endpoint relationships. The schema systematically evaluates and ranks the surrogacy status of biomarkers and surrogate endpoints using defined levels of evidence. The schema incorporates the three independent domains: Study Design, Target Outcome and Statistical Evaluation. Each domain has items ranked from zero to five. An additional category called Penalties incorporates additional considerations of biological plausibility, risk-benefit and generalizability. The total score (0-15) determines the level of evidence, with Level 1 the strongest and Level 5 the weakest. The term ;surrogate' is restricted to markers attaining Levels 1 or 2 only. Surrogacy status of markers can then be directly compared within and across different areas of medicine to guide individual, trial-based or drug-development decisions. This schema would facilitate communication between clinical, researcher, regulatory, industry and consumer participants necessary for evaluation of the biomarker-surrogate-clinical endpoint relationship in their different settings.

  5. Surrogate endpoints for overall survival in chemotherapy and radiotherapy trials in operable and locally advanced lung cancer: a re-analysis of meta-analyses of individual patients' data

    NARCIS (Netherlands)

    Mauguen, Audrey; Pignon, Jean-Pierre; Burdett, Sarah; Domerg, Caroline; Fisher, David; Paulus, Rebecca; Mandrekar, Samithra J.; Belani, Chandra P.; Shepherd, Frances A.; Eisen, Tim; Pang, Herbert; Collette, Laurence; Sause, William T.; Dahlberg, Suzanne E.; Crawford, Jeffrey; O'Brien, Mary; Schild, Steven E.; Parmar, Mahesh; Tierney, Jayne F.; Le Pechoux, Cécile; Michiels, Stefan; Burdett, S.; Fisher, D.; Le Péchoux, C.; Mauguen, A.; Michiels, S.; Pignon, J. P.; Tierney, J. F.; Belani, C. P.; Collette, L.; Dahlberg, S.; Eisen, T.; Mandrekar, S.; O'Brien, M.; Parmar, M.; Pang, H.; Paulus, R.; Crawford, J.; Sause, W.; Schild, S. E.; Shepherd, F.; Arriagada, R.; Atagi, S.; Auperin, A.; Ball, D.; Baumann, M.; Behrendt, K.; Belderbos, J.; Koning, C. C. E.; Uitterhoeve, A.

    2013-01-01

    The gold standard endpoint in clinical trials of chemotherapy and radiotherapy for lung cancer is overall survival. Although reliable and simple to measure, this endpoint takes years to observe. Surrogate endpoints that would enable earlier assessments of treatment effects would be useful. We

  6. Posttreatment prostatic-specific antigen doubling time as a surrogate endpoint for prostate cancer-specific survival: An analysis of Radiation Therapy Oncology Group Protocol 92-02

    International Nuclear Information System (INIS)

    Valicenti, Richard K.; DeSilvio, Michelle; Hanks, Gerald E.; Porter, Arthur; Brereton, Harmar; Rosenthal, Seth A.; Shipley, William U.; Sandler, Howard M.

    2006-01-01

    Purpose: We evaluated whether posttreatment prostatic-specific antigen doubling time (PSADT) was predictive of prostate cancer mortality by testing the Prentice requirements for a surrogate endpoint. Methods and Materials: We analyzed posttreatment PSA measurements in a cohort of 1,514 men with localized prostate cancer (T2c-4 and PSA level Cox = 0.002), PSADT Cox Cox Cox Cox = 0.4). The significant posttreatment PSADTs were also significant predictors of CSS (p Cox < 0.001). After adjusting for T stage, Gleason score and PSA, all of Prentice's requirements were not met, indicating that the effect of PSADT on CSS was not independent of the randomized treatment. Conclusions: Prostatic specific antigen doubling time is significantly associated with CSS, but did not meet all of Prentice's requirements for a surrogate endpoint of CSS. Thus, the risk of dying of prostate cancer is not fully explained by PSADT

  7. Importance of glomerular filtration rate change as surrogate endpoint for the future incidence of end-stage renal disease in general Japanese population: community-based cohort study.

    Science.gov (United States)

    Kanda, Eiichiro; Usui, Tomoko; Kashihara, Naoki; Iseki, Chiho; Iseki, Kunitoshi; Nangaku, Masaomi

    2018-04-01

    Because of the necessity for extended period and large costs until the event occurs, surrogate endpoints are indispensable for implementation of clinical studies to improve chronic kidney disease (CKD) patients' prognosis. Subjects with serum creatinine level for a baseline period over 1-3 years were enrolled (n = 69,238) in this community-based prospective cohort study in Okinawa, Japan, and followed up for 15 years. The endpoint was end-stage renal disease (ESRD). The percent of estimated glomerular filtration rate (%eGFR) change was calculated on the basis of the baseline period. Subjects had a mean ± SD age, 55.59 ± 14.69 years; eGFR, 80.15 ± 21.15 ml/min/1.73 m 2 . Among the subjects recruited, 15.81% had a low eGFR (<60 ml/min/1.73 m 2 ) and 36.1/100,000 person years developed ESRD. Cox proportional hazards models adjusted for baseline characteristics showed that the risk of ESRD tended to be high with high rates of decrease in %eGFR changes over 2 or 3 years in the high- and low-eGFR groups. The specificities and positive predictive values for ESRD based on a cutoff value of %eGFR change of less than -30% over 2 or 3 years were high in the high- and low-eGFR groups. %eGFR change tends to be associated with the risk of ESRD. %eGFR change of less than -30% over 2 or 3 years can be a candidate surrogate endpoint for ESRD in the general Japanese population.

  8. Changes in natriuretic peptides after acute hospital presentation for heart failure with preserved ejection fraction: A feasible surrogate trial endpoint? A report from the prospective Karen study.

    Science.gov (United States)

    Savarese, Gianluigi; Donal, Erwan; Hage, Camilla; Oger, Emmanuel; Persson, Hans; Daubert, Jean-Claude; Linde, Cecilia; Lund, Lars H

    2017-01-01

    In acute decompensated heart failure (ADHF) with preserved ejection fraction (HFpEF) there are no surrogate endpoints for early phase trials. The aim of the current study was to evaluate whether a reduction in natriuretic peptides (NP) between acute hospital presentation to stable follow-up is associated with improved mortality and morbidity. Patients presenting acutely to the hospital for ADHF with HFpEF enrolled in the Karolinska Rennes (KaRen) study and reporting N-terminal pro-B-type NP or B-type NP assessment at baseline hospital presentation and at 4-8weeks follow-up were prospectively studied. Logistic regression analyses were performed to detect the predictors of baseline and changes in NPs. Cox regression models were performed to assess the impact of NP reductions on mortality and the composite of mortality and HF hospitalization. Of 361 patients (median follow-up 585days), 267 (74%) reported an improvement in NPs, while 94 (26%) reported worsening. At baseline, the independent predictors of lower NPs were higher glomerular filtration rate (Odds Ratio [OR] per unit: 1.013; 95% Confidence Interval [CI]: 1.005-1.021) and younger age (OR per year: 0.972; CI: 0.947-0.998). Improvement in NPs at follow-up was predicted by higher heart rate at baseline (OR per bpm: 1.014; CI: 1.003-1.025). After adjustments, the hazard ratio for all-cause death was 0.730 (CI: 0.456-1.169) and for the composite outcome 0.814 (CI: 0.582-1.139) for patients who improved vs. worsened in NP levels. In patients presenting acutely to the hospital with HFPEF, an improvement in NP levels did not independently and significantly predict improved mortality and/or morbidity. NPs as surrogate endpoints in acute HFpEF require further study. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Time to second prostate specific antigen (PSA) failure is a surrogate endpoint for prostate cancer death in prospective trials of therapy for localized disease

    Energy Technology Data Exchange (ETDEWEB)

    Zietman, A L; Dallow, K C; Shipley, W U; Heney, N M; McManus, P L

    1995-07-01

    Purpose In assessing the efficacy of the competing curative therapies for prostate cancer the most relevant endpoint is cancer specific death. Due to the long natural history of the disease and the use of salvage androgen suppression prospective trials need to mature for at least a decade to provide meaningful results. An endpoint that predicted for cancer death with high probability would allow more rapid completion of prospective studies, hopefully before the tested therapies become outdated. Materials and methods 202 patients entered into a single institution prospective randomized study for T3-4 prostate cancer between 1982 and 1992 were evaluated. All received radical irradiation to either a standard dose of 67.2Gy or a higher dose of 75.6Gy (the latter employing a proton beam boost). 76 men have received androgen suppression or orchiectomy for salvage following relapse (median follow-up 6.9 years). Of this group 35 experienced a second relapse heralded by a rise in the serum PSA. Second failure was scored on the date that the serum PSA rose to greater than 10% above the post-androgen suppression nadir. Kaplan-Meier analysis was made of survival from the time of second PSA failure and the cause of death established in all patients who subsequently died. Results The median duration of response to hormone therapy following first failure was 27.2 months. The actuarial survival from the time of second biochemical relapse was 93%, 66%, 35%, and 0% at 1, 2, 3, and 4 years respectively (50% at 32 months). 16 patients have so far died after second failure all from causes related to their prostate cancer. Conclusion Second PSA failure appears to be a secure surrogate for impending prostate cancer death. Its use as an endpoint in prospective studies should allow earlier reporting by 2 - 3 years.

  10. Is blood pressure reduction a valid surrogate endpoint for stroke prevention? an analysis incorporating a systematic review of randomised controlled trials, a by-trial weighted errors-in-variables regression, the surrogate threshold effect (STE and the biomarker-surrogacy (BioSurrogate evaluation schema (BSES

    Directory of Open Access Journals (Sweden)

    Lassere Marissa N

    2012-03-01

    Full Text Available Abstract Background Blood pressure is considered to be a leading example of a valid surrogate endpoint. The aims of this study were to (i formally evaluate systolic and diastolic blood pressure reduction as a surrogate endpoint for stroke prevention and (ii determine what blood pressure reduction would predict a stroke benefit. Methods We identified randomised trials of at least six months duration comparing any pharmacologic anti-hypertensive treatment to placebo or no treatment, and reporting baseline blood pressure, on-trial blood pressure, and fatal and non-fatal stroke. Trials with fewer than five strokes in at least one arm were excluded. Errors-in-variables weighted least squares regression modelled the reduction in stroke as a function of systolic blood pressure reduction and diastolic blood pressure reduction respectively. The lower 95% prediction band was used to determine the minimum systolic blood pressure and diastolic blood pressure difference, the surrogate threshold effect (STE, below which there would be no predicted stroke benefit. The STE was used to generate the surrogate threshold effect proportion (STEP, a surrogacy metric, which with the R-squared trial-level association was used to evaluate blood pressure as a surrogate endpoint for stroke using the Biomarker-Surrogacy Evaluation Schema (BSES3. Results In 18 qualifying trials representing all pharmacologic drug classes of antihypertensives, assuming a reliability coefficient of 0.9, the surrogate threshold effect for a stroke benefit was 7.1 mmHg for systolic blood pressure and 2.4 mmHg for diastolic blood pressure. The trial-level association was 0.41 and 0.64 and the STEP was 66% and 78% for systolic and diastolic blood pressure respectively. The STE and STEP were more robust to measurement error in the independent variable than R-squared trial-level associations. Using the BSES3, assuming a reliability coefficient of 0.9, systolic blood pressure was a B + grade and

  11. Is blood pressure reduction a valid surrogate endpoint for stroke prevention? an analysis incorporating a systematic review of randomised controlled trials, a by-trial weighted errors-in-variables regression, the surrogate threshold effect (STE) and the biomarker-surrogacy (BioSurrogate) evaluation schema (BSES)

    Science.gov (United States)

    2012-01-01

    Background Blood pressure is considered to be a leading example of a valid surrogate endpoint. The aims of this study were to (i) formally evaluate systolic and diastolic blood pressure reduction as a surrogate endpoint for stroke prevention and (ii) determine what blood pressure reduction would predict a stroke benefit. Methods We identified randomised trials of at least six months duration comparing any pharmacologic anti-hypertensive treatment to placebo or no treatment, and reporting baseline blood pressure, on-trial blood pressure, and fatal and non-fatal stroke. Trials with fewer than five strokes in at least one arm were excluded. Errors-in-variables weighted least squares regression modelled the reduction in stroke as a function of systolic blood pressure reduction and diastolic blood pressure reduction respectively. The lower 95% prediction band was used to determine the minimum systolic blood pressure and diastolic blood pressure difference, the surrogate threshold effect (STE), below which there would be no predicted stroke benefit. The STE was used to generate the surrogate threshold effect proportion (STEP), a surrogacy metric, which with the R-squared trial-level association was used to evaluate blood pressure as a surrogate endpoint for stroke using the Biomarker-Surrogacy Evaluation Schema (BSES3). Results In 18 qualifying trials representing all pharmacologic drug classes of antihypertensives, assuming a reliability coefficient of 0.9, the surrogate threshold effect for a stroke benefit was 7.1 mmHg for systolic blood pressure and 2.4 mmHg for diastolic blood pressure. The trial-level association was 0.41 and 0.64 and the STEP was 66% and 78% for systolic and diastolic blood pressure respectively. The STE and STEP were more robust to measurement error in the independent variable than R-squared trial-level associations. Using the BSES3, assuming a reliability coefficient of 0.9, systolic blood pressure was a B + grade and diastolic blood pressure

  12. Validation of Progression‐Free Survival as a Surrogate Endpoint for Overall Survival in Malignant Mesothelioma: Analysis of Cancer and Leukemia Group B and North Central Cancer Treatment Group (Alliance) Trials

    Science.gov (United States)

    Wang, Xiaoyi; Hodgson, Lydia; George, Stephen L.; Sargent, Daniel J.; Foster, Nate R.; Ganti, Apar Kishor; Stinchcombe, Thomas E.; Crawford, Jeffrey; Kratzke, Robert; Adjei, Alex A.; Kindler, Hedy L.; Vokes, Everett E.; Pang, Herbert

    2017-01-01

    Abstract Purpose. The aim of this study was to investigate whether progression‐free survival (PFS) can be considered a surrogate endpoint for overall survival (OS) in malignant mesothelioma. Materials and Methods. Individual data were collected from 15 Cancer and Leukemia Group B (615 patients) and 2 North Central Cancer Treatment Group (101 patients) phase II trials. The effects of 5 risk factors for OS and PFS, including age, histology, performance status (PS), white blood cell count, and European Organisation for Research and Treatment of Cancer (EORTC) risk score, were used in the analysis. Individual‐level surrogacy was assessed by Kendall's tau through a Clayton bivariate Copula survival (CBCS) model. Summary‐level surrogacy was evaluated via the association between logarithms of the hazard ratio (log HR)—log HROS and log HRPFS—measured in R2 from a weighted least‐square (WLS) regression model and the CBCS model. Results. The median PFS for all patients was 3.0 months (95% confidence interval [CI], 2.8–3.5 months) and the median OS was 7.2 months (95% CI, 6.5–8.0 months). Moderate correlations between PFS and OS were observed across all risk factors at the individual level, with Kendall's tau ranging from 0.46 to 0.47. The summary‐level surrogacy varied among risk factors. The Copula R2 ranged from 0.51 for PS to 0.78 for histology. The WLS R2 ranged from 0.26 for EORTC and PS to 0.67 for age. Conclusions. The analyses demonstrated low to moderate individual‐level surrogacy between PFS and OS. At the summary level, the surrogacy between PFS and OS varied significantly across different risk factors. With a short postprogression survival and a moderate correlation between PFS and OS, there is no evidence that PFS is a valid surrogate endpoint for OS in malignant mesothelioma. Implications for Practice. For better disease management and for more efficient clinical trial designs, it is important to know if progression‐free survival (PFS) is

  13. Multi-Trial Evaluation of Progression-Free Survival (PFS) as a Surrogate Endpoint for Overall Survival (OS) in First-Line Extensive-Stage Small Cell Lung Cancer (ES-SCLC)

    Science.gov (United States)

    Foster, Nathan R.; Renfro, Lindsay A.; Schild, Steven E.; Redman, Mary W.; Wang, Xiaofei F.; Dahlberg, Suzanne E.; Ding, Keyue; Bradbury, Penelope A.; Ramalingam, Suresh S.; Gandara, David R.; Shibata, Taro; Saijo, Nagahiro; Vokes, Everett E.; Adjei, Alex A.; Mandrekar, Sumithra J.

    2015-01-01

    Introduction We previously reported that PFS may be a candidate surrogate endpoint for OS in first-line ES-SCLC using data from 3 randomized trials (Foster, Cancer 2011). In this validation study (N0424-Alliance), we assessed the patient- and trial-level surrogacy of PFS using data from 7 new first-line phase II/III ES-SCLC trials and across all 10 trials as well (7 new, 3 previous). Methods Individual patient data were utilized across the 7 new trials (2259 patients) and all 10 trials (2855 patients). Patient-level surrogacy (Kendall’s τ) was assessed using the Clayton copula bivariate survival model. Trial-level surrogacy was assessed via association of the log hazard ratios on OS and PFS across trials, including weighted (by trial size) least squares regression of Cox model effects (WLS R2) and correlation of the copula effects (Copula R2). The minimum effect on the surrogate (MES) needed to detect a non-zero treatment effect on OS was also calculated. Results The median OS and PFS across all 10 trials were 9.8 and 5.9 months, respectively. PFS showed strong surrogacy within the 7 new trials (Copula R2 = 0.90 (SE=0.27); WLS R2 = 0.83 (95% CI: 0.43, 0.95); MES=0.67; Kendall’s τ = 0.58) and across all 10 trials (Copula R2 =0.81 (SE=0.25); WLS R2=0.77 (95% CI: 0.47–0.91); MES=0.70; Kendall’s τ =0.57). Conclusions PFS demonstrated strong surrogacy for OS in first-line ES-SCLC based on this external validation study of individual patient data. PFS is a good alternative endpoint to OS and should be considered when resource constraints (time or patient) might make it useful or desirable in place of OS. Additional analyses are needed to assess its appropriateness for targeted agents in this disease setting. PMID:26134227

  14. Use of Surrogate end points in HTA

    Directory of Open Access Journals (Sweden)

    Mangiapane, Sandra

    2009-08-01

    Full Text Available The different actors involved in health system decision-making and regulation have to deal with the question which are valid parameters to assess the health value of health technologies.So called surrogate endpoints represent in the best case preliminary steps in the casual chain leading to the relevant outcome (e. g. mortality, morbidity and are not usually directly perceptible by patients. Surrogate endpoints are not only used in trials of pharmaceuticals but also in studies of other technologies. Their use in the assessment of the benefit of a health technology is however problematic. In this report we intend to answer the following research questions: Which criteria need to be fulfilled for a surrogate parameter to be considered a valid endpoint? Which methods have been described in the literature for the assessment of the validity of surrogate endpoints? Which methodological recommendations concerning the use of surrogate endpoints have been made by international HTA agencies? Which place has been given to surrogate endpoints in international and German HTA reports? For this purpose, we choose three different approaches. Firstly, we conduct a review of the methodological literature dealing with the issue of surrogate endpoints and their validation. Secondly, we analyse current methodological guidelines of HTA agencies members of the International network of agencies for Health Technology Assessment (INAHTA as well as of agencies concerned with assessments for reimbursement purposes. Finally, we analyse the outcome parameter used in a sample of HTA reports available for the public. The analysis of methodological guidelines shows a very cautious position of HTA institutions regarding the use of surrogate endpoints in technology assessment. Surrogate endpoints have not been prominently used in HTA reports. None of the analysed reports based its conclusions solely on the results of surrogate endpoints. The analysis of German HTA reports shows a

  15. Electrocardiogram PR Interval Is a Surrogate Marker to Predict New Occurrence of Atrial Fibrillation in Patients with Frequent Premature Atrial Contractions.

    Science.gov (United States)

    Chun, Kwang Jin; Hwang, Jin Kyung; Choi, So Ra; Park, Seung-Jung; On, Young Keun; Kim, June Soo; Park, Kyoung-Min

    2016-04-01

    The clinical significance of prolonged PR interval has not been evaluated in patients with frequent premature atrial contractions (PACs). We investigated whether prolonged PR interval could predict new occurrence of atrial fibrillation (AF) in patients with frequent PACs. We retrospectively analyzed 684 patients with frequent PACs (> 100 PACs/day) who performed repeated 24-hour Holter monitoring. Prolonged PR interval was defined as longer than 200 msec. Among 684 patients, 626 patients had normal PR intervals (group A) and 58 patients had prolonged PR intervals (group B). After a mean follow-up of 59.3 months, 14 patients (24.1%) in group B developed AF compared to 50 patients (8.0%) in group A (P PR interval (hazard ratio [HR], 1.950; 95% CI, 1.029-3.698; P = 0.041), age (HR, 1.033; 95% CI, 1.006-1.060; P = 0.015), and left atrial (LA) dimension (HR, 1.061; 95% CI, 1.012-1.112; P = 0.015) were associated with AF occurrence. Prolonged PR interval, advanced age, and enlarged LA dimension are independent risk factors of AF occurrence in patients with frequent PACs.

  16. The intermediate endpoint effect in logistic and probit regression

    Science.gov (United States)

    MacKinnon, DP; Lockwood, CM; Brown, CH; Wang, W; Hoffman, JM

    2010-01-01

    Background An intermediate endpoint is hypothesized to be in the middle of the causal sequence relating an independent variable to a dependent variable. The intermediate variable is also called a surrogate or mediating variable and the corresponding effect is called the mediated, surrogate endpoint, or intermediate endpoint effect. Clinical studies are often designed to change an intermediate or surrogate endpoint and through this intermediate change influence the ultimate endpoint. In many intermediate endpoint clinical studies the dependent variable is binary, and logistic or probit regression is used. Purpose The purpose of this study is to describe a limitation of a widely used approach to assessing intermediate endpoint effects and to propose an alternative method, based on products of coefficients, that yields more accurate results. Methods The intermediate endpoint model for a binary outcome is described for a true binary outcome and for a dichotomization of a latent continuous outcome. Plots of true values and a simulation study are used to evaluate the different methods. Results Distorted estimates of the intermediate endpoint effect and incorrect conclusions can result from the application of widely used methods to assess the intermediate endpoint effect. The same problem occurs for the proportion of an effect explained by an intermediate endpoint, which has been suggested as a useful measure for identifying intermediate endpoints. A solution to this problem is given based on the relationship between latent variable modeling and logistic or probit regression. Limitations More complicated intermediate variable models are not addressed in the study, although the methods described in the article can be extended to these more complicated models. Conclusions Researchers are encouraged to use an intermediate endpoint method based on the product of regression coefficients. A common method based on difference in coefficient methods can lead to distorted

  17. Surrogate motherhood

    OpenAIRE

    Arteta-Acosta Cindy

    2011-01-01

    Surrogate motherhood, also known as surrogacy, has recently become achance to exercise the right of paternity by some people. Surrogacy itself did notinvolve a disadvantaged idea, but when this is coupled with scientific experimentsand economic and personal interests, requires intervention of the State tolegislate about consequences arising from the unlimited execution of this practice. Since 70’s,developed countries have been creating laws, decrees and regulations to regulateassisted reprodu...

  18. Protocol of the Definition for the Assessment of Time-to-event Endpoints in CANcer trials (DATECAN) project: formal consensus method for the development of guidelines for standardised time-to-event endpoints' definitions in cancer clinical trials.

    Science.gov (United States)

    Bellera, Carine A; Pulido, Marina; Gourgou, Sophie; Collette, Laurence; Doussau, Adélaïde; Kramar, Andrew; Dabakuyo, Tienhan Sandrine; Ouali, Monia; Auperin, Anne; Filleron, Thomas; Fortpied, Catherine; Le Tourneau, Christophe; Paoletti, Xavier; Mauer, Murielle; Mathoulin-Pélissier, Simone; Bonnetain, Franck

    2013-03-01

    In randomised phase III cancer clinical trials, the most objectively defined and only validated time-to-event endpoint is overall survival (OS). The appearance of new types of treatments and the multiplication of lines of treatment have resulted in the use of surrogate endpoints for overall survival such as progression-free survival (PFS), or time-to-treatment failure. Their development is strongly influenced by the necessity of reducing clinical trial duration, cost and number of patients. However, while these endpoints are frequently used, they are often poorly defined and definitions can differ between trials which may limit their use as primary endpoints. Moreover, this variability of definitions can impact on the trial's results by affecting estimation of treatments' effects. The aim of the Definition for the Assessment of Time-to-event Endpoints in CANcer trials (DATECAN) project is to provide recommendations for standardised definitions of time-to-event endpoints in randomised cancer clinical trials. We will use a formal consensus methodology based on experts' opinions which will be obtained in a systematic manner. Definitions will be independently developed for several cancer sites, including pancreatic, breast, head and neck and colon cancer, as well as sarcomas and gastrointestinal stromal tumours (GISTs). The DATECAN project should lead to the elaboration of recommendations that can then be used as guidelines by researchers participating in clinical trials. This process should lead to a standardisation of the definitions of commonly used time-to-event endpoints, enabling appropriate comparisons of future trials' results. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. TBI Endpoints Development

    Science.gov (United States)

    2015-10-01

    therapy , and early mild physical activity, which result in fewer symptoms, lower mean severity of symptoms, less social disability, and fewer days off work...developing more precise TBI diagnostic tools, clinical endpoints, and effective therapies . We designed and executed an interactive program that combined...surgery, neuropsychology, neuroradiology, psychiatry, neurology, sports medicine, pediatrics, geriatrics , health economics, biostatistics, and informatics

  20. Biomarkers and correlative endpoints for immunotherapy trials.

    Science.gov (United States)

    Morse, Michael A; Osada, Takuya; Hobeika, Amy; Patel, Sandip; Lyerly, H Kim

    2013-01-01

    Immunotherapies for lung cancer are reaching phase III clinical trial, but the ultimate success likely will depend on developing biomarkers to guide development and choosing patient populations most likely to benefit. Because the immune response to cancer involves multiple cell types and cytokines, some spatially and temporally separated, it is likely that multiple biomarkers will be required to fully characterize efficacy of the vaccine and predict eventual benefit. Peripheral blood markers of response, such as the ELISPOT assay and cytokine flow cytometry analyses of peripheral blood mononuclear cells following immunotherapy, remain the standard approach, but it is increasingly important to obtain tissue to study the immune response at the site of the tumor. Earlier clinical endpoints such as response rate and progression-free survival do not correlate with overall survival demonstrated for some immunotherapies, suggesting the need to develop other intermediary clinical endpoints. Insofar as all these biomarkers and surrogate endpoints are relevant in multiple malignancies, it may be possible to extrapolate findings to immunotherapy of lung cancer.

  1. Trial endpoints for drug approval in oncology: Chemoprevention.

    Science.gov (United States)

    Beitz, J

    2001-04-01

    As with other drugs, new drug applications for marketing approval of chemopreventive drugs must include data from adequate and well-controlled clinical trials that demonstrate effectiveness and safety for the intended use. This article summarizes the regulatory requirements for traditional marketing approval, as well as for approval under the accelerated approval regulations. Unlike traditional approval, accelerated approval is based on a surrogate endpoint that is reasonably likely to predict clinical benefit. Discussions with the Food and Drug Administration (FDA) regarding the validity of trial endpoints that may serve as surrogates for clinical benefit for accelerated approval should take place as early as possible in drug development. Meetings with the FDA to discuss these issues may be requested throughout the clinical development of a new drug.

  2. Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials)

    NARCIS (Netherlands)

    Bonnetain, Franck; Bonsing, Bert; Conroy, Thierry; Dousseau, Adelaide; Glimelius, Bengt; Haustermans, Karin; Lacaine, François; van Laethem, Jean Luc; Aparicio, Thomas; Aust, Daniela; Bassi, Claudio; Berger, Virginie; Chamorey, Emmanuel; Chibaudel, Benoist; Dahan, Laeticia; de Gramont, Aimery; Delpero, Jean Robert; Dervenis, Christos; Ducreux, Michel; Gal, Jocelyn; Gerber, Erich; Ghaneh, Paula; Hammel, Pascal; Hendlisz, Alain; Jooste, Valérie; Labianca, Roberto; Latouche, Aurelien; Lutz, Manfred; Macarulla, Teresa; Malka, David; Mauer, Muriel; Mitry, Emmanuel; Neoptolemos, John; Pessaux, Patrick; Sauvanet, Alain; Tabernero, Josep; Taieb, Julien; van Tienhoven, Geertjan; Gourgou-Bourgade, Sophie; Bellera, Carine; Mathoulin-Pélissier, Simone; Collette, Laurence

    2014-01-01

    Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across

  3. Helicopter EMS: Research Endpoints and Potential Benefits

    Directory of Open Access Journals (Sweden)

    Stephen H. Thomas

    2012-01-01

    Full Text Available Patients, EMS systems, and healthcare regions benefit from Helicopter EMS (HEMS utilization. This article discusses these benefits in terms of specific endpoints utilized in research projects. The endpoint of interest, be it primary, secondary, or surrogate, is important to understand in the deployment of HEMS resources or in planning further HEMS outcomes research. The most important outcomes are those which show potential benefits to the patients, such as functional survival, pain relief, and earlier ALS care. Case reports are also important “outcomes” publications. The benefits of HEMS in the rural setting is the ability to provide timely access to Level I or Level II trauma centers and in nontrauma, interfacility transport of cardiac, stroke, and even sepsis patients. Many HEMS crews have pharmacologic and procedural capabilities that bring a different level of care to a trauma scene or small referring hospital, especially in the rural setting. Regional healthcare and EMS system's benefit from HEMS by their capability to extend the advanced level of care throughout a region, provide a “backup” for areas with limited ALS coverage, minimize transport times, make available direct transport to specialized centers, and offer flexibility of transport in overloaded hospital systems.

  4. Observations on Three Endpoint Properties and Their Relationship to Regulatory Outcomes of European Oncology Marketing Applications.

    Science.gov (United States)

    Liberti, Lawrence; Stolk, Pieter; McAuslane, James Neil; Schellens, Jan; Breckenridge, Alasdair M; Leufkens, Hubert

    2015-06-01

    Guidance and exploratory evidence indicate that the type of endpoints and the magnitude of their outcome can define a therapy's clinical activity; however, little empirical evidence relates specific endpoint properties with regulatory outcomes. We explored the relationship of 3 endpoint properties to regulatory outcomes by assessing 50 oncology marketing authorization applications (MAAs; reviewed from 2009 to 2013). Overall, 16 (32%) had a negative outcome. The most commonly used hard endpoints were overall survival (OS) and the duration of response or stable disease. OS was a component of 91% approved and 63% failed MAAs. The most commonly used surrogate endpoints were progression-free survival (PFS), response rate, and health-related quality of life assessments. There was no difference (p = .3801) between the approved and failed MAA cohorts in the proportion of hard endpoints used. A mean of slightly more than four surrogate endpoints were used per approved MAA compared with slightly more than two for failed MAAs. Longer OS and PFS duration outcomes were generally associated with approvals, often when not statistically significant. The approved cohort was associated with a preponderance of statistically significant (p < .05) improvements in primary endpoints (p < .0001 difference between the approved and failed groups). Three key endpoint properties (type of endpoint [hard/surrogate], magnitude of an endpoint outcome, and its statistical significance) are consistent with the European Medicines Agency guidance and, notwithstanding the contribution of unique disease-specific circumstances, are associated with a predictable positive outcome for oncology MAAs. Regulatory decisions made by the European Medicines Agency determine which new medicines will be available to European prescribers and for which therapeutic indications. Regulatory success or failure can be influenced by many factors. This study assessed three key properties of endpoints used in

  5. Surrogate marker evaluation from an information theory perspective.

    Science.gov (United States)

    Alonso, Ariel; Molenberghs, Geert

    2007-03-01

    The last 20 years have seen lots of work in the area of surrogate marker validation, partly devoted to frame the evaluation in a multitrial framework, leading to definitions in terms of the quality of trial- and individual-level association between a potential surrogate and a true endpoint (Buyse et al., 2000, Biostatistics 1, 49-67). A drawback is that different settings have led to different measures at the individual level. Here, we use information theory to create a unified framework, leading to a definition of surrogacy with an intuitive interpretation, offering interpretational advantages, and applicable in a wide range of situations. Our method provides a better insight into the chances of finding a good surrogate endpoint in a given situation. We further show that some of the previous proposals follow as special cases of our method. We illustrate our methodology using data from a clinical study in psychiatry.

  6. Birds as biodiversity surrogates

    DEFF Research Database (Denmark)

    Larsen, Frank Wugt; Bladt, Jesper Stentoft; Balmford, Andrew

    2012-01-01

    1. Most biodiversity is still unknown, and therefore, priority areas for conservation typically are identified based on the presence of surrogates, or indicator groups. Birds are commonly used as surrogates of biodiversity owing to the wide availability of relevant data and their broad popular...... and applications.?Good surrogates of biodiversity are necessary to help identify conservation areas that will be effective in preventing species extinctions. Birds perform fairly well as surrogates in cases where birds are relatively speciose, but overall effectiveness will be improved by adding additional data...... from other taxa, in particular from range-restricted species. Conservation solutions with focus on birds as biodiversity surrogate could therefore benefit from also incorporating species data from other taxa....

  7. Shared Contract-Obedient Endpoints

    Directory of Open Access Journals (Sweden)

    Étienne Lozes

    2012-12-01

    Full Text Available Most of the existing verification techniques for message-passing programs suppose either that channel endpoints are used in a linear fashion, where at most one thread may send or receive from an endpoint at any given time, or that endpoints may be used arbitrarily by any number of threads. The former approach usually forbids the sharing of channels while the latter limits what is provable about programs. In this paper we propose a midpoint between these techniques by extending a proof system based on separation logic to allow sharing of endpoints. We identify two independent mechanisms for supporting sharing: an extension of fractional shares to endpoints, and a new technique based on what we call reflexive ownership transfer. We demonstrate on a number of examples that a linear treatment of sharing is possible.

  8. Calorimetry end-point predictions

    International Nuclear Information System (INIS)

    Fox, M.A.

    1981-01-01

    This paper describes a portion of the work presently in progress at Rocky Flats in the field of calorimetry. In particular, calorimetry end-point predictions are outlined. The problems associated with end-point predictions and the progress made in overcoming these obstacles are discussed. The two major problems, noise and an accurate description of the heat function, are dealt with to obtain the most accurate results. Data are taken from an actual calorimeter and are processed by means of three different noise reduction techniques. The processed data are then utilized by one to four algorithms, depending on the accuracy desired to determined the end-point

  9. Surrogate waveform models

    Science.gov (United States)

    Blackman, Jonathan; Field, Scott; Galley, Chad; Scheel, Mark; Szilagyi, Bela; Tiglio, Manuel

    2015-04-01

    With the advanced detector era just around the corner, there is a strong need for fast and accurate models of gravitational waveforms from compact binary coalescence. Fast surrogate models can be built out of an accurate but slow waveform model with minimal to no loss in accuracy, but may require a large number of evaluations of the underlying model. This may be prohibitively expensive if the underlying is extremely slow, for example if we wish to build a surrogate for numerical relativity. We examine alternate choices to building surrogate models which allow for a more sparse set of input waveforms. Research supported in part by NSERC.

  10. Premixed flame chemistry of a gasoline primary reference fuel surrogate

    KAUST Repository

    Selim, Hatem; Mohamed, Samah; Hansen, Nils; Sarathy, Mani

    2017-01-01

    Investigating the combustion chemistry of gasoline surrogate fuels promises to improve detailed reaction mechanisms used for simulating their combustion. In this work, the combustion chemistry of one of the simplest, but most frequently used

  11. Bedload-surrogate monitoring technologies

    Science.gov (United States)

    Gray, John R.; Laronne, Jonathan B.; Marr, Jeffrey D.G.

    2010-01-01

    Advances in technologies for quantifying bedload fluxes and in some cases bedload size distributions in rivers show promise toward supplanting traditional physical samplers and sampling methods predicated on the collection and analysis of physical bedload samples. Four workshops held from 2002 to 2007 directly or peripherally addressed bedload-surrogate technologies, and results from these workshops have been compiled to evaluate the state-of-the-art in bedload monitoring. Papers from the 2007 workshop are published for the first time with this report. Selected research and publications since the 2007 workshop also are presented. Traditional samplers used for some or all of the last eight decades include box or basket samplers, pan or tray samplers, pressure-difference samplers, and trough or pit samplers. Although still useful, the future niche of these devices may be as a means for calibrating bedload-surrogate technologies operating with active- and passive-type sensors, in many cases continuously and automatically at a river site. Active sensors include acoustic Doppler current profilers (ADCPs), sonar, radar, and smart sensors. Passive sensors include geophones (pipes or plates) in direct contact with the streambed, hydrophones deployed in the water column, impact columns, and magnetic detection. The ADCP for sand and geophones for gravel are currently the most developed techniques, several of which have been calibrated under both laboratory and field conditions. Although none of the bedload-surrogate technologies described herein are broadly accepted for use in large-scale monitoring programs, several are under evaluation. The benefits of verifying and operationally deploying selected bedload-surrogate monitoring technologies could be considerable, providing for more frequent and consistent, less expensive, and arguably more accurate bedload data obtained with reduced personal risk for use in managing the world's sedimentary resources. Twenty-six papers are

  12. Surrogate Marker Evaluation from an Information Theory Perspective

    OpenAIRE

    Alonso Abad, Ariel; Molenberghs, Geert

    2006-01-01

    The last 20 years have seen lots of work in the area of surrogate marker validation, partly devoted to frame the evaluation in a multitrial framework, leading to definitions in terms of the quality of trial- and individual-level association between a potential surrogate and a true endpoint (Buyse et al., 2000, Biostatistics 1, 49–67). A drawback is that different settings have led to different measures at the individual level. Here, we use information theory to create a unified framework, lea...

  13. Endpoints in pediatric pain studies

    NARCIS (Netherlands)

    M. van Dijk (Monique); I. Ceelie (Ilse); D. Tibboel (Dick)

    2011-01-01

    textabstractAssessing pain intensity in (preverbal) children is more difficult than in adults. Tools to measure pain are being used as primary endpoints [e.g., pain intensity, time to first (rescue) analgesia, total analgesic consumption, adverse effects, and long-term effects] in studies on the

  14. Developments in Surrogating Methods

    Directory of Open Access Journals (Sweden)

    Hans van Dormolen

    2005-11-01

    Full Text Available In this paper, I would like to talk about the developments in surrogating methods for preservation. My main focus will be on the technical aspects of preservation surrogates. This means that I will tell you something about my job as Quality Manager Microfilming for the Netherlands’ national preservation program, Metamorfoze, which is coordinated by the National Library. I am responsible for the quality of the preservation microfilms, which are produced for Metamorfoze. Firstly, I will elaborate on developments in preservation methods in relation to the following subjects: · Preservation microfilms · Scanning of preservation microfilms · Preservation scanning · Computer Output Microfilm. In the closing paragraphs of this paper, I would like to tell you something about the methylene blue test. This is an important test for long-term storage of preservation microfilms. Also, I will give you a brief report on the Cellulose Acetate Microfilm Conference that was held in the British Library in London, May 2005.

  15. Establishing a group of endpoints to support collective operations without specifying unique identifiers for any endpoints

    Science.gov (United States)

    Archer, Charles J.; Blocksom, Michael A.; Ratterman, Joseph D.; Smith, Brian E.; Xue, Hanghon

    2016-02-02

    A parallel computer executes a number of tasks, each task includes a number of endpoints and the endpoints are configured to support collective operations. In such a parallel computer, establishing a group of endpoints receiving a user specification of a set of endpoints included in a global collection of endpoints, where the user specification defines the set in accordance with a predefined virtual representation of the endpoints, the predefined virtual representation is a data structure setting forth an organization of tasks and endpoints included in the global collection of endpoints and the user specification defines the set of endpoints without a user specification of a particular endpoint; and defining a group of endpoints in dependence upon the predefined virtual representation of the endpoints and the user specification.

  16. Is Doubling of Serum Creatinine a Valid Clinical 'Hard' Endpoint in Clinical Nephrology Trials?

    NARCIS (Netherlands)

    Lambers Heerspink, H. J.; Perkovic, V.; de Zeeuw, D.

    2011-01-01

    The composite of end stage renal disease (ESRD), doubling of serum creatinine and (renal) death, is a frequently used endpoint in randomized clinical trials in nephrology. Doubling of serum creatinine is a well-accepted part of this endpoint because a doubling of serum creatinine reflects a large

  17. Evaluation of early efficacy endpoints for proof-of-concept trials.

    Science.gov (United States)

    Chen, Cong; Sun, Linda; Li, Chih-Lin

    2013-03-11

    A Phase II proof-of-concept (POC) trial usually uses an early efficacy endpoint other than a clinical endpoint as the primary endpoint. Because of the advancement in bioscience and technology, which has yielded a number of new surrogate biomarkers, drug developers often have more candidate endpoints to choose from than they can handle. As a result, selection of endpoint and its effect size as well as choice of type I/II error rates are often at the center of heated debates in design of POC trials. While optimization of the trade-off between benefit and cost is the implicit objective in such a decision-making process, it is seldom explicitly accounted for in practice. In this research note, motivated by real examples from the oncology field, we provide practical measures for evaluation of early efficacy endpoints (E4) for POC trials. We further provide optimal design strategies for POC trials that include optimal Go-No Go decision criteria for initiation of Phase III and optimal resource allocation strategies for conducting multiple POC trials in a portfolio under fixed resources. Although oncology is used for illustration purpose, the same idea developed in this research note also applies to similar situations in other therapeutic areas or in early-stage drug development in that a Go-No Go decision has to rely on limited data from an early efficacy endpoint and cost-effectiveness is the main concern.

  18. Meet the surrogate fish

    International Nuclear Information System (INIS)

    Johnson, Bob; Neitzel, Duane; Moxon, Suzanne

    1999-01-01

    This article gives details of the US Department of Energy's innovative research into the development of a sensor system that will work as a surrogate fish to provide information to aid the design of fish-friendly turbines for hydroelectric power plants. The selection of the dams for the testing of sensor fish, the release and recovery of the sensor fish, the recording of the physical forces exerted on fish as they pass through the turbines, and use of the information gathered to build more sensor fish are discussed. Fish investigations conducted at the Pacific Northwest National Laboratory are briefly described. (UK)

  19. Conservative strategy-based ensemble surrogate model for optimal groundwater remediation design at DNAPLs-contaminated sites

    Science.gov (United States)

    Ouyang, Qi; Lu, Wenxi; Lin, Jin; Deng, Wenbing; Cheng, Weiguo

    2017-08-01

    The surrogate-based simulation-optimization techniques are frequently used for optimal groundwater remediation design. When this technique is used, surrogate errors caused by surrogate-modeling uncertainty may lead to generation of infeasible designs. In this paper, a conservative strategy that pushes the optimal design into the feasible region was used to address surrogate-modeling uncertainty. In addition, chance-constrained programming (CCP) was adopted to compare with the conservative strategy in addressing this uncertainty. Three methods, multi-gene genetic programming (MGGP), Kriging (KRG) and support vector regression (SVR), were used to construct surrogate models for a time-consuming multi-phase flow model. To improve the performance of the surrogate model, ensemble surrogates were constructed based on combinations of different stand-alone surrogate models. The results show that: (1) the surrogate-modeling uncertainty was successfully addressed by the conservative strategy, which means that this method is promising for addressing surrogate-modeling uncertainty. (2) The ensemble surrogate model that combines MGGP with KRG showed the most favorable performance, which indicates that this ensemble surrogate can utilize both stand-alone surrogate models to improve the performance of the surrogate model.

  20. Surrogate Modeling for Geometry Optimization

    DEFF Research Database (Denmark)

    Rojas Larrazabal, Marielba de la Caridad; Abraham, Yonas; Holzwarth, Natalie

    2009-01-01

    A new approach for optimizing the nuclear geometry of an atomic system is described. Instead of the original expensive objective function (energy functional), a small number of simpler surrogates is used.......A new approach for optimizing the nuclear geometry of an atomic system is described. Instead of the original expensive objective function (energy functional), a small number of simpler surrogates is used....

  1. Correlates of protection for rotavirus vaccines: Possible alternative trial endpoints, opportunities, and challenges.

    Science.gov (United States)

    Angel, Juana; Steele, A Duncan; Franco, Manuel A

    2014-01-01

    Rotavirus (RV) is a major vaccine-preventable killer of young children worldwide. Two RV vaccines are globally commercially available and other vaccines are in different stages of development. Due to the absence of a suitable correlate of protection (CoP), all RV vaccine efficacy trials have had clinical endpoints. These trials represent an important challenge since RV vaccines have to be introduced in many different settings, placebo-controlled studies are unethical due to the availability of licensed vaccines, and comparator assessments for new vaccines with clinical endpoints are very large, complex, and expensive to conduct. A CoP as a surrogate endpoint would allow predictions of vaccine efficacy for new RV vaccines and enable a regulatory pathway, contributing to the more rapid development of new RV vaccines. The goal of this review is to summarize experiences from RV natural infection and vaccine studies to evaluate potential CoP for use as surrogate endpoints for assessment of new RV vaccines, and to explore challenges and opportunities in the field.

  2. Frequent Questions on Recycling

    Science.gov (United States)

    This is a list of frequent questions on recycling, broken down into five categories. These are answers to common questions that EPA has received from press and web inquiries. This list is located on the Reduce, Reuse, Recycle website.

  3. Scalable Frequent Subgraph Mining

    KAUST Repository

    Abdelhamid, Ehab

    2017-01-01

    Given an input graph, the Frequent Subgraph Mining (FSM) task finds all subgraphs with frequencies exceeding a given threshold. FSM is crucial for graph analysis, and it is an essential building block in a variety

  4. Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE)

    DEFF Research Database (Denmark)

    Vestbo, J; Anderson, W; Coxson, H O

    2008-01-01

    Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and not well understood. The forced expiratory volume in one second is used for the diagnosis and staging of COPD, but there is wide acceptance that it is a crude measure and insensitive to change over shorter periods of time...

  5. Inconsistent selection and definition of local and regional endpoints in breast cancer research.

    Science.gov (United States)

    Moossdorff, M; van Roozendaal, L M; Schipper, R-J; Strobbe, L J A; Voogd, A C; Tjan-Heijnen, V C G; Smidt, M L

    2014-12-01

    Results in breast cancer research are reported using study endpoints. Most are composite endpoints (such as locoregional recurrence), consisting of several components (for example local recurrence) that are in turn composed of specific events (such as skin recurrence). Inconsistent endpoint selection and definition might lead to unjustified conclusions when comparing study outcomes. This study aimed to determine which locoregional endpoints are used in breast cancer studies, and how these endpoints and their components are defined. PubMed was searched for breast cancer studies published in nine leading journals in 2011. Articles using endpoints with a local or regional component were included and definitions were compared. Twenty-three different endpoints with a local or regional component were extracted from 44 articles. Most frequently used were disease-free survival (25 articles), recurrence-free survival (7), local control (4), locoregional recurrence-free survival (3) and event-free survival (3). Different endpoints were used for similar outcomes. Of 23 endpoints, five were not defined and 18 were defined only partially. Of these, 16 contained a local and 13 a regional component. Included events were not specified in 33 of 57 (local) and 27 of 50 (regional) cases. Definitions of local components inconsistently included carcinoma in situ and skin and chest wall recurrences. Regional components inconsistently included specific nodal sites and skin and chest wall recurrences. Breast cancer studies use many different endpoints with a locoregional component. Definitions of endpoints and events are either not provided or vary between trials. To improve transparency, facilitate trial comparison and avoid unjustified conclusions, authors should report detailed definitions of all endpoints. © 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.

  6. Comparison of treatment effect sizes from pivotal and postapproval trials of novel therapeutics approved by the FDA based on surrogate markers of disease: a meta-epidemiological study.

    Science.gov (United States)

    Wallach, Joshua D; Ciani, Oriana; Pease, Alison M; Gonsalves, Gregg S; Krumholz, Harlan M; Taylor, Rod S; Ross, Joseph S

    2018-03-21

    The U.S. Food and Drug Administration (FDA) often approves new drugs based on trials that use surrogate markers for endpoints, which involve certain trade-offs and may risk making erroneous inferences about the medical product's actual clinical effect. This study aims to compare the treatment effects among pivotal trials supporting FDA approval of novel therapeutics based on surrogate markers of disease with those observed among postapproval trials for the same indication. We searched Drugs@FDA and PubMed to identify published randomized superiority design pivotal trials for all novel drugs initially approved by the FDA between 2005 and 2012 based on surrogate markers as primary endpoints and published postapproval trials using the same surrogate markers or patient-relevant outcomes as endpoints. Summary ratio of odds ratios (RORs) and difference between standardized mean differences (dSMDs) were used to quantify the average difference in treatment effects between pivotal and matched postapproval trials. Between 2005 and 2012, the FDA approved 88 novel drugs for 90 indications based on one or multiple pivotal trials using surrogate markers of disease. Of these, 27 novel drugs for 27 indications were approved based on pivotal trials using surrogate markers as primary endpoints that could be matched to at least one postapproval trial, for a total of 43 matches. For nine (75.0%) of the 12 matches using the same non-continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than postapproval trials. On average, treatment effects were 50% higher (more beneficial) in the pivotal than the postapproval trials (ROR 1.5; 95% confidence interval CI 1.01-2.23). For 17 (54.8%) of the 31 matches using the same continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than the postapproval trials. On average, there was no difference in treatment effects between pivotal and postapproval trials (dSMDs 0.01; 95

  7. Mining frequent binary expressions

    NARCIS (Netherlands)

    Calders, T.; Paredaens, J.; Kambayashi, Y.; Mohania, M.K.; Tjoa, A.M.

    2000-01-01

    In data mining, searching for frequent patterns is a common basic operation. It forms the basis of many interesting decision support processes. In this paper we present a new type of patterns, binary expressions. Based on the properties of a specified binary test, such as reflexivity, transitivity

  8. Frequent hemodialysis in children.

    Science.gov (United States)

    Warady, Bradley A; Fischbach, Michel; Geary, Denis; Goldstein, Stuart L

    2007-07-01

    Frequent hemodialysis is currently conducted in a limited number of pediatric dialysis centers. However, the preliminary experience with children who have undergone procedures such as "daily" intensive hemodiafiltration and nocturnal hemodialysis has been positive, with the allowance for unrestricted diets and fluid intake, the lack of need for phosphate binders, excellent metabolic and blood pressure control, and, in the case of hemodiafiltration, excellent growth. The provision of frequent daily hemodialysis with the NxStage System has also recently been introduced to pediatrics. An overview about what is currently understood regarding the technical and clinical application of these approaches to therapy for children with end-stage renal disease form the basis for this article and highlight the impact of the procedures to date and the need for additional experience and collaborative data collection.

  9. Psychosocial aspects of surrogate motherhood.

    Science.gov (United States)

    van den Akker, Olga B A

    2007-01-01

    This review addresses the psychosocial research carried out on surrogacy triads (surrogate mothers, commissioning mothers and offspring) and shows that research has focused on a number of specific issues: attachment and disclosure to surrogate offspring; experiences, characteristics and motivations of surrogate mothers; and changes in profiles of the commissioning/intended mothers. Virtually all studies have used highly selected samples making generalizations difficult. There have been a notable lack of theory, no interventions and only a handful of longitudinal studies or studies comparing different populations. Few studies have specifically questioned the meaning of and need for a family or the influence and impact that professionals, treatment availability and financial factors have on the choices made for surrogate and intended mothers. Societal attitudes have changed somewhat; however, according to public opinion, women giving up babies still fall outside the acceptable remit. Surrogate and intended mothers appear to reconcile their unusual choice through a process of cognitive restructuring, and the success or failure of this cognitive appraisal affects people's willingness to be open and honest about their choices. Normal population surveys, on the contrary, are less accepting of third party reproduction; they have no personal need to reconsider and hence maintain their original normative cognitively consonant state.

  10. Licensing Surrogate Decision-Makers.

    Science.gov (United States)

    Rosoff, Philip M

    2017-06-01

    As medical technology continues to improve, more people will live longer lives with multiple chronic illnesses with increasing cumulative debilitation, including cognitive dysfunction. Combined with the aging of society in most developed countries, an ever-growing number of patients will require surrogate decision-makers. While advance care planning by patients still capable of expressing their preferences about medical interventions and end-of-life care can improve the quality and accuracy of surrogate decisions, this is often not the case, not infrequently leading to demands for ineffective, inappropriate and prolonged interventions. In 1980 LaFollette called for the licensing of prospective parents, basing his argument on the harm they can do to vulnerable people (children). In this paper, I apply his arguments to surrogate decision-makers for cognitively incapacitated patients, rhetorically suggesting that we require potential surrogates to qualify for this position by demonstrating their ability to make reasonable and rational decisions for others. I employ this theoretical approach to argue that the loose criteria by which we authorize surrogates' generally unchallenged power should be reconsidered.

  11. Surrogate alcohol: what do we know and where do we go?

    Science.gov (United States)

    Lachenmeier, Dirk W; Rehm, Jürgen; Gmel, Gerhard

    2007-10-01

    Consumption of surrogate alcohols (i.e., nonbeverage alcohols and illegally produced alcohols) was shown to impact on different causes of death, not only poisoning or liver disease, and appears to be a major public health problem in Russia and elsewhere. A computer-assisted literature review on chemical composition and health consequences of "surrogate alcohol" was conducted and more than 70 references were identified. A wider definition of the term "surrogate alcohol" was derived, including both nonbeverage alcohols and illegally produced alcohols that contain nonbeverage alcohols. Surrogate alcohol may contain substances that cause severe health consequences including death. Known toxic constituents include lead, which may lead to chronic toxicity, and methanol, which leads to acute poisoning. On the other hand, the role of higher alcohols (e.g., propanol, isobutanol, and isoamyl alcohol) in the etiology of surrogate-associated diseases is currently unclear. Whether other constituents of surrogates have contributed to the high all-cause mortality over and above the effect of ethanol in recent studies also remains unclear. Given the high public health importance associated with the consumption of surrogate alcohols, further knowledge on its chemical composition is required as well as research on its links to various disease endpoints should be undertaken with priority. Some interventions to reduce the harm resulting from surrogate alcohol could be undertaken already at this point. For example, the use of methanol or methanol-containing wood alcohol should be abolished in denatured alcohol. Other possible surrogates (e.g., automobile products) should be treated with bittering agents to avoid consumption.

  12. A web-based endpoint adjudication system for interim analyses in clinical trials.

    Science.gov (United States)

    Nolen, Tracy L; Dimmick, Bill F; Ostrosky-Zeichner, Luis; Kendrick, Amy S; Sable, Carole; Ngai, Angela; Wallace, Dennis

    2009-02-01

    A data monitoring committee (DMC) is often employed to assess trial progress and review safety data and efficacy endpoints throughout a trail. Interim analyses performed for the DMC should use data that are as complete and verified as possible. Such analyses are complicated when data verification involves subjective study endpoints or requires clinical expertise to determine each subject's status with respect to the study endpoint. Therefore, procedures are needed to obtain adjudicated data for interim analyses in an efficient manner. In the past, methods for handling such data included using locally reported results as surrogate endpoints, adjusting analysis methods for unadjudicated data, or simply performing the adjudication as rapidly as possible. These methods all have inadequacies that make their sole usage suboptimal. For a study of prophylaxis for invasive candidiasis, adjudication of both study eligibility criteria and clinical endpoints prior to two interim analyses was required. Because the study was expected to enroll at a moderate rate and the sponsor required adjudicated endpoints to be used for interim analyses, an efficient process for adjudication was required. We created a web-based endpoint adjudication system (WebEAS) that allows for expedited review by the endpoint adjudication committee (EAC). This system automatically identifies when a subject's data are complete, creates a subject profile from the study data, and assigns EAC reviewers. The reviewers use the WebEAS to review the subject profile and submit their completed review form. The WebEAS then compares the reviews, assigns an additional review as a tiebreaker if needed, and stores the adjudicated data. The study for which this system was originally built was administratively closed after 10 months with only 38 subjects enrolled. The adjudication process was finalized and the WebEAS system activated prior to study closure. Some website accessibility issues presented initially. However

  13. Establishing a group of endpoints in a parallel computer

    Science.gov (United States)

    Archer, Charles J.; Blocksome, Michael A.; Ratterman, Joseph D.; Smith, Brian E.; Xue, Hanhong

    2016-02-02

    A parallel computer executes a number of tasks, each task includes a number of endpoints and the endpoints are configured to support collective operations. In such a parallel computer, establishing a group of endpoints receiving a user specification of a set of endpoints included in a global collection of endpoints, where the user specification defines the set in accordance with a predefined virtual representation of the endpoints, the predefined virtual representation is a data structure setting forth an organization of tasks and endpoints included in the global collection of endpoints and the user specification defines the set of endpoints without a user specification of a particular endpoint; and defining a group of endpoints in dependence upon the predefined virtual representation of the endpoints and the user specification.

  14. A summation free β+-endpoint spectrometer

    International Nuclear Information System (INIS)

    Keller, H.; Kirchner, R.; Klepper, O.; Roeckl, E.; Schardt, D.; Simon, R.S.; Kleinheinz, P.; Liang, C.F.; Paris, P.

    1990-08-01

    A β + -endpoint spectrometer is described, where positrons are observed in an 11-mm thick silicon detector in coincidence with subsequent γ-rays meausred in a germanium detector, and where the summing of the positron energy with the annihilation radiation is prevented by detecting both 511-keV quanta in opposite segments of a BGO ring surrounding the silicon detector. The procedure of measuring and analyzing the data is outlined for the decay of the 11/2 - -isomer of 149 Tb; its endpoint energy is determined to be 1853(10) keV, in agreement with the literature. The accuracy and reliability of β + -endpoint measurements is discussed in comparison to the EC/β + -ratio method. (orig.)

  15. End-point sharpness in thermometric titrimetry.

    Science.gov (United States)

    Tyrrell, H J

    1967-07-01

    It is shown that the sharpness of an end-point in a thermometric titration where the simple reaction A + B right harpoon over left harpoon AB takes place, depends on Kc(A') where K is the equilibrium constant for the reaction, and c(A') is the total concentration of the titrand (A) in the reaction mixture. The end-point is sharp if, (i) the enthalpy change in the reaction is not negligible, and (ii) Kc(A') > 10(3). This shows that it should, for example, be possible to titrate 0.1 M acid, pK(A) = 10, using a thennometric end-point. Some aspects of thermometric titrimetry when Kc(A') < 10(3) are also considered.

  16. Scalable Frequent Subgraph Mining

    KAUST Repository

    Abdelhamid, Ehab

    2017-06-19

    A graph is a data structure that contains a set of nodes and a set of edges connecting these nodes. Nodes represent objects while edges model relationships among these objects. Graphs are used in various domains due to their ability to model complex relations among several objects. Given an input graph, the Frequent Subgraph Mining (FSM) task finds all subgraphs with frequencies exceeding a given threshold. FSM is crucial for graph analysis, and it is an essential building block in a variety of applications, such as graph clustering and indexing. FSM is computationally expensive, and its existing solutions are extremely slow. Consequently, these solutions are incapable of mining modern large graphs. This slowness is caused by the underlying approaches of these solutions which require finding and storing an excessive amount of subgraph matches. This dissertation proposes a scalable solution for FSM that avoids the limitations of previous work. This solution is composed of four components. The first component is a single-threaded technique which, for each candidate subgraph, needs to find only a minimal number of matches. The second component is a scalable parallel FSM technique that utilizes a novel two-phase approach. The first phase quickly builds an approximate search space, which is then used by the second phase to optimize and balance the workload of the FSM task. The third component focuses on accelerating frequency evaluation, which is a critical step in FSM. To do so, a machine learning model is employed to predict the type of each graph node, and accordingly, an optimized method is selected to evaluate that node. The fourth component focuses on mining dynamic graphs, such as social networks. To this end, an incremental index is maintained during the dynamic updates. Only this index is processed and updated for the majority of graph updates. Consequently, search space is significantly pruned and efficiency is improved. The empirical evaluation shows that the

  17. Forecasting interest rates with shifting endpoints

    DEFF Research Database (Denmark)

    Van Dijk, Dick; Koopman, Siem Jan; Wel, Michel van der

    2014-01-01

    We consider forecasting the term structure of interest rates with the assumption that factors driving the yield curve are stationary around a slowly time-varying mean or ‘shifting endpoint’. The shifting endpoints are captured using either (i) time series methods (exponential smoothing) or (ii......) long-range survey forecasts of either interest rates or inflation and output growth, or (iii) exponentially smoothed realizations of these macro variables. Allowing for shifting endpoints in yield curve factors provides substantial and significant gains in out-of-sample predictive accuracy, relative...... to stationary and random walk benchmarks. Forecast improvements are largest for long-maturity interest rates and for long-horizon forecasts....

  18. Systematic review: the effect on surrogates of making treatment decisions for others.

    Science.gov (United States)

    Wendler, David; Rid, Annette

    2011-03-01

    Clinical practice relies on surrogates to make or help to make treatment decisions for incapacitated adults; however, the effect of this practice on surrogates has not been evaluated. To assess the effect on surrogates of making treatment decisions for adults who cannot make their own decisions. Empirical studies published in English and listed in MEDLINE, EMBASE, CINAHL, BIOETHICSLINE, PsycINFO, or Scopus before 1 July 2010. Eligible studies provided quantitative or qualitative empirical data, by evaluating surrogates, regarding the effect on surrogates of making treatment decisions for an incapacitated adult. Information on study location, number and type of surrogates, timing of data collection, type of decisions, patient setting, methods, main findings, and limitations. 40 studies, 29 using qualitative and 11 using quantitative methods, provided data on 2854 surrogates, more than one half of whom were family members of the patient. Most surrogates were surveyed several months to years after making treatment decisions, the majority of which were end-of-life decisions. The quantitative studies found that at least one third of surrogates experienced a negative emotional burden as the result of making treatment decisions. The qualitative studies reported that many or most surrogates experienced negative emotional burden. The negative effects on surrogates were often substantial and typically lasted months or, in some cases, years. The most common negative effects cited by surrogates were stress, guilt over the decisions they made, and doubt regarding whether they had made the right decisions. Nine of the 40 studies also reported beneficial effects on a few surrogates, the most common of which were supporting the patient and feeling a sense of satisfaction. Knowing which treatment is consistent with the patient's preferences was frequently cited as reducing the negative effect on surrogates. Thirty-two of the 40 articles reported data collected in the United States

  19. Surrogate mothering: exploitation or empowerment?

    Science.gov (United States)

    Purdy, Laura M

    1989-01-01

    The morality of surrogate mothering is analyzed from a "consequentialist" framework which attempts to separate those consequences that invariably accompany a given act from those that accompany it only in particular circumstances. Critics of surrogacy argue that it transfers the burden and risk of pregnancy onto another woman, separates sex and reproduction, and separates reproduction and childrearing; none of these acts is necessarily wrong, either morally or for women's or society's basic interests. While surrogate mothering can be rendered immoral if women are coerced into the practice or become victims of subordinating or penalizing contracts, it has the potential to empower women and increase their status in society by providing a job that is less risky and more enjoyable than other jobs women are forced to take and by achieving greater social recognition for reproductive labor.

  20. Toward a Psychology of Surrogate Decision Making.

    Science.gov (United States)

    Tunney, Richard J; Ziegler, Fenja V

    2015-11-01

    In everyday life, many of the decisions that we make are made on behalf of other people. A growing body of research suggests that we often, but not always, make different decisions on behalf of other people than the other person would choose. This is problematic in the practical case of legally designated surrogate decision makers, who may not meet the substituted judgment standard. Here, we review evidence from studies of surrogate decision making and examine the extent to which surrogate decision making accurately predicts the recipient's wishes, or if it is an incomplete or distorted application of the surrogate's own decision-making processes. We find no existing domain-general model of surrogate decision making. We propose a framework by which surrogate decision making can be assessed and a novel domain-general theory as a unifying explanatory concept for surrogate decisions. © The Author(s) 2015.

  1. Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials).

    Science.gov (United States)

    Bonnetain, Franck; Bonsing, Bert; Conroy, Thierry; Dousseau, Adelaide; Glimelius, Bengt; Haustermans, Karin; Lacaine, François; Van Laethem, Jean Luc; Aparicio, Thomas; Aust, Daniela; Bassi, Claudio; Berger, Virginie; Chamorey, Emmanuel; Chibaudel, Benoist; Dahan, Laeticia; De Gramont, Aimery; Delpero, Jean Robert; Dervenis, Christos; Ducreux, Michel; Gal, Jocelyn; Gerber, Erich; Ghaneh, Paula; Hammel, Pascal; Hendlisz, Alain; Jooste, Valérie; Labianca, Roberto; Latouche, Aurelien; Lutz, Manfred; Macarulla, Teresa; Malka, David; Mauer, Muriel; Mitry, Emmanuel; Neoptolemos, John; Pessaux, Patrick; Sauvanet, Alain; Tabernero, Josep; Taieb, Julien; van Tienhoven, Geertjan; Gourgou-Bourgade, Sophie; Bellera, Carine; Mathoulin-Pélissier, Simone; Collette, Laurence

    2014-11-01

    Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9). For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items. The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Improved Endpoints for Cancer Immunotherapy Trials

    Science.gov (United States)

    Eggermont, Alexander M. M.; Janetzki, Sylvia; Hodi, F. Stephen; Ibrahim, Ramy; Anderson, Aparna; Humphrey, Rachel; Blumenstein, Brent; Wolchok, Jedd

    2010-01-01

    Unlike chemotherapy, which acts directly on the tumor, cancer immunotherapies exert their effects on the immune system and demonstrate new kinetics that involve building a cellular immune response, followed by changes in tumor burden or patient survival. Thus, adequate design and evaluation of some immunotherapy clinical trials require a new development paradigm that includes reconsideration of established endpoints. Between 2004 and 2009, several initiatives facilitated by the Cancer Immunotherapy Consortium of the Cancer Research Institute and partner organizations systematically evaluated an immunotherapy-focused clinical development paradigm and created the principles for redefining trial endpoints. On this basis, a body of clinical and laboratory data was generated that supports three novel endpoint recommendations. First, cellular immune response assays generate highly variable results. Assay harmonization in multicenter trials may minimize variability and help to establish cellular immune response as a reproducible biomarker, thus allowing investigation of its relationship with clinical outcomes. Second, immunotherapy may induce novel patterns of antitumor response not captured by Response Evaluation Criteria in Solid Tumors or World Health Organization criteria. New immune-related response criteria were defined to more comprehensively capture all response patterns. Third, delayed separation of Kaplan–Meier curves in randomized immunotherapy trials can affect results. Altered statistical models describing hazard ratios as a function of time and recognizing differences before and after separation of curves may allow improved planning of phase III trials. These recommendations may improve our tools for cancer immunotherapy trials and may offer a more realistic and useful model for clinical investigation. PMID:20826737

  3. Ethical Problems Related to Surrogate Motherhood

    OpenAIRE

    Erdem Aydin

    2006-01-01

    Being unable to have children is an important problem for married couples. At present, new reproduction techniques help these couples while those who can not find any solution try new approaches. One of these is the phenomenon of surrogate motherhood, which is based upon an agreement between the infertile couple and surrogate mother. Surrogate mother may conceive with the sperm of the male of the involved couple as well as by the transfer of the embryo formed by invitro fertilization. Couples...

  4. Interpretations, perspectives and intentions in surrogate motherhood

    OpenAIRE

    van Zyl, L.; van Niekerk, A.

    2000-01-01

    In this paper we examine the questions "What does it mean to be a surrogate mother?" and "What would be an appropriate perspective for a surrogate mother to have on her pregnancy?" In response to the objection that such contracts are alienating or dehumanising since they require women to suppress their evolving perspective on their pregnancies, liberal supporters of surrogate motherhood argue that the freedom to contract includes the freedom to enter a contract to bear a child for an infertil...

  5. Surrogatvalidierung durch Korrelation und Surrogate Threshold Effect – Ergebnisse von Simulationsstudien

    Directory of Open Access Journals (Sweden)

    Gillhaus, Johanna

    2017-01-01

    Full Text Available Background: Progression-free survival (PFS is often used instead of the patient-relevant endpoint overall survival (OS in cancer clinical trials. In order for PFS to be accepted as a patient-relevant outcome within the benefit assessment of pharmaceuticals in accordance with the German Social Code, Book Five (SGB V, section 35a, it has to be validated as a surrogate endpoint for OS in the relevant indication. As part of a rapid report the Institute for Quality and Efficiency in Health Care (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen – IQWiG presented methods for surrogate endpoints validation and recommendations for correlation-based procedures. These methods include the evaluation of the certainty of conclusion of study results and the correlation between estimates of surrogate outcome and patient-relevant outcome on trial-level. The correlation is estimated by sample Pearson correlation coefficient or coefficient of determination and respective confidence interval (CI. Requirements for surrogate validation are a high correlation and a high certainty of conclusion of the study results. In case of medium correlation IQWiG methods propose applying the concept of surrogate threshold effect (STE to determine thresholds for the estimate of the surrogate endpoint.Methods: In simulation studies we investigate the requirements for a successful surrogate validation when applying a correlation-based approach. Simulation parameters are the estimates of the surrogate and the patient-relevant outcome, the correlation between them, the number of patients and the number of studies. We analyzed different scenarios in order to figure out parameters contributing to high correlation. Furthermore, we investigate requirements of the STE method, allowing conclusions on patient-relevant endpoints by means of surrogate endpoints. Finally, in consideration of IQWiG methods we analyze the challenges of surrogate validation in practical use

  6. ETHICAL ISSUES IN THE SURROGATE MATERNITY PRACTICE

    OpenAIRE

    TÜRK, Rukiye; TERZİOĞLU, Fusun

    2014-01-01

    The assisted reproductive technology was initially considered to be a treatment tool for infertile couples. However, as it was started in time to use the uteri of other women for the embryos of the other ones, the concept of surrogate maternity appeared.The surrogate maternity is practiced in three types. In the first type of surrogate maternity, the sperm of the spouse of the prospective mother is inseminated with the ovum of the surrogate mother. The second method is the in-vitro inseminati...

  7. Surrogate Analysis and Index Developer (SAID) tool

    Science.gov (United States)

    Domanski, Marian M.; Straub, Timothy D.; Landers, Mark N.

    2015-10-01

    The use of acoustic and other parameters as surrogates for suspended-sediment concentrations (SSC) in rivers has been successful in multiple applications across the Nation. Tools to process and evaluate the data are critical to advancing the operational use of surrogates along with the subsequent development of regression models from which real-time sediment concentrations can be made available to the public. Recent developments in both areas are having an immediate impact on surrogate research and on surrogate monitoring sites currently (2015) in operation.

  8. Endpoint singularities in unintegrated parton distributions

    CERN Document Server

    Hautmann, F

    2007-01-01

    We examine the singular behavior from the endpoint region x -> 1 in parton distributions unintegrated in both longitudinal and transverse momenta. We identify and regularize the singularities by using the subtraction method, and compare this with the cut-off regularization method. The counterterms for the distributions with subtractive regularization are given in coordinate space by compact all-order expressions in terms of eikonal-line operators. We carry out an explicit calculation at one loop for the unintegrated quark distribution. We discuss the relation of the unintegrated parton distributions in subtractive regularization with the ordinary parton distributions.

  9. Surrogate marker analysis in cancer clinical trials through time-to-event mediation techniques.

    Science.gov (United States)

    Vandenberghe, Sjouke; Duchateau, Luc; Slaets, Leen; Bogaerts, Jan; Vansteelandt, Stijn

    2017-01-01

    The meta-analytic approach is the gold standard for validation of surrogate markers, but has the drawback of requiring data from several trials. We refine modern mediation analysis techniques for time-to-event endpoints and apply them to investigate whether pathological complete response can be used as a surrogate marker for disease-free survival in the EORTC 10994/BIG 1-00 randomised phase 3 trial in which locally advanced breast cancer patients were randomised to either taxane or anthracycline based neoadjuvant chemotherapy. In the mediation analysis, the treatment effect is decomposed into an indirect effect via pathological complete response and the remaining direct effect. It shows that only 4.2% of the treatment effect on disease-free survival after five years is mediated by the treatment effect on pathological complete response. There is thus no evidence from our analysis that pathological complete response is a valuable surrogate marker to evaluate the effect of taxane versus anthracycline based chemotherapies on progression free survival of locally advanced breast cancer patients. The proposed analysis strategy is broadly applicable to mediation analyses of time-to-event endpoints, is easy to apply and outperforms existing strategies in terms of precision as well as robustness against model misspecification.

  10. The Reparative Motive in Surrogate Mothers.

    Science.gov (United States)

    Kanefield, Linda

    1999-01-01

    Explores the motivations of surrogate mothers, focusing on underlying reparative motive--to compensate for or repair an earlier loss or sense of damage. Provides an overview of the typical surrogate's characteristics and personality, discusses the theoretical underpinnings of the reparative motive, and considers the tension between reparation and…

  11. 34 CFR 303.406 - Surrogate parents.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Surrogate parents. 303.406 Section 303.406 Education... DISABILITIES Procedural Safeguards General § 303.406 Surrogate parents. (a) General. Each lead agency shall ensure that the rights of children eligible under this part are protected if— (1) No parent (as defined...

  12. 34 CFR 300.519 - Surrogate parents.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Surrogate parents. 300.519 Section 300.519 Education... DISABILITIES Procedural Safeguards Due Process Procedures for Parents and Children § 300.519 Surrogate parents... parent (as defined in § 300.30) can be identified; (2) The public agency, after reasonable efforts...

  13. Imaging Seeker Surrogate for IRCM evaluation

    NARCIS (Netherlands)

    Schleijpen, H.M.A.; Carpenter, S.R.; Mellier, B.; Dimmeler, A.

    2007-01-01

    NATO-SCI-139 and its predecessor groups have more than a decade of history in the evaluation and recommendation of EO and IR Countermeasures against anti-aircraft missiles. Surrogate Seekers have proven to be a valuable tool for this work. The use of surrogate seekers in international co-operations

  14. Gene expression profiles in auricle skin as a possible additional endpoint for determination of sensitizers: A multi-endpoint evaluation of the local lymph node assay.

    Science.gov (United States)

    Tsuchiyama, Hiromi; Maeda, Akihisa; Nakajima, Mayumi; Kitsukawa, Mika; Takahashi, Kei; Miyoshi, Tomoya; Mutsuga, Mayu; Asaoka, Yoshiji; Miyamoto, Yohei; Oshida, Keiyu

    2017-10-05

    The murine local lymph node assay (LLNA) is widely used to test chemicals to induce skin sensitization. Exposure of mouse auricle skin to a sensitizer results in proliferation of local lymph node T cells, which has been measured by in vivo incorporation of H 3 -methyl thymidine or 5-bromo-2'-deoxyuridine (BrdU). The stimulation index (SI), the ratio of the mean proliferation in each treated group to that in the concurrent vehicle control group, is frequently used as a regulatory-authorized endpoint for LLNA. However, some non-sensitizing irritants, such as sodium dodecyl sulfate (SDS) or methyl salicylate (MS), have been reported as false-positives by this endpoint. In search of a potential endpoint to enhance the specificity of existing endpoints, we evaluated 3 contact sensitizers; (hexyl cinnamic aldehyde [HCA], oxazolone [OXA], and 2,4-dinitrochlorobenzene [DNCB]), 1 respiratory sensitizer (toluene 2,4-diisocyanate [TDI]), and 2 non-sensitizing irritants (MS and SDS) by several endpoints in LLNA. Each test substance was applied to both ears of female CBA/Ca mice daily for 3 consecutive days. The ears and auricle lymph node cells were analyzed on day 5 for endpoints including the SI value, lymph node cell count, cytokine release from lymph node cells, and histopathological changes and gene expression profiles in auricle skin. The SI values indicated that all the test substances induced significant proliferation of lymph node cells. The lymph node cell counts showed no significant changes by the non-sensitizers assessed. The inflammatory findings of histopathology were similar among the auricle skins treated by sensitizers and irritants. Gene expression profiles of cytokines IFN-γ, IL-4, and IL-17 in auricle skin were similar to the cytokine release profiles in draining lymph node cells. In addition, the gene expression of the chemokine CXCL1 and/or CXCL2 showed that it has the potential to discriminate sensitizers and non-sensitizing irritants. Our results

  15. The interactive surrogate travel system.

    Science.gov (United States)

    Nakajima, I; Ichimura, A; Juzoji, H; Mugita, K

    1999-01-01

    The Interactive Surrogate Travel (IST) system is based on the super-miniaturized system of virtual technology, Cave Automatic Virtual Environment (CAVE). Using bilateral virtual reality (VR-to-VR) communications, IST enables the testing of subjects via interactive communications. It appears that IST will find practical applications in the near future. We examined the utility of IST in medical treatment and psychiatric tests. Psychiatric symptoms reflect human pathos, which in turn are greatly influenced by culture. If these culture-bound symptoms can be adequately communicated between providers and clients of different cultures, we can develop effective telepsychiatric services across different societies and cultures. IST requires high-speed transmission and gigabyte circuits. A pilot project tested the utility of IST (through the use of optical fiber communications on earth) as a basis for experiments via the Gigabit satellite, to be launched in the year 2002.

  16. Extracting gluino endpoints with event topology patterns

    Energy Technology Data Exchange (ETDEWEB)

    Pietsch, N. [Hamburg Univ. (Germany). Inst. fuer Experimentalphysik; Reuter, J.; Sakurai, K.; Wiesler, D. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2012-06-15

    In this paper we study the gluino dijet mass edge measurement at the LHC in a realistic situation including both SUSY and combinatorical backgrounds together with effects of initial and final state radiation as well as a finite detector resolution. Three benchmark scenarios are examined in which the dominant SUSY production process and also the decay modes are different. Several new kinematical variables are proposed to minimize the impact of SUSY and combinatorial backgrounds in the measurement. By selecting events with a particular number of jets and leptons, we attempt to measure two distinct gluino dijet mass edges originating from wino g {yields} jjW and bino g {yields}jjB decay modes, separately. We determine the endpoints of distributions of proposed and existing variables and show that those two edges can be disentangled and measured within good accuracy, irrespective of the presence of ISR, FSR, and detector effects.

  17. Climate Leadership Awards Frequent Questions

    Science.gov (United States)

    Provides answers to frequently asked questions regarding the Climate Leadership Awards, sponsored by EPA's Center for Corporate Climate Leadership with co-sponsorship from the Center for Climate and Energy Solutions and The Climate Registry.

  18. Radiological endpoints relevant to ecological risk assessment

    International Nuclear Information System (INIS)

    Harrison, F.

    1997-01-01

    Because of the potential risk from radiation due to the releases of radionuclides from anthropogenic activities, considerable research was performed to determine for humans the levels of dose received, their responses to the doses and mechanisms of action of radioactivity on living matter. More recently, there is an increased interest in the effects of radioactivity on non-human species. There are differences in approach between risk assessment for humans and ecosystems. For protection of humans, the focus is the individual and the endpoint of primary concern is cancer induction. For protection of ecosystems, the focus is on population stability and the endpoint of concern is reproductive success for organisms important ecologically and economically. For these organisms, information is needed on their responses to irradiation and the potential impact of the doses absorbed on their reproductive success. Considerable information is available on the effects of radiation on organisms from different phyla and types of ecosystems. Databases useful for assessing risk from exposures of populations to radioactivity are the effects of irradiation on mortality, fertility and sterility, the latter two of which are important components of reproductive success. Data on radiation effects on mortality are available both from acute and chronic irradiation. In relation to radiation effects, reproductive success for a given population is related to a number of characteristics of the species, including inherent radiosensitivity of reproductive tissues and early life stages, processes occurring during gametogenesis, reproductive strategy and exposure history. The available data on acute and chronic radiation doses is reviewed for invertebrates, fishes and mammals. The information reviewed indicates that wide ranges in responses with species can be expected. Parameters that most likely contribute to inherent radiosensitivity are discussed. (author)

  19. Surrogacy assessment using principal stratification when surrogate and outcome measures are multivariate normal.

    Science.gov (United States)

    Conlon, Anna S C; Taylor, Jeremy M G; Elliott, Michael R

    2014-04-01

    In clinical trials, a surrogate outcome variable (S) can be measured before the outcome of interest (T) and may provide early information regarding the treatment (Z) effect on T. Using the principal surrogacy framework introduced by Frangakis and Rubin (2002. Principal stratification in causal inference. Biometrics 58, 21-29), we consider an approach that has a causal interpretation and develop a Bayesian estimation strategy for surrogate validation when the joint distribution of potential surrogate and outcome measures is multivariate normal. From the joint conditional distribution of the potential outcomes of T, given the potential outcomes of S, we propose surrogacy validation measures from this model. As the model is not fully identifiable from the data, we propose some reasonable prior distributions and assumptions that can be placed on weakly identified parameters to aid in estimation. We explore the relationship between our surrogacy measures and the surrogacy measures proposed by Prentice (1989. Surrogate endpoints in clinical trials: definition and operational criteria. Statistics in Medicine 8, 431-440). The method is applied to data from a macular degeneration study and an ovarian cancer study.

  20. Hypothesis test for synchronization: twin surrogates revisited.

    Science.gov (United States)

    Romano, M Carmen; Thiel, Marco; Kurths, Jürgen; Mergenthaler, Konstantin; Engbert, Ralf

    2009-03-01

    The method of twin surrogates has been introduced to test for phase synchronization of complex systems in the case of passive experiments. In this paper we derive new analytical expressions for the number of twins depending on the size of the neighborhood, as well as on the length of the trajectory. This allows us to determine the optimal parameters for the generation of twin surrogates. Furthermore, we determine the quality of the twin surrogates with respect to several linear and nonlinear statistics depending on the parameters of the method. In the second part of the paper we perform a hypothesis test for phase synchronization in the case of experimental data from fixational eye movements. These miniature eye movements have been shown to play a central role in neural information processing underlying the perception of static visual scenes. The high number of data sets (21 subjects and 30 trials per person) allows us to compare the generated twin surrogates with the "natural" surrogates that correspond to the different trials. We show that the generated twin surrogates reproduce very well all linear and nonlinear characteristics of the underlying experimental system. The synchronization analysis of fixational eye movements by means of twin surrogates reveals that the synchronization between the left and right eye is significant, indicating that either the centers in the brain stem generating fixational eye movements are closely linked, or, alternatively that there is only one center controlling both eyes.

  1. Surrogacy: the experiences of surrogate mothers.

    Science.gov (United States)

    Jadva, Vasanti; Murray, Clare; Lycett, Emma; MacCallum, Fiona; Golombok, Susan

    2003-10-01

    This study examined the motivations, experiences and psychological consequences of surrogacy for surrogate mothers. Thirty-four women who had given birth to a surrogate child approximately 1 year previously were interviewed by trained researchers, and the data rated using standardized coding criteria. Information was obtained on: (i) reasons for the woman's decision to become a surrogate mother; (ii) her retrospective view of the relationship with the commissioning couple before the pregnancy, during the pregnancy, and after the birth; (iii) her experiences during and after relinquishing the child; and (iv) how others reacted to her decision to become a surrogate mother. It was found that surrogate mothers do not generally experience major problems in their relationship with the commissioning couple, in handing over the baby, or from the reactions of those around them. The emotional problems experienced by some surrogate mothers in the weeks following the birth appeared to lessen over time. Surrogate mothers do not appear to experience psychological problems as a result of the surrogacy arrangement.

  2. So not mothers: responsibility for surrogate orphans.

    Science.gov (United States)

    Parks, Jennifer A; Murphy, Timothy F

    2018-04-12

    The law ordinarily recognises the woman who gives birth as the mother of a child, but in certain jurisdictions, it will recognise the commissioning couple as the legal parents of a child born to a commercial surrogate. Some commissioning parents have, however, effectively abandoned the children they commission, and in such cases, commercial surrogates may find themselves facing unexpected maternal responsibility for children they had fully intended to give up. Any assumption that commercial surrogates ought to assume maternal responsibility for abandoned children runs contrary to the moral suppositions that typically govern contract surrogacy, in particular, assumptions that gestational carriers are not 'mothers' in any morally significant sense. In general, commercial gestational surrogates are almost entirely conceptualised as 'vessels'. In a moral sense, it is deeply inconsistent to expect commercial surrogates to assume maternal responsibility simply because commissioning parents abandon children for one reason or another. We identify several instances of child abandonment and discuss their implications with regard to the moral conceptualisation of commercial gestational surrogates. We conclude that if gestational surrogates are to remain conceptualised as mere vessels, they should not be expected to assume responsibility for children abandoned by commissioning parents, not even the limited responsibility of giving them up for adoption or surrendering them to the state. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. Evaluating time to cancer recurrence as a surrogate marker for survival from an information theory perspective.

    Science.gov (United States)

    Alonso, Ariel; Molenberghs, Geert

    2008-10-01

    The last two decades have seen a lot of development in the area of surrogate marker validation. One of these approaches places the evaluation in a meta-analytic framework, leading to definitions in terms of trial- and individual-level association. A drawback of this methodology is that different settings have led to different measures at the individual level. Using information theory, Alonso et al. proposed a unified framework, leading to a new definition of surrogacy, which offers interpretational advantages and is applicable in a wide range of situations. In this work, we illustrate how this information-theoretic approach can be used to evaluate surrogacy when both endpoints are of a time-to-event type. Two meta-analyses, in early and advanced colon cancer, respectively, are then used to evaluate the performance of time to cancer recurrence as a surrogate for overall survival.

  4. Surrogate Motherhood II: Reflections after "Baby M."

    Science.gov (United States)

    Schwartz, Lita Linzer

    1988-01-01

    Discusses the "Baby M" surrogate motherhood case which has produced heated debate in popular media, legal publications, and other professional journals. Summarizes arguments offered and reasoning behind actions of judiciary. (Author/ABL)

  5. Magnetic resonance imaging (MRI)-based indication for neoadjuvant treatment of rectal carcinoma and the surrogate endpoint CRM status.

    Science.gov (United States)

    Strassburg, Joachim; Junginger, Theo; Trinh, Trong; Püttcher, Olaf; Oberholzer, Katja; Heald, Richard J; Hermanek, Paul

    2008-11-01

    Is it possible to reduce the frequency of neoadjuvant therapy for rectal carcinoma and nevertheless achieve a rate of more than 90% circumferential resection margin (CRM)-negative resection specimens by a novel concept of magnetic resonance imaging (MRI)-based therapy planning? One hundred eighty-one patients from Berlin and Mainz, Germany, with primary rectal carcinoma, without distant metastasis, underwent radical surgery with curative intention. Surgical procedures applied were anterior resection with total mesorectal excision (TME) or partial mesorectal excision (PME; PME for tumours of the upper rectum) or abdominoperineal excision with TME. With MRI selection of the highest-risk cases, neoadjuvant therapy was given to only 62 of 181 (34.3%). The rate of CRM-negative resection specimens on histology was 170 of 181 (93.9%) for all patients, and in Berlin, only 1 of 93 (1%) specimens was CRM-positive. Patients selected for primary surgery had CRM-negative specimens on histology in 114 of 119 (95.8%). Those selected for neoadjuvant therapy had a lower rate of clear margin: 56 of 62 (90%). By applying a MRI-based indication, the frequency of neoadjuvant treatment with its acute and late adverse effects can be reduced to 30-35% without reduction of pathologically CRM-negative resection specimens and, thus, without the danger of worsening the oncological long-term results. This concept should be confirmed in prospective multicentre observation studies with quality assurance of MRI, surgery and pathology.

  6. The Most Frequent English Homonyms

    Science.gov (United States)

    Parent, Kevin

    2012-01-01

    This article distinguishes homonymy, homophony, homography and polysemy, and provides a list of the most frequent homonyms using corpus-derived data. For most of the homonyms, the most common meaning accounts for 90% or more of the total uses of the form. The pedagogical and research implications of these findings are discussed. (Contains 5…

  7. Corporate Governance Frequently Asked Questions

    OpenAIRE

    International Finance Corporation

    2016-01-01

    This guidebook is designed to address common questionson corporate governance that are frequently asked byowners and managers of companies in the Middle Eastand North Africa (MENA) region. It familiarizes readerswith the basic concepts of corporate governance,providing a comprehensive overview of the subject matter,using case studies as practical examples of corporategovernance application...

  8. Endpoint distinctiveness facilitates analogical mapping in pigeons.

    Science.gov (United States)

    Hagmann, Carl Erick; Cook, Robert G

    2015-03-01

    Analogical thinking necessitates mapping shared relations across two separate domains. We investigated whether pigeons could learn faster with ordinal mapping of relations across two physical dimensions (circle size & choice spatial position) relative to random mapping of these relations. Pigeons were trained to relate six circular samples of different sizes to horizontally positioned choice locations in a six alternative matching-to-sample task. Three pigeons were trained in a mapped condition in which circle size mapped directly onto choice spatial position. Three other pigeons were trained in a random condition in which the relations between size and choice position were arbitrarily assigned. The mapped group showed an advantage over the random group in acquiring this task. In a subsequent second phase, relations between the dimensions were ordinally reversed for the mapped group and re-randomized for the random group. There was no difference in how quickly matching accuracy re-emerged in the two groups, although the mapped group eventually performed more accurately. Analyses suggested this mapped advantage was likely due to endpoint distinctiveness and the benefits of proximity errors during choice responding rather than a conceptual or relational advantage attributable to the common or ordinal mapping of the two dimensions. This potential difficulty in mapping relations across dimensions may limit the pigeons' capacity for more advanced types of analogical reasoning. This article is part of a Special Issue entitled: Tribute to Tom Zentall. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Endpoint Distinctiveness Facilitates Analogical Mapping in Pigeons

    Science.gov (United States)

    Hagmann, Carl Erick; Cook, Robert G.

    2015-01-01

    Analogical thinking necessitates mapping shared relations across two separate domains. We investigated whether pigeons could learn faster with ordinal mapping of relations across two physical dimensions (circle size & choice spatial position) relative to random mapping of these relations. Pigeons were trained to relate six circular samples of different sizes to horizontally positioned choice locations in a six alternative matching-to-sample task. Three pigeons were trained in a mapped condition in which circle size mapped directly onto choice spatial position. Three other pigeons were trained in a random condition in which the relations between size and choice position were arbitrarily assigned. The mapped group showed an advantage over the random group in acquiring this task. In a subsequent second phase, reassignment, relations between the dimensions were ordinally reversed for the mapped group and re-randomized for the random group. There was no difference in how quickly matching accuracy re-emerged in the two groups, although the mapped group eventually performed more accurately. Analyses suggested this mapped advantage was likely due endpoint distinctiveness and the benefits of proximity errors during choice responding rather than a conceptual or relational advantage attributable to the common or ordinal map of the two dimensions. This potential difficulty in mapping relations across dimensions may limit the pigeons’ capacity for more advanced types of analogical reasoning. PMID:25447511

  10. Surrogate versus couple therapy in vaginismus.

    Science.gov (United States)

    Ben-Zion, Itzhak; Rothschild, Shelly; Chudakov, Bella; Aloni, Ronit

    2007-05-01

    Women who do not have a cooperative partner cannot complete the usual therapeutic process in the treatment of vaginismus, because they cannot progress to the stage of practicing the insertion of the man partner's fingers and the insertion of a penis. To compare traditional couple therapy with therapy utilizing a surrogate partner. The study was controlled and retrospective. Data were obtained from the treatment charts of patients who had come to the clinic for treatment of vaginismus. Sixteen vaginismus patients who were treated with a man surrogate partner were compared with 16 vaginismus patients who were treated with their own partners. Successful pain-free intercourse upon completion of therapy. One hundred percent of the surrogate patients succeeded in penile-vaginal intercourse compared with 75% in the couples group (P = 0.1). All surrogate patients ended the therapy because it was fully successful, compared with 69% in the couples group. Twelve percent of the couples group ended the therapy because it failed, and 19% because the couples decided to separate. Treating vaginismus with a man surrogate partner was at least as effective as couple therapy. Surrogate therapy may be considered for vaginismus patients who have no cooperative partner.

  11. Sample size determination for equivalence assessment with multiple endpoints.

    Science.gov (United States)

    Sun, Anna; Dong, Xiaoyu; Tsong, Yi

    2014-01-01

    Equivalence assessment between a reference and test treatment is often conducted by two one-sided tests (TOST). The corresponding power function and sample size determination can be derived from a joint distribution of the sample mean and sample variance. When an equivalence trial is designed with multiple endpoints, it often involves several sets of two one-sided tests. A naive approach for sample size determination in this case would select the largest sample size required for each endpoint. However, such a method ignores the correlation among endpoints. With the objective to reject all endpoints and when the endpoints are uncorrelated, the power function is the production of all power functions for individual endpoints. With correlated endpoints, the sample size and power should be adjusted for such a correlation. In this article, we propose the exact power function for the equivalence test with multiple endpoints adjusted for correlation under both crossover and parallel designs. We further discuss the differences in sample size for the naive method without and with correlation adjusted methods and illustrate with an in vivo bioequivalence crossover study with area under the curve (AUC) and maximum concentration (Cmax) as the two endpoints.

  12. Ordered kinematic endpoints for 5-body cascade decays

    Energy Technology Data Exchange (ETDEWEB)

    Klimek, Matthew D. [Theory Group, Department of Physics and Texas Cosmology Center,University of Texas at Austin, 2515 Speedway, Stop C1608, Austin, TX, 78712 (United States)

    2016-12-23

    We present expressions for the kinematic endpoints of 5-body cascade decay chains proceeding through all possible combinations of 2-body and 3-body decays, with one stable invisible particle in the final decay stage. When an invariant mass can be formed in multiple ways by choosing different final state particles from a common vertex, we introduce techniques for finding the sub-leading endpoints for all indistinguishable versions of the invariant mass. In contrast to short decay chains, where sub-leading endpoints are linearly related to the leading endpoints, we find that in 5-body decays, they provide additional independent constraints on the mass spectrum.

  13. Recent progress in gasoline surrogate fuels

    KAUST Repository

    Sarathy, Mani

    2017-12-06

    Petroleum-derived gasoline is currently the most widely used fuel for transportation propulsion. The design and operation of gasoline fuels is governed by specific physical and chemical kinetic fuel properties. These must be thoroughly understood in order to improve sustainable gasoline fuel technologies in the face of economical, technological, and societal challenges. For this reason, surrogate mixtures are formulated to emulate the thermophysical, thermochemical, and chemical kinetic properties of the real fuel, so that fundamental experiments and predictive simulations can be conducted. Early studies on gasoline combustion typically adopted single component or binary mixtures (n-heptane/isooctane) as surrogates. However, the last decade has seen rapid progress in the formulation and utilization of ternary mixtures (n-heptane/isooctane/toluene), as well as multicomponent mixtures that span the entire carbon number range of gasoline fuels (C4–C10). The increased use of oxygenated fuels (ethanol, butanol, MTBE, etc.) as blending components/additives has also motivated studies on their addition to gasoline fuels. This comprehensive review presents the available experimental and chemical kinetic studies which have been performed to better understand the combustion properties of gasoline fuels and their surrogates. Focus is on the development and use of surrogate fuels that emulate real fuel properties governing the design and operation of engines. A detailed analysis is presented for the various classes of compounds used in formulating gasoline surrogate fuels, including n-paraffins, isoparaffins, olefins, naphthenes, and aromatics. Chemical kinetic models for individual molecules and mixtures of molecules to emulate gasoline surrogate fuels are presented. Despite the recent progress in gasoline surrogate fuel combustion research, there are still major gaps remaining; these are critically discussed, as well as their implications on fuel formulation and engine

  14. Recent progress in gasoline surrogate fuels

    KAUST Repository

    Sarathy, Mani; Farooq, Aamir; Kalghatgi, Gautam T.

    2017-01-01

    Petroleum-derived gasoline is currently the most widely used fuel for transportation propulsion. The design and operation of gasoline fuels is governed by specific physical and chemical kinetic fuel properties. These must be thoroughly understood in order to improve sustainable gasoline fuel technologies in the face of economical, technological, and societal challenges. For this reason, surrogate mixtures are formulated to emulate the thermophysical, thermochemical, and chemical kinetic properties of the real fuel, so that fundamental experiments and predictive simulations can be conducted. Early studies on gasoline combustion typically adopted single component or binary mixtures (n-heptane/isooctane) as surrogates. However, the last decade has seen rapid progress in the formulation and utilization of ternary mixtures (n-heptane/isooctane/toluene), as well as multicomponent mixtures that span the entire carbon number range of gasoline fuels (C4–C10). The increased use of oxygenated fuels (ethanol, butanol, MTBE, etc.) as blending components/additives has also motivated studies on their addition to gasoline fuels. This comprehensive review presents the available experimental and chemical kinetic studies which have been performed to better understand the combustion properties of gasoline fuels and their surrogates. Focus is on the development and use of surrogate fuels that emulate real fuel properties governing the design and operation of engines. A detailed analysis is presented for the various classes of compounds used in formulating gasoline surrogate fuels, including n-paraffins, isoparaffins, olefins, naphthenes, and aromatics. Chemical kinetic models for individual molecules and mixtures of molecules to emulate gasoline surrogate fuels are presented. Despite the recent progress in gasoline surrogate fuel combustion research, there are still major gaps remaining; these are critically discussed, as well as their implications on fuel formulation and engine

  15. Hippeastrum hybridum anthocyanins as indicators of endpoint in acid

    African Journals Online (AJOL)

    Anthocyanins from Hippeastrum hybridum (Amaryllis) were investigated as indicators of endpoint in acid- base titrations. Extraction of the anthocyanins was done using distilled water, methanol and methanol containing 0.5% acetic acid. The extracts were used in determination of endpoint in titrations between strong.

  16. Hippeastrum hybridum anthocyanins as indicators of endpoint in ...

    African Journals Online (AJOL)

    Anthocyanins from Hippeastrum hybridum (Amaryllis) were investigated as indicators of endpoint in acid- base titrations. Extraction of the anthocyanins was done using distilled water, methanol and methanol containing 0.5% acetic acid. The extracts were used in determination of endpoint in titrations between strong ...

  17. The impact of endpoint measures in rheumatoid arthritis clinical trials

    NARCIS (Netherlands)

    van der Heide, A.; Jacobs, J. W.; Dinant, H. J.; Bijlsma, J. W.

    1992-01-01

    In clinical trials on the effectiveness of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA), it is common to apply a large number of endpoint measures. This practice has several disadvantages. To determine which endpoint measures are most valuable, reports of

  18. Attitudes toward surrogate motherhood in Canada.

    Science.gov (United States)

    Krishnan, V

    1994-01-01

    The issue of surrogate motherhood captured worldwide attention with the Baby M case in the United States. Some medical practitioners now claim that the surrogate arrangement may be the answer for certain women who are unable to conceive children naturally. Feminist activists are highly critical about the issue. In her landmark book The Mother Machine, Corea (1985) called surrogates "breeders," women whose bodies are being used by men. Lawyers and ethicists debate whether surrogacy is baby selling or not, and religious fundamentalists have condemned any form of procreation outside the "normal" or "natural" form of sexual relations within a marriage. But what do Canadian women think about commercial surrogacy? Findings pertaining to this issue from the latest national fertility survey of 5,315 women in the reproductive ages of 18-49 are reported.

  19. Legal regulation of surrogate motherhood in Israel.

    Science.gov (United States)

    Frenkel, D A

    2001-01-01

    The Israeli Law on surrogate motherhood demands a preconception agreement to include payments to be made to the surrogate mother. Surrogacy arrangements with family members are forbidden. Commercial surrogacy is allowed and encouraged. The Law causes many problems. Validity of consent given by surrogate mothers is doubtful. Possible future psychological harm are ignored. There is a danger of "commodification" of children. Abusing women of low socio-economic status as breeding machines may be another outcome. No clear responsibility is imposed on the "intended parents" for an impaired child. The law ignores possibility of divorce or death of the "intended parents" before the child's birth. Splitting motherhood is another social problem that has to be dealt with. So far the sperm of the husband from the "intended parents" has to be used, but further steps may follow. It is not certain that a policy of "positive eugenics" will not develop.

  20. Premixed flame chemistry of a gasoline primary reference fuel surrogate

    KAUST Repository

    Selim, Hatem

    2017-03-10

    Investigating the combustion chemistry of gasoline surrogate fuels promises to improve detailed reaction mechanisms used for simulating their combustion. In this work, the combustion chemistry of one of the simplest, but most frequently used gasoline surrogates – primary reference fuel 84 (PRF 84, 84 vol% iso-octane and 16 vol% n-heptane), has been examined in a stoichiometric premixed laminar flame. Time-of-flight mass spectrometry coupled with a vacuum ultraviolet (VUV) synchrotron light source for species photoionization was used. Reactants, major end-products, stable intermediates, free radicals, and isomeric species were detected and quantified. Numerical simulations were conducted using a detailed chemical kinetic model with the most recently available high temperature sub-mechanisms for iso-octane and heptane, built on the top of an updated pentane isomers model and AramcoMech 2.0 (C0C4) base chemistry. A detailed interpretation of the major differences between the mechanistic pathways of both fuel components is given. A comparison between the experimental and numerical results is depicted and rate of production and sensitivity analyses are shown for the species with considerable disagreement between the experimental and numerical findings.

  1. Reduced cost mission design using surrogate models

    Science.gov (United States)

    Feldhacker, Juliana D.; Jones, Brandon A.; Doostan, Alireza; Hampton, Jerrad

    2016-01-01

    This paper uses surrogate models to reduce the computational cost associated with spacecraft mission design in three-body dynamical systems. Sampling-based least squares regression is used to project the system response onto a set of orthogonal bases, providing a representation of the ΔV required for rendezvous as a reduced-order surrogate model. Models are presented for mid-field rendezvous of spacecraft in orbits in the Earth-Moon circular restricted three-body problem, including a halo orbit about the Earth-Moon L2 libration point (EML-2) and a distant retrograde orbit (DRO) about the Moon. In each case, the initial position of the spacecraft, the time of flight, and the separation between the chaser and the target vehicles are all considered as design inputs. The results show that sample sizes on the order of 102 are sufficient to produce accurate surrogates, with RMS errors reaching 0.2 m/s for the halo orbit and falling below 0.01 m/s for the DRO. A single function call to the resulting surrogate is up to two orders of magnitude faster than computing the same solution using full fidelity propagators. The expansion coefficients solved for in the surrogates are then used to conduct a global sensitivity analysis of the ΔV on each of the input parameters, which identifies the separation between the spacecraft as the primary contributor to the ΔV cost. Finally, the models are demonstrated to be useful for cheap evaluation of the cost function in constrained optimization problems seeking to minimize the ΔV required for rendezvous. These surrogate models show significant advantages for mission design in three-body systems, in terms of both computational cost and capabilities, over traditional Monte Carlo methods.

  2. Ecosystem services as assessment endpoints for ecological risk assessment.

    Science.gov (United States)

    Munns, Wayne R; Rea, Anne W; Suter, Glenn W; Martin, Lawrence; Blake-Hedges, Lynne; Crk, Tanja; Davis, Christine; Ferreira, Gina; Jordan, Steve; Mahoney, Michele; Barron, Mace G

    2016-07-01

    Ecosystem services are defined as the outputs of ecological processes that contribute to human welfare or have the potential to do so in the future. Those outputs include food and drinking water, clean air and water, and pollinated crops. The need to protect the services provided by natural systems has been recognized previously, but ecosystem services have not been formally incorporated into ecological risk assessment practice in a general way in the United States. Endpoints used conventionally in ecological risk assessment, derived directly from the state of the ecosystem (e.g., biophysical structure and processes), and endpoints based on ecosystem services serve different purposes. Conventional endpoints are ecologically important and susceptible entities and attributes that are protected under US laws and regulations. Ecosystem service endpoints are a conceptual and analytical step beyond conventional endpoints and are intended to complement conventional endpoints by linking and extending endpoints to goods and services with more obvious benefit to humans. Conventional endpoints can be related to ecosystem services even when the latter are not considered explicitly during problem formulation. To advance the use of ecosystem service endpoints in ecological risk assessment, the US Environmental Protection Agency's Risk Assessment Forum has added generic endpoints based on ecosystem services (ES-GEAE) to the original 2003 set of generic ecological assessment endpoints (GEAEs). Like conventional GEAEs, ES-GEAEs are defined by an entity and an attribute. Also like conventional GEAEs, ES-GEAEs are broadly described and will need to be made specific when applied to individual assessments. Adoption of ecosystem services as a type of assessment endpoint is intended to improve the value of risk assessment to environmental decision making, linking ecological risk to human well-being, and providing an improved means of communicating those risks. Integr Environ Assess Manag

  3. Videotrees: Improving video surrogate presentation using hierarchy

    NARCIS (Netherlands)

    Jansen, Michel; Heeren, W.F.L.; van Dijk, Elisabeth M.A.G.

    As the amount of available video content increases, so does the need for better ways of browsing all this material. Because the nature of video makes it hard to process, the need arises for adequate surrogates for video that can readily be skimmed and browsed. In this paper, the effects of the use

  4. Ethical Problems Related to Surrogate Motherhood

    Directory of Open Access Journals (Sweden)

    Erdem Aydin

    2006-03-01

    Full Text Available Being unable to have children is an important problem for married couples. At present, new reproduction techniques help these couples while those who can not find any solution try new approaches. One of these is the phenomenon of surrogate motherhood, which is based upon an agreement between the infertile couple and surrogate mother. Surrogate mother may conceive with the sperm of the male of the involved couple as well as by the transfer of the embryo formed by invitro fertilization. Couples who choose to have a child born from a pregnancy or to whom they are genetically partially connected rather than adopting a child give rise to the emergence of some ethical problems. Traditional family notion based upon having children after the union of the reproductive cells of the mother and father do not receive the pheneomenon of surrogate mother favourably. Such practices are criticised as they are far from being natural and other ethical problems are faced in the implementation.

  5. Combustion Kinetic Studies of Gasolines and Surrogates

    KAUST Repository

    Javed, Tamour

    2016-01-01

    . These measurements were performed in shock tubes and rapid compression machines over a wide range of experimental conditions (650 – 1250 K, 10 – 40 bar) relevant to internal combustion engines. Using the measured the data and chemical kinetic analyses, the surrogate

  6. Active Subspaces for Wind Plant Surrogate Modeling

    Energy Technology Data Exchange (ETDEWEB)

    King, Ryan N [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Quick, Julian [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Dykes, Katherine L [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Adcock, Christiane [Massachusetts Institute of Technology

    2018-01-12

    Understanding the uncertainty in wind plant performance is crucial to their cost-effective design and operation. However, conventional approaches to uncertainty quantification (UQ), such as Monte Carlo techniques or surrogate modeling, are often computationally intractable for utility-scale wind plants because of poor congergence rates or the curse of dimensionality. In this paper we demonstrate that wind plant power uncertainty can be well represented with a low-dimensional active subspace, thereby achieving a significant reduction in the dimension of the surrogate modeling problem. We apply the active sub-spaces technique to UQ of plant power output with respect to uncertainty in turbine axial induction factors, and find a single active subspace direction dominates the sensitivity in power output. When this single active subspace direction is used to construct a quadratic surrogate model, the number of model unknowns can be reduced by up to 3 orders of magnitude without compromising performance on unseen test data. We conclude that the dimension reduction achieved with active subspaces makes surrogate-based UQ approaches tractable for utility-scale wind plants.

  7. Planning and analyzing clinical trials with composite endpoints

    CERN Document Server

    Rauch, Geraldine; Kieser, Meinhard

    2017-01-01

    This book addresses the most important aspects of how to plan and evaluate clinical trials with a composite primary endpoint to guarantee a clinically meaningful and valid interpretation of the results. Composite endpoints are often used as primary efficacy variables for clinical trials, particularly in the fields of oncology and cardiology. These endpoints combine several variables of interest within a single composite measure, and as a result, all variables that are of major clinical relevance can be considered in the primary analysis without the need to adjust for multiplicity. Moreover, composite endpoints are intended to increase the size of the expected effects thus making clinical trials more powerful. The book offers practical advice for statisticians and medical experts involved in the planning and analysis of clinical trials. For readers who are mainly interested in the application of the methods, all the approaches are illustrated with real-world clinical trial examples, and the software codes requ...

  8. Gastroenterological endpoints in drug trials for cystic fibrosis

    NARCIS (Netherlands)

    Bodewes, Frank A. J. A.; Verkade, Henkjan J.; Wilschanski, Micheal

    2016-01-01

    The phenotype of cystic fibrosis includes a wide variety of clinical and biochemical gastrointestinal presentations. These gastrointestinal characteristics of the disease have come under renewed interest as potential outcome measures and clinical endpoints for therapeutic trials in cystic fibrosis.

  9. Endpoint behavior of high-energy scattering cross sections

    International Nuclear Information System (INIS)

    Chay, Junegone; Kim, Chul

    2010-01-01

    In high-energy processes near the endpoint, there emerge new contributions associated with spectator interactions. Away from the endpoint region, these new contributions are suppressed compared to the leading contribution, but the leading contribution becomes suppressed as we approach the endpoint and the new contributions become comparable. We present how the new contributions scale as we reach the endpoint and show that they are comparable to the suppressed leading contributions in deep inelastic scattering by employing a power-counting analysis. The hadronic tensor in deep inelastic scattering is shown to factorize including the spectator interactions, and it can be expressed in terms of the light cone distribution amplitudes of initial hadrons. We also consider the contribution of the spectator contributions in Drell-Yan processes. Here the spectator interactions are suppressed compared to double parton annihilation according to the power counting.

  10. The frequent occurrence of MIC

    Energy Technology Data Exchange (ETDEWEB)

    Graff, Matthias [Gesellschaft fuer Technische Mikrobiologie und Hygieneueberwachung - Dr. Graff und Partner, Stadtweg 9, D-38176 Wendeburg (Germany); Neubert, Volkmar [Institut fuer Materialpruefung und Werkstofftechnik Dr. Doelling und Dr. Neubert GmbH, Freiberger Strasse 1, D-38678 Clausthal-Zellerfeld (Germany)

    2004-07-01

    Microbial induced corrosion (MIC) is not as rare as many materials scientist and corrosion practitioners do believe. It is not an exotic and scarce event, but can be found frequently in many fields of corrosion research, provided that it is looked for. The reason for the relatively few descriptions of MIC cases seems to be the fact, that the microbiological approach is not widely known and applied in the world of materials science. MIC is not so much a corrosion mechanism on its own, but it enhances the corrosion rates of the 'normal' mechanisms to such an extent, that in some cases 'incredible' fast corrosion progress can be observed. The reason is the microorganisms' function as bio-catalysts: Chemical reactions, which are very slow under normal chemical conditions can be highly accelerated by living organisms. Besides that, several microorganisms do produce very corrosive substances which in natural environments do not occur without the activity of microorganisms, e. g. sulfuric or nitric acid. We want to point out, that it can be very worthy to take microbial induced corrosion into account. MIC is not the general answer for all unsolved corrosion problems, but to think about it helps in many corrosion cases as the authors had to experience. The initial indication for the presence of MIC are markedly increased corrosion rates. In the following, some of our 'lessons' are presented as short case studies: Two of them deal with steel corrosion characterized by increased corrosion rates. The third example presents corrosion damage of aluminium structures, where from a technical point of view corrosion was not expected, least of all microbial induced corrosion. (authors)

  11. Combustion Kinetic Studies of Gasolines and Surrogates

    KAUST Repository

    Javed, Tamour

    2016-11-01

    Future thrusts for gasoline engine development can be broadly summarized into two categories: (i) efficiency improvements in conventional spark ignition engines, and (ii) development of advance compression ignition (ACI) concepts. Efficiency improvements in conventional spark ignition engines requires downsizing (and turbocharging) which may be achieved by using high octane gasolines, whereas, low octane gasolines fuels are anticipated for ACI concepts. The current work provides the essential combustion kinetic data, targeting both thrusts, that is needed to develop high fidelity gasoline surrogate mechanisms and surrogate complexity guidelines. Ignition delay times of a wide range of certified gasolines and surrogates are reported here. These measurements were performed in shock tubes and rapid compression machines over a wide range of experimental conditions (650 – 1250 K, 10 – 40 bar) relevant to internal combustion engines. Using the measured the data and chemical kinetic analyses, the surrogate complexity requirements for these gasolines in homogeneous environments are specified. For the discussions presented here, gasolines are classified into three categories: (i)\\tLow octane gasolines including Saudi Aramco’s light naphtha fuel (anti-knock index, AKI = (RON + MON)/2 = 64; Sensitivity (S) = RON – MON = 1), certified FACE (Fuels for Advanced Combustion Engines) gasoline I and J (AKI ~ 70, S = 0.7 and 3 respectively), and their Primary Reference Fuels (PRF, mixtures of n-heptane and iso-octane) and multi-component surrogates. (ii)\\t Mid octane gasolines including FACE A and C (AKI ~ 84, S ~ 0 and 1 respectively) and their PRF surrogates. Laser absorption measurements of intermediate and product species formed during gasoline/surrogate oxidation are also reported. (iii)\\t A wide range of n-heptane/iso-octane/toluene (TPRF) blends to adequately represent the octane and sensitivity requirements of high octane gasolines including FACE gasoline F and G

  12. A novel surrogate index for hepatic insulin resistance.

    LENUS (Irish Health Repository)

    Vangipurapu, J

    2011-03-01

    In epidemiological and genetic studies surrogate indices are needed to investigate insulin resistance in different insulin-sensitive tissues. Our objective was to develop a surrogate index for hepatic insulin resistance.

  13. Surrogate losses: Understandings of pregnancy loss and assisted reproduction among surrogate mothers.

    Science.gov (United States)

    Berend, Zsuzsa

    2010-06-01

    I explore surrogate mothers' narrative construction of pregnancy loss on surrogacy support websites. Communicating via the Internet, women construct the public online world of surrogacy. Drawing on anthropological and sociological literature I investigate the connections between conceptualizations of loss and understandings of technological practices and the consequences of these understandings for assisted reproduction. Surrogate mothers define loss broadly, ranging from failure to conceive to miscarriage and stillbirth; loss means the failure to give a baby to the intended parents. Assisted reproductive technologies contribute to loss by raising expectations of success, by attempting to maximize results through the transfer of multiple fertilized ova, and by early monitoring and testing. However, surrogates collectively understand technology as a positive force and advocate for reproductive technology. Surrogates' resolve to "give the gift of life" makes them vulnerable to failure and loss, yet also informs repeated efforts to bear children for others with technological assistance.

  14. System Reliability Analysis Capability and Surrogate Model Application in RAVEN

    Energy Technology Data Exchange (ETDEWEB)

    Rabiti, Cristian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Alfonsi, Andrea [Idaho National Lab. (INL), Idaho Falls, ID (United States); Huang, Dongli [Idaho National Lab. (INL), Idaho Falls, ID (United States); Gleicher, Frederick [Idaho National Lab. (INL), Idaho Falls, ID (United States); Wang, Bei [Idaho National Lab. (INL), Idaho Falls, ID (United States); Adbel-Khalik, Hany S. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Pascucci, Valerio [Idaho National Lab. (INL), Idaho Falls, ID (United States); Smith, Curtis L. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-11-01

    This report collect the effort performed to improve the reliability analysis capabilities of the RAVEN code and explore new opportunity in the usage of surrogate model by extending the current RAVEN capabilities to multi physics surrogate models and construction of surrogate models for high dimensionality fields.

  15. Validity of fish, birds and mammals as surrogates for amphibians and reptiles in pesticide toxicity assessment.

    Science.gov (United States)

    Ortiz-Santaliestra, Manuel E; Maia, Joao P; Egea-Serrano, Andrés; Lopes, Isabel

    2018-02-28

    Amphibians and reptiles are the two most endangered groups of vertebrates. Environmental pollution by pesticides is recognised as one of the major factors threatening populations of these groups. However, the effects of pesticides on amphibians and reptiles have been studied for few substances, which is partly related to the fact that these animals are not included in the mandatory toxicity testing conducted as part of environmental risk assessments of pesticides. Whether risks of pesticides to amphibians and reptiles are addressed by surrogate taxa used in risk assessment is currently under debate. In order to develop a scientifically sound and robust risk assessment scheme, information needs to be gathered to examine whether fish, birds and mammals are valid surrogates for amphibians and reptiles. We updated a systematic review of scientific literature that was recently published compiling toxicity data on amphibians and reptiles. The outcome of this review was analysed with the purposes to (1) compare endpoints from amphibians and reptiles with the available information from fish, birds and mammals, and (2) develop species sensitivity distributions (SSDs) for those substances tested in at least six amphibian species (no substances were found tested in at least six reptile species) to identify a candidate amphibian model species to be used as surrogate in risk assessment. A positive correlation was found between toxicity recorded on fish and amphibians, the former revealing, in general, to be more sensitive than the latter to waterborne pollutants. In the terrestrial environment, although birds and mammals were more sensitive than amphibians and reptiles to at least 60% of tested substances, just a few weak significant correlations were observed. As a general rule, homoeothermic vertebrates are not good surrogates for reptiles and terrestrial amphibians in pesticide risk assessment. However, some chemical-dependent trends were detected, with pyrethroids and

  16. Voices of African American, Caucasian, and Hispanic surrogates on the burdens of end-of-life decision making.

    Science.gov (United States)

    Braun, Ursula K; Beyth, Rebecca J; Ford, Marvella E; McCullough, Laurence B

    2008-03-01

    End-of-life decisions are frequently made by patients' surrogates. Race and ethnicity may affect such decision making. Few studies have described how different racial/ethnic groups experience end-of-life surrogate decision making. To describe the self-reported experience the self-reported experience of African-American, Caucasian, and Hispanic surrogate decision makers of seriously ill patients and to examine the relationship of race, ethnicity, and culture to that experience. Purposive sample to include racial/ethnic minorities in a qualitative study using focus group interviews. The participants of the study were 44 experienced, mostly female, surrogate decision makers for older veterans. Transcripts were qualitatively analyzed to identify major themes, with particular attention to themes that might be unique to each of the three groups. The experience of burden of end-of-life decision making was similar in all three groups. This burden in its medical, personal, and familial dimensions is compounded by uncertainty about prognosis and the patient's preferences. Racial/ethnic variations of responses to this burden concerned the physician-family relationship, religion and faith, and past experiences with race/ethnicity concordant versus non-concordant physicians. Regardless of race/ethnicity, surrogates for seriously ill patients appeared to experience increased significant, multidimensional burdens of decision making under conditions of uncertainty about a patient's preferences. This aspect of the burden of surrogate decision making may not be fully appreciated by physicians. Physicians should identify and be especially attentive to strategies used by surrogates, which may vary by race/ethnicity, to reduce the uncertainty about a patient's preferences and thus the burden of surrogate decision making to assist them in this difficult process.

  17. Surrogate decision making and intellectual virtue.

    Science.gov (United States)

    Bock, Gregory L

    2014-01-01

    Patients can be harmed by a religiously motivated surrogate decision maker whose decisions are contrary to the standard of care; therefore, surrogate decision making should be held to a high standard. Stewart Eskew and Christopher Meyers proposed a two-part rule for deciding which religiously based decisions to honor: (1) a secular reason condition and (2) a rationality condition. The second condition is based on a coherence theory of rationality, which they claim is accessible, generous, and culturally sensitive. In this article, I will propose strengthening the rationality condition by grounding it in a theory of intellectual virtue, which is both rigorous and culturally sensitive. Copyright 2014 The Journal of Clinical Ethics. All rights reserved.

  18. Self- and surrogate-reported communication functioning in aphasia.

    Science.gov (United States)

    Doyle, Patrick J; Hula, William D; Austermann Hula, Shannon N; Stone, Clement A; Wambaugh, Julie L; Ross, Katherine B; Schumacher, James G

    2013-06-01

    To evaluate the dimensionality and measurement invariance of the aphasia communication outcome measure (ACOM), a self- and surrogate-reported measure of communicative functioning in aphasia. Responses to a large pool of items describing communication activities were collected from 133 community-dwelling persons with aphasia of ≥ 1 month post-onset and their associated surrogate respondents. These responses were evaluated using confirmatory and exploratory factor analysis. Chi-square difference tests of nested factor models were used to evaluate patient-surrogate measurement invariance and the equality of factor score means and variances. Association and agreement between self- and surrogate reports were examined using correlation and scatterplots of pairwise patient-surrogate differences. Three single-factor scales (Talking, Comprehension, and Writing) approximating patient-surrogate measurement invariance were identified. The variance of patient-reported scores on the Talking and Writing scales was higher than surrogate-reported variances on these scales. Correlations between self- and surrogate reports were moderate-to-strong, but there were significant disagreements in a substantial number of individual cases. Despite minimal bias and relatively strong association, surrogate reports of communicative functioning in aphasia are not reliable substitutes for self-reports by persons with aphasia. Furthermore, although measurement invariance is necessary for direct comparison of self- and surrogate reports, the costs of obtaining invariance in terms of scale reliability and content validity may be substantial. Development of non-invariant self- and surrogate report scales may be preferable for some applications.

  19. Surrogate end points in clinical research: hazardous to your health.

    Science.gov (United States)

    Grimes, David A; Schulz, Kenneth F

    2005-05-01

    Surrogate end points in clinical research pose real danger. A surrogate end point is an outcome measure, commonly a laboratory test, that substitutes for a clinical event of true importance. Resistance to activated protein C, for example, has been used as a surrogate for venous thrombosis in women using oral contraceptives. Other examples of inappropriate surrogate end points in contraception include the postcoital test instead of pregnancy to evaluate new spermicides, breakage and slippage instead of pregnancy to evaluate condoms, and bone mineral density instead of fracture to assess the safety of depo-medroxyprogesterone acetate. None of these markers captures the effect of the treatment on the true outcome. A valid surrogate end point must both correlate with and accurately predict the outcome of interest. Although many surrogate markers correlate with an outcome, few have been shown to capture the effect of a treatment (for example, oral contraceptives) on the outcome (venous thrombosis). As a result, thousands of useless and misleading reports on surrogate end points litter the medical literature. New drugs have been shown to benefit a surrogate marker, but, paradoxically, triple the risk of death. Thousands of patients have died needlessly because of reliance on invalid surrogate markers. Researchers should avoid surrogate end points unless they have been validated; that requires at least one well done trial using both the surrogate and true outcome. The clinical maxim that "a difference to be a difference must make a difference" applies to research as well. Clinical research should focus on outcomes that matter.

  20. [Biomedical Perspective of the Surrogate Motherhood].

    Science.gov (United States)

    Jouve de la Barreda, Nicolás

    2017-01-01

    The subrogated motherhood takes place when an embryo created by in vitro fertilization (IVF) technology is implanted in a surrogate, sometimes called a gestational mother, by means a contract with her. It can imply to natural families (woman and man) with or without infertility problems, or to monoparental or biparental families of the same sex. Concerning the origin of the gametes used in the IVF emerges different implications on the genetic relationship of the resulting child with the surrogate and the future parents. The subrogated motherhood was initially considered an option to solve infertility problems. Nevertheless this practice has become a possible and attractive option as a source of economic resources for poor women. The cases of benefit of a pregnancy without mediating a contract are exceptional and they are not properly cases of ″subrogated maternity″ but of ″altruistic maternity″ and must be considered as heterologous in vitro fertilization. In this article are analyzed the medical, genetic and bioethics aspects of this new derivation of the fertilization in vitro. As points of special attention are considered the following questions: Is it the surrogate motherhood used preferably to solve infertility problems? Is not this actually a new form of exploitation of the woman? Does not suppose an attack to the natural family? Does not suppose in addition an attack to the dignity of the human being?

  1. Sample size determination in clinical trials with multiple endpoints

    CERN Document Server

    Sozu, Takashi; Hamasaki, Toshimitsu; Evans, Scott R

    2015-01-01

    This book integrates recent methodological developments for calculating the sample size and power in trials with more than one endpoint considered as multiple primary or co-primary, offering an important reference work for statisticians working in this area. The determination of sample size and the evaluation of power are fundamental and critical elements in the design of clinical trials. If the sample size is too small, important effects may go unnoticed; if the sample size is too large, it represents a waste of resources and unethically puts more participants at risk than necessary. Recently many clinical trials have been designed with more than one endpoint considered as multiple primary or co-primary, creating a need for new approaches to the design and analysis of these clinical trials. The book focuses on the evaluation of power and sample size determination when comparing the effects of two interventions in superiority clinical trials with multiple endpoints. Methods for sample size calculation in clin...

  2. Technological advances in suspended‐sediment surrogate monitoring

    Science.gov (United States)

    Gray, John R.; Gartner, Jeffrey W.

    2009-01-01

    continuous suspended sediment data by instruments that require only periodic calibration for correlation to mean concentrations in river cross sections. Broad application of proven suspended sediment surrogate technologies has the potential to revolutionize fluvial sediment monitoring. Once applied, benefits could be enormous, providing for safer, more frequent and consistent, arguably more accurate, and ultimately less expensive sediment data for managing the world's sedimentary resources.

  3. Sensitivity of submersed freshwater macrophytes and endpoints in laboratory toxicity tests

    International Nuclear Information System (INIS)

    Arts, Gertie H.P.; Belgers, J. Dick M.; Hoekzema, Conny H.; Thissen, Jac T.N.M.

    2008-01-01

    The toxicological sensitivity and variability of a range of macrophyte endpoints were statistically tested with data from chronic, non-axenic, macrophyte toxicity tests. Five submersed freshwater macrophytes, four pesticides/biocides and 13 endpoints were included in the statistical analyses. Root endpoints, reflecting root growth, were most sensitive in the toxicity tests, while endpoints relating to biomass, growth and shoot length were less sensitive. The endpoints with the lowest coefficients of variation were not necessarily the endpoints, which were toxicologically most sensitive. Differences in sensitivity were in the range of 10-1000 for different macrophyte-specific endpoints. No macrophyte species was consistently the most sensitive. Criteria to select endpoints in macrophyte toxicity tests should include toxicological sensitivity, variance and ecological relevance. Hence, macrophyte toxicity tests should comprise an array of endpoints, including very sensitive endpoints like those relating to root growth. - A range of endpoints is more representative of macrophyte fitness than biomass and growth only

  4. Measuring titratable alkalinity by single versus double endpoint titration: An evaluation in two cyprinodont species and implications for characterizing net H+ flux in aquatic organisms.

    Science.gov (United States)

    Brix, Kevin V; Wood, Chris M; Grosell, Martin

    2013-01-01

    In this study, Na(+) uptake and acid-base balance in the euryhaline pupfish Cyprinodon variegatus variegatus were characterized when fish were exposed to pH 4.5 freshwater (7mM Na(+)). Similar to the related cyprinodont, Fundulus heteroclitus, Na(+) uptake was significantly inhibited when exposed to low pH water. However, it initially appeared that C. v. variegatus increased apparent net acid excretion at low pH relative to circumneutral pH. This result is opposite to previous observations for F. heteroclitus under similar conditions where fish were observed to switch from apparent net H(+) excretion at circumneutral pH to apparent net H(+) uptake at low pH. Further investigation revealed disparate observations between these studies were the result of using double endpoint titrations to measure titratable alkalinity fluxes in the current study, while the earlier study utilized single endpoint titrations to measure these fluxes (i.e.,. Cyprinodon acid-base transport is qualitatively similar to Fundulus when characterized using single endpoint titrations). This led to a comparative investigation of these two methods. We hypothesized that either the single endpoint methodology was being influenced by a change in the buffer capacity of the water (e.g., mucus being released by the fish) at low pH, or the double endpoint methodology was not properly accounting for ammonia flux by the fish. A series of follow-up experiments indicated that buffer capacity of the water did not change significantly, that excretion of protein (a surrogate for mucus) was actually reduced at low pH, and that the double endpoint methodology does not properly account for NH(3) excretion by fish under low pH conditions. As a result, it overestimates net H(+) excretion during low pH exposure. After applying the maximum possible correction for this error (i.e., assuming that all ammonia is excreted as NH(3)), the double endpoint methodology indicates that net H(+) transport was reduced to

  5. Frequently Asked Questions about Bunion Surgery

    Science.gov (United States)

    ... A | Print | Share Frequently Asked Questions About Bunion Surgery Here are some frequently asked questions (FAQs) and ... best for you. 5. How can I avoid surgery? Sometimes observation of the bunion is all that ...

  6. Quantitative GPCR and ion channel transcriptomics in primary alveolar macrophages and macrophage surrogates

    Directory of Open Access Journals (Sweden)

    Groot-Kormelink Paul J

    2012-10-01

    Full Text Available Abstract Background Alveolar macrophages are one of the first lines of defence against invading pathogens and play a central role in modulating both the innate and acquired immune systems. By responding to endogenous stimuli within the lung, alveolar macrophages contribute towards the regulation of the local inflammatory microenvironment, the initiation of wound healing and the pathogenesis of viral and bacterial infections. Despite the availability of protocols for isolating primary alveolar macrophages from the lung these cells remain recalcitrant to expansion in-vitro and therefore surrogate cell types, such as monocyte derived macrophages and phorbol ester-differentiated cell lines (e.g. U937, THP-1, HL60 are frequently used to model macrophage function. Methods The availability of high throughput gene expression technologies for accurate quantification of transcript levels enables the re-evaluation of these surrogate cell types for use as cellular models of the alveolar macrophage. Utilising high-throughput TaqMan arrays and focussing on dynamically regulated families of integral membrane proteins, we explore the similarities and differences in G-protein coupled receptor (GPCR and ion channel expression in alveolar macrophages and their widely used surrogates. Results The complete non-sensory GPCR and ion channel transcriptome is described for primary alveolar macrophages and macrophage surrogates. The expression of numerous GPCRs and ion channels whose expression were hitherto not described in human alveolar macrophages are compared across primary macrophages and commonly used macrophage cell models. Several membrane proteins known to have critical roles in regulating macrophage function, including CXCR6, CCR8 and TRPV4, were found to be highly expressed in macrophages but not expressed in PMA-differentiated surrogates. Conclusions The data described in this report provides insight into the appropriate choice of cell models for

  7. The Asthma Control Questionnaire as a clinical trial endpoint

    DEFF Research Database (Denmark)

    Barnes, P J; Casale, T B; Dahl, Ronald

    2014-01-01

    these component endpoints; however, there is no consensus on the optimal instrument for use in clinical trials. The Asthma Control Questionnaire (ACQ) has been shown to be a valid, reliable instrument that allows accurate and reproducible assessment of asthma control that compares favourably with other commonly...

  8. Variable reliability of surrogate measures of insulin sensitivity after Roux-en-Y gastric bypass

    DEFF Research Database (Denmark)

    Bojsen-Møller, Kirstine N; Dirksen, Carsten; Svane, Maria Saur

    2017-01-01

    ) are frequently used, but have not been validated after RYGB. Our aim was to evaluate whether surrogate indices reliably estimate changes in insulin sensitivity after RYGB. Four fasting (inverse-HOMA-IR, HOMA2-%S, QUICKI, revised-QUICKI) and three OGTT-derived surrogates (Matsuda, Gutt, OGIS) were compared...... postoperatively. Post-RYGB changes in inverse-HOMA-IR and HOMA2-%S did not correlate with changes in Rd at any visit, but were comparable to changes in HISI at 1 week. Changes in QUICKI and revised-QUICKI correlated with Rd/I after surgery. Changes in Matsuda and Gutt did not correlate with changes in Rd/I and Rd...

  9. Biomechanical constraints on the feedforward regulation of endpoint stiffness.

    Science.gov (United States)

    Hu, Xiao; Murray, Wendy M; Perreault, Eric J

    2012-10-01

    Although many daily tasks tend to destabilize arm posture, it is still possible to have stable interactions with the environment by regulating the multijoint mechanics of the arm in a task-appropriate manner. For postural tasks, this regulation involves the appropriate control of endpoint stiffness, which represents the stiffness of the arm at the hand. Although experimental studies have been used to evaluate endpoint stiffness control, including the orientation of maximal stiffness, the underlying neural strategies remain unknown. Specifically, the relative importance of feedforward and feedback mechanisms has yet to be determined due to the difficulty separately identifying the contributions of these mechanisms in human experiments. This study used a previously validated three-dimensional musculoskeletal model of the arm to quantify the degree to which the orientation of maximal endpoint stiffness could be changed using only steady-state muscle activations, used to represent feedforward motor commands. Our hypothesis was that the feedforward control of endpoint stiffness orientation would be significantly constrained by the biomechanical properties of the musculoskeletal system. Our results supported this hypothesis, demonstrating substantial biomechanical constraints on the ability to regulate endpoint stiffness throughout the workspace. The ability to regulate stiffness orientation was further constrained by additional task requirements, such as the need to support the arm against gravity or exert forces on the environment. Together, these results bound the degree to which slowly varying feedforward motor commands can be used to regulate the orientation of maximum arm stiffness and provide a context for better understanding conditions in which feedback control may be needed.

  10. Modeling hard clinical end-point data in economic analyses.

    Science.gov (United States)

    Kansal, Anuraag R; Zheng, Ying; Palencia, Roberto; Ruffolo, Antonio; Hass, Bastian; Sorensen, Sonja V

    2013-11-01

    The availability of hard clinical end-point data, such as that on cardiovascular (CV) events among patients with type 2 diabetes mellitus, is increasing, and as a result there is growing interest in using hard end-point data of this type in economic analyses. This study investigated published approaches for modeling hard end-points from clinical trials and evaluated their applicability in health economic models with different disease features. A review of cost-effectiveness models of interventions in clinically significant therapeutic areas (CV diseases, cancer, and chronic lower respiratory diseases) was conducted in PubMed and Embase using a defined search strategy. Only studies integrating hard end-point data from randomized clinical trials were considered. For each study included, clinical input characteristics and modeling approach were summarized and evaluated. A total of 33 articles (23 CV, eight cancer, two respiratory) were accepted for detailed analysis. Decision trees, Markov models, discrete event simulations, and hybrids were used. Event rates were incorporated either as constant rates, time-dependent risks, or risk equations based on patient characteristics. Risks dependent on time and/or patient characteristics were used where major event rates were >1%/year in models with fewer health states (Models of infrequent events or with numerous health states generally preferred constant event rates. The detailed modeling information and terminology varied, sometimes requiring interpretation. Key considerations for cost-effectiveness models incorporating hard end-point data include the frequency and characteristics of the relevant clinical events and how the trial data is reported. When event risk is low, simplification of both the model structure and event rate modeling is recommended. When event risk is common, such as in high risk populations, more detailed modeling approaches, including individual simulations or explicitly time-dependent event rates, are

  11. Surrogate pregnancy: a guide for Canadian prenatal health care providers

    OpenAIRE

    Reilly, Dan R.

    2007-01-01

    Providing health care for a woman with a surrogate pregnancy involves unique challenges. Although the ethical debate surrounding surrogacy continues, Canada has banned commercial, but not altruistic, surrogacy. In the event of a custody dispute between a surrogate mother and the individual(s) intending to parent the child, it is unclear how Canadian courts would rule. The prenatal health care provider must take extra care to protect the autonomy and privacy rights of the surrogate. There is l...

  12. Unsuitability of lymphoblastoid cell lines as surrogate of cryopreserved isolated lymphocytes for the analysis of DNA double-strand break repair activity

    Energy Technology Data Exchange (ETDEWEB)

    Zijno, Andrea [Department of Environment and Primary Prevention, Istituto Superiore di Sanita, Rome (Italy); Porcedda, Paola [Department of Clinical and Biological Sciences, University of Turin (Italy); Saini, Francesca [Department of Environment and Primary Prevention, Istituto Superiore di Sanita, Rome (Italy); Allione, Alessandra [Institute for Scientific Interchange (ISI) Foundation, Villa Gualino, Turin (Italy); Garofalo, Bruno; Marcon, Francesca [Department of Environment and Primary Prevention, Istituto Superiore di Sanita, Rome (Italy); Guarrera, Simonetta [Institute for Scientific Interchange (ISI) Foundation, Villa Gualino, Turin (Italy); Turinetto, Valentina; Minieri, Valentina [Department of Clinical and Biological Sciences, University of Turin (Italy); Funaro, Ada [Department of Genetics, Biology and Biochemistry, University of Turin (Italy); Crebelli, Riccardo [Department of Environment and Primary Prevention, Istituto Superiore di Sanita, Rome (Italy); Giachino, Claudia [Department of Clinical and Biological Sciences, University of Turin (Italy); Matullo, Giuseppe, E-mail: giuseppe.matullo@unito.it [Institute for Scientific Interchange (ISI) Foundation, Villa Gualino, Turin (Italy); Department of Genetics, Biology and Biochemistry, University of Turin (Italy)

    2010-02-03

    As first task of a comprehensive investigation on DNA repair genotype-phenotype correlations, the suitability of Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) as surrogate of cryopreserved peripheral blood mononuclear cells (PBMCs) in DNA repair phenotypic assays was evaluated. To this aim the amount of DNA damage induced by {gamma}-rays and DNA repair capacity were evaluated in unstimulated (G{sub 0}) and mitogen-simulated (G{sub 2}) PBMC from 20 healthy subjects and in EBV-transformed LCL obtained from the same individuals. Phosphorylation of histone H2AX, micronuclei and chromosomal aberrations were the end-points investigated. The results obtained show higher basal frequencies of binucleated cells bearing micronuclei and nucleoplasmic bridge (NPB) in LCL with respect to PBMC, suggesting that EBV transformation may be associated with chromosomal instability. After irradiation, higher levels of micronuclei were induced in G{sub 0}-treated PBMC compared to cycling LCL; conversely, NPB were more frequent in LCL than in PBMC. Moreover, higher levels of chromosomal aberrations were observed in G{sub 2}-treated PBMC compared to LCL. Concerning {gamma}-H2AX measurements, phosphorylation levels 1 h after treatment and dephosphorylation kinetics were basically similar in LCL and in PBMC. However, while Spearman's test showed a strong correlation between the results obtained in replicated experiments with PBMC, high inter-experimental variability and poor reproducibility was observed in the experiments performed with LCL, possibly due to the intrinsic instability of LCL. In summary, both the analysis of {gamma}-H2AX and the evaluation of chromosome damage highlighted a larger inter-experimental variability in the results obtained with LCL compared to PBMC. Noteworthy, the two set of results proved to lack any significant correlation at the individual level. These results indicate that LCL may be unsuitable for investigating genotype

  13. Airfoil Shape Optimization based on Surrogate Model

    Science.gov (United States)

    Mukesh, R.; Lingadurai, K.; Selvakumar, U.

    2018-02-01

    Engineering design problems always require enormous amount of real-time experiments and computational simulations in order to assess and ensure the design objectives of the problems subject to various constraints. In most of the cases, the computational resources and time required per simulation are large. In certain cases like sensitivity analysis, design optimisation etc where thousands and millions of simulations have to be carried out, it leads to have a life time of difficulty for designers. Nowadays approximation models, otherwise called as surrogate models (SM), are more widely employed in order to reduce the requirement of computational resources and time in analysing various engineering systems. Various approaches such as Kriging, neural networks, polynomials, Gaussian processes etc are used to construct the approximation models. The primary intention of this work is to employ the k-fold cross validation approach to study and evaluate the influence of various theoretical variogram models on the accuracy of the surrogate model construction. Ordinary Kriging and design of experiments (DOE) approaches are used to construct the SMs by approximating panel and viscous solution algorithms which are primarily used to solve the flow around airfoils and aircraft wings. The method of coupling the SMs with a suitable optimisation scheme to carryout an aerodynamic design optimisation process for airfoil shapes is also discussed.

  14. Patients’ preferences for selection of endpoints in cardiovascular clinical trials

    Directory of Open Access Journals (Sweden)

    Robert D. Chow

    2014-02-01

    Full Text Available Background: To reduce the duration and overall costs of cardiovascular trials, use of the combined endpoints in trial design has become commonplace. Though this methodology may serve the needs of investigators and trial sponsors, the preferences of patients or potential trial subjects in the trial design process has not been studied. Objective: To determine the preferences of patients in the design of cardiovascular trials. Design: Participants were surveyed in a pilot study regarding preferences among various single endpoints commonly used in cardiovascular trials, preference for single vs. composite endpoints, and the likelihood of compliance with a heart medication if patients similar to them participated in the trial design process. Participants: One hundred adult English-speaking patients, 38% male, from a primary care ambulatory practice located in an urban setting. Key results: Among single endpoints, participants rated heart attack as significantly more important than death from other causes (4.53 vs. 3.69, p=0.004 on a scale of 1–6. Death from heart disease was rated as significantly more important than chest pain (4.73 vs. 2.47, p<0.001, angioplasty/PCI/CABG (4.73 vs. 2.43, p<0.001, and stroke (4.73 vs. 2.43, p<0.001. Participants also expressed a slight preference for combined endpoints over single endpoint (43% vs. 57%, incorporation of the opinions of the study patient population into the design of trials (48% vs. 41% for researchers, and a greater likelihood of medication compliance if patient preferences were considered during trial design (67% indicated a significant to major effect. Conclusions: Patients are able to make judgments and express preferences regarding trial design. They prefer that the opinions of the study population rather than the general population be incorporated into the design of the study. This novel approach to study design would not only incorporate patient preferences into medical decision making, but

  15. Approving cancer treatments based on endpoints other than overall survival: an analysis of historical data using the PACE Continuous Innovation Indicators™ (CII).

    Science.gov (United States)

    Brooks, Neon; Campone, Mario; Paddock, Silvia; Shortenhaus, Scott; Grainger, David; Zummo, Jacqueline; Thomas, Samuel; Li, Rose

    2017-01-01

    There is an active debate about the role that endpoints other than overall survival (OS) should play in the drug approval process. Yet the term 'surrogate endpoint' implies that OS is the only critical metric for regulatory approval of cancer treatments. We systematically analyzed the relationship between U.S. Food and Drug Administration (FDA) approval and publication of OS evidence to understand better the risks and benefits of delaying approval until OS evidence is available. Using the PACE Continuous Innovation Indicators (CII) platform, we analyzed the effects of cancer type, treatment goal, and year of approval on the lag time between FDA approval and publication of first significant OS finding for 53 treatments approved between 1952 and 2016 for 10 cancer types (n = 71 approved indications). Greater than 59% of treatments were approved before significant OS data for the approved indication were published. Of the drugs in the sample, 31% had lags between approval and first published OS evidence of 4 years or longer. The average number of years between approval and first OS evidence varied by cancer type and did not reliably predict the eventual amount of OS evidence accumulated. Striking the right balance between early access and minimizing risk is a central challenge for regulators worldwide. We illustrate that endpoints other than OS have long helped to provide timely access to new medicines, including many current standards of care. We found that many critical drugs are approved many years before OS data are published, and that OS may not be the most appropriate endpoint in some treatment contexts. Our examination of approved treatments without significant OS data suggests contexts where OS may not be the most relevant endpoint and highlights the importance of using a wide variety of fit-for-purpose evidence types in the approval process.

  16. Gene expression profiling reveals multiple toxicity endpoints induced by hepatotoxicants

    Energy Technology Data Exchange (ETDEWEB)

    Huang Qihong; Jin Xidong; Gaillard, Elias T.; Knight, Brian L.; Pack, Franklin D.; Stoltz, James H.; Jayadev, Supriya; Blanchard, Kerry T

    2004-05-18

    Microarray technology continues to gain increased acceptance in the drug development process, particularly at the stage of toxicology and safety assessment. In the current study, microarrays were used to investigate gene expression changes associated with hepatotoxicity, the most commonly reported clinical liability with pharmaceutical agents. Acetaminophen, methotrexate, methapyrilene, furan and phenytoin were used as benchmark compounds capable of inducing specific but different types of hepatotoxicity. The goal of the work was to define gene expression profiles capable of distinguishing the different subtypes of hepatotoxicity. Sprague-Dawley rats were orally dosed with acetaminophen (single dose, 4500 mg/kg for 6, 24 and 72 h), methotrexate (1 mg/kg per day for 1, 7 and 14 days), methapyrilene (100 mg/kg per day for 3 and 7 days), furan (40 mg/kg per day for 1, 3, 7 and 14 days) or phenytoin (300 mg/kg per day for 14 days). Hepatic gene expression was assessed using toxicology-specific gene arrays containing 684 target genes or expressed sequence tags (ESTs). Principal component analysis (PCA) of gene expression data was able to provide a clear distinction of each compound, suggesting that gene expression data can be used to discern different hepatotoxic agents and toxicity endpoints. Gene expression data were applied to the multiplicity-adjusted permutation test and significantly changed genes were categorized and correlated to hepatotoxic endpoints. Repression of enzymes involved in lipid oxidation (acyl-CoA dehydrogenase, medium chain, enoyl CoA hydratase, very long-chain acyl-CoA synthetase) were associated with microvesicular lipidosis. Likewise, subsets of genes associated with hepatotocellular necrosis, inflammation, hepatitis, bile duct hyperplasia and fibrosis have been identified. The current study illustrates that expression profiling can be used to: (1) distinguish different hepatotoxic endpoints; (2) predict the development of toxic endpoints; and

  17. Pulmonary Endpoints in Duchenne Muscular Dystrophy. A Workshop Summary.

    Science.gov (United States)

    Finder, Jonathan; Mayer, Oscar Henry; Sheehan, Daniel; Sawnani, Hemant; Abresch, R Ted; Benditt, Joshua; Birnkrant, David J; Duong, Tina; Henricson, Erik; Kinnett, Kathi; McDonald, Craig M; Connolly, Anne M

    2017-08-15

    Development of novel therapeutics for treatment of Duchenne muscular dystrophy (DMD) has led to clinical trials that include pulmonary endpoints that allow assessment of respiratory muscle status, especially in nonambulatory subjects. Parent Project Muscular Dystrophy (PPMD) convened a workshop in Bethesda, Maryland, on April 14 and 15, 2016, to summarize published respiratory data in DMD and give guidance to clinical researchers assessing the effect of interventions on pulmonary outcomes in DMD.

  18. Exposing the cancer genome atlas as a SPARQL endpoint

    Science.gov (United States)

    Deus, Helena F.; Veiga, Diogo F.; Freire, Pablo R.; Weinstein, John N.; Mills, Gordon B.; Almeida, Jonas S.

    2011-01-01

    The Cancer Genome Atlas (TCGA) is a multidisciplinary, multi-institutional effort to characterize several types of cancer. Datasets from biomedical domains such as TCGA present a particularly challenging task for those interested in dynamically aggregating its results because the data sources are typically both heterogeneous and distributed. The Linked Data best practices offer a solution to integrate and discover data with those characteristics, namely through exposure of data as Web services supporting SPARQL, the Resource Description Framework query language. Most SPARQL endpoints, however, cannot easily be queried by data experts. Furthermore, exposing experimental data as SPARQL endpoints remains a challenging task because, in most cases, data must first be converted to Resource Description Framework triples. In line with those requirements, we have developed an infrastructure to expose clinical, demographic and molecular data elements generated by TCGA as a SPARQL endpoint by assigning elements to entities of the Simple Sloppy Semantic Database (S3DB) management model. All components of the infrastructure are available as independent Representational State Transfer (REST) Web services to encourage reusability, and a simple interface was developed to automatically assemble SPARQL queries by navigating a representation of the TCGA domain. A key feature of the proposed solution that greatly facilitates assembly of SPARQL queries is the distinction between the TCGA domain descriptors and data elements. Furthermore, the use of the S3DB management model as a mediator enables queries to both public and protected data without the need for prior submission to a single data source. PMID:20851208

  19. Congenital Adrenal Hyperplasia: Classification of Studies Employing Psychological Endpoints

    Directory of Open Access Journals (Sweden)

    Sandberg DavidE

    2010-08-01

    Full Text Available Psychological outcomes in persons with congenital adrenal hyperplasia (CAH have received substantial attention. The objectives of this paper were to (1 catalog psychological endpoints assessed in CAH outcome studies and (2 classify the conceptual/theoretical model shaping the research design and interpretation of CAH-related psychological effects. A total of 98 original research studies, published between 1955 and 2009, were categorized based on psychological endpoints examined as well as the research design and conceptual model guiding analysis and interpretation of data. The majority of studies (68% investigated endpoints related to psychosexual differentiation. The preponderance of studies (76% examined a direct relationship (i.e., inferring causality between prenatal androgen exposure and psychological outcomes. Findings are discussed in relation to the observed imbalance between theoretical interest in the role of prenatal androgens in shaping psychosexual differentiation and a broader conceptual model that examines the role of other potential factors in mediating or moderating the influence of CAH pathophysiology on psychological outcomes in both affected females and males. The latter approach offers to identify factors amenable to clinical intervention that enhance both health and quality of life outcomes in CAH as well as other disorders of sex development.

  20. Surrogate motherhood in illness that does not cause infertility

    African Journals Online (AJOL)

    Surrogate motherhood in South Africa (SA) is regulated by the. Children's Act,[1] the National Health Act[2] and its regulations,[3] and court cases.[4-6] The Children's Act formulates the legal requirement for a commissioning parent or parents to legally access surrogacy:[1]. 'A court may not confirm a surrogate motherhood ...

  1. Term clouds as surrogates for user generated speech

    NARCIS (Netherlands)

    Tsagkias, M.; Larson, M.; de Rijke, M.; Myaeng, S.-H.; Oard, D.W.; Sebastiani, F.; Chua, T.-S.; Leong, M.-K.

    2008-01-01

    User generated spoken audio remains a challenge for Automatic Speech Recognition (ASR) technology and content-based audio surrogates derived from ASR-transcripts must be error robust. An investigation of the use of term clouds as surrogates for podcasts demonstrates that ASR term clouds closely

  2. TOXICITY OF PENTACHLOROPHENOL TO ENDANGERED AND SURROGATE FISH SPECIES

    Science.gov (United States)

    Water quality criteria (WQC) generally are based on the responses of easily cultured and tested surrogate species. Little is known about the relative sensitivity of surrogate and endangered species. The objective of this study was to compare acute and chronic (early life-stage) ...

  3. Nonspinning numerical relativity waveform surrogates: assessing the model

    Science.gov (United States)

    Field, Scott; Blackman, Jonathan; Galley, Chad; Scheel, Mark; Szilagyi, Bela; Tiglio, Manuel

    2015-04-01

    Recently, multi-modal gravitational waveform surrogate models have been built directly from data numerically generated by the Spectral Einstein Code (SpEC). I will describe ways in which the surrogate model error can be quantified. This task, in turn, requires (i) characterizing differences between waveforms computed by SpEC with those predicted by the surrogate model and (ii) estimating errors associated with the SpEC waveforms from which the surrogate is built. Both pieces can have numerous sources of numerical and systematic errors. We make an attempt to study the most dominant error sources and, ultimately, the surrogate model's fidelity. These investigations yield information about the surrogate model's uncertainty as a function of time (or frequency) and parameter, and could be useful in parameter estimation studies which seek to incorporate model error. Finally, I will conclude by comparing the numerical relativity surrogate model to other inspiral-merger-ringdown models. A companion talk will cover the building of multi-modal surrogate models.

  4. Human surrogate neck response to +Gz vertical impact

    NARCIS (Netherlands)

    Rooij, L. van; Uittenbogaard, J.

    2011-01-01

    For the evaluation of impact scenarios with a substantial vertical component, the performance of current human surrogates - the RID 3D hardware dummy and two numerical human models - was evaluated. Volunteer tests with 10G and 6G pulses were compared to reconstructed tests with human surrogates.

  5. On Design Mining: Coevolution and Surrogate Models.

    Science.gov (United States)

    Preen, Richard J; Bull, Larry

    2017-01-01

    Design mining is the use of computational intelligence techniques to iteratively search and model the attribute space of physical objects evaluated directly through rapid prototyping to meet given objectives. It enables the exploitation of novel materials and processes without formal models or complex simulation. In this article, we focus upon the coevolutionary nature of the design process when it is decomposed into concurrent sub-design-threads due to the overall complexity of the task. Using an abstract, tunable model of coevolution, we consider strategies to sample subthread designs for whole-system testing and how best to construct and use surrogate models within the coevolutionary scenario. Drawing on our findings, we then describe the effective design of an array of six heterogeneous vertical-axis wind turbines.

  6. [Surrogate maternity--literature review and practice].

    Science.gov (United States)

    Pilka, L; Rumpík, D; Pilka, R; Koudelka, M; Prudil, L

    2009-04-01

    This review summarizes opinions on surrogacy including internatinal and governmental organizations attitudes, as well as some religious concerns. Literature review. Reprofit International, Brno, Reproductive medicine and gynecology centre, Zlin, Department of obstetrics and gynecology, Palacky University, Olomouc. The developments in the field of assissted reproduction during the last twenty years have attracted unexpected public interest in some of its ethical and moral aspects. It is very difficult to find a uniform attitude to ethical concerns of assisted conception in plural society. Surrogate mother is defined as a woman who bears and relinquishes a child for another person. The european congress on human reproduction in Barcelona 2008 adopted following résumé on surrogacy: Public opinion has shifted to a position where surrogacy is recognized as an appropriate response to infertility in some circumstances and it is to be expected that this approach will be further strenghtened with stress on positive aspects of familiar life.

  7. Progression-free survival as a potential surrogate for overall survival in metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Beauchemin C

    2014-06-01

    this study indicate a significant association between PFS/TTP and OS in mBC, which may justify the use of PFS/TTP in the approval for commercialization and reimbursement of new anti-cancer drugs in this cancer setting.Keywords: progression-free survival, time to progression, surrogate endpoint, metastatic breast cancer

  8. Naturally occurring flavonoids against human norovirus surrogates.

    Science.gov (United States)

    Su, Xiaowei; D'Souza, Doris H

    2013-06-01

    Naturally occurring plant-derived flavonoids are reported to have antibacterial, antiviral, and pharmacological activities. The objectives of this study were to determine the antiviral effects of four flavonoids (myricetin, L-epicatechin, tangeretin, and naringenin) on the infectivity of food borne norovirus surrogates after 2 h at 37 °C. The lab-culturable surrogates, feline calicivirus (FCV-F9) at titers of ~7 log₁₀ PFU/ml (high titer) or ~5 log₁₀ PFU/ml (low titer) and murine norovirus (MNV-1) at ~5 log₁₀ PFU/ml, were mixed with equal volumes of myricetin, L-epicatechin, tangeretin, or naringenin at concentrations of 0.5 or 1 mM, and incubated for 2 h at 37 °C. Treatments of viruses were neutralized in cell culture medium containing 10 % heat-inactivated fetal bovine serum, serially diluted, and plaque assayed. Each treatment was replicated thrice and assayed in duplicate. FCV-F9 (low titer) was not found to be reduced by tangeretin or naringenin, but was reduced to undetectable levels by myricetin at both concentrations. Low titer FCV-F9 was also decreased by 1.40 log₁₀ PFU/ml with L-epicatechin at 0.5 mM. FCV-F9 at high titers was decreased by 3.17 and 0.72 log₁₀ PFU/ml with myricetin and L-epicatechin at 0.5 mM, and 1.73 log10 PFU/ml with myricetin at 0.25 mM, respectively. However, MNV-1 showed no significant inactivation by the four tested treatments. The antiviral effects of the tested flavonoids are dependent on the virus type, titer, and dose. Further research will focus on understanding the antiviral mechanism of myricetin and L-epicatechin.

  9. Surrogate Motherhood and Abortion for Fetal Abnormality.

    Science.gov (United States)

    Walker, Ruth; van Zyl, Liezl

    2015-10-01

    A diagnosis of fetal abnormality presents parents with a difficult - even tragic - moral dilemma. Where this diagnosis is made in the context of surrogate motherhood there is an added difficulty, namely that it is not obvious who should be involved in making decisions about abortion, for the person who would normally have the right to decide - the pregnant woman - does not intend to raise the child. This raises the question: To what extent, if at all, should the intended parents be involved in decision-making? In commercial surrogacy it is thought that as part of the contractual agreement the intended parents acquire the right to make this decision. By contrast, in altruistic surrogacy the pregnant woman retains the right to make these decisions, but the intended parents are free to decide not to adopt the child. We argue that both these strategies are morally unsound, and that the problems encountered serve to highlight more fundamental defects within the commercial and altruistic models, as well as in the legal and institutional frameworks that support them. We argue in favour of the professional model, which acknowledges the rights and responsibilities of both parties and provides a legal and institutional framework that supports good decision-making. In particular, the professional model acknowledges the surrogate's right to decide whether to undergo an abortion, and the intended parents' obligation to accept legal custody of the child. While not solving all the problems that arise in surrogacy, the model provides a framework that supports good decision-making. © 2015 John Wiley & Sons Ltd.

  10. Multiple Surrogate Modeling for Wire-Wrapped Fuel Assembly Optimization

    International Nuclear Information System (INIS)

    Raza, Wasim; Kim, Kwang-Yong

    2007-01-01

    In this work, shape optimization of seven pin wire wrapped fuel assembly has been carried out in conjunction with RANS analysis in order to evaluate the performances of surrogate models. Previously, Ahmad and Kim performed the flow and heat transfer analysis based on the three-dimensional RANS analysis. But numerical optimization has not been applied to the design of wire-wrapped fuel assembly, yet. Surrogate models are being widely used in multidisciplinary optimization. Queipo et al. reviewed various surrogates based models used in aerospace applications. Goel et al. developed weighted average surrogate model based on response surface approximation (RSA), radial basis neural network (RBNN) and Krigging (KRG) models. In addition to the three basic models, RSA, RBNN and KRG, the multiple surrogate model, PBA also has been employed. Two geometric design variables and a multi-objective function with a weighting factor have been considered for this problem

  11. Comments on Surrogates measures and consistent surrogates (by Tyler VanderWeele)

    Science.gov (United States)

    2013-03-01

    as a criterion for “good” surrogate, why can’t we create a new, formal definition of “ surrogacy ” that (1) will automatically avoid the paradox and (2...requirement of avoiding the paradox could not, in itself, constitute a satisfactory definition of surrogacy . As with other paradoxes of causal...situation in practice. A treatment that has such a negative direct effect on outcome would rarely be a candidate for surrogacy analysis. In practice

  12. Incidence of Changes in Respiration-Induced Tumor Motion and Its Relationship With Respiratory Surrogates During Individual Treatment Fractions

    International Nuclear Information System (INIS)

    Malinowski, Kathleen; McAvoy, Thomas J.; George, Rohini; Dietrich, Sonja; D’Souza, Warren D.

    2012-01-01

    Purpose: To determine how frequently (1) tumor motion and (2) the spatial relationship between tumor and respiratory surrogate markers change during a treatment fraction in lung and pancreas cancer patients. Methods and Materials: A Cyberknife Synchrony system radiographically localized the tumor and simultaneously tracked three respiratory surrogate markers fixed to a form-fitting vest. Data in 55 lung and 29 pancreas fractions were divided into successive 10-min blocks. Mean tumor positions and tumor position distributions were compared across 10-min blocks of data. Treatment margins were calculated from both 10 and 30 min of data. Partial least squares (PLS) regression models of tumor positions as a function of external surrogate marker positions were created from the first 10 min of data in each fraction; the incidence of significant PLS model degradation was used to assess changes in the spatial relationship between tumors and surrogate markers. Results: The absolute change in mean tumor position from first to third 10-min blocks was >5 mm in 13% and 7% of lung and pancreas cases, respectively. Superior–inferior and medial–lateral differences in mean tumor position were significantly associated with the lobe of lung. In 61% and 54% of lung and pancreas fractions, respectively, margins calculated from 30 min of data were larger than margins calculated from 10 min of data. The change in treatment margin magnitude for superior–inferior motion was >1 mm in 42% of lung and 45% of pancreas fractions. Significantly increasing tumor position prediction model error (mean ± standard deviation rates of change of 1.6 ± 2.5 mm per 10 min) over 30 min indicated tumor–surrogate relationship changes in 63% of fractions. Conclusions: Both tumor motion and the relationship between tumor and respiratory surrogate displacements change in most treatment fractions for patient in-room time of 30 min.

  13. Incidence of Changes in Respiration-Induced Tumor Motion and Its Relationship With Respiratory Surrogates During Individual Treatment Fractions

    Energy Technology Data Exchange (ETDEWEB)

    Malinowski, Kathleen [Department of Bioengineering, A. James Clark School of Engineering, University of Maryland, College Park, MD (United States); Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); McAvoy, Thomas J. [Department of Bioengineering, A. James Clark School of Engineering, University of Maryland, College Park, MD (United States); Institute of Systems Research, University of Maryland, College Park, MD (United States); George, Rohini [Department of Bioengineering, A. James Clark School of Engineering, University of Maryland, College Park, MD (United States); Dietrich, Sonja [Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, CA (United States); D' Souza, Warren D., E-mail: wdsou001@umaryland.edu [Department of Bioengineering, A. James Clark School of Engineering, University of Maryland, College Park, MD (United States); Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States)

    2012-04-01

    Purpose: To determine how frequently (1) tumor motion and (2) the spatial relationship between tumor and respiratory surrogate markers change during a treatment fraction in lung and pancreas cancer patients. Methods and Materials: A Cyberknife Synchrony system radiographically localized the tumor and simultaneously tracked three respiratory surrogate markers fixed to a form-fitting vest. Data in 55 lung and 29 pancreas fractions were divided into successive 10-min blocks. Mean tumor positions and tumor position distributions were compared across 10-min blocks of data. Treatment margins were calculated from both 10 and 30 min of data. Partial least squares (PLS) regression models of tumor positions as a function of external surrogate marker positions were created from the first 10 min of data in each fraction; the incidence of significant PLS model degradation was used to assess changes in the spatial relationship between tumors and surrogate markers. Results: The absolute change in mean tumor position from first to third 10-min blocks was >5 mm in 13% and 7% of lung and pancreas cases, respectively. Superior-inferior and medial-lateral differences in mean tumor position were significantly associated with the lobe of lung. In 61% and 54% of lung and pancreas fractions, respectively, margins calculated from 30 min of data were larger than margins calculated from 10 min of data. The change in treatment margin magnitude for superior-inferior motion was >1 mm in 42% of lung and 45% of pancreas fractions. Significantly increasing tumor position prediction model error (mean {+-} standard deviation rates of change of 1.6 {+-} 2.5 mm per 10 min) over 30 min indicated tumor-surrogate relationship changes in 63% of fractions. Conclusions: Both tumor motion and the relationship between tumor and respiratory surrogate displacements change in most treatment fractions for patient in-room time of 30 min.

  14. Neutron-induced cross-sections via the surrogate method

    International Nuclear Information System (INIS)

    Boutoux, G.

    2011-11-01

    The surrogate reaction method is an indirect way of determining neutron-induced cross sections through transfer or inelastic scattering reactions. This method presents the advantage that in some cases the target material is stable or less radioactive than the material required for a neutron-induced measurement. The method is based on the hypothesis that the excited nucleus is a compound nucleus whose decay depends essentially on its excitation energy and on the spin and parity state of the populated compound state. Nevertheless, the spin and parity population differences between the compound-nuclei produced in the neutron and transfer-induced reactions may be different. This work reviews the surrogate method and its validity. Neutron-induced fission cross sections obtained with the surrogate method are in general good agreement. However, it is not yet clear to what extent the surrogate method can be applied to infer radiative capture cross sections. We performed an experiment to determine the gamma decay probabilities for 176 Lu and 173 Yb by using the surrogate reactions 174 Yb( 3 He,pγ) 176 Lu * and 174 Yb( 3 He,αγ) 173 Yb * , respectively, and compare them with the well-known corresponding probabilities obtained in the 175 Lu(n,γ) and 172 Yb(n,γ) reactions. This experiment provides answers to understand why, in the case of gamma-decay, the surrogate method gives significant deviations compared to the corresponding neutron-induced reaction. In this work, we have also assessed whether the surrogate method can be applied to extract capture probabilities in the actinide region. Previous experiments on fission have also been reinterpreted. Thus, this work provides new insights into the surrogate method. This work is organised in the following way: in chapter 1, the theoretical aspects related to the surrogate method will be introduced. The validity of the surrogate method will be investigated by means of statistical model calculations. In chapter 2, a review on

  15. Frequently Asked Questions about Radiation Emergencies

    Science.gov (United States)

    ... Frequently Asked Questions (FAQ) about Radiation Emergencies Language: English (US) Español (Spanish) Recommend on Facebook Tweet Share Compartir For more information on radiation, go to the Radiation Dictionary . Get Inside: Why should I get inside during ...

  16. Frequent Pattern Mining Algorithms for Data Clustering

    DEFF Research Database (Denmark)

    Zimek, Arthur; Assent, Ira; Vreeken, Jilles

    2014-01-01

    that frequent pattern mining was at the cradle of subspace clustering—yet, it quickly developed into an independent research field. In this chapter, we discuss how frequent pattern mining algorithms have been extended and generalized towards the discovery of local clusters in high-dimensional data......Discovering clusters in subspaces, or subspace clustering and related clustering paradigms, is a research field where we find many frequent pattern mining related influences. In fact, as the first algorithms for subspace clustering were based on frequent pattern mining algorithms, it is fair to say....... In particular, we discuss several example algorithms for subspace clustering or projected clustering as well as point out recent research questions and open topics in this area relevant to researchers in either clustering or pattern mining...

  17. Suicide in America: Frequently Asked Questions

    Science.gov (United States)

    ... Trials? Finding Help Reprints For More Information Share Suicide in America: Frequently Asked Questions Download PDF Download ... a week. Text “HOME” to 741741. What Is Suicide? Suicide is when people direct violence at themselves ...

  18. Frequent flyer business travelers: major exposure hazards.

    Science.gov (United States)

    Tompkins, Olga S; Randolph, Susan A; Ostendorf, Judith S

    2005-02-01

    Bagshaw (2004) notes "the modern commercial aircraft cabin is maintained with adequate environmental control for the comfort of most healthy individuals" (p. 417). Occupational health nurses frequently deal with a population that may include unhealthy individuals or those with pre-existing conditions. It is critical for occupational health nurses to stay current with major hazards faced by frequent flyer business travelers to assist in identifying and preventing adverse health effects associated with these exposures.

  19. Exposing the cancer genome atlas as a SPARQL endpoint.

    Science.gov (United States)

    Deus, Helena F; Veiga, Diogo F; Freire, Pablo R; Weinstein, John N; Mills, Gordon B; Almeida, Jonas S

    2010-12-01

    The Cancer Genome Atlas (TCGA) is a multidisciplinary, multi-institutional effort to characterize several types of cancer. Datasets from biomedical domains such as TCGA present a particularly challenging task for those interested in dynamically aggregating its results because the data sources are typically both heterogeneous and distributed. The Linked Data best practices offer a solution to integrate and discover data with those characteristics, namely through exposure of data as Web services supporting SPARQL, the Resource Description Framework query language. Most SPARQL endpoints, however, cannot easily be queried by data experts. Furthermore, exposing experimental data as SPARQL endpoints remains a challenging task because, in most cases, data must first be converted to Resource Description Framework triples. In line with those requirements, we have developed an infrastructure to expose clinical, demographic and molecular data elements generated by TCGA as a SPARQL endpoint by assigning elements to entities of the Simple Sloppy Semantic Database (S3DB) management model. All components of the infrastructure are available as independent Representational State Transfer (REST) Web services to encourage reusability, and a simple interface was developed to automatically assemble SPARQL queries by navigating a representation of the TCGA domain. A key feature of the proposed solution that greatly facilitates assembly of SPARQL queries is the distinction between the TCGA domain descriptors and data elements. Furthermore, the use of the S3DB management model as a mediator enables queries to both public and protected data without the need for prior submission to a single data source. Copyright © 2010 Elsevier Inc. All rights reserved.

  20. Development of a frequent heartburn index.

    Science.gov (United States)

    Stull, Donald E; van Hanswijck de Jonge, Patricia; Houghton, Katherine; Kocun, Christopher; Sandor, David W

    2011-09-01

    The aim of this study is to develop and validate a brief instrument for the measurement of overall psychosocial impact of frequent heartburn (heartburn experienced 2+ times weekly) in the general U.S. population, yielding a single, composite score. Item reduction and psychometric analyses of an existing Frequent Heartburn (FHB) Survey, a 52-item, 13-domain, patient-reported outcomes (PRO) survey assessing the impact of frequent heartburn on psychosocial quality of life. Item reduction resulted in 9 items from the original FHB Survey measuring all domains. All retained items in this full Frequent Heartburn Index (FHBI-Full) had moderate to strong factor loadings on the underlying factor (range: 0.66-0.85) and acceptable overall model fit (CFI = 0.93, SRMR = 0.04). Coefficient alpha was 0.92. A shorter FHBI (FHBI-Brief) was created that excludes the two employment-related items. The FHBI-Brief had a coefficient alpha of 0.90. Both FHBI versions have good psychometric properties and capture a full range of psychosocial effects of frequent heartburn. Normed national scores for the FHBI are available against which an individual can compare their own FHBI score. The FHBI-Full and FHBI-Brief show promise as PRO instruments that may help individuals and clinicians better understand the effect of frequent heartburn on psychosocial functioning.

  1. Two-temperature LATE-PCR endpoint genotyping

    Directory of Open Access Journals (Sweden)

    Reis Arthur H

    2006-12-01

    Full Text Available Abstract Background In conventional PCR, total amplicon yield becomes independent of starting template number as amplification reaches plateau and varies significantly among replicate reactions. This paper describes a strategy for reconfiguring PCR so that the signal intensity of a single fluorescent detection probe after PCR thermal cycling reflects genomic composition. The resulting method corrects for product yield variations among replicate amplification reactions, permits resolution of homozygous and heterozygous genotypes based on endpoint fluorescence signal intensities, and readily identifies imbalanced allele ratios equivalent to those arising from gene/chromosomal duplications. Furthermore, the use of only a single colored probe for genotyping enhances the multiplex detection capacity of the assay. Results Two-Temperature LATE-PCR endpoint genotyping combines Linear-After-The-Exponential (LATE-PCR (an advanced form of asymmetric PCR that efficiently generates single-stranded DNA and mismatch-tolerant probes capable of detecting allele-specific targets at high temperature and total single-stranded amplicons at a lower temperature in the same reaction. The method is demonstrated here for genotyping single-nucleotide alleles of the human HEXA gene responsible for Tay-Sachs disease and for genotyping SNP alleles near the human p53 tumor suppressor gene. In each case, the final probe signals were normalized against total single-stranded DNA generated in the same reaction. Normalization reduces the coefficient of variation among replicates from 17.22% to as little as 2.78% and permits endpoint genotyping with >99.7% accuracy. These assays are robust because they are consistent over a wide range of input DNA concentrations and give the same results regardless of how many cycles of linear amplification have elapsed. The method is also sufficiently powerful to distinguish between samples with a 1:1 ratio of two alleles from samples comprised of

  2. Endpoint-based parallel data processing in a parallel active messaging interface of a parallel computer

    Science.gov (United States)

    Archer, Charles J.; Blocksome, Michael A.; Ratterman, Joseph D.; Smith, Brian E.

    2014-08-12

    Endpoint-based parallel data processing in a parallel active messaging interface (`PAMI`) of a parallel computer, the PAMI composed of data communications endpoints, each endpoint including a specification of data communications parameters for a thread of execution on a compute node, including specifications of a client, a context, and a task, the compute nodes coupled for data communications through the PAMI, including establishing a data communications geometry, the geometry specifying, for tasks representing processes of execution of the parallel application, a set of endpoints that are used in collective operations of the PAMI including a plurality of endpoints for one of the tasks; receiving in endpoints of the geometry an instruction for a collective operation; and executing the instruction for a collective operation through the endpoints in dependence upon the geometry, including dividing data communications operations among the plurality of endpoints for one of the tasks.

  3. Emotional experiences in surrogate mothers: A qualitative study.

    Science.gov (United States)

    Ahmari Tehran, Hoda; Tashi, Shohreh; Mehran, Nahid; Eskandari, Narges; Dadkhah Tehrani, Tahmineh

    2014-07-01

    Surrogacy is one of the new techniques of assisted reproduction technology in which a woman carries and bears a child for another woman. In Iran, many Shia clerics and jurists considered it permissible so there is no religious prohibition for it. In addition to the risk of physical complications for complete surrogate mothers, the possibility of psychological complications resulted from emotional attachment to a living creature in the surrogate mother as another injury requires counseling and assessment prior to acceptance by infertile couples and complete surrogate mothers. The purpose of this study was to assess the emotional experiences of surrogate mothers. This was a qualitative, phenomenological study. We selected eight complete surrogate mothers in Isfahan. We used convenient sampling method and in-depth interview to collect the information. The data analysis was fulfilled via Colaizzi's seven-stage method. Reliability and validity study of the roots in the four-axis was done. The findings of these interviews were classified into two main themes and four sub themes: acquired experiences in pregnancy (feelings toward pregnancy, relationship with family, relatives and commissioning couple) and consequences of surrogacy (complications of pregnancy, religious and financial problems of surrogacy). Surrogacy pregnancy should be considered as high-risk emotional experience because many of surrogate mothers may face negative experiences. Therefore, it is recommended that surrogates should receive professional counseling prior to, during and following pregnancy.

  4. [The surrogate: Partner in the shared decision-making].

    Science.gov (United States)

    Sarradon-Eck, Aline; Capodano, Géraldine; Bureau, Eve; Julian-Reynier, Claire

    2016-01-01

    The legislative process of the surrogate appears to be unclear to health professionals and to patients and next of kin. To better adapt this process to the clinical practice our objective was here to document how the persons designated as surrogate perceived their role and how they described the difficulties encountered in oncology. Qualitative survey with an ethnographic approach carried out in 2014-2015, fieldwork, face-to-face interviews (n=26 including 20 surrogates and 6 patients) in a mobile palliative care unit located at a Regional Comprehensive Cancer Centre. Close relationship, psychological and cognitive competences were the main attribute to designate a surrogate. Perceived roles included the fact to be involved in decisions, to protect the patient, to be present, and to be a messenger. This process gives the next of kin the feeling to be part of the patient management. In the context of divorced families, it sometimes allows to rehabilitate and to reinforce the affective links. Our data highlight the confusion between the designation of the 'person to call' and 'the surrogate'. Our results highlight the 'surrogate' protective role of the patient, and the positive sides of the process, in particular in the context of divorced/rebuilt families. We recommend splitting the process to designate the 'person to call' and the 'surrogate', as administrative and medical duties, respectively. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  5. Adaptive surrogate model based multiobjective optimization for coastal aquifer management

    Science.gov (United States)

    Song, Jian; Yang, Yun; Wu, Jianfeng; Wu, Jichun; Sun, Xiaomin; Lin, Jin

    2018-06-01

    In this study, a novel surrogate model assisted multiobjective memetic algorithm (SMOMA) is developed for optimal pumping strategies of large-scale coastal groundwater problems. The proposed SMOMA integrates an efficient data-driven surrogate model with an improved non-dominated sorted genetic algorithm-II (NSGAII) that employs a local search operator to accelerate its convergence in optimization. The surrogate model based on Kernel Extreme Learning Machine (KELM) is developed and evaluated as an approximate simulator to generate the patterns of regional groundwater flow and salinity levels in coastal aquifers for reducing huge computational burden. The KELM model is adaptively trained during evolutionary search to satisfy desired fidelity level of surrogate so that it inhibits error accumulation of forecasting and results in correctly converging to true Pareto-optimal front. The proposed methodology is then applied to a large-scale coastal aquifer management in Baldwin County, Alabama. Objectives of minimizing the saltwater mass increase and maximizing the total pumping rate in the coastal aquifers are considered. The optimal solutions achieved by the proposed adaptive surrogate model are compared against those solutions obtained from one-shot surrogate model and original simulation model. The adaptive surrogate model does not only improve the prediction accuracy of Pareto-optimal solutions compared with those by the one-shot surrogate model, but also maintains the equivalent quality of Pareto-optimal solutions compared with those by NSGAII coupled with original simulation model, while retaining the advantage of surrogate models in reducing computational burden up to 94% of time-saving. This study shows that the proposed methodology is a computationally efficient and promising tool for multiobjective optimizations of coastal aquifer managements.

  6. Surrogate motherhood as a medical treatment procedure for women's infertility.

    Science.gov (United States)

    Jovic, Olga S

    2011-03-01

    The content of this work is conceived on the research of the consequences of surrogate motherhood as a process of assisted procreation, which represent a way of parenthood in cases when it is not possible to realize parenthood through a natural way. Surrogate motherhood is a process in which a woman (surrogate mother) agrees to carry a pregnancy with the intent to give the child to the couple with whom she has made a contract on surrogate maternity after the birth. This process of conception and birth makes the determination of the child's origin on its mother's side hard to determine, because of the distinction of the genetic and gestation phases of the two women. The concept of surrogate motherhood is to appear in two forms, depending on the existence or the non-existence of the genetic link between the surrogate mother and the child she gives birth to. There are gestation (full) and genetic (partial) surrogates each with different modalities and legal and ethical implications. In Serbia, Infertility Treatment and the Bio-medically Assisted Procreation Act from 2009 explicitly forbids surrogate motherhood, despite the fact that an infertile couple decides to use it, as a rule, after having tried all other treatment procedures, in cases when there is a diagnosis but the conventional treatment applied has not produced the desired results. Given the fact that no one has the right to ignore the sufferings of people who cannot procreate naturally, the medical practice and legal science in our country plead for a formulation of a legal framework in which to apply surrogate motherhood as an infertility treatment, under particular conditions.

  7. A minimalist functional group (MFG) approach for surrogate fuel formulation

    KAUST Repository

    Abdul Jameel, Abdul Gani; Naser, Nimal; Issayev, Gani; Touitou, Jamal; Ghosh, Manik Kumer; Emwas, Abdul-Hamid M.; Farooq, Aamir; Dooley, Stephen; Sarathy, Mani

    2018-01-01

    Surrogate fuel formulation has drawn significant interest due to its relevance towards understanding combustion properties of complex fuel mixtures. In this work, we present a novel approach for surrogate fuel formulation by matching target fuel functional groups, while minimizing the number of surrogate species. Five key functional groups; paraffinic CH, paraffinic CH, paraffinic CH, naphthenic CH–CH and aromatic C–CH groups in addition to structural information provided by the Branching Index (BI) were chosen as matching targets. Surrogates were developed for six FACE (Fuels for Advanced Combustion Engines) gasoline target fuels, namely FACE A, C, F, G, I and J. The five functional groups present in the fuels were qualitatively and quantitatively identified using high resolution H Nuclear Magnetic Resonance (NMR) spectroscopy. A further constraint was imposed in limiting the number of surrogate components to a maximum of two. This simplifies the process of surrogate formulation, facilitates surrogate testing, and significantly reduces the size and time involved in developing chemical kinetic models by reducing the number of thermochemical and kinetic parameters requiring estimation. Fewer species also reduces the computational expenses involved in simulating combustion in practical devices. The proposed surrogate formulation methodology is denoted as the Minimalist Functional Group (MFG) approach. The MFG surrogates were experimentally tested against their target fuels using Ignition Delay Times (IDT) measured in an Ignition Quality Tester (IQT), as specified by the standard ASTM D6890 methodology, and in a Rapid Compression Machine (RCM). Threshold Sooting Index (TSI) and Smoke Point (SP) measurements were also performed to determine the sooting propensities of the surrogates and target fuels. The results showed that MFG surrogates were able to reproduce the aforementioned combustion properties of the target FACE gasolines across a wide range of conditions

  8. A minimalist functional group (MFG) approach for surrogate fuel formulation

    KAUST Repository

    Abdul Jameel, Abdul Gani

    2018-03-20

    Surrogate fuel formulation has drawn significant interest due to its relevance towards understanding combustion properties of complex fuel mixtures. In this work, we present a novel approach for surrogate fuel formulation by matching target fuel functional groups, while minimizing the number of surrogate species. Five key functional groups; paraffinic CH, paraffinic CH, paraffinic CH, naphthenic CH–CH and aromatic C–CH groups in addition to structural information provided by the Branching Index (BI) were chosen as matching targets. Surrogates were developed for six FACE (Fuels for Advanced Combustion Engines) gasoline target fuels, namely FACE A, C, F, G, I and J. The five functional groups present in the fuels were qualitatively and quantitatively identified using high resolution H Nuclear Magnetic Resonance (NMR) spectroscopy. A further constraint was imposed in limiting the number of surrogate components to a maximum of two. This simplifies the process of surrogate formulation, facilitates surrogate testing, and significantly reduces the size and time involved in developing chemical kinetic models by reducing the number of thermochemical and kinetic parameters requiring estimation. Fewer species also reduces the computational expenses involved in simulating combustion in practical devices. The proposed surrogate formulation methodology is denoted as the Minimalist Functional Group (MFG) approach. The MFG surrogates were experimentally tested against their target fuels using Ignition Delay Times (IDT) measured in an Ignition Quality Tester (IQT), as specified by the standard ASTM D6890 methodology, and in a Rapid Compression Machine (RCM). Threshold Sooting Index (TSI) and Smoke Point (SP) measurements were also performed to determine the sooting propensities of the surrogates and target fuels. The results showed that MFG surrogates were able to reproduce the aforementioned combustion properties of the target FACE gasolines across a wide range of conditions

  9. Mother-daughter in vitro fertilization triplet surrogate pregnancy.

    Science.gov (United States)

    Michelow, M C; Bernstein, J; Jacobson, M J; McLoughlin, J L; Rubenstein, D; Hacking, A I; Preddy, S; Van der Wat, I J

    1988-02-01

    A successful triplet pregnancy has been established in a surrogate gestational mother following the transfer of five embryos fertilized in vitro. The oocytes were donated by her biological daughter, and the sperm obtained from the daughter's husband. The daughter's infertility followed a total abdominal hysterectomy performed for a postpartum hemorrhage as a result of a placenta accreta. Synchronization of both their menstrual cycles was obtained using oral contraceptive suppression for 2 months, followed by stimulation of both the surrogate gestational mother and her daughter such that embryo transfer would occur at least 48 hr after the surrogate gestational mother's own ovulation. This case raises a number of medical, social, psychological, and ethical issues.

  10. Verification of models for ballistic movement time and endpoint variability.

    Science.gov (United States)

    Lin, Ray F; Drury, Colin G

    2013-01-01

    A hand control movement is composed of several ballistic movements. The time required in performing a ballistic movement and its endpoint variability are two important properties in developing movement models. The purpose of this study was to test potential models for predicting these two properties. Twelve participants conducted ballistic movements of specific amplitudes using a drawing tablet. The measured data of movement time and endpoint variability were then used to verify the models. This study was successful with Hoffmann and Gan's movement time model (Hoffmann, 1981; Gan and Hoffmann 1988) predicting more than 90.7% data variance for 84 individual measurements. A new theoretically developed ballistic movement variability model, proved to be better than Howarth, Beggs, and Bowden's (1971) model, predicting on average 84.8% of stopping-variable error and 88.3% of aiming-variable errors. These two validated models will help build solid theoretical movement models and evaluate input devices. This article provides better models for predicting end accuracy and movement time of ballistic movements that are desirable in rapid aiming tasks, such as keying in numbers on a smart phone. The models allow better design of aiming tasks, for example button sizes on mobile phones for different user populations.

  11. Time-dependent efficacy of longitudinal biomarker for clinical endpoint.

    Science.gov (United States)

    Kolamunnage-Dona, Ruwanthi; Williamson, Paula R

    2018-06-01

    Joint modelling of longitudinal biomarker and event-time processes has gained its popularity in recent years as they yield more accurate and precise estimates. Considering this modelling framework, a new methodology for evaluating the time-dependent efficacy of a longitudinal biomarker for clinical endpoint is proposed in this article. In particular, the proposed model assesses how well longitudinally repeated measurements of a biomarker over various time periods (0,t) distinguish between individuals who developed the disease by time t and individuals who remain disease-free beyond time t. The receiver operating characteristic curve is used to provide the corresponding efficacy summaries at various t based on the association between longitudinal biomarker trajectory and risk of clinical endpoint prior to each time point. The model also allows detecting the time period over which a biomarker should be monitored for its best discriminatory value. The proposed approach is evaluated through simulation and illustrated on the motivating dataset from a prospective observational study of biomarkers to diagnose the onset of sepsis.

  12. Cortical plasticity as a new endpoint measurement for chronic pain

    Directory of Open Access Journals (Sweden)

    Zhuo Min

    2011-07-01

    Full Text Available Abstract Animal models of chronic pain are widely used to investigate basic mechanisms of chronic pain and to evaluate potential novel drugs for treating chronic pain. Among the different criteria used to measure chronic pain, behavioral responses are commonly used as the end point measurements. However, not all chronic pain conditions can be easily measured by behavioral responses such as the headache, phantom pain and pain related to spinal cord injury. Here I propose that cortical indexes, that indicate neuronal plastic changes in pain-related cortical areas, can be used as endpoint measurements for chronic pain. Such cortical indexes are not only useful for those chronic pain conditions where a suitable animal model is lacking, but also serve as additional screening methods for potential drugs to treat chronic pain in humans. These cortical indexes are activity-dependent immediate early genes, electrophysiological identified plastic changes and biochemical assays of signaling proteins. It can be used to evaluate novel analgesic compounds that may act at peripheral or spinal sites. I hope that these new cortical endpoint measurements will facilitate our search for new, and more effective, pain medicines, and help to reduce false lead drug targets.

  13. A yeast screening system for simultaneously monitoring multiple genetic endpoints

    International Nuclear Information System (INIS)

    Dixon, M.L.; Mortimer, R.K.

    1986-01-01

    Mutation, recombination, and mitochondrial deficiencies have been proposed to have roles in the carcinogenic process. The authors describe a diploid strain of the yeast Saccharomyces cerevisiae capable of detecting this wide spectrum of genetic changes. The markers used for monitoring these events have been especially well characterized genetically. Ultraviolet light was chosen as a model carcinogenic agent to test this system. In addition to highly significant increases in the frequencies of each genetic change, increases in the absolute numbers of each change indicated induction and not selective survival. The relative amounts of each type of genetic change varied with dose. The wide spectrum of endpoints monitored in the XD83 yeast system may allow the detection of certain carcinogens and other genetically toxic agents which have escaped detection in more limited systems. Since only one strain is required to simultaneously monitor these genetic changes, this assay system should facilitate comparisons of the induced changes and be more efficient than using multiple strains to monitor the same endpoints. (Auth.)

  14. Parametric Study of Beta-Endpoint Energy in Direct Energy Converters

    Science.gov (United States)

    2007-01-01

    value to the endpoint energy of nickel-63 ( Ni63 ), whose endpoint energy is 66 keV. Only an approximation is sought. Nickel-63 is an easily...is known to vary from Sr90’s spectrum, where instead of peaking at approximately one third of the endpoint energy, the peak of Ni63 ’s output spectrum

  15. Performance Evaluation of Frequent Subgraph Discovery Techniques

    Directory of Open Access Journals (Sweden)

    Saif Ur Rehman

    2014-01-01

    Full Text Available Due to rapid development of the Internet technology and new scientific advances, the number of applications that model the data as graphs increases, because graphs have highly expressive power to model a complicated structure. Graph mining is a well-explored area of research which is gaining popularity in the data mining community. A graph is a general model to represent data and has been used in many domains such as cheminformatics, web information management system, computer network, and bioinformatics, to name a few. In graph mining the frequent subgraph discovery is a challenging task. Frequent subgraph mining is concerned with discovery of those subgraphs from graph dataset which have frequent or multiple instances within the given graph dataset. In the literature a large number of frequent subgraph mining algorithms have been proposed; these included FSG, AGM, gSpan, CloseGraph, SPIN, Gaston, and Mofa. The objective of this research work is to perform quantitative comparison of the above listed techniques. The performances of these techniques have been evaluated through a number of experiments based on three different state-of-the-art graph datasets. This novel work will provide base for anyone who is working to design a new frequent subgraph discovery technique.

  16. A Large-Scale Study of Surrogate Physicality and Gesturing on Human–Surrogate Interactions in a Public Space

    Directory of Open Access Journals (Sweden)

    Kangsoo Kim

    2017-07-01

    Full Text Available Technological human surrogates, including robotic and virtual humans, have been popularly used in various scenarios, including training, education, and entertainment. Prior research has investigated the effects of the surrogate’s physicality and gesturing in human perceptions and social influence of the surrogate. However, those studies have been carried out in research laboratories, where the participants were aware that it was an experiment, and the participant demographics are typically relatively narrow—e.g., college students. In this paper, we describe and share results from a large-scale exploratory user study involving 7,685 people in a public space, where they were unaware of the experimental nature of the setting, to investigate the effects of surrogate physicality and gesturing on their behavior during human–surrogate interactions. We evaluate human behaviors using several variables, such as proactivity and reactivity, and proximity. We have identified several interesting phenomena that could lead to hypotheses developed as part of future hypothesis-based studies. Based on the measurements of the variables, we believe people are more likely to be engaged in a human–surrogate interaction when the surrogate is physically present, but movements and gesturing with its body parts have not shown the expected benefits for the interaction engagement. Regarding the demographics of the people in the study, we found higher overall engagement for females than males, and higher reactivity for younger than older people. We discuss implications for practitioners aiming to design a technological surrogate that will directly interact with real humans.

  17. Surrogate Motherhood: A Trust-Based Approach.

    Science.gov (United States)

    Beier, Katharina

    2015-12-01

    Because it is often argued that surrogacy should not be treated as contractual, the question arises in which terms this practice might then be couched. In this article, I argue that a phenomenology of surrogacy centering on the notion of trust provides a description that is illuminating from the moral point of view. My thesis is that surrogacy establishes a complex and extended reproductive unit--the "surrogacy triad" consisting of the surrogate mother, the child, and the intending parents--whose constituents are bound together by mutual trustful commitments. Even though a trust-based approach does not provide an ultimate answer to whether surrogacy should be sanctioned or prohibited, it allows for at least some practical suggestions. In particular, I will argue that, under certain conditions, surrogacy is tenable within familial or other significant relationships, and I will stress the necessity of acknowledging the new relationships and moral commitments that result from this practice. © The Author 2015. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. SURROGATE MOTHER DALAM PERSPEKTIF HUKUM PIDANA INDONESIA

    Directory of Open Access Journals (Sweden)

    Mr. Muntaha

    2013-04-01

    Full Text Available The development of science and technology, in particular in the field of health, has already recently brought a huge advantage and problem in human life. An example of technological marvel that not only requires deep legal thoughts but also at the same time solution is the bio-medical technology advancement of surrogacy. Surrogacy deals with human’s inclination towards reproductive activity. However, it opens up legal complication, in particular with regards to the potential commission of a criminal action as well as to the notion of doctor’s liability. Perkembangan ilmu dan teknologi di bidang kesehatan yang semakin maju dan pesat telah membawa berbagai manfaat dan masalah dalam kehidupan manusia dewasa ini. Salah satu perkembangan yang tidak hanya membutuhkan pemikiran di bidang hukum, tetapi juga sekaligus solusinya adalah mengenai kecanggihan teknologi bio-medis surrogate mother. Surrogacy menyentuh sisi kemanusiaan seorang insan terhadap reproduksi. Akan tetapi, lembaga surrogacy juga membawa komplikasi hukum terutama terkait dengan potensi tindak pidana dan dengan persoalan tanggung jawab dokter.

  19. Polynomial Chaos Surrogates for Bayesian Inference

    KAUST Repository

    Le Maitre, Olivier

    2016-01-06

    The Bayesian inference is a popular probabilistic method to solve inverse problems, such as the identification of field parameter in a PDE model. The inference rely on the Bayes rule to update the prior density of the sought field, from observations, and derive its posterior distribution. In most cases the posterior distribution has no explicit form and has to be sampled, for instance using a Markov-Chain Monte Carlo method. In practice the prior field parameter is decomposed and truncated (e.g. by means of Karhunen- Lo´eve decomposition) to recast the inference problem into the inference of a finite number of coordinates. Although proved effective in many situations, the Bayesian inference as sketched above faces several difficulties requiring improvements. First, sampling the posterior can be a extremely costly task as it requires multiple resolutions of the PDE model for different values of the field parameter. Second, when the observations are not very much informative, the inferred parameter field can highly depends on its prior which can be somehow arbitrary. These issues have motivated the introduction of reduced modeling or surrogates for the (approximate) determination of the parametrized PDE solution and hyperparameters in the description of the prior field. Our contribution focuses on recent developments in these two directions: the acceleration of the posterior sampling by means of Polynomial Chaos expansions and the efficient treatment of parametrized covariance functions for the prior field. We also discuss the possibility of making such approach adaptive to further improve its efficiency.

  20. Heavy metals in atmospheric surrogate dry deposition

    Science.gov (United States)

    Morselli; Cecchini; Grandi; Iannuccilli; Barilli; Olivieri

    1999-02-01

    This paper describes a methodological approach for the assessment of the amount of surrogate dry deposition of several toxic heavy metals (Cd, Cr, Cu, Ni, Pb, V, Zn) associated with atmospheric particulate matter at ground level. The objectives of the study were twofold: i) the evaluation of several techniques for the digestion of dry deposition samples for trace metal analysis; ii) the comparison of the results from two samplers with different collecting surfaces. A dry solid surface sampler (DRY sampler, Andersen--USA) and a water layer surface sampler (DAS sampler--MTX Italy) were employed. The samples were collected over a one-year period in an urban site of Bologna (northern Italy). A description is given of the complete procedure, from sampling to data elaboration, including sample storage, digestion and analytical methods. According to the results obtained with three different digestion techniques (Teflon bomb, microwave digester and Teflon flask with vapour cooling system), the highest recovery rate was achieved by the Teflon bomb procedure employing an NBS 1648 Standard Reference Material; 90-95% of the elements considered were recovered by dissolution in a pressurized Teflon bomb with an HNO3-HF mixture. Given these results, the technique was adopted for dry deposition sample digestion. On the basis of the amount of heavy metals measured as monthly deposition fluxes (microg/m2), the collecting efficiency of the DAS sampler for a number of elements was found to be as much as two to three times greater than that of the DRY sampler.

  1. Frequent price changes under menu costs

    DEFF Research Database (Denmark)

    Hansen, Per Svejstrup

    1999-01-01

    , the price may be changed more frequent in the short run, and in the long run it definitely will. Hence, observing frequent price changes is not necessarily inconsistent with a firm operating under menu costs. This paper relies on an article by Dixit (1991), (Review of Economic studies, 58, 141......This paper investigates the effect of uncertainty on a single firm's pricing behaviour in a dynamic menu cost model that results in (S,s)-rules where the price is fixed inside a band. It will be demonstrated that even though the band of inaction widens in response to increased uncertainty...

  2. Frequently cited journals in forensic psychology.

    Science.gov (United States)

    Black, Steve

    2012-02-01

    Works cited in six forensic psychology journals published 2008-2010 were counted to identify the most frequently cited journals. The sample of works cited (N = 21,776) was not a definitive ranked list of important journals in forensic psychology, but was large enough to indicate high-impact journals. The list of frequently cited publications included more general psychiatry and psychology journals than titles specific to forensic psychology. The implications of the proportion of general versus specific titles for collections supporting research in forensic psychology were discussed.

  3. The Decomposition of Surrogate Fuel Molecules During Combustion

    National Research Council Canada - National Science Library

    Tsang, Wing; Manion, Jeffrey A

    2006-01-01

    This project is aimed at developing a chemical kinetic database consisting of the rate constants of fundamental single step reactions that describe the pyrolytic decomposition of surrogate fuels molecules...

  4. A Parallel and Distributed Surrogate Model Implementation for Computational Steering

    KAUST Repository

    Butnaru, Daniel; Buse, Gerrit; Pfluger, Dirk

    2012-01-01

    of the input parameters. Such an exploration process is however not possible if the simulation is computationally too expensive. For these cases we present in this paper a scalable computational steering approach utilizing a fast surrogate model as substitute

  5. Altruistic surrogacy: the necessary objectification of surrogate mothers.

    Science.gov (United States)

    Tieu, M M

    2009-03-01

    One of the major concerns about surrogacy is the potential harm that may be inflicted upon the surrogate mother and the child after relinquishment. Even if one were to take the liberal view that surrogacy should be presumptively allowed on the basis of autonomy and/or compassion, evidence of harm must be taken seriously. In this paper I review the evidence from psychological studies on the effect that relinquishing a child has on the surrogate mother and while it appears that many surrogates are able to cope with relinquishment, I argue that there are good reasons, grounded in empirical evidence, to support the view that the subsequent management of the relinquishment necessarily objectifies the surrogate mother.

  6. SURROGATE SPECIES IN ASSESSING CONTAMINANT RISK FOR ENDANGERED FISHES

    Science.gov (United States)

    Rainbow trout, fathead minnows, and sheepshead minnows were tested as surrogate species to assess contaminant risk for 17 endangered fishes and one toad species. Acute toxicity tests were conducted with carbaryl, copper, 4-nonylphenol, pentachlorophenol, and permethrin in accord...

  7. Hepatology may have problems with putative surrogate outcome measures

    DEFF Research Database (Denmark)

    Gluud, Christian; Brok, Jesper; Gong, Yan

    2007-01-01

    A surrogate outcome measure is a laboratory measurement, a physical sign, or another intermediate substitute that is able to predict an intervention's effect on a clinically meaningful outcome. A clinical outcome detects how a patient feels, functions, or survives. Surrogate outcome measures occur...... faster or more often, are cheaper, and/or are less invasively achieved than the clinical outcome. In practice, validation is surprisingly often overlooked, especially if a biologic plausible rationale is proposed. Surrogate outcomes must be validated before use. The first step in validation...... predicts the intervention's effect on the clinical outcome. In hepatology a number of putative surrogate outcomes are used both in clinical research and in clinical practice without having been properly validated. Sustained virological response to interferons and ribavirin in patients with chronic...

  8. Reduced order surrogate modelling (ROSM) of high dimensional deterministic simulations

    Science.gov (United States)

    Mitry, Mina

    Often, computationally expensive engineering simulations can prohibit the engineering design process. As a result, designers may turn to a less computationally demanding approximate, or surrogate, model to facilitate their design process. However, owing to the the curse of dimensionality, classical surrogate models become too computationally expensive for high dimensional data. To address this limitation of classical methods, we develop linear and non-linear Reduced Order Surrogate Modelling (ROSM) techniques. Two algorithms are presented, which are based on a combination of linear/kernel principal component analysis and radial basis functions. These algorithms are applied to subsonic and transonic aerodynamic data, as well as a model for a chemical spill in a channel. The results of this thesis show that ROSM can provide a significant computational benefit over classical surrogate modelling, sometimes at the expense of a minor loss in accuracy.

  9. A frequent flyer program for nuclear mythology

    International Nuclear Information System (INIS)

    Robertson, J.A.L.

    1997-01-01

    The anti-nuclear literature contains many erroneous and misleading allegations, collectively constituting a mythology. These are repeated endlessly, however often they are refuted, and are quoted uncritically by the media. Many are collected here, together with my rebuttals. For an explanation of the use here of the term 'frequent flyers', read on... (author)

  10. IMS Learning Design Frequently Asked Questions

    NARCIS (Netherlands)

    Tattersall, Colin; Manderveld, Jocelyn; Hummel, Hans; Sloep, Peter; Koper, Rob; De Vries, Fred

    2004-01-01

    This list of frequently asked questions was composed on the basis of questions asked of the Educational Technology Expertise Centrum. The questions addessed are: Where can I find the IMS Learning Design Specification? What is meant by the phrase “Learning Design”? What is the IMS LD Specification

  11. Treatment of Anthrax Disease Frequently Asked Questions

    Energy Technology Data Exchange (ETDEWEB)

    Judd, Kathleen S.; Young, Joan E.; Lesperance, Ann M.; Malone, John D.

    2010-05-14

    This document provides a summary of Frequently Asked Questions (FAQs) on the treatment of anthrax disease caused by a wide-area release of Bacillus anthracis spores as an act bioterrorism. These FAQs are intended to provide the public health and medical community, as well as others, with guidance and communications to support the response and long-term recovery from an anthrax event.

  12. Emotional experiences in surrogate mothers: A qualitative study

    OpenAIRE

    Ahmari Tehran, Hoda; Tashi, Shohreh; Mehran, Nahid; Eskandari, Narges; Dadkhah Tehrani, Tahmineh

    2014-01-01

    Background: Surrogacy is one of the new techniques of assisted reproduction technology in which a woman carries and bears a child for another woman. In Iran, many Shia clerics and jurists considered it permissible so there is no religious prohibition for it. In addition to the risk of physical complications for complete surrogate mothers, the possibility of psychological complications resulted from emotional attachment to a living creature in the surrogate mother as another injury requires co...

  13. Families in the making: gestational surrogate mothers in California

    OpenAIRE

    Bjørn, Henriette Hårseide

    2014-01-01

    This thesis is based on a field work I conducted in California from January to June 2012, where I explore how gestational surrogate mothers experience the process of surrogacy and how California law has dealt with ART-cases. Through exploring surrogacy from different view point, and in particular from the view of surrogate mothers, this has given an insightful view into surrogacy in California. I have identified two court cases which are important for the establishment of parental rights in s...

  14. Act relating to surrogate parenthood contracts, 10 February 1988.

    Science.gov (United States)

    1988-01-01

    This Nebraska Act provides that surrogate parenthood contracts are void and unenforceable and that the "biological father of a child born pursuant to such a contract shall have all the rights and obligations imposed by law with respect to the child." A surrogate parenthood contract is defined as "a contract by which a woman is to be compensated for bearing a child of a man who is not her husband." full text

  15. Error modeling for surrogates of dynamical systems using machine learning

    Science.gov (United States)

    Trehan, Sumeet; Carlberg, Kevin T.; Durlofsky, Louis J.

    2017-12-01

    A machine-learning-based framework for modeling the error introduced by surrogate models of parameterized dynamical systems is proposed. The framework entails the use of high-dimensional regression techniques (e.g., random forests, LASSO) to map a large set of inexpensively computed `error indicators' (i.e., features) produced by the surrogate model at a given time instance to a prediction of the surrogate-model error in a quantity of interest (QoI). This eliminates the need for the user to hand-select a small number of informative features. The methodology requires a training set of parameter instances at which the time-dependent surrogate-model error is computed by simulating both the high-fidelity and surrogate models. Using these training data, the method first determines regression-model locality (via classification or clustering), and subsequently constructs a `local' regression model to predict the time-instantaneous error within each identified region of feature space. We consider two uses for the resulting error model: (1) as a correction to the surrogate-model QoI prediction at each time instance, and (2) as a way to statistically model arbitrary functions of the time-dependent surrogate-model error (e.g., time-integrated errors). We apply the proposed framework to model errors in reduced-order models of nonlinear oil--water subsurface flow simulations. The reduced-order models used in this work entail application of trajectory piecewise linearization with proper orthogonal decomposition. When the first use of the method is considered, numerical experiments demonstrate consistent improvement in accuracy in the time-instantaneous QoI prediction relative to the original surrogate model, across a large number of test cases. When the second use is considered, results show that the proposed method provides accurate statistical predictions of the time- and well-averaged errors.

  16. Evaluation and comparison of predictive individual-level general surrogates.

    Science.gov (United States)

    Gabriel, Erin E; Sachs, Michael C; Halloran, M Elizabeth

    2018-07-01

    An intermediate response measure that accurately predicts efficacy in a new setting at the individual level could be used both for prediction and personalized medical decisions. In this article, we define a predictive individual-level general surrogate (PIGS), which is an individual-level intermediate response that can be used to accurately predict individual efficacy in a new setting. While methods for evaluating trial-level general surrogates, which are predictors of trial-level efficacy, have been developed previously, few, if any, methods have been developed to evaluate individual-level general surrogates, and no methods have formalized the use of cross-validation to quantify the expected prediction error. Our proposed method uses existing methods of individual-level surrogate evaluation within a given clinical trial setting in combination with cross-validation over a set of clinical trials to evaluate surrogate quality and to estimate the absolute prediction error that is expected in a new trial setting when using a PIGS. Simulations show that our method performs well across a variety of scenarios. We use our method to evaluate and to compare candidate individual-level general surrogates over a set of multi-national trials of a pentavalent rotavirus vaccine.

  17. Statistical characteristics of surrogate data based on geophysical measurements

    Directory of Open Access Journals (Sweden)

    V. Venema

    2006-01-01

    Full Text Available In this study, the statistical properties of a range of measurements are compared with those of their surrogate time series. Seven different records are studied, amongst others, historical time series of mean daily temperature, daily rain sums and runoff from two rivers, and cloud measurements. Seven different algorithms are used to generate the surrogate time series. The best-known method is the iterative amplitude adjusted Fourier transform (IAAFT algorithm, which is able to reproduce the measured distribution as well as the power spectrum. Using this setup, the measurements and their surrogates are compared with respect to their power spectrum, increment distribution, structure functions, annual percentiles and return values. It is found that the surrogates that reproduce the power spectrum and the distribution of the measurements are able to closely match the increment distributions and the structure functions of the measurements, but this often does not hold for surrogates that only mimic the power spectrum of the measurement. However, even the best performing surrogates do not have asymmetric increment distributions, i.e., they cannot reproduce nonlinear dynamical processes that are asymmetric in time. Furthermore, we have found deviations of the structure functions on small scales.

  18. Improving Communication With Surrogate Decision-Makers: A Pilot Initiative.

    Science.gov (United States)

    Meltzer, Ellen C; Shi, Zhenzhen; Suppes, Alexandra; Hersh, Jennifer E; Orlander, Jay D; Calhoun, Aaron W; Tung, Judy; Logio, Lia; Manna, Ruth; Bialer, Philip A; Acres, Cathleen A; Fins, Joseph J

    2017-08-01

    Difficult conversations in medical care often occur between physicians and patients' surrogates, individuals entrusted with medical decisions for patients who lack the capacity to make them. Poor communication between patients' surrogates and physicians may exacerbate anxiety and guilt for surrogates, and may contribute to physician stress and burnout. This pilot study assesses the effectiveness of an experiential learning workshop that was conducted in a clinical setting, and aimed at improving resident physician communication skills with a focus on surrogate decision-making. From April through June 2016, we assessed internal medicine residents' baseline communication skills through an objective structured clinical examination (OSCE) with actors representing standardized surrogates. After an intensive, 6-hour communication skills workshop, residents were reassessed via an OSCE on the same day. A faculty facilitator and the surrogate evaluated participants' communication skills via the expanded Gap Kalamazoo Consensus Statement Assessment Form. Wilcoxon signed rank tests (α of .05) compared mean pre- and postworkshop scores. Of 44 residents, 33 (75%) participated. Participants' average preworkshop OSCE scores ( M  = 3.3, SD = 0.9) were significantly lower than postworkshop scores ( M  = 4.3; SD = 0.8; Z  = 4.193; P  decision-making benefit from focused interventions. Our pilot assessment of a workshop showed promise, and additionally demonstrated the feasibility of bringing OSCEs and simulated encounters into a busy clinical practice.

  19. Biomarkers of Host Response Predict Primary End-Point Radiological Pneumonia in Tanzanian Children with Clinical Pneumonia: A Prospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Laura K Erdman

    Full Text Available Diagnosing pediatric pneumonia is challenging in low-resource settings. The World Health Organization (WHO has defined primary end-point radiological pneumonia for use in epidemiological and vaccine studies. However, radiography requires expertise and is often inaccessible. We hypothesized that plasma biomarkers of inflammation and endothelial activation may be useful surrogates for end-point pneumonia, and may provide insight into its biological significance.We studied children with WHO-defined clinical pneumonia (n = 155 within a prospective cohort of 1,005 consecutive febrile children presenting to Tanzanian outpatient clinics. Based on x-ray findings, participants were categorized as primary end-point pneumonia (n = 30, other infiltrates (n = 31, or normal chest x-ray (n = 94. Plasma levels of 7 host response biomarkers at presentation were measured by ELISA. Associations between biomarker levels and radiological findings were assessed by Kruskal-Wallis test and multivariable logistic regression. Biomarker ability to predict radiological findings was evaluated using receiver operating characteristic curve analysis and Classification and Regression Tree analysis.Compared to children with normal x-ray, children with end-point pneumonia had significantly higher C-reactive protein, procalcitonin and Chitinase 3-like-1, while those with other infiltrates had elevated procalcitonin and von Willebrand Factor and decreased soluble Tie-2 and endoglin. Clinical variables were not predictive of radiological findings. Classification and Regression Tree analysis generated multi-marker models with improved performance over single markers for discriminating between groups. A model based on C-reactive protein and Chitinase 3-like-1 discriminated between end-point pneumonia and non-end-point pneumonia with 93.3% sensitivity (95% confidence interval 76.5-98.8, 80.8% specificity (72.6-87.1, positive likelihood ratio 4.9 (3.4-7.1, negative likelihood ratio 0

  20. Biomarkers of Host Response Predict Primary End-Point Radiological Pneumonia in Tanzanian Children with Clinical Pneumonia: A Prospective Cohort Study

    Science.gov (United States)

    Erdman, Laura K.; D’Acremont, Valérie; Hayford, Kyla; Kilowoko, Mary; Kyungu, Esther; Hongoa, Philipina; Alamo, Leonor; Streiner, David L.; Genton, Blaise; Kain, Kevin C.

    2015-01-01

    Background Diagnosing pediatric pneumonia is challenging in low-resource settings. The World Health Organization (WHO) has defined primary end-point radiological pneumonia for use in epidemiological and vaccine studies. However, radiography requires expertise and is often inaccessible. We hypothesized that plasma biomarkers of inflammation and endothelial activation may be useful surrogates for end-point pneumonia, and may provide insight into its biological significance. Methods We studied children with WHO-defined clinical pneumonia (n = 155) within a prospective cohort of 1,005 consecutive febrile children presenting to Tanzanian outpatient clinics. Based on x-ray findings, participants were categorized as primary end-point pneumonia (n = 30), other infiltrates (n = 31), or normal chest x-ray (n = 94). Plasma levels of 7 host response biomarkers at presentation were measured by ELISA. Associations between biomarker levels and radiological findings were assessed by Kruskal-Wallis test and multivariable logistic regression. Biomarker ability to predict radiological findings was evaluated using receiver operating characteristic curve analysis and Classification and Regression Tree analysis. Results Compared to children with normal x-ray, children with end-point pneumonia had significantly higher C-reactive protein, procalcitonin and Chitinase 3-like-1, while those with other infiltrates had elevated procalcitonin and von Willebrand Factor and decreased soluble Tie-2 and endoglin. Clinical variables were not predictive of radiological findings. Classification and Regression Tree analysis generated multi-marker models with improved performance over single markers for discriminating between groups. A model based on C-reactive protein and Chitinase 3-like-1 discriminated between end-point pneumonia and non-end-point pneumonia with 93.3% sensitivity (95% confidence interval 76.5–98.8), 80.8% specificity (72.6–87.1), positive likelihood ratio 4.9 (3.4–7

  1. Low dose response analysis through a cytogenetic end-point

    International Nuclear Information System (INIS)

    Bojtor, I.; Koeteles, G.J.

    1998-01-01

    The effects of low doses were studied on human lymphocytes of various individuals. The frequency of micronuclei in cytokinesis-blocked cultured lymphocytes was taken as end-point. The probability distribution of radiation-induced increment was statistically proved and identified as to be asymmetric when the blood samples had been irradiated with doses of 0.01-0.05 Gy of X-rays, similarly to that in unirradiated control population. On the contrary, at or above 1 Gy the corresponding normal curve could be accepted only reflecting an approximately symmetrical scatter of the increments about their mean value. It was found that the slope as well as the closeness of correlation of the variables considerably changed when lower and lower dose ranges had been selected. Below approximately 0.2 Gy even an unrelatedness was found betwen the absorbed dose and the increment

  2. Hausdorff dimension of exponential parameter rays and their endpoints

    International Nuclear Information System (INIS)

    Bailesteanu, Mihai; Balan, Horia Vlad; Schleicher, Dierk

    2008-01-01

    We investigate the set I of parameters κ for which the singular value of z map e z + κ converges to ∞. The set I consists of uncountably many parameter rays, plus landing points of some of these rays (Förster et al 2008 Proc Am. Math. Soc. 136 at press (Preprint math.DS/0311427)). We show that the parameter rays have Hausdorff dimension 1, which implies (Qiu 1994 Acta Math. Sin. (N.S.) 10 362–8) that the ray endpoints in I alone have dimension 2. Analogous results were known for dynamical planes of exponential maps (Karpińska 1999 C. R. Acad. Sci. Paris Sér. I: Math. 328 1039–44; Schleicher and Zimmer 2003 J. Lond. Math. Soc. 67 380–400); our result shows that this also holds in parameter space

  3. Biomarkers of intermediate endpoints in environmental and occupational health

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E; Hansen, Ase M

    2007-01-01

    The use of biomarkers in environmental and occupational health is increasing due to increasing demands on information about health risks from unfavourable exposures. Biomarkers provide information about individual loads. Biomarkers of intermediate endpoints benefit in comparison with biomarkers...... of exposure from the fact that they are closer to the adverse outcome in the pathway from exposure to health effects and may provide powerful information for intervention. Some biomarkers are specific, e.g., DNA and protein adducts, while others are unspecific like the cytogenetic biomarkers of chromosomal...... health effect from the result of the measurement has been performed for the cytogenetic biomarkers showing a predictive value of high levels of CA and increased risk of cancer. The use of CA in future studies is, however, limited by the laborious and sensitive procedure of the test and lack of trained...

  4. Frequent methodological errors in clinical research.

    Science.gov (United States)

    Silva Aycaguer, L C

    2018-03-07

    Several errors that are frequently present in clinical research are listed, discussed and illustrated. A distinction is made between what can be considered an "error" arising from ignorance or neglect, from what stems from a lack of integrity of researchers, although it is recognized and documented that it is not easy to establish when we are in a case and when in another. The work does not intend to make an exhaustive inventory of such problems, but focuses on those that, while frequent, are usually less evident or less marked in the various lists that have been published with this type of problems. It has been a decision to develop in detail the examples that illustrate the problems identified, instead of making a list of errors accompanied by an epidermal description of their characteristics. Copyright © 2018 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  5. Botulism: A Frequently Forgotten Old Malady

    Directory of Open Access Journals (Sweden)

    Teguh Thajeb

    2007-09-01

    Full Text Available A frequently forgotten old malady called botulism has been recognized for more than a century. This ailment occurs worldwide, afflicts human of all age groups from infants to elderly and affects Oriental people more often in several regions of China. Occurrence in Taiwan is uncommon, and therefore, it is often overlooked. The outbreaks of human botulism in various regions of the world, the clinical types, the molecular mechanisms, and the electrophysiologic findings will be highlighted.

  6. Discovering More Accurate Frequent Web Usage Patterns

    OpenAIRE

    Bayir, Murat Ali; Toroslu, Ismail Hakki; Cosar, Ahmet; Fidan, Guven

    2008-01-01

    Web usage mining is a type of web mining, which exploits data mining techniques to discover valuable information from navigation behavior of World Wide Web users. As in classical data mining, data preparation and pattern discovery are the main issues in web usage mining. The first phase of web usage mining is the data processing phase, which includes the session reconstruction operation from server logs. Session reconstruction success directly affects the quality of the frequent patterns disc...

  7. How to perform a cost-effectiveness analysis with surrogate endpoint: renal denervation in patients with resistant hypertension (DENERHTN) trial as an example.

    Science.gov (United States)

    Bulsei, Julie; Darlington, Meryl; Durand-Zaleski, Isabelle; Azizi, Michel

    2018-04-01

    Whilst much uncertainty exists as to the efficacy of renal denervation (RDN), the positive results of the DENERHTN study in France confirmed the interest of an economic evaluation in order to assess efficiency of RDN and inform local decision makers about the costs and benefits of this intervention. The uncertainty surrounding both the outcomes and the costs can be described using health economic methods such as the non-parametric bootstrap. Internationally, numerous health economic studies using a cost-effectiveness model to assess the impact of RDN in terms of cost and effectiveness compared to antihypertensive medical treatment have been conducted. The DENERHTN cost-effectiveness study was the first health economic evaluation specifically designed to assess the cost-effectiveness of RDN using individual data. Using the DENERHTN results as an example, we provide here a summary of the principle methods used to perform a cost-effectiveness analysis.

  8. Assessment of Correlation Between Early and Late Efficacy Endpoints to Identify Potential Surrogacy Relationships in Non-Hodgkin Lymphoma: a Literature-Based Meta-analysis of 108 Phase II and Phase III Studies.

    Science.gov (United States)

    Zhu, Rui; Lu, Dan; Chu, Yu-Waye; Chai, Akiko; Green, Michelle; Zhang, Nancy; Jin, Jin Yan

    2017-05-01

    Correlations between early and late efficacy endpoints were assessed to identify potential surrogate endpoints for overall survival (OS) or progression-free survival (PFS) with clinical trial-level data in three non-Hodgkin lymphoma (NHL) subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). One hundred and eight phase II-III trials (129 trial arms) in DLBCL, FL, and MCL were identified and included in the database. Correlations between efficacy endpoints were analyzed using weighted linear regression and Pearson's coefficient of determination (R 2 ). In newly diagnosed DLBCL, 6-month PFS was strongly correlated with 2-year OS (R 2  = 0.81, 95% confidence interval [CI] 0.51-0.96). Six-month PFS was strongly correlated with 3-year PFS (R 2  = 0.89, 95% CI 0.62-0.96) in FL and was moderately correlated with 2-year OS (R 2  = 0.69, 95% CI 0.40-0.91) in MCL trials. Linear regression determined that a 10% increase in 6-month PFS would yield a 13% ± 1.2% increase in 2-year OS in DLBCL, a 23% ± 1.1% increase in 3-year PFS in FL, or a 6.7% ± 1.0% increase in 2-year OS in MCL. Both 6-month PFS and complete response (CR) rate were moderately correlated with median PFS in FL trials with R 2  = 0.66 (95% CI 0.52-0.98) and R 2  = 0.69 (95% CI 0.22-0.89), respectively. Six-month PFS is a potential surrogate endpoint for 2-year OS in newly diagnosed DLBCL and MCL and for 3-year PFS in FL. Both 6-month PFS and CR rate are potential surrogate endpoints for median PFS in FL patients. Confirmation and validation of these correlations may facilitate early interpretation of NHL trials.

  9. Gating treatment delivery QA based on a surrogate motion analysis

    International Nuclear Information System (INIS)

    Chojnowski, J.; Simpson, E.

    2011-01-01

    Full text: To develop a methodology to estimate intrafractional target position error during a phase-based gated treatment. Westmead Cancer Care Centre is using respiratory correlated phase-based gated beam delivery in the treatment of lung cancer. The gating technique is managed by the Varian Real-time Position Management (RPM) system, version 1.7.5. A 6-dot block is placed on the abdomen of the patient and acts as a surrogate for the target motion. During a treatment session, the motion of the surrogate can be recorded by RPM application. Analysis of the surrogate motion file by in-house developed software allows the intrafractional error of the treatment session to be computed. To validate the computed error, a simple test that involves the introduction of deliberate errors is performed. Errors of up to 1.1 cm are introduced to a metal marker placed on a surrogate using the Varian Breathing Phantom. The moving marker was scanned in prospective mode using a GE Lightspeed 16 CT scanner. Using the CT images, a difference of the marker position with and without introduced errors is compared to the calculated errors based on the surrogate motion. The average and standard deviation of a difference between calculated target position errors and measured introduced artificial errors of the marker position is 0.02 cm and 0.07 cm respectively. Conclusion The calculated target positional error based on surrogate motion analysis provides a quantitative measure of intrafractional target positional errors during treatment. Routine QA for gated treatment using surrogate motion analysis is relatively quick and simple.

  10. Development of a Human Cranial Bone Surrogate for Impact Studies

    International Nuclear Information System (INIS)

    Roberts, Jack C.; Merkle, Andrew C.; Carneal, Catherine M.; Voo, Liming M.; Johannes, Matthew S.; Paulson, Jeff M.; Tankard, Sara; Uy, O. Manny

    2013-01-01

    In order to replicate the fracture behavior of the intact human skull under impact it becomes necessary to develop a material having the mechanical properties of cranial bone. The most important properties to replicate in a surrogate human skull were found to be the fracture toughness and tensile strength of the cranial tables as well as the bending strength of the three-layer (inner table-diplöe-outer table) architecture of the human skull. The materials selected to represent the surrogate cranial tables consisted of two different epoxy resins systems with random milled glass fiber to enhance the strength and stiffness and the materials to represent the surrogate diplöe consisted of three low density foams. Forty-one three-point bending fracture toughness tests were performed on nine material combinations. The materials that best represented the fracture toughness of cranial tables were then selected and formed into tensile samples and tested. These materials were then used with the two surrogate diplöe foam materials to create the three-layer surrogate cranial bone samples for three-point bending tests. Drop tower tests were performed on flat samples created from these materials and the fracture patterns were very similar to the linear fractures in pendulum impacts of intact human skulls, previously reported in the literature. The surrogate cranial tables had the quasi-static fracture toughness and tensile strength of 2.5 MPa√ m and 53 ± 4.9 MPa, respectively, while the same properties of human compact bone were 3.1 ± 1.8 MPa√ m and 68 ± 18 MPa, respectively. The cranial surrogate had a quasi-static bending strength of 68 ± 5.7 MPa, while that of cranial bone was 82 ± 26 MPa. This material/design is currently being used to construct spherical shell samples for drop tower and ballistic tests.

  11. Frequent video game players resist perceptual interference.

    Directory of Open Access Journals (Sweden)

    Aaron V Berard

    Full Text Available Playing certain types of video games for a long time can improve a wide range of mental processes, from visual acuity to cognitive control. Frequent gamers have also displayed generalized improvements in perceptual learning. In the Texture Discrimination Task (TDT, a widely used perceptual learning paradigm, participants report the orientation of a target embedded in a field of lines and demonstrate robust over-night improvement. However, changing the orientation of the background lines midway through TDT training interferes with overnight improvements in overall performance on TDT. Interestingly, prior research has suggested that this effect will not occur if a one-hour break is allowed in between the changes. These results have suggested that after training is over, it may take some time for learning to become stabilized and resilient against interference. Here, we tested whether frequent gamers have faster stabilization of perceptual learning compared to non-gamers and examined the effect of daily video game playing on interference of training of TDT with one background orientation on perceptual learning of TDT with a different background orientation. As a result, we found that non-gamers showed overnight performance improvement only on one background orientation, replicating previous results with the interference in TDT. In contrast, frequent gamers demonstrated overnight improvements in performance with both background orientations, suggesting that they are better able to overcome interference in perceptual learning. This resistance to interference suggests that video game playing not only enhances the amplitude and speed of perceptual learning but also leads to faster and/or more robust stabilization of perceptual learning.

  12. Frequent video game players resist perceptual interference.

    Science.gov (United States)

    Berard, Aaron V; Cain, Matthew S; Watanabe, Takeo; Sasaki, Yuka

    2015-01-01

    Playing certain types of video games for a long time can improve a wide range of mental processes, from visual acuity to cognitive control. Frequent gamers have also displayed generalized improvements in perceptual learning. In the Texture Discrimination Task (TDT), a widely used perceptual learning paradigm, participants report the orientation of a target embedded in a field of lines and demonstrate robust over-night improvement. However, changing the orientation of the background lines midway through TDT training interferes with overnight improvements in overall performance on TDT. Interestingly, prior research has suggested that this effect will not occur if a one-hour break is allowed in between the changes. These results have suggested that after training is over, it may take some time for learning to become stabilized and resilient against interference. Here, we tested whether frequent gamers have faster stabilization of perceptual learning compared to non-gamers and examined the effect of daily video game playing on interference of training of TDT with one background orientation on perceptual learning of TDT with a different background orientation. As a result, we found that non-gamers showed overnight performance improvement only on one background orientation, replicating previous results with the interference in TDT. In contrast, frequent gamers demonstrated overnight improvements in performance with both background orientations, suggesting that they are better able to overcome interference in perceptual learning. This resistance to interference suggests that video game playing not only enhances the amplitude and speed of perceptual learning but also leads to faster and/or more robust stabilization of perceptual learning.

  13. Valuing real options: frequently made errors

    OpenAIRE

    Fernández, Pablo

    2002-01-01

    In this paper we analyze frequently made errors when valuing real options. The best way of doing it is through examples. We start by analyzing Damodaran's proposal to value the option to expand the business of Home Depot. Some of the errors and problems of this and other approaches are: - Assuming that the option is replicable and using Black and Scholes' formula. - The estimation of the option's volatility is arbitrary and has a decisive effect on the option's value. - As there is no riskles...

  14. Uncertainty quantification for accident management using ACE surrogates

    International Nuclear Information System (INIS)

    Varuttamaseni, A.; Lee, J. C.; Youngblood, R. W.

    2012-01-01

    The alternating conditional expectation (ACE) regression method is used to generate RELAP5 surrogates which are then used to determine the distribution of the peak clad temperature (PCT) during the loss of feedwater accident coupled with a subsequent initiation of the feed and bleed (F and B) operation in the Zion-1 nuclear power plant. The construction of the surrogates assumes conditional independence relations among key reactor parameters. The choice of parameters to model is based on the macroscopic balance statements governing the behavior of the reactor. The peak clad temperature is calculated based on the independent variables that are known to be important in determining the success of the F and B operation. The relationship between these independent variables and the plant parameters such as coolant pressure and temperature is represented by surrogates that are constructed based on 45 RELAP5 cases. The time-dependent PCT for different values of F and B parameters is calculated by sampling the independent variables from their probability distributions and propagating the information through two layers of surrogates. The results of our analysis show that the ACE surrogates are able to satisfactorily reproduce the behavior of the plant parameters even though a quasi-static assumption is primarily used in their construction. The PCT is found to be lower in cases where the F and B operation is initiated, compared to the case without F and B, regardless of the F and B parameters used. (authors)

  15. Surrogate for oropharyngeal cancer HPV status in cancer database studies.

    Science.gov (United States)

    Megwalu, Uchechukwu C; Chen, Michelle M; Ma, Yifei; Divi, Vasu

    2017-12-01

    The utility of cancer databases for oropharyngeal cancer studies is limited by lack of information on human papillomavirus (HPV) status. The purpose of this study was to develop a surrogate that can be used to adjust for the effect of HPV status on survival. The study cohort included 6419 patients diagnosed with oropharyngeal squamous cell carcinoma between 2004 and 2012, identified in the National Cancer Database (NCDB). The HPV surrogate score was developed using a logistic regression model predicting HPV-positive status. The HPV surrogate score was predictive of HPV status (area under the curve [AUC] 0.73; accuracy of 70.4%). Similar to HPV-positive tumors, HPV surrogate positive tumors were associated with improved overall survival (OS; hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.59-0.91; P = .005), after adjusting for important covariates. The HPV surrogate score is useful for adjusting for the effect of HPV status on survival in studies utilizing cancer databases. © 2017 Wiley Periodicals, Inc.

  16. Surrogate-Based Optimization of Biogeochemical Transport Models

    Science.gov (United States)

    Prieß, Malte; Slawig, Thomas

    2010-09-01

    First approaches towards a surrogate-based optimization method for a one-dimensional marine biogeochemical model of NPZD type are presented. The model, developed by Oschlies and Garcon [1], simulates the distribution of nitrogen, phytoplankton, zooplankton and detritus in a water column and is driven by ocean circulation data. A key issue is to minimize the misfit between the model output and given observational data. Our aim is to reduce the overall optimization cost avoiding expensive function and derivative evaluations by using a surrogate model replacing the high-fidelity model in focus. This in particular becomes important for more complex three-dimensional models. We analyse a coarsening in the discretization of the model equations as one way to create such a surrogate. Here the numerical stability crucially depends upon the discrete stepsize in time and space and the biochemical terms. We show that for given model parameters the level of grid coarsening can be choosen accordingly yielding a stable and satisfactory surrogate. As one example of a surrogate-based optimization method we present results of the Aggressive Space Mapping technique (developed by John W. Bandler [2, 3]) applied to the optimization of this one-dimensional biogeochemical transport model.

  17. Solubility of actinides and surrogates in nuclear glasses

    International Nuclear Information System (INIS)

    Lopez, Ch.

    2003-01-01

    The nuclear wastes are currently incorporated in borosilicate glass matrices. The resulting glass must be perfectly homogeneous. The work discussed here is a study of actinide (thorium and plutonium) solubility in borosilicate glass, undertaken to assess the extent of actinide solubility in the glass and to understand the mechanisms controlling actinide solubilization. Glass specimens containing; actinide surrogates were used to prepare and optimize the fabrication of radioactive glass samples. These preliminary studies revealed that actinide Surrogates solubility in the glass was enhanced by controlling the processing temperature, the dissolution kinetic of the surrogate precursors, the glass composition and the oxidizing versus reducing conditions. The actinide solubility was investigated in the borosilicate glass. The evolution of thorium solubility in borosilicate glass was determined for temperatures ranging from 1200 deg C to 1400 deg C.Borosilicate glass specimens containing plutonium were fabricated. The experimental result showed that the plutonium solubility limit ranged from 1 to 2.5 wt% PuO 2 at 1200 deg C. A structural approach based on the determination of the local structure around actinides and their surrogates by EXAFS spectroscopy was used to determine their structural role in the glass and the nature of their bonding with the vitreous network. This approach revealed a correlation between the length of these bonds and the solubility of the actinides and their surrogates. (author)

  18. SpEnD: Linked Data SPARQL Endpoints Discovery Using Search Engines

    Science.gov (United States)

    Yumusak, Semih; Dogdu, Erdogan; Kodaz, Halife; Kamilaris, Andreas; Vandenbussche, Pierre-Yves

    In this study, a novel metacrawling method is proposed for discovering and monitoring linked data sources on the Web. We implemented the method in a prototype system, named SPARQL Endpoints Discovery (SpEnD). SpEnD starts with a "search keyword" discovery process for finding relevant keywords for the linked data domain and specifically SPARQL endpoints. Then, these search keywords are utilized to find linked data sources via popular search engines (Google, Bing, Yahoo, Yandex). By using this method, most of the currently listed SPARQL endpoints in existing endpoint repositories, as well as a significant number of new SPARQL endpoints, have been discovered. Finally, we have developed a new SPARQL endpoint crawler (SpEC) for crawling and link analysis.

  19. [Frequently accidents and injury at school].

    Science.gov (United States)

    Gautier Vargas, María; Martínez González, Vanesa

    2011-01-01

    During the time we have been in a private company that provide schools with medical care, we were surprised by the frequent and constant phone calls received to ask for our services. This fact made us take the decision to carry out a survey to find out the accidents and the most frequent injuries. According to the retrospective study we realized throughout two different academic courses in several schools in Cantabria, the 3.23% of the students have any accidents or injuries. We found out children between 11 and 15 have the highest accident rate, being 10.8 % higher when boys (rather than girls) are involved. The most common injuries are contusions 42.85%, followed by sprains 23.45%, being blows the reason in 42% of the cases, and surprisingly acts of aggression in 1%. It was also unexpected to learn that gyms, where children are taught in physical education, have the highest percent on accident rate. All these inquiries lead us to think that age, play and sports are determinant factors in the accidents happened in the school area.

  20. Screening mammography interpretation test: more frequent mistakes

    International Nuclear Information System (INIS)

    Gozzi, Gino; Ganzetti, Alessandra; Martinoli, Carlo; Bacigalupo, Lorenzo; Bodini, Maria; Fiorentino, Carla; Marini, Ugo Paolo; Santini, Dolores

    2005-01-01

    Purpose: To present the mammographic cases most commonly misinterpreted by the participants in the mammography self-test proposed by the Italian Society of Medical Radiology (SIRM) National Congress in Rimini, Italy, 2002, by analysing the findings responsible for errors, suggesting reasons for the errors, and assessing possible inadequacies in the format of the test. Materials and methods: The self-test was performed on the mammograms of 160 cases (32 positive and 128 negative for cancer as confirmed by histology). The mammograms had been taken in the four standard projections and placed on four multi-panel diaphanoscopes, each displaying a set of 40 cases comprising benign and malignant cases in equal proportions. The participants were given pre-printed forms on which to note down their diagnostic judgement. We evaluated a total of 134 fully-completed forms. Among these, we identified the 23 cases most frequently misread by over 15 participants in percentages varying between 40-90%. Of these cases, 10 were malignancies and 13 were negative mammograms. On review, we also assessed the diagnostic contribution of complementary investigations (not available the participants). The 134 fully-completed forms (all of the 40 cases) yielded a total of 5360 responses, 1180 of which (22.01%) were incorrect. Of these 823 out of the 4288 cases expected to be negative (19.2%) were false positive, and 357 out of the 1072 cases expected to be positive (33.3%) were false negative. As regards the 23 most frequently misread cases, these were 10/32 (31.25%) mammograms positive for malignancy and 13/128 (10.15%) negative mammograms or mammograms showing benign disease. The 10 malignancies included 7 infiltrating ductal carcinomas, 1 infiltrating cribriform carcinoma, 1 infiltrating tubular carcinoma, and 1 carcinoma in situ. The 13 cases of benign disease - as established by histology or long-term follow-up - mistaken for malignancies by the test participants were fibrocystic breast

  1. Sensitive endpoints in extended one-generation reproductive toxicity study versus two generation?

    DEFF Research Database (Denmark)

    Christiansen, Sofie

    . The protocol includes assessment of novel endpoints of concern and developmental landmarks such as anogenital distance, nipple retention (both sensitive endpoints for anti-androgenic effects in male offspring) and mammary gland development (sensitive endpoint for oestrogen action) and may also include...... during critical period of development in contrast to the parental generation. Retrospective analysis of available two-generation studies, however, indicate that the assessment included in the study of other endpoints in the male offspring such as histopathology of reproductive organs and semen quality...

  2. The interpolation method based on endpoint coordinate for CT three-dimensional image

    International Nuclear Information System (INIS)

    Suto, Yasuzo; Ueno, Shigeru.

    1997-01-01

    Image interpolation is frequently used to improve slice resolution to reach spatial resolution. Improved quality of reconstructed three-dimensional images can be attained with this technique as a result. Linear interpolation is a well-known and widely used method. The distance-image method, which is a non-linear interpolation technique, is also used to convert CT value images to distance images. This paper describes a newly developed method that makes use of end-point coordinates: CT-value images are initially converted to binary images by thresholding them and then sequences of pixels with 1-value are arranged in vertical or horizontal directions. A sequence of pixels with 1-value is defined as a line segment which has starting and end points. For each pair of adjacent line segments, another line segment was composed by spatial interpolation of the start and end points. Binary slice images are constructed from the composed line segments. Three-dimensional images were reconstructed from clinical X-ray CT images, using three different interpolation methods and their quality and processing speed were evaluated and compared. (author)

  3. Surrogate Model for Recirculation Phase LBLOCA and DET Application

    International Nuclear Information System (INIS)

    Fynan, Douglas A; Ahn, Kwang-Il; Lee, John C.

    2014-01-01

    In the nuclear safety field, response surfaces were used in the first demonstration of the code scaling, applicability, and uncertainty (CSAU) methodology to quantify the uncertainty of the peak clad temperature (PCT) during a large-break loss-of-coolant accident (LBLOCA). Surrogates could have applications in other nuclear safety areas such as dynamic probabilistic safety assessment (PSA). Dynamic PSA attempts to couple the probabilistic nature of failure events, component transitions, and human reliability to deterministic calculations of time-dependent nuclear power plant (NPP) responses usually through the use of thermal-hydraulic (TH) system codes. The overall mathematical complexity of the dynamic PSA architectures with many embedded computational expensive TH code calculations with large input/output data streams have limited realistic studies of NPPs. This paper presents a time-dependent surrogate model for the recirculation phase of a hot leg LBLOCA in the OPR-1000. The surrogate model is developed through the ACE algorithm, a powerful nonparametric regression technique, trained on RELAP5 simulations of the LBLOCA. Benchmarking of the surrogate is presented and an application to a simplified dynamic event tree (DET). A time-dependent surrogate model to predict core subcooling during the recirculation phase of a hot leg LBLOCA in the OPR-1000 has been developed. The surrogate assumed the structure of a general discrete time dynamic model and learned the nonlinear functional form by performing nonparametric regression on RELAP5 simulations with the ACE algorithm. The surrogate model input parameters represent mass and energy flux terms to the RCS that appeared as user supplied or code calculated boundary conditions in the RELAP5 model. The surrogate accurately predicted the TH behavior of the core for a variety of HPSI system performance and containment conditions when compared with RELAP5 simulations. The surrogate was applied in a DET application replacing

  4. Surrogate pregnancy: a guide for Canadian prenatal health care providers

    Science.gov (United States)

    Reilly, Dan R.

    2007-01-01

    Providing health care for a woman with a surrogate pregnancy involves unique challenges. Although the ethical debate surrounding surrogacy continues, Canada has banned commercial, but not altruistic, surrogacy. In the event of a custody dispute between a surrogate mother and the individual(s) intending to parent the child, it is unclear how Canadian courts would rule. The prenatal health care provider must take extra care to protect the autonomy and privacy rights of the surrogate. There is limited evidence about the medical and psychological risks ofsurrogacy. Whether theoretical concerns about these risks are clinically relevant remains unknown. In the face of these uncertainties, the prenatal health care provider should have a low threshold for seeking obstetrical, social work, ethical and legal support. PMID:17296962

  5. Surrogate pregnancy: a guide for Canadian prenatal health care providers.

    Science.gov (United States)

    Reilly, Dan R

    2007-02-13

    Providing health care for a woman with a surrogate pregnancy involves unique challenges. Although the ethical debate surrounding surrogacy continues, Canada has banned commercial, but not altruistic, surrogacy. In the event of a custody dispute between a surrogate mother and the individual(s) intending to parent the child, it is unclear how Canadian courts would rule. The prenatal health care provider must take extra care to protect the autonomy and privacy rights of the surrogate. There is limited evidence about the medical and psychological risks of surrogacy. Whether theoretical concerns about these risks are clinically relevant remains unknown. In the face of these uncertainties, the prenatal health care provider should have a low threshold for seeking obstetrical, social work, ethical and legal support.

  6. Bladder injuries frequently missed in polytrauma patients

    Directory of Open Access Journals (Sweden)

    Tanweer Karim

    2010-05-01

    Full Text Available Tanweer Karim, Margaret Topno, Vinod Sharma, Raymond Picardo, Ankur HastirSurgery, MGM Medical College, Kamothe, Navi Mumbai, IndiaAbstract: Bladder injuries are very common in patients who have had road traffic accidents. The method of diagnosis and management of such injuries is well established and accepted. However, trauma to the bladder can be associated with other life-threatening injuries which are frequently missed, and often diagnosed during laparotomy for other reasons. The aim of this study was to diagnose bladder injury in polytrauma patients as early as possible, taking into consideration the fact that these patients are hemodynamically unstable and require rapid evaluation and management. In order to achieve our objective, we used bedside sonography with retrograde instillation of normal saline to diagnose bladder injury in addition to use of the conventional retrograde cystogram.Keywords: bladder injury, bladder rupture, retrograde cystogram

  7. Legal Briefing: Adult Orphans and the Unbefriended: Making Medical Decisions for Unrepresented Patients without Surrogates.

    Science.gov (United States)

    Pope, Thaddeus Mason

    2015-01-01

    This issue's "Legal Briefing" column covers recent legal developments involving medical decision making for incapacitated patients who have no available legally authorized surrogate decision maker. These individuals are frequently referred to either as "adult orphans" or as "unbefriended," "isolated," or "unrepresented" patients. The challenges involved in obtaining consent for medical treatment on behalf of these individuals have been the subject of major policy reports. Indeed, caring for the unbefriended has even been described as the "single greatest category of problems" encountered in bioethics consultation. In 2012, JCE published a comprehensive review of the available mechanisms by which to make medical decisions for the unbefriended. The purpose of this "Legal Briefing" is to update the 2012 study. Accordingly, this "Legal Briefing" collects and describes significant legal developments from only the past three years. My basic assessment has not changed. "Existing mechanisms to address the issue of decision making for the unbefriended are scant and not uniform." Most facilities are "muddling through on an ad hoc basis." But the situation is not wholly negative. There have been a number of promising new initiatives. I group these developments into the following seven categories: 1. Increased Attention and Discussion 2. Prevention through Better Advance Care Planning 3. Prevention through Expanded Default Surrogate Lists 4. Statutorily Authorized Intramural Mechanisms 5. California Litigation Challenging the Team Approach 6. Public Guardianship 7. Improving Existing Guardianship Processes. Copyright 2015 The Journal of Clinical Ethics. All rights reserved.

  8. Limitations of habitats as biodiversity surrogates for conservation planning in estuaries.

    Science.gov (United States)

    Shokri, Mohammad Reza; Gladstone, William

    2013-04-01

    Increasing pressures on global biodiversity and lack of data on the number and abundance of species have motivated conservation planners and researchers to use more readily available information as proxies or surrogates for biodiversity. "Habitat" is one of the most frequently used surrogates but its assumed value in marine conservation planning is not often tested. The present study developed and tested three alternative habitat classification schemes of increasing complexity for a large estuary in south-east Australia and tested their effectiveness in predicting spatial variation in macroinvertebrate biodiversity and selecting estuarine protected areas to represent species. The three habitat classification schemes were: (1) broad-scale habitats (e.g., mangroves and seagrass), (2) subdivision of each broad-scale habitat by a suite of environmental variables that varied significantly throughout the estuary, and (3) subdivision of each broad-scale habitat by the subset of environmental variables that best explained spatial variation in macroinvertebrate biodiversity. Macroinvertebrate assemblages differed significantly among the habitats in each classification scheme. For each classification scheme, habitat richness was significantly correlated with species richness, total density of macroinvertebrates, assemblage dissimilarity, and summed irreplaceability. However, in a reserve selection process designed to represent examples of each habitat, no habitat classification scheme represented species significantly better than a random selection of sites. Habitat classification schemes may represent variation in estuarine biodiversity; however, the results of this study suggest they are inefficient in designing representative networks of estuarine protected areas.

  9. Frequent job change and associated health.

    Science.gov (United States)

    Metcalfe, Chris; Davey Smith, George; Sterne, Jonathan A C; Heslop, Pauline; Macleod, John; Hart, Carole

    2003-01-01

    The contemporary labour market is widely regarded as having become more "flexible". It is proposed that such flexibility is a characteristic of employment histories which will have effects on psychosocial status, health-related behaviour, and physical health. Recent increases in flexibility are unlikely to have accumulated over sufficient portions of individual employment histories for any effect on health to be apparent, but a "preview" of these effects may be gained from study of older cohorts. This cross-sectional study is based on data collected in the early 1970s from 5399 men and 945 women in paid work, recruited from 27 workplaces in the west of Scotland. A flexible employment history was defined as one encompassing a large number of changes between jobs. Perceived psychological stress, health behaviour (cigarette smoking, alcohol consumption, physical exercise), physiology (diastolic blood pressure, body mass index, forced expiratory volume, plasma cholesterol concentration) and current health (angina, myocardial ischaemia) were assessed. Those individuals who reported having experienced frequent job change were more likely to smoke, consume greater amounts of alcohol, and perhaps to exercise less. Similar findings were observed in both males and females, and for different age and socio-economic groups. We found no suggestion that this association was due to higher levels of psychosocial stress, and the expected consequences for health were not observed. Interpretation of these findings is not straightforward due to an uncertain direction of causation, and a possible selection bias. However, the observed relationship between frequent job changing and a higher incidence of health risk behaviours, in the absence of a relationship with poorer health, invites further research.

  10. Frequent activation of EGFR in advanced chordomas

    Directory of Open Access Journals (Sweden)

    Dewaele Barbara

    2011-07-01

    Full Text Available Abstract Background Chordomas are rare neoplasms, arising from notochordal remnants in the midline skeletal axis, for which the current treatment is limited to surgery and radiotherapy. Recent reports suggest that receptor tyrosine kinases (RTK might be essential for the survival or proliferation of chordoma cells, providing a rationale for RTK targeted therapy. Nevertheless, the reported data are conflicting, most likely due to the assorted tumor specimens used for the studies and the heterogeneous methodological approaches. In the present study, we performed a comprehensive characterization of this rare entity using a wide range of assays in search for relevant therapeutic targets. Methods Histopathological features of 42 chordoma specimens, 21 primary and 21 advanced, were assessed by immunohistochemistry and fluorescent in situ hybridization (FISH using PDGFRB, CSF1R, and EGFR probes. Twenty-two of these cases, for which frozen material was available (nine primary and 13 advanced tumors, were selectively analyzed using the whole-genome 4.3 K TK-CGH-array, phospho-kinase antibody array or Western immunoblotting. The study was supplemented by direct sequencing of KIT, PDGFRB, CSF1R and EGFR. Results We demonstrated that EGFR is frequently and the most significantly activated RTK in chordomas. Furthermore, concurrent to EGFR activation, the tumors commonly reveal co-activation of alternative RTK. The consistent activation of AKT, the frequent loss of the tumor suppressor PTEN allele, the recurrent activation of upstream RTK and of downstream effectors like p70S6K and mTOR, all indicate the PI3K/AKT pathway as an important mediator of transformation in chordomas. Conclusions Given the complexity of the signaling in chordomas, combined treatment regimens targeting multiple RTK and downstream effectors are likely to be the most effective in these tumors. Personalized therapy with careful selection of the patients, based on the molecular profile of

  11. Frequent Exertion and Frequent Standing at Work, by Industry and Occupation Group - United States, 2015.

    Science.gov (United States)

    Shockey, Taylor M; Luckhaupt, Sara E; Groenewold, Matthew R; Lu, Ming-Lun

    2018-01-12

    Repeated exposure to occupational ergonomic hazards, such as frequent exertion (repetitive bending or twisting) and frequent standing, can lead to injuries, most commonly musculoskeletal disorders (1). Work-related musculoskeletal disorders have been estimated to cost the United States approximately $2.6 billion in annual direct and indirect costs (2). A recent literature review provided evidence that prolonged standing at work also leads to adverse health outcomes, such as back pain, physical fatigue, and muscle pain (3). To determine which industry and occupation groups currently have the highest prevalence rates of frequent exertion at work and frequent standing at work, CDC analyzed data from the 2015 National Health Interview Survey (NHIS) Occupational Health Supplement (OHS) regarding currently employed adults in the United States. By industry, the highest prevalence of both frequent exertion and frequent standing at work was among those in the agriculture, forestry, fishing, and hunting industry group (70.9%); by occupation, the highest prevalence was among those in the construction and extraction occupation group (76.9%). Large differences among industry and occupation groups were found with regard to these ergonomic hazards, suggesting a need for targeted interventions designed to reduce workplace exposure.

  12. Disinfection byproduct regulatory compliance surrogates and bromide-associated risk.

    Science.gov (United States)

    Kolb, Chelsea; Francis, Royce A; VanBriesen, Jeanne M

    2017-08-01

    Natural and anthropogenic factors can alter bromide concentrations in drinking water sources. Increasing source water bromide concentrations increases the formation and alters the speciation of disinfection byproducts (DBPs) formed during drinking water treatment. Brominated DBPs are more toxic than their chlorinated analogs, and thus have a greater impact on human health. However, DBPs are regulated based on the mass sum of DBPs within a given class (e.g., trihalomethanes and haloacetic acids), not based on species-specific risk or extent of bromine incorporation. The regulated surrogate measures are intended to protect against not only the species they directly represent, but also against unregulated DBPs that are not routinely measured. Surrogates that do not incorporate effects of increasing bromide may not adequately capture human health risk associated with drinking water when source water bromide is elevated. The present study analyzes trihalomethanes (THMs), measured as TTHM, with varying source water bromide concentrations, and assesses its correlation with brominated THM, TTHM risk and species-specific THM concentrations and associated risk. Alternative potential surrogates are evaluated to assess their ability to capture THM risk under different source water bromide concentration conditions. The results of the present study indicate that TTHM does not adequately capture risk of the regulated species when source water bromide concentrations are elevated, and thus would also likely be an inadequate surrogate for many unregulated brominated species. Alternative surrogate measures, including THM 3 and the bromodichloromethane concentration, are more robust surrogates for species-specific THM risk at varying source water bromide concentrations. Copyright © 2017. Published by Elsevier B.V.

  13. Fast Prediction and Evaluation of Gravitational Waveforms Using Surrogate Models

    Science.gov (United States)

    Field, Scott E.; Galley, Chad R.; Hesthaven, Jan S.; Kaye, Jason; Tiglio, Manuel

    2014-07-01

    We propose a solution to the problem of quickly and accurately predicting gravitational waveforms within any given physical model. The method is relevant for both real-time applications and more traditional scenarios where the generation of waveforms using standard methods can be prohibitively expensive. Our approach is based on three offline steps resulting in an accurate reduced order model in both parameter and physical dimensions that can be used as a surrogate for the true or fiducial waveform family. First, a set of m parameter values is determined using a greedy algorithm from which a reduced basis representation is constructed. Second, these m parameters induce the selection of m time values for interpolating a waveform time series using an empirical interpolant that is built for the fiducial waveform family. Third, a fit in the parameter dimension is performed for the waveform's value at each of these m times. The cost of predicting L waveform time samples for a generic parameter choice is of order O(mL+mcfit) online operations, where cfit denotes the fitting function operation count and, typically, m ≪L. The result is a compact, computationally efficient, and accurate surrogate model that retains the original physics of the fiducial waveform family while also being fast to evaluate. We generate accurate surrogate models for effective-one-body waveforms of nonspinning binary black hole coalescences with durations as long as 105M, mass ratios from 1 to 10, and for multiple spherical harmonic modes. We find that these surrogates are more than 3 orders of magnitude faster to evaluate as compared to the cost of generating effective-one-body waveforms in standard ways. Surrogate model building for other waveform families and models follows the same steps and has the same low computational online scaling cost. For expensive numerical simulations of binary black hole coalescences, we thus anticipate extremely large speedups in generating new waveforms with a

  14. Fast Prediction and Evaluation of Gravitational Waveforms Using Surrogate Models

    Directory of Open Access Journals (Sweden)

    Scott E. Field

    2014-07-01

    Full Text Available We propose a solution to the problem of quickly and accurately predicting gravitational waveforms within any given physical model. The method is relevant for both real-time applications and more traditional scenarios where the generation of waveforms using standard methods can be prohibitively expensive. Our approach is based on three offline steps resulting in an accurate reduced order model in both parameter and physical dimensions that can be used as a surrogate for the true or fiducial waveform family. First, a set of m parameter values is determined using a greedy algorithm from which a reduced basis representation is constructed. Second, these m parameters induce the selection of m time values for interpolating a waveform time series using an empirical interpolant that is built for the fiducial waveform family. Third, a fit in the parameter dimension is performed for the waveform’s value at each of these m times. The cost of predicting L waveform time samples for a generic parameter choice is of order O(mL+mc_{fit} online operations, where c_{fit} denotes the fitting function operation count and, typically, m≪L. The result is a compact, computationally efficient, and accurate surrogate model that retains the original physics of the fiducial waveform family while also being fast to evaluate. We generate accurate surrogate models for effective-one-body waveforms of nonspinning binary black hole coalescences with durations as long as 10^{5}M, mass ratios from 1 to 10, and for multiple spherical harmonic modes. We find that these surrogates are more than 3 orders of magnitude faster to evaluate as compared to the cost of generating effective-one-body waveforms in standard ways. Surrogate model building for other waveform families and models follows the same steps and has the same low computational online scaling cost. For expensive numerical simulations of binary black hole coalescences, we thus anticipate extremely large speedups in

  15. The social context for surrogates' motivations and satisfaction.

    Science.gov (United States)

    Berend, Zsuzsa

    2014-10-01

    This Commentary takes up two of the main findings by Imrie and Jadva's study, namely surrogates' satisfaction with the post-surrogacy contact with intended parents and their motivation for surrogacy. It argues that the findings are in keeping with other qualitative research on surrogacy and that this similarity is not the result of the similarity of surrogates' psychological makeup. The Commentary highlights the centrality of social meanings and definitions, and following Howard Becker, insists on taking into account the collective doings that inform and shape individual feelings and behaviour. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  16. Food Safety: Recommendations for Determining Doneness in Consumer Egg Dish Recipes and Measurement of Endpoint Temperatures When Recipes Are Followed

    Directory of Open Access Journals (Sweden)

    Sandria Godwin

    2016-06-01

    Full Text Available Many consumers do not follow recommended food safety practices for cooking egg dishes, such as pies, quiches, and casseroles, potentially leading to foodborne illnesses such as Salmonellosis. The United States Department of Agriculture (USDA recommends cooking egg mixtures until the center reaches 71 °C (160 °F. The objectives of this study were to determine what endpoint temperature information consumers receive from egg dish recipes, and if recipes would lead to safe temperatures when followed. Egg dish recipes (n = 226 from 65 websites, 50 cookbooks, and nine magazine titles (multiple issues of each were analyzed. Time was the most frequently used indicator, given in 92% of the recipes, with 15% using only time. Other indicators included: set (89, browned (76, clean toothpick/knife (60, puffed (27, and jiggled (13. Only two recipes indicated final endpoint temperatures. Three recipes (a pie, a quiche, and an egg casserole were chosen and prepared in triplicate to see if they would reach recommended temperatures. The pie and quiche were still liquid at 71 °C, and were well over the recommended temperature when cooked according to instructions, but the egg casserole was not consistently above 71 °C, when the recipe instructions indicated it was done and the center was light brown and “jiggled” This research indicates that consumers are not receiving information on endpoint temperatures in egg recipes, but the likelihood of foodborne illness is low since most dishes probably be cooked past the recommended temperature before the consumer considers them done unless there are many inclusions that may absorb liquid and reduce the appearance of liquid in the dish.

  17. Food Safety: Recommendations for Determining Doneness in Consumer Egg Dish Recipes and Measurement of Endpoint Temperatures When Recipes Are Followed

    Science.gov (United States)

    Godwin, Sandria; Maughan, Curtis; Chambers, Edgar

    2016-01-01

    Many consumers do not follow recommended food safety practices for cooking egg dishes, such as pies, quiches, and casseroles, potentially leading to foodborne illnesses such as Salmonellosis. The United States Department of Agriculture (USDA) recommends cooking egg mixtures until the center reaches 71 °C (160 °F). The objectives of this study were to determine what endpoint temperature information consumers receive from egg dish recipes, and if recipes would lead to safe temperatures when followed. Egg dish recipes (n = 226) from 65 websites, 50 cookbooks, and nine magazine titles (multiple issues of each) were analyzed. Time was the most frequently used indicator, given in 92% of the recipes, with 15% using only time. Other indicators included: set (89), browned (76), clean toothpick/knife (60), puffed (27), and jiggled (13). Only two recipes indicated final endpoint temperatures. Three recipes (a pie, a quiche, and an egg casserole) were chosen and prepared in triplicate to see if they would reach recommended temperatures. The pie and quiche were still liquid at 71 °C, and were well over the recommended temperature when cooked according to instructions, but the egg casserole was not consistently above 71 °C, when the recipe instructions indicated it was done and the center was light brown and “jiggled” This research indicates that consumers are not receiving information on endpoint temperatures in egg recipes, but the likelihood of foodborne illness is low since most dishes probably be cooked past the recommended temperature before the consumer considers them done unless there are many inclusions that may absorb liquid and reduce the appearance of liquid in the dish. PMID:28231140

  18. Food Safety: Recommendations for Determining Doneness in Consumer Egg Dish Recipes and Measurement of Endpoint Temperatures When Recipes Are Followed.

    Science.gov (United States)

    Godwin, Sandria; Maughan, Curtis; Chambers, Edgar

    2016-06-23

    Many consumers do not follow recommended food safety practices for cooking egg dishes, such as pies, quiches, and casseroles, potentially leading to foodborne illnesses such as Salmonellosis. The United States Department of Agriculture (USDA) recommends cooking egg mixtures until the center reaches 71 °C (160 °F). The objectives of this study were to determine what endpoint temperature information consumers receive from egg dish recipes, and if recipes would lead to safe temperatures when followed. Egg dish recipes ( n = 226) from 65 websites, 50 cookbooks, and nine magazine titles (multiple issues of each) were analyzed. Time was the most frequently used indicator, given in 92% of the recipes, with 15% using only time. Other indicators included: set (89), browned (76), clean toothpick/knife (60), puffed (27), and jiggled (13). Only two recipes indicated final endpoint temperatures. Three recipes (a pie, a quiche, and an egg casserole) were chosen and prepared in triplicate to see if they would reach recommended temperatures. The pie and quiche were still liquid at 71 °C, and were well over the recommended temperature when cooked according to instructions, but the egg casserole was not consistently above 71 °C, when the recipe instructions indicated it was done and the center was light brown and "jiggled" This research indicates that consumers are not receiving information on endpoint temperatures in egg recipes, but the likelihood of foodborne illness is low since most dishes probably be cooked past the recommended temperature before the consumer considers them done unless there are many inclusions that may absorb liquid and reduce the appearance of liquid in the dish.

  19. Frequently asked questions in hypoxia research

    Directory of Open Access Journals (Sweden)

    Wenger RH

    2015-09-01

    Full Text Available Roland H Wenger,1,2 Vartan Kurtcuoglu,1,2 Carsten C Scholz,1,2 Hugo H Marti,3 David Hoogewijs1,2,4 1Institute of Physiology and Zurich Center for Human Physiology (ZIHP, University of Zurich, 2National Center of Competence in Research “Kidney.CH”, Zurich, Switzerland; 3Institute of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, 4Institute of Physiology, University of Duisburg-Essen, Essen, Germany Abstract: “What is the O2 concentration in a normoxic cell culture incubator?” This and other frequently asked questions in hypoxia research will be answered in this review. Our intention is to give a simple introduction to the physics of gases that would be helpful for newcomers to the field of hypoxia research. We will provide background knowledge about questions often asked, but without straightforward answers. What is O2 concentration, and what is O2 partial pressure? What is normoxia, and what is hypoxia? How much O2 is experienced by a cell residing in a culture dish in vitro vs in a tissue in vivo? By the way, the O2 concentration in a normoxic incubator is 18.6%, rather than 20.9% or 20%, as commonly stated in research publications. And this is strictly only valid for incubators at sea level. Keywords: gas laws, hypoxia-inducible factor, Krogh tissue cylinder, oxygen diffusion, partial pressure, tissue oxygen levels

  20. Right-handed currents at B→ K l+l− kinematic endpoint

    Indian Academy of Sciences (India)

    2017-10-09

    Oct 9, 2017 ... The recent LHCb measured values of these observables are used to conclude an evidence of right-handed currents at the kinematic endpoint of this decay mode. As the conclusion is drawn at the maximum dilepton invariant mass square ( q 2 ) kinematic endpoint, it relies only on heavy quark symmetries ...

  1. Restoration for the future: Setting endpoints and targets and selecting indicators of progress and success

    Science.gov (United States)

    Daniel C. Dey; Callie Jo Schweitzer; John M. Kabrick

    2014-01-01

    Setting endpoints and targets in forest restoration is a complicated task that is best accomplished in cooperative partnerships that account for the ecology of the system, production of desired ecosystem goods and services, economics and well-being of society, and future environments. Clearly written and quantitative endpoints and intermediary targets need to be...

  2. Restoration for the future: endpoints, targets, and indicators of progress and success

    Science.gov (United States)

    Daniel C. Dey; Callie Jo. Schweitzer

    2014-01-01

    Setting endpoints and targets in forest restoration is a complicated task that is best accomplished in cooperative partnerships that account for the ecology of the system, production of desired ecosystem goods and services, economics and well-being of society, and future environments. Clearly described and quantitative endpoints and intermediary targets are needed to...

  3. OPERA models for predicting physicochemical properties and environmental fate endpoints.

    Science.gov (United States)

    Mansouri, Kamel; Grulke, Chris M; Judson, Richard S; Williams, Antony J

    2018-03-08

    The collection of chemical structure information and associated experimental data for quantitative structure-activity/property relationship (QSAR/QSPR) modeling is facilitated by an increasing number of public databases containing large amounts of useful data. However, the performance of QSAR models highly depends on the quality of the data and modeling methodology used. This study aims to develop robust QSAR/QSPR models for chemical properties of environmental interest that can be used for regulatory purposes. This study primarily uses data from the publicly available PHYSPROP database consisting of a set of 13 common physicochemical and environmental fate properties. These datasets have undergone extensive curation using an automated workflow to select only high-quality data, and the chemical structures were standardized prior to calculation of the molecular descriptors. The modeling procedure was developed based on the five Organization for Economic Cooperation and Development (OECD) principles for QSAR models. A weighted k-nearest neighbor approach was adopted using a minimum number of required descriptors calculated using PaDEL, an open-source software. The genetic algorithms selected only the most pertinent and mechanistically interpretable descriptors (2-15, with an average of 11 descriptors). The sizes of the modeled datasets varied from 150 chemicals for biodegradability half-life to 14,050 chemicals for logP, with an average of 3222 chemicals across all endpoints. The optimal models were built on randomly selected training sets (75%) and validated using fivefold cross-validation (CV) and test sets (25%). The CV Q 2 of the models varied from 0.72 to 0.95, with an average of 0.86 and an R 2 test value from 0.71 to 0.96, with an average of 0.82. Modeling and performance details are described in QSAR model reporting format and were validated by the European Commission's Joint Research Center to be OECD compliant. All models are freely available as an open

  4. Defining the end-point of mastication: A conceptual model.

    Science.gov (United States)

    Gray-Stuart, Eli M; Jones, Jim R; Bronlund, John E

    2017-10-01

    properties define the end-point texture and enduring sensory perception of the food. © 2017 Wiley Periodicals, Inc.

  5. Mapping surrogate gasoline compositions into RON/MON space

    NARCIS (Netherlands)

    Morgan, N.; Smallbone, A.; Bhave, A.; Kraft, M.; Cracknell, R.; Kalghatgi, G.T.

    2010-01-01

    In this paper, new experimentally determined octane numbers (RON and MON) of blends of a tri-component surrogate consisting of toluene, n-heptane, i-octane (called toluene reference fuel TRF) arranged in an augmented simplex design are used to derive a simple response surface model for the octane

  6. Frequency response as a surrogate eigenvalue problem in topology optimization

    DEFF Research Database (Denmark)

    Andreassen, Erik; Ferrari, Federico; Sigmund, Ole

    2018-01-01

    This article discusses the use of frequency response surrogates for eigenvalue optimization problems in topology optimization that may be used to avoid solving the eigenvalue problem. The motivation is to avoid complications that arise from multiple eigenvalues and the computational complexity as...

  7. Development of Cranial Bone Surrogate Structures Using Stereolithographic Additive Manufacturing

    Science.gov (United States)

    2017-09-29

    Additive Manufacturing by Jared M Gardner and Thomas A Plaisted Approved for public release; distribution is unlimited...Laboratory Development of Cranial Bone Surrogate Structures Using Stereolithographic Additive Manufacturing by Thomas A Plaisted Weapons...Structures Using Stereolithographic Additive Manufacturing 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Jared

  8. Mechanical Properties of K Basin Sludge Constituents and Their Surrogates

    International Nuclear Information System (INIS)

    Delegard, Calvin H.; Schmidt, Andrew J.; Chenault, Jeffrey W.

    2004-01-01

    A survey of the technical literature was performed to summarize the mechanical properties of inorganic components in K Basins sludge. The components included gibbsite, ferrihydrite, lepidocrocite and goethite, hematite, quartz, anorthite, calcite, basalt, Zircaloy, aluminum, and, in particular, irradiated uranium metal and uranium dioxide. Review of the technical literature showed that information on the hardness of uranium metal at irradiation exposures similar to those experienced by the N Reactor fuel present in the K Basins (typically up to 3000 MWd/t) were not available. Measurements therefore were performed to determine the hardness of coupons taken from three irradiated N Reactor uranium metal fuel elements taken from K Basins. Hardness values averaged 30 ± 8 Rockwell C units, similar to values previously reported for uranium irradiated to ∼1200 MWd/t. The physical properties of candidate uranium metal and uranium dioxide surrogates were gathered and compared. Surrogates having properties closest to those of irradiated uranium metal appear to be alloys of tungsten. The surrogate for uranium dioxide, present both as particles and agglomerates in actual K Basin sludge, likely requires two materials. Cerium oxide, CeO2, was identified as a surrogate of the smaller UO2 particles while steel grit was identified for the UO2 agglomerates

  9. Predicting freshwater habitat integrity using land-use surrogates

    African Journals Online (AJOL)

    2007-04-02

    Apr 2, 2007 ... Quantification of potential surrogates of freshwater habitat integrity. We chose a series of land-use variables that might be suitable predictors for assessing freshwater habitat integrity from the land cover map (CSIR 2005) and added separate GIS surfaces for human population density and the distribution of ...

  10. Summary of Remediated Nitrate Salt Surrogate Formulation and Testing

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Geoffrey Wayne [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Leonard, Philip [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Hartline, Ernest Leon [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Tian, Hongzhao [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-05-05

    High Explosives Science and Technology (M-7) completed all required formulation and testing of Remediated Nitrate Salt (RNS) surrogates on April 27, 2016 as specified in PLAN-TA9-2443 Rev B, "Remediated Nitrate Salt (RNS) Surrogate Formulation and Testing Standard Procedure", released February 16, 2016. This report summarizes the results of the work and also includes additional documentation required in that test plan. All formulation and testing was carried out according to PLAN-TA9-2443 Rev B. The work was carried out in three rounds, with the full matrix of samples formulated and tested in each round. Results from the first round of formulation and testing were documented in memorandum M7-J6-6042, " Results from First Round of Remediated Nitrate Salt Surrogate Formulation and Testing." Results from the second round of formulation and testing were documented in M7-16-6053 , "Results from the Second Round of Remediated Nitrate Salt Surrogate Formulation and Testing." Initial results from the third round were documented in M7-16-6057, "Initial Results from the Third Round of Remediated Nitrate Salt Formulation and Testing."

  11. Surrogate motherhood in illness that does not cause infertility ...

    African Journals Online (AJOL)

    The threshold requirement for surrogate motherhood requires that a commissioning parent or parents are permanently unable to give birth to a child. The question has arisen of a commissioning mother who suffers from a permanent illness that does not cause infertility but that renders pregnancy a significant health risk to ...

  12. Endpoints and cutpoints in head and neck oncology trials: methodical background, challenges, current practice and perspectives.

    Science.gov (United States)

    Hezel, Marcus; von Usslar, Kathrin; Kurzweg, Thiemo; Lörincz, Balazs B; Knecht, Rainald

    2016-04-01

    This article reviews the methodical and statistical basics of designing a trial, with a special focus on the process of defining and choosing endpoints and cutpoints as the foundations of clinical research, and ultimately that of evidence-based medicine. There has been a significant progress in the treatment of head and neck cancer in the past few decades. Currently available treatment options can have a variety of different goals, depending e.g. on tumor stage, among other factors. The outcome of a specific treatment in clinical trials is measured using endpoints. Besides classical endpoints, such as overall survival or organ preservation, other endpoints like quality of life are becoming increasingly important in designing and conducting a trial. The present work is based on electronic research and focuses on the solid methodical and statistical basics of a clinical trial, on the structure of study designs and on the presentation of various endpoints.

  13. Recent Progress in the Development of Diesel Surrogate Fuels

    Energy Technology Data Exchange (ETDEWEB)

    Pitz, W J; Mueller, C J

    2009-12-09

    There has been much recent progress in the area of surrogate fuels for diesel. In the last few years, experiments and modeling have been performed on higher molecular weight components of relevance to diesel fuel such as n-hexadecane (n-cetane) and 2,2,4,4,6,8,8-heptamethylnonane (iso-cetane). Chemical kinetic models have been developed for all the n-alkanes up to 16 carbon atoms. Also, there has been much experimental and modeling work on lower molecular weight surrogate components such as n-decane and n-dodecane that are most relevant to jet fuel surrogates, but are also relevant to diesel surrogates where simulation of the full boiling point range is desired. For two-ring compounds, experimental work on decalin and tetralin recently has been published. For multi-component surrogate fuel mixtures, recent work on modeling of these mixtures and comparisons to real diesel fuel is reviewed. Detailed chemical kinetic models for surrogate fuels are very large in size. Significant progress also has been made in improving the mechanism reduction tools that are needed to make these large models practicable in multi-dimensional reacting flow simulations of diesel combustion. Nevertheless, major research gaps remain. In the case of iso-alkanes, there are experiments and modeling work on only one of relevance to diesel: iso-cetane. Also, the iso-alkanes in diesel are lightly branched and no detailed chemical kinetic models or experimental investigations are available for such compounds. More components are needed to fill out the iso-alkane boiling point range. For the aromatic class of compounds, there has been no new work for compounds in the boiling point range of diesel. Most of the new work has been on alkyl aromatics that are of the range C7 to C8, below the C10 to C20 range that is needed. For the chemical class of cycloalkanes, experiments and modeling on higher molecular weight components are warranted. Finally for multi-component surrogates needed to treat real

  14. Hall et al., 2016 Artificial Turf Surrogate Surface Methods Paper Data File

    Data.gov (United States)

    U.S. Environmental Protection Agency — Mercury dry deposition data quantified via static water surrogate surface (SWSS) and artificial turf surrogate surface (ATSS) collectors. This dataset is associated...

  15. Multi-model polynomial chaos surrogate dictionary for Bayesian inference in elasticity problems

    KAUST Repository

    Contreras, Andres A.; Le Maî tre, Olivier P.; Aquino, Wilkins; Knio, Omar

    2016-01-01

    of stiff inclusions embedded in a soft matrix, mimicking tumors in soft tissues. We rely on a polynomial chaos (PC) surrogate to accelerate the inference process. The PC surrogate predicts the dependence of the displacements field with the random elastic

  16. Considerations in choosing a primary endpoint that measures durability of virological suppression in an antiretroviral trial.

    Science.gov (United States)

    Gilbert, P B; Ribaudo, H J; Greenberg, L; Yu, G; Bosch, R J; Tierney, C; Kuritzkes, D R

    2000-09-08

    At present, many clinical trials of anti-HIV-1 therapies compare treatments by a primary endpoint that measures the durability of suppression of HIV-1 replication. Several durability endpoints are compared. Endpoints are compared by their implicit assumptions regarding surrogacy for clinical outcomes, sample size requirements, and accommodations for inter-patient differences in baseline plasma HIV-1-RNA levels and in initial treatment response. Virological failure is defined by the non-suppression of virus levels at a prespecified follow-up time T(early virological failure), or by relapse. A binary virological failure endpoint is compared with three time-to-virological failure endpoints: time from (i) randomization that assigns early failures a failure time of T weeks; (ii) randomization that extends the early failure time T for slowly responding subjects; and (iii) virological response that assigns non-responders a failure time of 0 weeks. Endpoint differences are illustrated with Agouron's trial 511. In comparing high with low-dose nelfinavir (NFV) regimens in Agouron 511, the difference in Kaplan-Meier estimates of the proportion not failing by 24 weeks is 16.7% (P = 0.048), 6.5% (P = 0.29) and 22.9% (P = 0.0030) for endpoints (i), (ii) and (iii), respectively. The results differ because NFV suppresses virus more quickly at the higher dose, and the endpoints weigh this treatment difference differently. This illustrates that careful consideration needs to be given to choosing a primary endpoint that will detect treatment differences of interest. A time from randomization endpoint is usually recommended because of its advantages in flexibility and sample size, especially at interim analyses, and for its interpretation for patient management.

  17. A data-driven weighting scheme for multivariate phenotypic endpoints recapitulates zebrafish developmental cascades

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Guozhu, E-mail: gzhang6@ncsu.edu [Bioinformatics Research Center, North Carolina State University, Raleigh, NC (United States); Roell, Kyle R., E-mail: krroell@ncsu.edu [Bioinformatics Research Center, North Carolina State University, Raleigh, NC (United States); Truong, Lisa, E-mail: lisa.truong@oregonstate.edu [Department of Environmental and Molecular Toxicology, Sinnhuber Aquatic Research Laboratory, Oregon State University, Corvallis, OR (United States); Tanguay, Robert L., E-mail: robert.tanguay@oregonstate.edu [Department of Environmental and Molecular Toxicology, Sinnhuber Aquatic Research Laboratory, Oregon State University, Corvallis, OR (United States); Reif, David M., E-mail: dmreif@ncsu.edu [Bioinformatics Research Center, North Carolina State University, Raleigh, NC (United States); Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, NC (United States)

    2017-01-01

    Zebrafish have become a key alternative model for studying health effects of environmental stressors, partly due to their genetic similarity to humans, fast generation time, and the efficiency of generating high-dimensional systematic data. Studies aiming to characterize adverse health effects in zebrafish typically include several phenotypic measurements (endpoints). While there is a solid biomedical basis for capturing a comprehensive set of endpoints, making summary judgments regarding health effects requires thoughtful integration across endpoints. Here, we introduce a Bayesian method to quantify the informativeness of 17 distinct zebrafish endpoints as a data-driven weighting scheme for a multi-endpoint summary measure, called weighted Aggregate Entropy (wAggE). We implement wAggE using high-throughput screening (HTS) data from zebrafish exposed to five concentrations of all 1060 ToxCast chemicals. Our results show that our empirical weighting scheme provides better performance in terms of the Receiver Operating Characteristic (ROC) curve for identifying significant morphological effects and improves robustness over traditional curve-fitting approaches. From a biological perspective, our results suggest that developmental cascade effects triggered by chemical exposure can be recapitulated by analyzing the relationships among endpoints. Thus, wAggE offers a powerful approach for analysis of multivariate phenotypes that can reveal underlying etiological processes. - Highlights: • Introduced a data-driven weighting scheme for multiple phenotypic endpoints. • Weighted Aggregate Entropy (wAggE) implies differential importance of endpoints. • Endpoint relationships reveal developmental cascade effects triggered by exposure. • wAggE is generalizable to multi-endpoint data of different shapes and scales.

  18. Global Optimization Employing Gaussian Process-Based Bayesian Surrogates

    Directory of Open Access Journals (Sweden)

    Roland Preuss

    2018-03-01

    Full Text Available The simulation of complex physics models may lead to enormous computer running times. Since the simulations are expensive it is necessary to exploit the computational budget in the best possible manner. If for a few input parameter settings an output data set has been acquired, one could be interested in taking these data as a basis for finding an extremum and possibly an input parameter set for further computer simulations to determine it—a task which belongs to the realm of global optimization. Within the Bayesian framework we utilize Gaussian processes for the creation of a surrogate model function adjusted self-consistently via hyperparameters to represent the data. Although the probability distribution of the hyperparameters may be widely spread over phase space, we make the assumption that only the use of their expectation values is sufficient. While this shortcut facilitates a quickly accessible surrogate, it is somewhat justified by the fact that we are not interested in a full representation of the model by the surrogate but to reveal its maximum. To accomplish this the surrogate is fed to a utility function whose extremum determines the new parameter set for the next data point to obtain. Moreover, we propose to alternate between two utility functions—expected improvement and maximum variance—in order to avoid the drawbacks of each. Subsequent data points are drawn from the model function until the procedure either remains in the points found or the surrogate model does not change with the iteration. The procedure is applied to mock data in one and two dimensions in order to demonstrate proof of principle of the proposed approach.

  19. Unwarranted claims of drug efficacy in pharmaceutical sales visits: are drugs approved on the basis of surrogate outcomes promoted appropriately?

    Science.gov (United States)

    Habibi, Roojin; Lexchin, Joel; Mintzes, Barbara; Holbrook, Anne

    2017-11-01

    This study compares physicians' recall of the claims of benefits on cardiovascular disease and diabetes made by pharmaceutical sales representatives for drugs approved on the basis of a surrogate outcome, i.e., an off-label claim, compared with those approved on the basis of a serious morbidity or mortality (clinical) outcome. Physicians in primary care practices in Montreal, Vancouver, Sacramento and Toulouse, who saw sales representatives as part of their usual practice and served a non-referral population, were contacted in blocks of 25 from a randomized list of all physicians practising in the relevant metropolitan area. We compared how frequently physicians reported that sales reps made claims of serious morbidity or mortality (clinically meaningful) benefits for drugs approved on the basis of surrogate outcomes vs. drugs approved on the basis of clinical outcomes. There were 448 promotions for 58 unique brand name cardiovascular and diabetes drugs. Claims of clinically meaningful benefit were reported in 156 (45%) of the 347 promotions for surrogate outcome drugs, constituting unwarranted efficacy claims, i.e., off-label promotion. Claims of clinical benefit were reported in 72 of the 101 promotions (71%) for drugs approved on the basis of clinical outcomes, adjusted OR = 0.3 (95% CI 0.2, 0.6), P sales visit promotions for drugs approved only on the basis of surrogate outcomes extended beyond the regulator-approved efficacy information for the product in almost half of promotions. Unapproved claims of drug efficacy constitute a form of off-label promotion and merit greater attention from regulators. © 2017 The British Pharmacological Society.

  20. Pollutant threshold concentration determination in marine ecosystems using an ecological interaction endpoint

    International Nuclear Information System (INIS)

    Wang, Changyou; Liang, Shengkang; Guo, Wenting; Yu, Hua; Xing, Wenhui

    2015-01-01

    The threshold concentrations of pollutants are determined by extrapolating single-species effect data to community-level effects. This assumes the most sensitive endpoint of the life cycle of individuals and the species sensitivity distribution from single-species toxic effect tests, thus, ignoring the ecological interactions. The uncertainties due to this extrapolation can be partially overcome using the equilibrium point of a customized ecosystem. This method incorporates ecological interactions and integrates the effects on growth, survival, and ingestion into a single effect measure, the equilibrium point excursion in the customized ecosystem, in order to describe the toxic effects on plankton. A case study showed that the threshold concentration of copper calculated with the endpoint of the equilibrium point was 10 μg L −1 , which is significantly different from the threshold calculated with a single-species endpoint. The endpoint calculated using this method provides a more relevant measure of the ecological impact than any single individual-level endpoint. - Highlights: • Ecotoxicological effect of exposure to copper was tested on a customized ecosystem. • Equilibrium point of biomasses in the customized ecosystem was used as an endpoint. • Exposure–response relationship in a community level was built on equilibrium point. • A threshold concentration incorporating ecological interactions was derived. - The equilibrium biomass incorporating ecological interactions in a customized ecosystem was used as an endpoint to calculate the threshold concentration at a community level

  1. A comparison of chemoembolization endpoints using angiographic versus transcatheter intraarterial perfusion/MR imaging monitoring.

    Science.gov (United States)

    Lewandowski, Robert J; Wang, Dingxin; Gehl, James; Atassi, Bassel; Ryu, Robert K; Sato, Kent; Nemcek, Albert A; Miller, Frank H; Mulcahy, Mary F; Kulik, Laura; Larson, Andrew C; Salem, Riad; Omary, Reed A

    2007-10-01

    Transcatheter arterial chemoembolization (TACE) is an established treatment for unresectable liver cancer. This study was conducted to test the hypothesis that angiographic endpoints during TACE are measurable and reproducible by comparing subjective angiographic versus objective magnetic resonance (MR) endpoints of TACE. The study included 12 consecutive patients who presented for TACE for surgically unresectable HCC or progressive hepatic metastases despite chemotherapy. All procedures were performed with a dedicated imaging system. Angiographic series before and after TACE were reviewed independently by three board-certified interventional radiologists. A subjective angiographic chemoembolization endpoint (SACE) classification scheme, modified from an established angiographic grading system in the cardiology literature, was designed to assist in reproducibly classifying angiographic endpoints. Reproducibility in SACE classification level was compared among operators, and MR imaging perfusion reduction was compared with SACE levels for each observer. Twelve patients successfully underwent 15 separate TACE sessions. SACE levels ranged from I through IV. There was moderate agreement in SACE classification (kappa = 0.46 +/- 0.12). There was no correlation between SACE level and MR perfusion reduction (r = 0.16 for one operator and 0.02 for the other two). Angiographic endpoints during TACE vary widely, have moderate reproducibility among operators, and do not correlate with functional MR imaging perfusion endpoints. Future research should aim to determine ideal angiographic and functional MR imaging endpoints for TACE according to outcome measures such as imaging response, pathologic response, and survival.

  2. A step towards standardization: A method for end-point titer determination by fluorescence index of an automated microscope. End-point titer determination by fluorescence index.

    Science.gov (United States)

    Carbone, Teresa; Gilio, Michele; Padula, Maria Carmela; Tramontano, Giuseppina; D'Angelo, Salvatore; Pafundi, Vito

    2018-05-01

    Indirect Immunofluorescence (IIF) is widely considered the Gold Standard for Antinuclear Antibody (ANA) screening. However, the high inter-reader variability remains the major disadvantage associated with ANA testing and the main reason for the increasing demand of the computer-aided immunofluorescence microscope. Previous studies proposed the quantification of the fluorescence intensity as an alternative for the classical end-point titer evaluation. However, the different distribution of bright/dark light linked to the nature of the self-antigen and its location in the cells result in different mean fluorescence intensities. The aim of the present study was to correlate Fluorescence Index (F.I.) with end-point titers for each well-defined ANA pattern. Routine serum samples were screened for ANA testing on HEp-2000 cells using Immuno Concepts Image Navigator System, and positive samples were serially diluted to assign the end-point titer. A comparison between F.I. and end-point titers related to 10 different staining patterns was made. According to our analysis, good technical performance of F.I. (97% sensitivity and 94% specificity) was found. A significant correlation between quantitative reading of F.I. and end-point titer groups was observed using Spearman's test and regression analysis. A conversion scale of F.I. in end-point titers for each recognized ANA-pattern was obtained. The Image Navigator offers the opportunity to improve worldwide harmonization of ANA test results. In particular, digital F.I. allows quantifying ANA titers by using just one sample dilution. It could represent a valuable support for the routine laboratory and an effective tool to reduce inter- and intra-laboratory variability. Copyright © 2018. Published by Elsevier B.V.

  3. Ovarian cancer clinical trial endpoints: Society of Gynecologic Oncology white paper

    Science.gov (United States)

    Herzog, Thomas J.; Armstrong, Deborah K.; Brady, Mark F.; Coleman, Robert L.; Einstein, Mark H.; Monk, Bradley J.; Mannel, Robert S.; Thigpen, J. Tate; Umpierre, Sharee A.; Villella, Jeannine A.; Alvarez, Ronald D.

    2015-01-01

    Objective To explore the value of multiple clinical endpoints in the unique setting of ovarian cancer. Methods A clinical trial workgroup was established by the Society of Gynecologic Oncology to develop a consensus statement via multiple conference calls, meetings and white paper drafts. Results Clinical trial endpoints have profound effects on late phase clinical trial design, result interpretation, drug development, and regulatory approval of therapeutics. Selection of the optimal clinical trial endpoint is particularly provocative in ovarian cancer where long overall survival (OS) is observed. The lack of new regulatory approvals and the lack of harmony between regulatory bodies globally for ovarian cancer therapeutics are of concern. The advantages and disadvantages of the numerous endpoints available are herein discussed within the unique context of ovarian cancer where both crossover and post-progression therapies potentially uncouple surrogacy between progression-free survival (PFS) and OS, the two most widely supported and utilized endpoints. The roles of patient reported outcomes (PRO) and health related quality of life (HRQoL) are discussed, but even these widely supported parameters are affected by the unique characteristics of ovarian cancer where a significant percentage of patients may be asymptomatic. Original data regarding the endpoint preferences of ovarian cancer advocates is presented. Conclusions Endpoint selection in ovarian cancer clinical trials should reflect the impact on disease burden and unique characteristics of the treatment cohort while reflecting true patient benefit. Both OS and PFS have led to regulatory approvals and are clinically important. OS remains the most objective and accepted endpoint because it is least vulnerable to bias; however, the feasibility of OS in ovarian cancer is compromised by the requirement for large trial size, prolonged time-line for final analysis, and potential for unintended loss of treatment effect

  4. Ovarian cancer clinical trial endpoints: Society of Gynecologic Oncology white paper.

    Science.gov (United States)

    Herzog, Thomas J; Armstrong, Deborah K; Brady, Mark F; Coleman, Robert L; Einstein, Mark H; Monk, Bradley J; Mannel, Robert S; Thigpen, J Tate; Umpierre, Sharee A; Villella, Jeannine A; Alvarez, Ronald D

    2014-01-01

    To explore the value of multiple clinical endpoints in the unique setting of ovarian cancer. A clinical trial workgroup was established by the Society of Gynecologic Oncology to develop a consensus statement via multiple conference calls, meetings and white paper drafts. Clinical trial endpoints have profound effects on late phase clinical trial design, result interpretation, drug development, and regulatory approval of therapeutics. Selection of the optimal clinical trial endpoint is particularly provocative in ovarian cancer where long overall survival (OS) is observed. The lack of new regulatory approvals and the lack of harmony between regulatory bodies globally for ovarian cancer therapeutics are of concern. The advantages and disadvantages of the numerous endpoints available are herein discussed within the unique context of ovarian cancer where both crossover and post-progression therapies potentially uncouple surrogacy between progression-free survival (PFS) and OS, the two most widely supported and utilized endpoints. The roles of patient reported outcomes (PRO) and health related quality of life (HRQoL) are discussed, but even these widely supported parameters are affected by the unique characteristics of ovarian cancer where a significant percentage of patients may be asymptomatic. Original data regarding the endpoint preferences of ovarian cancer advocates is presented. Endpoint selection in ovarian cancer clinical trials should reflect the impact on disease burden and unique characteristics of the treatment cohort while reflecting true patient benefit. Both OS and PFS have led to regulatory approvals and are clinically important. OS remains the most objective and accepted endpoint because it is least vulnerable to bias; however, the feasibility of OS in ovarian cancer is compromised by the requirement for large trial size, prolonged time-line for final analysis, and potential for unintended loss of treatment effect from active post-progression therapies

  5. Successful surrogate pregnancy after ovarian transposition, pelvic irradiation and hysterectomy.

    Science.gov (United States)

    Zinger, Michael; Liu, James H; Husseinzadeh, Nader; Thomas, Michael A

    2004-07-01

    Treatment of cervical cancer is often effective but at the cost of the woman's fertility. Ovarian transposition with subsequent oocyte retrieval and surrogate pregnancy can enable these patients to become genetic parents. We present the third reported such case. A 22-year-old woman was diagnosed with bulky, stage IB cervical cancer. Following transposition of both ovaries to the upper abdomen, she underwent pelvic irradiation followed by total abdominal hysterectomy. Eleven years later she presented for assisted reproduction. Two oocytes were retrieved following ovarian stimulation and transcutaneous, abdominal oocyte retrieval. One embryo was transferred to the gestational surrogate, resulting in a single intrauterine pregnancy and successful delivery at term. These procedures can preservefertility while successfully treating cervical cancer.

  6. Emulating facial biomechanics using multivariate partial least squares surrogate models.

    Science.gov (United States)

    Wu, Tim; Martens, Harald; Hunter, Peter; Mithraratne, Kumar

    2014-11-01

    A detailed biomechanical model of the human face driven by a network of muscles is a useful tool in relating the muscle activities to facial deformations. However, lengthy computational times often hinder its applications in practical settings. The objective of this study is to replace precise but computationally demanding biomechanical model by a much faster multivariate meta-model (surrogate model), such that a significant speedup (to real-time interactive speed) can be achieved. Using a multilevel fractional factorial design, the parameter space of the biomechanical system was probed from a set of sample points chosen to satisfy maximal rank optimality and volume filling. The input-output relationship at these sampled points was then statistically emulated using linear and nonlinear, cross-validated, partial least squares regression models. It was demonstrated that these surrogate models can mimic facial biomechanics efficiently and reliably in real-time. Copyright © 2014 John Wiley & Sons, Ltd.

  7. Counterfactual reasoning in surrogate decision making -- another look.

    Science.gov (United States)

    Johansson, Mats; Broström, Linus

    2011-06-01

    Incompetent patients need to have someone else make decisions on their behalf. According to the Substituted Judgment Standard the surrogate decision maker ought to make the decision that the patient would have made, had he or she been competent. Objections have been raised against this traditional construal of the standard on the grounds that it involves flawed counterfactual reasoning, and amendments have been suggested within the framework of possible worlds semantics. The paper shows that while this approach may circumvent the alleged problem, the way it has so far been elaborated reflects insufficient understanding of the moral underpinnings of the idea of substituted judgment. Proper recognition of these moral underpinnings has potentially far-reaching implications for our normative assumptions about accuracy and objectivity in surrogate decision making.

  8. A Parallel and Distributed Surrogate Model Implementation for Computational Steering

    KAUST Repository

    Butnaru, Daniel

    2012-06-01

    Understanding the influence of multiple parameters in a complex simulation setting is a difficult task. In the ideal case, the scientist can freely steer such a simulation and is immediately presented with the results for a certain configuration of the input parameters. Such an exploration process is however not possible if the simulation is computationally too expensive. For these cases we present in this paper a scalable computational steering approach utilizing a fast surrogate model as substitute for the time-consuming simulation. The surrogate model we propose is based on the sparse grid technique, and we identify the main computational tasks associated with its evaluation and its extension. We further show how distributed data management combined with the specific use of accelerators allows us to approximate and deliver simulation results to a high-resolution visualization system in real-time. This significantly enhances the steering workflow and facilitates the interactive exploration of large datasets. © 2012 IEEE.

  9. Toward a psychology of surrogate decision-making

    OpenAIRE

    Tunney, Richard J.; Ziegler, Fenja

    2016-01-01

    Many of the decisions that we make in everyday life are made for the benefit of other people. However, research suggests that people often make decisions on behalf of other people that are different from those that the other person would choose for himself or herself. This raises practical problems in the case of legally designated surrogate decision-makers who may not meet the legal normative benchmark — the substituted judgment standard. We review evidence from our own ...

  10. Current issues on a standard for surrogate pregnancy procedures

    OpenAIRE

    Ha, Jung-Ok

    2012-01-01

    While Korea does not have any legal statement on surrogacy, treatments are carried out in practice. As a result, every Institutional Review Board (IRB) of each fertility clinic faces an ethical predicament in reviewing each case. There is a need to arrange the institutions' own standards of surrogate pregnancy procedures before the establishment of national or professional regulation. This article examines the legal, social, and medical issues of surrogacy to help IRBs to judge their cases.

  11. Current issues on a standard for surrogate pregnancy procedures.

    Science.gov (United States)

    Ha, Jung-Ok

    2012-12-01

    While Korea does not have any legal statement on surrogacy, treatments are carried out in practice. As a result, every Institutional Review Board (IRB) of each fertility clinic faces an ethical predicament in reviewing each case. There is a need to arrange the institutions' own standards of surrogate pregnancy procedures before the establishment of national or professional regulation. This article examines the legal, social, and medical issues of surrogacy to help IRBs to judge their cases.

  12. Mexican Surrogates and the Concept of Reproductive Labor

    Directory of Open Access Journals (Sweden)

    María Eugenia Olavarría Patiño

    2018-01-01

    Full Text Available This article explores the meanings of surrogacy motherhood in Mexico throughout its actor’s practices and author’s discourses. The comparisons and analogies established with the mother, the nurse, the concubine and the prostitute are now confronted with testimonies based on an ethnographic fieldwork developed by the 2016. Finally, this article proposes that surrogates women, as a relative modern character, can be understood as a face of the reproductive labor sequence.

  13. ACOG committee opinion number 397, February 2008: surrogate motherhood.

    Science.gov (United States)

    2008-02-01

    Ethical responsibilities are described for obstetrician-gynecologists who choose to participate in surrogacy arrangements by 1) advising couples who are considering surrogacy, 2) counseling potential surrogate mothers, 3) providing obstetric services for pregnant women participating in surrogacy, or 4) offering assisted reproductive technologies related to surrogacy. Although the obligations of physicians will vary depending on the type and level of their involvement, in all cases physicians should carefully examine all relevant issues related to surrogacy, including medical, ethical, legal, and psychologic aspects.

  14. Commercial agencies and surrogate motherhood: a transaction cost approach.

    Science.gov (United States)

    Galbraith, Mhairi; McLachlan, Hugh V; Swales, J Kim

    2005-03-01

    In this paper we investigate the legal arrangements involved in UK surrogate motherhood from a transaction-cost perspective. We outline the specific forms the transaction costs take and critically comment on the way in which the UK institutional and organisational arrangements at present adversely influence transaction costs. We then focus specifically on the potential role of surrogacy agencies and look at UK and US evidence on commercial and voluntary agencies. Policy implications follow.

  15. Pan masala advertisements are surrogate for tobacco products

    OpenAIRE

    Sushma C; Sharang C

    2005-01-01

    BACKGROUND: Pan masala is a comparatively recent habit in India and is marketed with and without tobacco. Advertisements of tobacco products have been banned in India since 1st May 2004. The advertisements of plain pan masala, which continue in Indian media, have been suspected to be surrogate for tobacco products bearing the same name. The study was carried out to assess whether these advertisements were for the intended product, or for tobacco products with same brand name. MATERIALS AND ...

  16. Regression calibration with more surrogates than mismeasured variables

    KAUST Repository

    Kipnis, Victor

    2012-06-29

    In a recent paper (Weller EA, Milton DK, Eisen EA, Spiegelman D. Regression calibration for logistic regression with multiple surrogates for one exposure. Journal of Statistical Planning and Inference 2007; 137: 449-461), the authors discussed fitting logistic regression models when a scalar main explanatory variable is measured with error by several surrogates, that is, a situation with more surrogates than variables measured with error. They compared two methods of adjusting for measurement error using a regression calibration approximate model as if it were exact. One is the standard regression calibration approach consisting of substituting an estimated conditional expectation of the true covariate given observed data in the logistic regression. The other is a novel two-stage approach when the logistic regression is fitted to multiple surrogates, and then a linear combination of estimated slopes is formed as the estimate of interest. Applying estimated asymptotic variances for both methods in a single data set with some sensitivity analysis, the authors asserted superiority of their two-stage approach. We investigate this claim in some detail. A troubling aspect of the proposed two-stage method is that, unlike standard regression calibration and a natural form of maximum likelihood, the resulting estimates are not invariant to reparameterization of nuisance parameters in the model. We show, however, that, under the regression calibration approximation, the two-stage method is asymptotically equivalent to a maximum likelihood formulation, and is therefore in theory superior to standard regression calibration. However, our extensive finite-sample simulations in the practically important parameter space where the regression calibration model provides a good approximation failed to uncover such superiority of the two-stage method. We also discuss extensions to different data structures.

  17. Regression calibration with more surrogates than mismeasured variables

    KAUST Repository

    Kipnis, Victor; Midthune, Douglas; Freedman, Laurence S.; Carroll, Raymond J.

    2012-01-01

    In a recent paper (Weller EA, Milton DK, Eisen EA, Spiegelman D. Regression calibration for logistic regression with multiple surrogates for one exposure. Journal of Statistical Planning and Inference 2007; 137: 449-461), the authors discussed fitting logistic regression models when a scalar main explanatory variable is measured with error by several surrogates, that is, a situation with more surrogates than variables measured with error. They compared two methods of adjusting for measurement error using a regression calibration approximate model as if it were exact. One is the standard regression calibration approach consisting of substituting an estimated conditional expectation of the true covariate given observed data in the logistic regression. The other is a novel two-stage approach when the logistic regression is fitted to multiple surrogates, and then a linear combination of estimated slopes is formed as the estimate of interest. Applying estimated asymptotic variances for both methods in a single data set with some sensitivity analysis, the authors asserted superiority of their two-stage approach. We investigate this claim in some detail. A troubling aspect of the proposed two-stage method is that, unlike standard regression calibration and a natural form of maximum likelihood, the resulting estimates are not invariant to reparameterization of nuisance parameters in the model. We show, however, that, under the regression calibration approximation, the two-stage method is asymptotically equivalent to a maximum likelihood formulation, and is therefore in theory superior to standard regression calibration. However, our extensive finite-sample simulations in the practically important parameter space where the regression calibration model provides a good approximation failed to uncover such superiority of the two-stage method. We also discuss extensions to different data structures.

  18. 2'-Deoxyguanosine as a surrogate trapping agent for DNA reactive drug metabolites.

    Science.gov (United States)

    Häkkinen, Merja R; Laine, Jaana E; Juvonen, Risto O; Auriola, Seppo; Häyrinen, Jukka; Pasanen, Markku

    2011-11-10

    Drug metabolism can result in the production of highly reactive metabolites that may form adducts with cellular macromolecules, and thus initiate adverse drug reactions, cause toxicity, and even require the withdrawal of drug from the market. In this study, a 2'-deoxyguanosine (dG)-based chemical trapping test system was developed for use as a fast screening tool for DNA adducting metabolites of new drug candidates. Reactive metabolites were generated from parent compounds in in vitro incubations with phenobarbital-induced mouse liver microsomes, human liver microsomes and different recombinant human CYP enzymes in the presence of dG. The formed dG-adducts were separated, characterized and their stability was studied by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method was evaluated with six test compounds, aflatoxin B1, estrone, clozapine, tolcapone, ticlopidine and imipramine. Estrone and aflatoxin B1 formed dG adducts with phenobarbital-induced mouse liver microsomes, human liver microsomes and human recombinant CYP enzymes. Adduct formation was also observed with tolcapone when phenobarbital-induced mouse liver microsomes were used as the enzyme source. The stability of each formed adduct was independent of the different enzyme sources. No dG-adducts were identified with ticlopidine, clozapine and imipramine. Compared to other classical DNA reactivity tests, e.g. Ames test, the present surrogate endpoint, the dG adduct, is faster, enables the characterization of the formed compounds, and also permits the investigation of more unstable adducts. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. Evaluation of bone surrogates for indirect and direct ballistic fractures.

    Science.gov (United States)

    Bir, Cynthia; Andrecovich, Chris; DeMaio, Marlene; Dougherty, Paul J

    2016-04-01

    The mechanism of injury for fractures to long bones has been studied for both direct ballistic loading as well as indirect. However, the majority of these studies have been conducted on both post-mortem human subjects (PMHS) and animal surrogates which have constraints in terms of storage, preparation and testing. The identification of a validated bone surrogate for use in forensic, medical and engineering testing would provide the ability to investigate ballistic loading without these constraints. Two specific bone surrogates, Sawbones and Synbone, were evaluated in comparison to PMHS for both direct and indirect ballistic loading. For the direct loading, the mean velocity to produce fracture was 121 ± 19 m/s for the PMHS, which was statistically different from the Sawbones (140 ± 7 m/s) and Synbone (146 ± 3 m/s). The average distance to fracture in the indirect loading was .70 cm for the PMHS. The Synbone had a statistically similar average distance to fracture (.61 cm, p=0.54) however the Sawbones average distance to fracture was statistically different (.41 cm, pballistic testing was not identified and future work is warranted. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Progress in Chemical Kinetic Modeling for Surrogate Fuels

    Energy Technology Data Exchange (ETDEWEB)

    Pitz, W J; Westbrook, C K; Herbinet, O; Silke, E J

    2008-06-06

    Gasoline, diesel, and other alternative transportation fuels contain hundreds to thousands of compounds. It is currently not possible to represent all these compounds in detailed chemical kinetic models. Instead, these fuels are represented by surrogate fuel models which contain a limited number of representative compounds. We have been extending the list of compounds for detailed chemical models that are available for use in fuel surrogate models. Detailed models for components with larger and more complicated fuel molecular structures are now available. These advancements are allowing a more accurate representation of practical and alternative fuels. We have developed detailed chemical kinetic models for fuels with higher molecular weight fuel molecules such as n-hexadecane (C16). Also, we can consider more complicated fuel molecular structures like cyclic alkanes and aromatics that are found in practical fuels. For alternative fuels, the capability to model large biodiesel fuels that have ester structures is becoming available. These newly addressed cyclic and ester structures in fuels profoundly affect the reaction rate of the fuel predicted by the model. Finally, these surrogate fuel models contain large numbers of species and reactions and must be reduced for use in multi-dimensional models for spark-ignition, HCCI and diesel engines.

  1. Love as a regulative ideal in surrogate decision making.

    Science.gov (United States)

    Stonestreet, Erica Lucast

    2014-10-01

    This discussion aims to give a normative theoretical basis for a "best judgment" model of surrogate decision making rooted in a regulative ideal of love. Currently, there are two basic models of surrogate decision making for incompetent patients: the "substituted judgment" model and the "best interests" model. The former draws on the value of autonomy and responds with respect; the latter draws on the value of welfare and responds with beneficence. It can be difficult to determine which of these two models is more appropriate for a given patient, and both approaches may seem inadequate for a surrogate who loves the patient. The proposed "best judgment" model effectively draws on the values incorporated in each of the traditional standards, but does so because these values are important to someone who loves a patient, since love responds to the patient as the specific person she is. © The Author 2014. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Mapping people's views regarding the acceptability of surrogate motherhood.

    Science.gov (United States)

    Petitfils, Charlotte; Munoz Sastre, Maria Teresa; Sorum, Paul Clay; Mullet, Etienne

    2017-02-01

    The aims of the present study were to map French laypersons' views regarding the acceptability of maternal surrogacy and to delineate the circumstances under which surrogacy is considered, by different groups of people, as especially problematic. Participants (N = 236) were presented with a number of scenarios depicting the circumstances in which a couple has contracted with a surrogate mother and were asked to indicate the extent to which such a contract may present a moral problem. The scenarios were created by varying four factors: the type of surrogacy (traditional or gestational), the surrogate mother's level of autonomy, the family context in which the surrogate mother lives, and whether surrogacy was commercial or altruistic. Three qualitatively different personal positions were found: (a) a majority group for which surrogacy always (30%) or often (34%) presents a moral problem, (b) a minority group (14%) for which maternal surrogacy does not systematically present a moral problem, and (c) another minority group (22%) for which circumstances - mainly the mother's level of autonomy and the family context in which she lives - were completely determining.

  3. Surrogate Assisted Design Optimization of an Air Turbine

    Directory of Open Access Journals (Sweden)

    Rameez Badhurshah

    2014-01-01

    Full Text Available Surrogates are cheaper to evaluate and assist in designing systems with lesser time. On the other hand, the surrogates are problem dependent and they need evaluation for each problem to find a suitable surrogate. The Kriging variants such as ordinary, universal, and blind along with commonly used response surface approximation (RSA model were used in the present problem, to optimize the performance of an air impulse turbine used for ocean wave energy harvesting by CFD analysis. A three-level full factorial design was employed to find sample points in the design space for two design variables. A Reynolds-averaged Navier Stokes solver was used to evaluate the objective function responses, and these responses along with the design variables were used to construct the Kriging variants and RSA functions. A hybrid genetic algorithm was used to find the optimal point in the design space. It was found that the best optimal design was produced by the universal Kriging while the blind Kriging produced the worst. The present approach is suggested for renewable energy application.

  4. Endpoint behavior of the pion distribution amplitude in QCD sum rules with nonlocal condensates

    International Nuclear Information System (INIS)

    Mikhailov, S. V.; Pimikov, A. V.; Stefanis, N. G.

    2010-01-01

    Starting from the QCD sum rules with nonlocal condensates for the pion distribution amplitude, we derive another sum rule for its derivative and its ''integral derivatives''--defined in this work. We use this new sum rule to analyze the fine details of the pion distribution amplitude in the endpoint region x∼0. The results for endpoint-suppressed and flattop (or flatlike) pion distribution amplitudes are compared with those we obtained with differential sum rules by employing two different models for the distribution of vacuum-quark virtualities. We determine the range of values of the derivatives of the pion distribution amplitude and show that endpoint-suppressed distribution amplitudes lie within this range, while those with endpoint enhancement--flat-type or Chernyak-Zhitnitsky like--yield values outside this range.

  5. 78 FR 49530 - Gastroenterology Regulatory Endpoints and the Advancement of Therapeutics; Public Workshop

    Science.gov (United States)

    2013-08-14

    ...] Gastroenterology Regulatory Endpoints and the Advancement of Therapeutics; Public Workshop AGENCY: Food and Drug... for Drug Evaluation and Research, in cosponsorship with the American College of Gastroenterology, the... American Society for Pediatric Gastroenterology, Hepatology, and Nutrition, and the Pediatric IBD...

  6. On weighted hardy inequalities on semiaxis for functions vanishing at the endpoints

    Directory of Open Access Journals (Sweden)

    Stepanov Vladimir

    1997-01-01

    Full Text Available We study the weighted Hardy inequalities on the semiaxis of the form for functions vanishing at the endpoints together with derivatives up to the order . The case is completely characterized.

  7. 76 FR 51993 - Draft Guidance for Industry on Standards for Clinical Trial Imaging Endpoints; Availability

    Science.gov (United States)

    2011-08-19

    ... clinical trials of therapeutic drugs and biological products. The draft guidance describes standards... important imaging endpoint is used in a clinical trial of a therapeutic drug or biological product... Services to the Chairman of [[Page 51994

  8. Reporting and evaluation of HIV-related clinical endpoints in two multicenter international clinical trials

    DEFF Research Database (Denmark)

    Lifson, A; Rhame, F; Bellosa, W

    2006-01-01

    adjudication between reviewers before diagnostic certainty was assigned. CONCLUSION: Important requirements for HIV trials using clinical endpoints include objective definitions of "confirmed" and "probable," a formal reporting process with adequate information and supporting source documentation, evaluation......PURPOSE: The processes for reporting and review of progression of HIV disease clinical endpoints are described for two large phase III international clinical trials. METHOD: SILCAAT and ESPRIT are multicenter randomized HIV trials evaluating the impact of interleukin-2 on disease progression...... and death in HIV-infected patients receiving antiretroviral therapy. We report definitions used for HIV progression of disease endpoints, procedures for site reporting of such events, processes for independent review of reported events by an Endpoint Review Committee (ERC), and the procedure...

  9. Urethral and periurethral dosimetry in prostate brachytherapy: is there a convenient surrogate?

    International Nuclear Information System (INIS)

    Bucci, Joseph; Spadinger, Ingrid; Hilts, Michelle; Sidhu, Sabeena; Smith, Clarke; Keyes, Mira; Morris, W. James

    2002-01-01

    Purpose: To assess and compare two models for a surrogate urethra to be used for postimplant dosimetry in prostate brachytherapy. Methods and Materials: Twenty men with a urinary catheter present at the time of postimplant computed tomographic imaging were studied. Urethral and periurethral volumes were defined as 5-mm and 10-mm diameter volumes, respectively. Three contours of each were used: one contour of the true urethra (and periurethra), and two surrogate models. The true volumes were centered on the catheter center. One surrogate model used volumes centered on the geometrical center of each prostate contour (centered surrogate). The other surrogate model was based on the average deviation of the true urethra from a reference line through the geometrical center of the axial midplane of the prostate (deviated surrogate). Maximum point doses and the D 10 , D 25 , D 50 , D 90 , V 100 , V 120 , and V 150 of the true and surrogate volumes were measured and compared (D n is the minimum dose [Gy] received by n% of the structure, and V m is the volume [%] of the structure that received m% of the prescribed dose) as well as the distances between the surrogate urethras and the true urethra. Results: Doses determined from both surrogate urethral and periurethral volumes were in good agreement with the true urethral and periurethral doses except in the superior third of the gland. The deviated surrogate provided a physically superior likeness to the true urethra. Certain dose-volume histogram (DVH)-based parameters could also be predicted reasonably well on the basis of the surrogates. Correlation coefficients ≥0.85 were seen for D 25 , D 50 , V 100 , V 120 , and V 150 for both models. All the other parameters had correlation coefficients in the range of 0.73 - 0.85. Conclusions: Both surrogate models predicted true urethral dosimetry reasonably well. It is recommended that the simpler deviated surrogate would be a more suitable surrogate for routine clinical practice

  10. Effectiveness of biological surrogates for predicting patterns of marine biodiversity: a global meta-analysis.

    Directory of Open Access Journals (Sweden)

    Camille Mellin

    Full Text Available The use of biological surrogates as proxies for biodiversity patterns is gaining popularity, particularly in marine systems where field surveys can be expensive and species richness high. Yet, uncertainty regarding their applicability remains because of inconsistency of definitions, a lack of standard methods for estimating effectiveness, and variable spatial scales considered. We present a Bayesian meta-analysis of the effectiveness of biological surrogates in marine ecosystems. Surrogate effectiveness was defined both as the proportion of surrogacy tests where predictions based on surrogates were better than random (i.e., low probability of making a Type I error; P and as the predictability of targets using surrogates (R(2. A total of 264 published surrogacy tests combined with prior probabilities elicited from eight international experts demonstrated that the habitat, spatial scale, type of surrogate and statistical method used all influenced surrogate effectiveness, at least according to either P or R(2. The type of surrogate used (higher-taxa, cross-taxa or subset taxa was the best predictor of P, with the higher-taxa surrogates outperforming all others. The marine habitat was the best predictor of R(2, with particularly low predictability in tropical reefs. Surrogate effectiveness was greatest for higher-taxa surrogates at a <10-km spatial scale, in low-complexity marine habitats such as soft bottoms, and using multivariate-based methods. Comparisons with terrestrial studies in terms of the methods used to study surrogates revealed that marine applications still ignore some problems with several widely used statistical approaches to surrogacy. Our study provides a benchmark for the reliable use of biological surrogates in marine ecosystems, and highlights directions for future development of biological surrogates in predicting biodiversity.

  11. SpEnD: Linked Data SPARQL Endpoints Discovery Using Search Engines

    OpenAIRE

    Yumusak, Semih; Dogdu, Erdogan; Kodaz, Halife; Kamilaris, Andreas

    2016-01-01

    In this study, a novel metacrawling method is proposed for discovering and monitoring linked data sources on the Web. We implemented the method in a prototype system, named SPARQL Endpoints Discovery (SpEnD). SpEnD starts with a "search keyword" discovery process for finding relevant keywords for the linked data domain and specifically SPARQL endpoints. Then, these search keywords are utilized to find linked data sources via popular search engines (Google, Bing, Yahoo, Yandex). By using this ...

  12. [Surrogate pregnancy with regard to marriage between persons of the same sex].

    Science.gov (United States)

    Henrion, Roger

    2014-01-01

    After first defining surrogacy, distinguishing between cases in which the pregnancy results from the surrogate's own egg or a donor egg, and examining the different configurations of male homosexual families, the authors outline French and foreign legislation and provide a summary of the literature and of French working group hearings. Arguments for and against lifting the ban on surrogacy for gay couples are examined. The main arguments for lifting the ban are the following: 1) the same-sex couple's desire to start a family from their own gene pool, 2) current obstacles to adoption, 3) the notion of equality between heterosexual and homosexual couples, 4) frequent recourse to surrogacy abroad, which is not only very costly but also leaves the child in a state of legal limbo on its return to France, and 5) the lack of access to therapeutic alternatives. Some arguments against lifting the ban are of a medical nature: (1) physical and psychological risks for the surrogate, 2) the fact that exchanges between the mother and fetus during pregnancy are more complex than previously thought (microchimerism, epigenetics) and never negligible, and 3) the physical and psychological risks for the child. Other arguments are of an ethical nature: 1) surrogacy may undermine the status of motherhood, 2) surrogacy is becoming a societal rather than a medical issue, implying a profound bioethical upheaval, 3) the increasing commercialization of the human body, 4) subjugation of women to men's desires, 5) the risks for the surrogate's own couple and children, and for the host couple, 6) unavoidable financial aspects, and (7) the risk of abuse. The aim of this study is to bring together all the factors potentially influencing the health consequences of surrogacy, for both the mother and the child, especially if surrogacy were to be legalized for male homosexual couples. Surrogacy raises issues far beyond purely medical considerations and is primarily a societal issue that must be

  13. The use of intermediate endpoints in the design of type 1 diabetes prevention trials.

    Science.gov (United States)

    Krischer, Jeffrey P

    2013-09-01

    This paper presents a rationale for the selection of intermediate endpoints to be used in the design of type 1 diabetes prevention clinical trials. Relatives of individuals diagnosed with type 1 diabetes were enrolled on the TrialNet Natural History Study and screened for diabetes-related autoantibodies. Those with two or more such autoantibodies were analysed with respect to increased HbA1c, decreased C-peptide following an OGTT, or abnormal OGTT values as intermediate markers of disease progression. Over 2 years, a 10% increase in HbA1c, and a 20% or 30% decrease in C-peptide from baseline, or progression to abnormal OGTT, occurred with a frequency between 20% and 41%. The 3- to 5-year risk of type 1 diabetes following each intermediate endpoint was high, namely 47% to 84%. The lower the incidence of the endpoint being reached, the higher the risk of diabetes. A diabetes prevention trial using these intermediate endpoints would require a 30% to 50% smaller sample size than one using type 1 diabetes as the endpoint. The use of an intermediate endpoint in diabetes prevention is based on the generally held view of disease progression from initial occurrence of autoantibodies through successive immunological and metabolic changes to manifest type 1 diabetes. Thus, these markers are suitable for randomised phase 2 trials, which can more rapidly screen promising new therapies, allowing them to be subsequently confirmed in definitive phase 3 trials.

  14. Development of Cardiovascular and Neurodevelopmental Metrics as Sublethal Endpoints for the Fish Embryo Toxicity Test.

    Science.gov (United States)

    Krzykwa, Julie C; Olivas, Alexis; Jeffries, Marlo K Sellin

    2018-06-19

    The fathead minnow fish embryo toxicity (FET) test has been proposed as a more humane alternative to current toxicity testing methods, as younger organisms are thought to experience less distress during toxicant exposure. However, the FET test protocol does not include endpoints that allow for the prediction of sublethal adverse outcomes, limiting its utility relative to other test types. Researchers have proposed the development of sublethal endpoints for the FET test to increase its utility. The present study 1) developed methods for previously unmeasured sublethal metrics in fathead minnows (i.e., spontaneous contraction frequency and heart rate) and 2) investigated the responsiveness of several sublethal endpoints related to growth (wet weight, length, and growth-related gene expression), neurodevelopment (spontaneous contraction frequency, and neurodevelopmental gene expression), and cardiovascular function and development (pericardial area, eye size and cardiovascular related gene expression) as additional FET test metrics using the model toxicant 3,4-dichloroaniline. Of the growth, neurological and cardiovascular endpoints measured, length, eye size and pericardial area were found to more responsive than the other endpoints, respectively. Future studies linking alterations in these endpoints to longer-term adverse impacts are needed to fully evaluate the predictive power of these metrics in chemical and whole effluent toxicity testing. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. Guide and manual of frequent special radiological procedures pertaining frequent pediatric patient

    International Nuclear Information System (INIS)

    Quesada Rodriguez, Marco V.

    2012-01-01

    A set of instructions and / or recommendations are afforded, developed in a systematic way, whose purpose is to help treating doctors to make decisions about the mode of study appropriate for a specialized clinical circumstance. The instructions are aimed at radiologists, in order to facilitate the selection and realization of special studies in the pediatric patient images, so that in this way, guide of the best and most efficient way to the resolution of the cases before diagnostic doubts that seek to clarify the treating clinician. The studies most frequently requested are exposed, as well as those with their prompt realization will lead to a quick and timely medical care and / or surgical of a specific problem [es

  16. Investigation of microalgae HTL fuel effects on diesel engine performance and exhaust emissions using surrogate fuels

    International Nuclear Information System (INIS)

    Hossain, Farhad M.; Nabi, Md. Nurun; Rainey, Thomas J.; Bodisco, Timothy; Rahman, Md. Mostafizur; Suara, Kabir; Rahman, S.M.A.; Van, Thuy Chu; Ristovski, Zoran; Brown, Richard J.

    2017-01-01

    Highlights: • Development of a microalgae HTL surrogate of biocrude fuel using chemical compounds. • Physiochemical properties of surrogate blends were analysed. • Experimentally investigated diesel engine performance and emissions using surrogate fuels. • No significant changes in engine performance were observed with HTL surrogate blends. • Major emissions including PM, PN and CO were reduced significantly with increasing of NOx emission. - Abstract: This paper builds on previous work using surrogate fuel to investigate advanced internal combustion engine fuels. To date, a surrogate fuel of this nature has not been used for microalgae hydrothermal liquefaction (HTL) biocrude. This research used five different chemical groups found in microalgae HTL biocrude to design a surrogate fuel. Those five chemical groups constitute around 65% (by weight) of a microalgae biocrude produced by HTL. Weight percentage of the microalgae HTL biocrude chemical compounds were used to design the surrogate fuel, which was miscible with diesel at all percentages. The engine experiments were conducted on a EURO IIIA turbocharged common-rail direct-injection six-cylinder diesel engine to test engine performance and emissions. Exhaust emissions, including particulate matter and other gaseous emissions, were measured with the surrogate fuel and a reference diesel fuel. Experimental results showed that without significantly deteriorating engine performance, lower particulate mass, particulate number and CO emissions were observed with a penalty in NOx emissions for all surrogate blends compared to those of the reference diesel.

  17. Influence of Frequent Nocturnal Home Hemodialysis on Food Preference

    NARCIS (Netherlands)

    Ipema, Karin; Franssen, Casper; van der Schans, Cees; Smit, Lianne; Noordman, Sabine; Haisma, Hinke

    Objective: Dialysis patients frequently report a change of taste that is reversible after renal transplantation, suggesting that uremic toxins may negatively influence taste. Currently, frequent nocturnal home hemodialysis (NHHD) is the most effective method of hemodialysis, and is associated with

  18. Comparing three novel endpoints for developmental osteotoxicity in the embryonic stem cell test

    International Nuclear Information System (INIS)

    Nieden, Nicole I. zur; Davis, Lesley A.; Rancourt, Derrick E.

    2010-01-01

    Birth defects belong to the most serious side effects of pharmaceutical compounds or environmental chemicals. In vivo, teratogens most often affect the normal development of bones, causing growth retardation, limb defects or craniofacial malformations. The embryonic stem cell test (EST) is one of the most promising models that allow the in vitro prediction of embryotoxicity, with one of its endpoints being bone tissue development. The present study was designed to describe three novel inexpensive endpoints to assess developmental osteotoxicity using the model compounds penicillin G (non-teratogenic), 5-fluorouracil (strong teratogen) and all-trans retinoic acid (bone teratogen). These three endpoints were: quantification of matrix incorporated calcium by (1) morphometric analysis and (2) measurement of calcium levels as well as (3) activity of alkaline phosphatase, an enzyme involved in matrix calcification. To evaluate our data, we have compared the concentration curves and resulting ID 50 s of the new endpoints with mRNA expression for osteocalcin. Osteocalcin is an exclusive marker found only in mineralized tissues, is regulated upon compound treatment and reliably predicts the potential of a chemical entity acting as a bone teratogen. By comparing the new endpoints to quantitative expression of osteocalcin, which we previously identified as suitable to detect developmental osteotoxicity, we were ultimately able to illustrate IMAGE analysis and Ca 2+ deposition assays as two reliable novel endpoints for the EST. This is of particular importance for routine industrial assessment of novel compounds as these two new endpoints may substitute previously used molecular read-out methods, which are often costly and time-consuming.

  19. Diesel Surrogate Fuels for Engine Testing and Chemical-Kinetic Modeling: Compositions and Properties.

    Science.gov (United States)

    Mueller, Charles J; Cannella, William J; Bays, J Timothy; Bruno, Thomas J; DeFabio, Kathy; Dettman, Heather D; Gieleciak, Rafal M; Huber, Marcia L; Kweon, Chol-Bum; McConnell, Steven S; Pitz, William J; Ratcliff, Matthew A

    2016-02-18

    The primary objectives of this work were to formulate, blend, and characterize a set of four ultralow-sulfur diesel surrogate fuels in quantities sufficient to enable their study in single-cylinder-engine and combustion-vessel experiments. The surrogate fuels feature increasing levels of compositional accuracy (i.e., increasing exactness in matching hydrocarbon structural characteristics) relative to the single target diesel fuel upon which the surrogate fuels are based. This approach was taken to assist in determining the minimum level of surrogate-fuel compositional accuracy that is required to adequately emulate the performance characteristics of the target fuel under different combustion modes. For each of the four surrogate fuels, an approximately 30 L batch was blended, and a number of the physical and chemical properties were measured. This work documents the surrogate-fuel creation process and the results of the property measurements.

  20. Biopolicies and biotechnologies: reflections on surrogate maternity in India

    Directory of Open Access Journals (Sweden)

    Mónica Amador

    2010-07-01

    Full Text Available This article explores the impact of biotechnology, particularly on assisted reproductive technologies such as surrogate motherhood. The study is based on interviews and field work conducted in the city of Hyderabad in India within the frame of the seminar on “Research Methodology” given by Dr. Rohan D´Souza at the Centre for Studies in Science Policy at the Jawaharlal Nehru University in India. The theoretical framework of this analysis focuses on exploring concepts such as cyborg (Haraway,1991 and subaltern subject (Spivak, 1998 in the context of biotechnological production in India

  1. Surrogate based approaches to parameter inference in ocean models

    KAUST Repository

    Knio, Omar

    2016-01-06

    This talk discusses the inference of physical parameters using model surrogates. Attention is focused on the use of sampling schemes to build suitable representations of the dependence of the model response on uncertain input data. Non-intrusive spectral projections and regularized regressions are used for this purpose. A Bayesian inference formalism is then applied to update the uncertain inputs based on available measurements or observations. To perform the update, we consider two alternative approaches, based on the application of Markov Chain Monte Carlo methods or of adjoint-based optimization techniques. We outline the implementation of these techniques to infer dependence of wind drag, bottom drag, and internal mixing coefficients.

  2. Surrogate based approaches to parameter inference in ocean models

    KAUST Repository

    Knio, Omar

    2016-01-01

    This talk discusses the inference of physical parameters using model surrogates. Attention is focused on the use of sampling schemes to build suitable representations of the dependence of the model response on uncertain input data. Non-intrusive spectral projections and regularized regressions are used for this purpose. A Bayesian inference formalism is then applied to update the uncertain inputs based on available measurements or observations. To perform the update, we consider two alternative approaches, based on the application of Markov Chain Monte Carlo methods or of adjoint-based optimization techniques. We outline the implementation of these techniques to infer dependence of wind drag, bottom drag, and internal mixing coefficients.

  3. Endpoint in plasma etch process using new modified w-multivariate charts and windowed regression

    Science.gov (United States)

    Zakour, Sihem Ben; Taleb, Hassen

    2017-09-01

    Endpoint detection is very important undertaking on the side of getting a good understanding and figuring out if a plasma etching process is done in the right way, especially if the etched area is very small (0.1%). It truly is a crucial part of supplying repeatable effects in every single wafer. When the film being etched has been completely cleared, the endpoint is reached. To ensure the desired device performance on the produced integrated circuit, the high optical emission spectroscopy (OES) sensor is employed. The huge number of gathered wavelengths (profiles) is then analyzed and pre-processed using a new proposed simple algorithm named Spectra peak selection (SPS) to select the important wavelengths, then we employ wavelet analysis (WA) to enhance the performance of detection by suppressing noise and redundant information. The selected and treated OES wavelengths are then used in modified multivariate control charts (MEWMA and Hotelling) for three statistics (mean, SD and CV) and windowed polynomial regression for mean. The employ of three aforementioned statistics is motivated by controlling mean shift, variance shift and their ratio (CV) if both mean and SD are not stable. The control charts show their performance in detecting endpoint especially W-mean Hotelling chart and the worst result is given by CV statistic. As the best detection of endpoint is given by the W-Hotelling mean statistic, this statistic will be used to construct a windowed wavelet Hotelling polynomial regression. This latter can only identify the window containing endpoint phenomenon.

  4. Bioremediation of hydrocarbon-contaminated soils: are treatability and ecotoxicity endpoints related?

    International Nuclear Information System (INIS)

    Visser, S.

    1999-01-01

    To determine if there is a relationship between biotreatability and ecotoxicity endpoints in a wide range of hydrocarbon-contaminated soils, including medium and heavy crude oil-contaminated flare pit wastes and lubrication oil contaminated soil, research was conducted. Each test material was analyzed for pH, water repellency, electrical conductivity, available N and P, total extractable hydrocarbons, oil and grease, and toxicity to seedling emergence, root elongation in barley, lettuce and canola, earthworm survival and luminescent bacteria (Microtox), prior to, and following three months of bioremediation in the laboratory. By monitoring soil respiration, progress of the bioremediation process and determination of a treatment endpoint were assessed. The time required to attain a treatment endpoint under laboratory conditions can range from 30 days to 100 days depending on the concentration of hydrocarbons and degree of weathering. Most flare pits are biotreatable, averaging a loss of 25-30% of hydrocarbons during bioremediation. Once a treatment endpoint is achieved, residual hydrocarbons contents almost always exceeds Alberta Tier I criteria for mineral oil and grease. As a result of bioremediation treatments, hydrophobicity is often reduced from severe to low. Many flare pit materials are still moderately to extremely toxic after reaching a treatment endpoint. (Abstract only)

  5. Multi-Toxic Endpoints of the Foodborne Mycotoxins in Nematode Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Zhendong Yang

    2015-12-01

    Full Text Available Aflatoxins B1 (AFB1, deoxynivalenol (DON, fumonisin B1 (FB1, T-2 toxin (T-2, and zearalenone (ZEA are the major foodborne mycotoxins of public health concerns. In the present study, the multiple toxic endpoints of these naturally-occurring mycotoxins were evaluated in Caenorhabditis elegans model for their lethality, toxic effects on growth and reproduction, as well as influence on lifespan. We found that the lethality endpoint was more sensitive for T-2 toxicity with the EC50 at 1.38 mg/L, the growth endpoint was relatively sensitive for AFB1 toxic effects, and the reproduction endpoint was more sensitive for toxicities of AFB1, FB1, and ZEA. Moreover, the lifespan endpoint was sensitive to toxic effects of all five tested mycotoxins. Data obtained from this study may serve as an important contribution to knowledge on assessment of mycotoxin toxic effects, especially for assessing developmental and reproductive toxic effects, using the C. elegans model.

  6. Pollutant threshold concentration determination in marine ecosystems using an ecological interaction endpoint.

    Science.gov (United States)

    Wang, Changyou; Liang, Shengkang; Guo, Wenting; Yu, Hua; Xing, Wenhui

    2015-09-01

    The threshold concentrations of pollutants are determined by extrapolating single-species effect data to community-level effects. This assumes the most sensitive endpoint of the life cycle of individuals and the species sensitivity distribution from single-species toxic effect tests, thus, ignoring the ecological interactions. The uncertainties due to this extrapolation can be partially overcome using the equilibrium point of a customized ecosystem. This method incorporates ecological interactions and integrates the effects on growth, survival, and ingestion into a single effect measure, the equilibrium point excursion in the customized ecosystem, in order to describe the toxic effects on plankton. A case study showed that the threshold concentration of copper calculated with the endpoint of the equilibrium point was 10 μg L(-1), which is significantly different from the threshold calculated with a single-species endpoint. The endpoint calculated using this method provides a more relevant measure of the ecological impact than any single individual-level endpoint. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Focus Group Study Exploring Factors Related to Frequent Sickness Absence.

    Science.gov (United States)

    Notenbomer, Annette; Roelen, Corné A M; van Rhenen, Willem; Groothoff, Johan W

    2016-01-01

    Research investigating frequent sickness absence (3 or more episodes per year) is scarce and qualitative research from the perspective of frequent absentees themselves is lacking. The aim of the current study is to explore awareness, determinants of and solutions to frequent sickness absence from the perspective of frequent absentees themselves. We performed a qualitative study of 3 focus group discussions involving a total of 15 frequent absentees. Focus group discussions were audiotaped and transcribed verbatim. Results were analyzed with the Graneheim method using the Job Demands Resources (JD-R) model as theoretical framework. Many participants were not aware of their frequent sickness absence and the risk of future long-term sickness absence. As determinants, participants mentioned job demands, job resources, home demands, poor health, chronic illness, unhealthy lifestyles, and diminished feeling of responsibility to attend work in cases of low job resources. Managing these factors and improving communication (skills) were regarded as solutions to reduce frequent sickness absence. The JD-R model provided a framework for determinants of and solutions to frequent sickness absence. Additional determinants were poor health, chronic illness, unhealthy lifestyles, and diminished feeling of responsibility to attend work in cases of low job resources. Frequent sickness absence should be regarded as a signal that something is wrong. Managers, supervisors, and occupational health care providers should advise and support frequent absentees to accommodate job demands, increase both job and personal resources, and improve health rather than express disapproval of frequent sickness absence and apply pressure regarding work attendance.

  8. Progression-free survival, post-progression survival, and tumor response as surrogate markers for overall survival in patients with extensive small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Hisao Imai

    2015-01-01

    Full Text Available Objectives: The effects of first-line chemotherapy on overall survival (OS might be confounded by subsequent therapies in patients with small cell lung cancer (SCLC. We examined whether progression-free survival (PFS, post-progression survival (PPS, and tumor response could be valid surrogate endpoints for OS after first-line chemotherapies for patients with extensive SCLC using individual-level data. Methods: Between September 2002 and November 2012, we analyzed 49 cases of patients with extensive SCLC who were treated with cisplatin and irinotecan as first-line chemotherapy. The relationships of PFS, PPS, and tumor response with OS were analyzed at the individual level. Results: Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS (r = 0.97, p < 0.05, R 2 = 0.94, PFS was moderately correlated with OS (r = 0.58, p < 0.05, R 2 = 0.24, and tumor shrinkage was weakly correlated with OS (r = 0.37, p < 0.05, R 2 = 0.13. The best response to second-line treatment, and the number of regimens employed after progression beyond first-line chemotherapy were both significantly associated with PPS ( p ≤ 0.05. Conclusion: PPS is a potential surrogate for OS in patients with extensive SCLC. Our findings also suggest that subsequent treatment after disease progression following first-line chemotherapy may greatly influence OS.

  9. Psychological Well-Being, Maternal-Foetal Bonding and Experiences of Indian Surrogates

    OpenAIRE

    Lamba, Nishtha

    2018-01-01

    Over the past two decades, India has become an international hub of cross-border surrogacy. The extreme economic and cultural differences between international couples seeking surrogacy and the surrogates themselves, clinics compromising health of surrogates for profit, the stigmatisation of surrogacy in India, and the constant surveillance of these women living in a ‘surrogate house’, have raised concerns regarding the potentially negative psychological impact of surrogacy on Indian surrogat...

  10. The psychological well-being and prenatal bonding of gestational surrogates.

    OpenAIRE

    Lamba, Nishtha; Jadva, Vasanti Harish; Kadam, K; Golombok, Susan Esther

    2018-01-01

    Study question: How does the psychological well-being and prenatal bonding of Indian surrogates differ from a comparison group of mothers? Summary answer: Surrogates had higher levels of depression during pregnancy and post-birth, displayed lower emotional connection with the unborn baby, and greater care towards the healthy growth of the foetus, than the comparison group of mothers. What is already known: Studies in the West have found that surrogates do not suffer long-term psychol...

  11. The representation of healthcare end users' perspectives by surrogates in healthcare decisions: a literature review.

    Science.gov (United States)

    Shah, Syed Ghulam Sarwar; Farrow, Alexandra; Robinson, Ian

    2009-12-01

    The representation of end users' perspectives in healthcare decisions requires involvement of their surrogates when the end users, i.e. certain patients, elderly people, children and people with disabilities, are unable to present their views. To review critical issues, and the advantages and disadvantages of involving surrogates in representing end users' perspectives in healthcare decisions. A systematic review of literature published in peer-reviewed journals from 1990 to 2005. Findings show that surrogates are used widely in health care and that they are necessary to represent end users' perspectives in healthcare decisions when the latter are unable to do so themselves. Critical issues in using surrogates include key ethical, social, cultural, legal and medico-technological factors; ascertaining the best interest of end users; potential conflict of interest; possible biased decisions and the burden on surrogates. The key advantage of surrogate involvement in healthcare decisions is their ability to represent end users' needs, values and wishes. The main disadvantages include potential discrepancies between the decisions and conclusions of surrogates and end users; the failure of surrogates to predict end users' preferences accurately and the lack of certainty that useful information will be obtained through the surrogacy process. This systematic review has revealed that the involvement of surrogates is an additional vital way to represent end users' perspectives in healthcare decisions where for a range of reasons their opinions are unable to be effectively ascertained. However, because of the heterogeneity of surrogates and end users, the selection of appropriate surrogates and deploying surrogate decisions require particularly careful consideration of their value in individual cases; thus, subsequent decision-making must be reviewed on a case-to-case basis to seek to ensure that the best interests, needs and wishes of the end user are fully and accurately

  12. Design and endpoints of clinical and translational trials in advanced colorectal cancer. a proposal from GROUP Español Multidisciplinar en Cancer Digestivo (GEMCAD).

    Science.gov (United States)

    Carrera, Gemma; Garcia-Albeniz, Xabier; Ayuso, Juan Ramón; Aparicio, Jorge; Castells, Antoni; Codony-Servat, Jordi; Feliu, Jaime; Fuster, David; Gallego, Rosa; Pagés, Mario; Torres, Ferran; Maurel, Joan

    2011-05-01

    Meta-analytic reviews of Randomized Clinical Trials (RCT) have reached contradictory conclusions regarding the benefit of medical interventions in Advanced Colorectal Cancer (ACRC). Surrogate markers of survival benefit, such as response rate (RR) and progression free-survival (PFS) often show contradictory and highly variable correlations. These contradictions can be due to differences in 1) the studies analysed (sources), 2) the quality of clinical trials (intrinsic bias in the design, biased data analysis, heterogeneous PFS definitions) and 3) the second-line strategies between arms. PFS is a more vulnerable target than overall survival (OS), but the latter can also be affected by different biases and additional medical interventions such as secondary resection of metastases or second-line therapies. Therefore the correlation between PFS and survival must be clearly stated if PFS is to be considered as a primary endpoint. Of the differences between studies, only the quality of clinical trials can be improved by a deeper knowledge of both the area of study (i.e. colorectal cancer) and the methodology needed (i.e., clinical and translational trials). The aim of this manuscript is to offer the basic resources to develop experimental trials in ACRC. To this end, techniques for diagnosis and for response assessment are discussed, prognostic factors and treatment standards are critically exposed, and notes about how to design useful translational studies are provided.

  13. Drop-out from cardiovascular magnetic resonance in a randomized controlled trial of ST-elevation myocardial infarction does not cause selection bias on endpoints

    DEFF Research Database (Denmark)

    Laursen, Peter Nørkjær; Holmvang, L.; Kelbæk, H.

    2017-01-01

    Background: The extent of selection bias due to drop-out in clinical trials of ST-elevation myocardial infarction (STEMI) using cardiovascular magnetic resonance (CMR) as surrogate endpoints is unknown. We sought to interrogate the characteristics and prognosis of patients who dropped out before...... years of follow-up were assessed and compared between CMR-drop-outs and CMR-participants using the trial screening log and the Eastern Danish Heart Registry. Results: The drop-out rate from acute CMR was 28% (n = 92). These patients had a significantly worse clinical risk profile upon admission...... as evaluated by the TIMI-risk score (3.7 (± 2.1) vs 4.0 (± 2.6), p = 0.043) and by left ventricular ejection fraction (43 (± 9) vs. 47 (± 10), p = 0.029). CMR drop-outs had a higher incidence of known hypertension (39% vs. 35%, p = 0.043), known diabetes (14% vs. 7%, p = 0.025), known cardiac disease (11% vs...

  14. Effects of frequent hemodialysis on perceived caregiver burden in the Frequent Hemodialysis Network trials.

    Science.gov (United States)

    Suri, Rita S; Larive, Brett; Hall, Yoshio; Kimmel, Paul L; Kliger, Alan S; Levin, Nathan; Tamura, Manjula Kurella; Chertow, Glenn M

    2014-05-01

    Patients receiving hemodialysis often perceive their caregivers are overburdened. We hypothesize that increasing hemodialysis frequency would result in higher patient perceptions of burden on their unpaid caregivers. In two separate trials, 245 patients were randomized to receive in-center daily hemodialysis (6 days/week) or conventional hemodialysis (3 days/week) while 87 patients were randomized to receive home nocturnal hemodialysis (6 nights/week) or home conventional hemodialysis for 12 months. Changes in overall mean scores over time in the 10-question Cousineau perceived burden scale were compared. In total, 173 of 245 (70%) and 80 of 87 (92%) randomized patients in the Daily and Nocturnal Trials, respectively, reported having an unpaid caregiver at baseline or during follow-up. Relative to in-center conventional dialysis, the 12-month change in mean perceived burden score with in-center daily hemodialysis was -2.1 (95% confidence interval, -9.4 to +5.3; P=0.58). Relative to home conventional dialysis, the 12-month change in mean perceived burden score with home nocturnal dialysis was +6.1 (95% confidence interval, -0.8 to +13.1; P=0.08). After multiple imputation for missing data in the Nocturnal Trial, the relative difference between home nocturnal and home conventional hemodialysis was +9.4 (95% confidence interval, +0.55 to +18.3; P=0.04). In the Nocturnal Trial, changes in perceived burden were inversely correlated with adherence to dialysis treatments (Pearson r=-0.35; P=0.02). Relative to conventional hemodialysis, in-center daily hemodialysis did not result in higher perceptions of caregiver burden. There was a trend to higher perceived caregiver burden among patients randomized to home nocturnal hemodialysis. These findings may have implications for the adoption of and adherence to frequent nocturnal hemodialysis.

  15. The psychological well-being and prenatal bonding of gestational surrogates.

    Science.gov (United States)

    Lamba, N; Jadva, V; Kadam, K; Golombok, S

    2018-02-23

    How does the psychological well-being and prenatal bonding of Indian surrogates differ from a comparison group of mothers? Surrogates had higher levels of depression during pregnancy and post-birth, displayed lower emotional connection with the unborn baby, and greater care towards the healthy growth of the foetus, than the comparison group of mothers. Studies in the West have found that surrogates do not suffer long-term psychological harm. One study has shown that surrogates bond less with the foetus than expectant mothers. This study uses a prospective, longitudinal and cross-sectional design. Surrogates and a matched group of expectant mothers were seen twice, during 4-9 months of pregnancy and 4-6 months after the birth. Semi-structured interviews and standardized questionnaires were administered to 50 surrogates and 69 expectant mothers during pregnancy and 45 surrogates and 49 expectant mothers post-birth. All gestational surrogates were hosting pregnancies for international intended parents. Surrogates had higher levels of depression compared to the comparison group of mothers, during pregnancy and post-birth (P surrogacy and criticism from others were found to be predictive of higher depression in surrogates post-birth (P < 0.05). Regarding prenatal bonding, surrogates interacted less with and thought less about the foetus but adopted better eating habits and were more likely to avoid unhealthy practices during pregnancy, than expectant mothers (P < 0.05). No associations were found between greater prenatal bonding and greater psychological distress during pregnancy or after relinquishment. All surrogates were recruited from one clinic in Mumbai, and thus the representativeness of this sample is not known. Also, the possibility of socially desirable responding from surrogates cannot be ruled out. As this is the first study of the psychological well-being of surrogates in low-income countries, the findings have important policy implications. Providing

  16. Surrogate Parenthood Act 1988 (No. 65 of 1988), 6 October 1988.

    Science.gov (United States)

    1988-01-01

    This document contains provisions of the 1988 Queensland Australia Act prohibiting surrogate parenthood contracts. The Act defines "surrogate parent" and "prescribed contract" and prohibits the publication of any type of document which intends to induce a person to act as a surrogate parent, to seek such a person, or to state willingness to act as a surrogate. Offering to enter into a prescribed contract holds a penalty of 100 penalty units or three years' imprisonment or both. This Act applies if the offense occurs in Queensland or if the offender is normally a resident of Queensland, irrespective of where the offense occurs.

  17. Meeting report: Measuring endocrine-sensitive endpoints within the first years of life

    DEFF Research Database (Denmark)

    Arbuckle, T.E.; Hauser, R.; Swan, S.H.

    2008-01-01

    An international workshop tided "Assessing Endocrine-Related Endpoints within the First Years of Life" was held 30 April-1 May 2007, in Ottawa, Ontario, Canada. Representatives from a number of pregnancy cohort studies in North America and Europe presented options for measuring various endocrine......-sensitive endpoints in early life and discussed issues related to performing and using those measures. The workshop focused on measuring reproductive tract developmental endpoints [e.g., anogenital distance (AGD)], endocrine status, and infant anthropometry. To the extent possible, workshop participants strove...... on the genital exam. Although a number of outcome measures recommended during the genital exam have been associated with exposure to endocrine-disrupting chemicals, little is known about how predictive these effects are of later reproductive health or other chronic health conditions....

  18. Deep inelastic scattering near the endpoint in soft-collinear effective theory

    International Nuclear Information System (INIS)

    Chay, Junegone; Kim, Chul

    2007-01-01

    We apply the soft-collinear effective theory to deep inelastic scattering near the endpoint region. The forward scattering amplitude and the structure functions are shown to factorize as a convolution of the Wilson coefficients, the jet functions, and the parton distribution functions. The behavior of the parton distribution functions near the endpoint region is considered. It turns out that it evolves with the Altarelli-Parisi kernel even in the endpoint region, and the parton distribution function can be factorized further into a collinear part and the soft Wilson line. The factorized form for the structure functions is obtained by the two-step matching, and the radiative corrections or the evolution for each factorized part can be computed in perturbation theory. We present the radiative corrections of each factorized part to leading order in α s , including the zero-bin subtraction for the collinear part

  19. Implementation of minimally invasive and objective humane endpoints in the study of murine Plasmodium infections

    DEFF Research Database (Denmark)

    Dellavalle, B; Kirchhoff, J; Maretty, L

    2014-01-01

    SUMMARY Defining appropriate and objective endpoints for animal research can be difficult. Previously we evaluated and implemented a body temperature (BT) of ECM) and were interested in a similar endpoint for a model of severe malarial...... anaemia (SMA). Furthermore, we investigate the potential of a minimally invasive, non-contact infrared thermometer for repeated BT measurement. ECM was induced with Plasmodium berghei ANKA infection in C57Bl/6 mice. SMA was induced with Plasmodium chabaudi AS infection in A/J mice. Our previous published...... endpoint was applied in ECM and 30 °C was pre-determined as the lowest permitted limit for termination in SMA according to consultation with the Danish Animal Inspectorate. Infrared thermometer was compared with the rectal probe after cervical dislocation, ECM and SMA. Linear regression analysis of rectal...

  20. Behavior of radioactive metal surrogates under various waste combustion conditions

    International Nuclear Information System (INIS)

    Yang, Hee Chul; Lee, Jae Hee; Kim, Jung Guk; Yoo, Jae Hyung; Kim, Joon Hyung

    2002-01-01

    A laboratory investigation of the behavior of radioactive metals under the various waste combustion atmospheres was conducted to predict the parameters that influence their partitioning behavior during waste incineration. Neodymium, samarium, cerium, gadolinium, cesium and cobalt were used as non-radioactive surrogate metals that are representative of uranium, plutonium, americium, curium, radioactive cesium, and radioactive cobalt, respectively. Except for cesium, all of the investigated surrogate metal compounds converted into each of their stable oxides at medium temperatures from 400 to 900 .deg. C, under oxygen-deficient and oxygen-sufficient atmospheres (0.001-atm and 0.21-atm O 2 ). At high temperatures above 1,400 .deg. C, cerium, neodymium and samarium in the form of their oxides started to vaporize but the vaporization rates were very slow up to 1500 .deg. C. Inorganic chlorine (NaCl) as well as organic chlorine (PVC) did not impact the volatility of investigated Nd 2 O 3 , CoO and Cs 2 O. The results of laboratory investigations suggested that the combustion chamber operating parameters affecting the entrainment of particulate and filtration equipment operating parameters affecting particle collection efficiency be the governing parameters of alpha radionuclides partitioning during waste incineration

  1. Surrogate modeling of joint flood risk across coastal watersheds

    Science.gov (United States)

    Bass, Benjamin; Bedient, Philip

    2018-03-01

    This study discusses the development and performance of a rapid prediction system capable of representing the joint rainfall-runoff and storm surge flood response of tropical cyclones (TCs) for probabilistic risk analysis. Due to the computational demand required for accurately representing storm surge with the high-fidelity ADvanced CIRCulation (ADCIRC) hydrodynamic model and its coupling with additional numerical models to represent rainfall-runoff, a surrogate or statistical model was trained to represent the relationship between hurricane wind- and pressure-field characteristics and their peak joint flood response typically determined from physics based numerical models. This builds upon past studies that have only evaluated surrogate models for predicting peak surge, and provides the first system capable of probabilistically representing joint flood levels from TCs. The utility of this joint flood prediction system is then demonstrated by improving upon probabilistic TC flood risk products, which currently account for storm surge but do not take into account TC associated rainfall-runoff. Results demonstrate the source apportionment of rainfall-runoff versus storm surge and highlight that slight increases in flood risk levels may occur due to the interaction between rainfall-runoff and storm surge as compared to the Federal Emergency Management Association's (FEMAs) current practices.

  2. Eight years' experience with an IVF surrogate gestational pregnancy programme.

    Science.gov (United States)

    Raziel, Arieh; Schachter, Morey; Strassburger, Deborah; Komarovsky, Dafna; Ron-El, Raphael; Friedler, Shevach

    2005-08-01

    The aim of this study was to retrospectively audit eight years' experience of an IVF surrogate gestational programme and to compare the outcome of surrogacy due to absence of the uterus with surrogacy indicated for repeated IVF failure and recurrent abortions. A total of 60 cycles of IVF surrogate pregnancy were initiated in 19 treated couples. Absence of the uterus was the indication for surrogacy in 10 cases: Rokitansky syndrome (eight cases) and post-hysterectomy (two cases) designated as group A. The indications in the remaining nine patients (group B) were: IVF implantation failure (three cases), habitual abortions (four cases) and deteriorating maternal diseases (two cases). IVF performance and subsequent pregnancy outcome of groups A and B were compared. There was no difference in ovarian stimulation parameters and in IVF performance between the groups A and B. The overall pregnancy rate per transfer was 10/60 (17%). The pregnancy rates per patient and per transfer were 7/10 (70%) and 7/35 (20%) in group A compared with 3/9 (33%) and 3/25 (12%) in group B. A median number of three treatment cycles were needed to achieve pregnancy. In conclusion, the existence or absence of the uterus in the commissioning mothers is irrelevant for their IVF performance and conception rates. In patients who conceived after more than three IVF cycles, an additional 'oocyte factor' might be present.

  3. Simultaneous Thermal Analysis of Remediated Nitrate Salt Surrogates

    Energy Technology Data Exchange (ETDEWEB)

    Wayne, David Matthew [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-05-13

    The actinide engineering and science group (MET-1) have completed simultaneous thermal analysis and offgas analysis by mass spectrometry (STA-MS) of remediated nitrate salt (RNS) surrogates formulated by the high explosives science and technology group (M-7). The 1.0 to 1.5g surrogate samples were first analyzed as received, then a new set was analyzed with 100-200mL 10M HNO3 +0.3 MHF added, and a third set was analyzed after 200 mL of a concentrated Pu-AM spike (in 10M HNO3 +0.3 MHF) was added. The acid and spike solutions were formulated by the actinide analytical chemistry group (C-AAC) using reagent-grade HNO3 and HF, which was also used to dissolve a small quantity of mixed, high-fired PuO2/ AmO2 oxide.

  4. The development of radioactive sample surrogates for training and exercises

    Energy Technology Data Exchange (ETDEWEB)

    Martha Finck; Bevin Brush; Dick Jansen; David Chamberlain; Don Dry; George Brooks; Margaret Goldberg

    2012-03-01

    The development of radioactive sample surrogates for training and exercises Source term information is required for to reconstruct a device used in a dispersed radiological dispersal device. Simulating a radioactive environment to train and exercise sampling and sample characterization methods with suitable sample materials is a continued challenge. The Idaho National Laboratory has developed and permitted a Radioactive Response Training Range (RRTR), an 800 acre test range that is approved for open air dispersal of activated KBr, for training first responders in the entry and exit from radioactively contaminated areas, and testing protocols for environmental sampling and field characterization. Members from the Department of Defense, Law Enforcement, and the Department of Energy participated in the first contamination exercise that was conducted at the RRTR in the July 2011. The range was contaminated using a short lived radioactive Br-82 isotope (activated KBr). Soil samples contaminated with KBr (dispersed as a solution) and glass particles containing activated potassium bromide that emulated dispersed radioactive materials (such as ceramic-based sealed source materials) were collected to assess environmental sampling and characterization techniques. This presentation summarizes the performance of a radioactive materials surrogate for use as a training aide for nuclear forensics.

  5. Bayesian calibration of the Community Land Model using surrogates

    Energy Technology Data Exchange (ETDEWEB)

    Ray, Jaideep; Hou, Zhangshuan; Huang, Maoyi; Swiler, Laura Painton

    2014-02-01

    We present results from the Bayesian calibration of hydrological parameters of the Community Land Model (CLM), which is often used in climate simulations and Earth system models. A statistical inverse problem is formulated for three hydrological parameters, conditional on observations of latent heat surface fluxes over 48 months. Our calibration method uses polynomial and Gaussian process surrogates of the CLM, and solves the parameter estimation problem using a Markov chain Monte Carlo sampler. Posterior probability densities for the parameters are developed for two sites with different soil and vegetation covers. Our method also allows us to examine the structural error in CLM under two error models. We find that surrogate models can be created for CLM in most cases. The posterior distributions are more predictive than the default parameter values in CLM. Climatologically averaging the observations does not modify the parameters' distributions significantly. The structural error model reveals a correlation time-scale which can be used to identify the physical process that could be contributing to it. While the calibrated CLM has a higher predictive skill, the calibration is under-dispersive.

  6. Physical and mechanical properties of degraded waste surrogate material

    International Nuclear Information System (INIS)

    Hansen, F.D.; Mellegard, K.D.

    1998-03-01

    This paper discusses rock mechanics testing of surrogate materials to provide failure criteria for compacted, degraded nuclear waste. This daunting proposition was approached by first assembling all known parameters such as the initial waste inventory and rock mechanics response of the underground setting after the waste is stored. Conservative assumptions allowing for extensive degradation processes helped quantify the lowest possible strength conditions of the future state of the waste. In the larger conceptual setting, computations involve degraded waste behavior in transient pressure gradients as gas exits the waste horizon into a wellbore. Therefore, a defensible evaluation of tensile strength is paramount for successful analyses and intentionally provided maximal failed volumes. The very conservative approach assumes rampant degradation to define waste surrogate composition. Specimens prepared from derivative degradation product were consolidated into simple geometries for rock mechanics testing. Tensile strength thus derived helped convince a skeptical peer review panel that drilling into the Waste Isolation Pilot Plant (WIPP) would not likely expel appreciable solids via the drill string

  7. Characterization of surrogate radioactive cemented waste: a laboratory study

    International Nuclear Information System (INIS)

    Fiset, J.F.; Lastra, R.; Bilodeau, A.; Bouzoubaa

    2011-01-01

    Portland cement is commonly used to stabilize intermediate and low level of radioactive wastes. The stabilization/solidification process needs to be well understood as waste constituents can retard or activate cement hydration. The objectives of this project were to prepare surrogate radioactive cemented waste (SRCW), develop a comminution strategy for SRCW, determine its chemical characteristics, and develop processes for long term storage. This paper emphasizes on the characterization of surrogate radioactive cemented waste. The SRCW produced showed a high degree of heterogeneity mainly due to the method used to add the solution to the host cement. Heavy metals such as uranium and mercury were not distributed uniformly in the pail. Mineralogical characterization (SEM, EDS) showed that uranium is located around the rims of hydrated cement particles. In the SRCW, uranium occurs possibly in the form of a hydrated calcium uranate.The SEM-EDS results also suggest that mercury occurs mainly in the form of HgO although some metallic mercury may be also present as a result of partial decomposition of the HgO. (author)

  8. The effectiveness of surrogate taxa to conserve freshwater biodiversity

    Science.gov (United States)

    Stewart, David R.; Underwood, Zachary E.; Rahel, Frank J.; Walters, Annika W.

    2018-01-01

    Establishing protected areas has long been an effective conservation strategy, and is often based on more readily surveyed species. The potential of any freshwater taxa to be a surrogate of other aquatic groups has not been fully explored. We compiled occurrence data on 72 species of freshwater fish, amphibians, mussels, and aquatic reptiles for the Great Plains, Wyoming. We used hierarchical Bayesian multi-species mixture models and MaxEnt models to describe species distributions, and program Zonation to identify conservation priority areas for each aquatic group. The landscape-scale factors that best characterized aquatic species distributions differed among groups. There was low agreement and congruence among taxa-specific conservation priorities (<20%), meaning that no surrogate priority areas would include or protect the best habitats of other aquatic taxa. We found that common, wide-ranging aquatic species were included in taxa-specific priority areas, but rare freshwater species were not included. Thus, the development of conservation priorities based on a single freshwater aquatic group would not protect all species in the other aquatic groups.

  9. Defining useful surrogates for user participation in online medical learning.

    LENUS (Irish Health Repository)

    Beddy, Peter

    2012-02-01

    "School for Surgeons" is a web-based distance learning program which provides online clinical-based tutorials to surgical trainees. Our aim was to determine surrogates of active participation and to assess the efficacy of methods to improve usage. Server logs of the 82 participants in the "School for Surgeons" were assessed for the two terms of the first year of the program. Data collected included total time online, mean session time, page requests, numbers of sessions online and the total number of assignments. An intervention regarding comparative peer usage patterns was delivered to the cohort between terms one and two. Of the 82 trainees enrolled, 83% (85% second term) logged into the program. Of all participants 88% (97% second term) submitted at least one assignment. Median submissions were four (eight second term) per trainee. Assignment submission closely correlated with number of sessions, total time online, downloads and page requests. Peer-based comparative feedback resulted in a significant increase in the number of assignments submitted (p < 0.01). Despite its recent introduction, "School for Surgeons" has a good participation rate. Assignment submission is a valid surrogate for usage. Students can be encouraged to move from passive observation to active participation in a virtual learning environment by providing structured comparative feedback ranking their performance.

  10. Surrogate reservoir models for CSI well probabilistic production forecast

    Directory of Open Access Journals (Sweden)

    Saúl Buitrago

    2017-09-01

    Full Text Available The aim of this work is to present the construction and use of Surrogate Reservoir Models capable of accurately predicting cumulative oil production for every well stimulated with cyclic steam injection at any given time in a heavy oil reservoir in Mexico considering uncertain variables. The central composite experimental design technique was selected to capture the maximum amount of information from the model response with a minimum number of reservoir models simulations. Four input uncertain variables (the dead oil viscosity with temperature, the reservoir pressure, the reservoir permeability and oil sand thickness hydraulically connected to the well were selected as the ones with more impact on the initial hot oil production rate according to an analytical production prediction model. Twenty five runs were designed and performed with the STARS simulator for each well type on the reservoir model. The results show that the use of Surrogate Reservoir Models is a fast viable alternative to perform probabilistic production forecasting of the reservoir.

  11. Comparison of RNA-seq and microarray-based models for clinical endpoint prediction.

    Science.gov (United States)

    Zhang, Wenqian; Yu, Ying; Hertwig, Falk; Thierry-Mieg, Jean; Zhang, Wenwei; Thierry-Mieg, Danielle; Wang, Jian; Furlanello, Cesare; Devanarayan, Viswanath; Cheng, Jie; Deng, Youping; Hero, Barbara; Hong, Huixiao; Jia, Meiwen; Li, Li; Lin, Simon M; Nikolsky, Yuri; Oberthuer, André; Qing, Tao; Su, Zhenqiang; Volland, Ruth; Wang, Charles; Wang, May D; Ai, Junmei; Albanese, Davide; Asgharzadeh, Shahab; Avigad, Smadar; Bao, Wenjun; Bessarabova, Marina; Brilliant, Murray H; Brors, Benedikt; Chierici, Marco; Chu, Tzu-Ming; Zhang, Jibin; Grundy, Richard G; He, Min Max; Hebbring, Scott; Kaufman, Howard L; Lababidi, Samir; Lancashire, Lee J; Li, Yan; Lu, Xin X; Luo, Heng; Ma, Xiwen; Ning, Baitang; Noguera, Rosa; Peifer, Martin; Phan, John H; Roels, Frederik; Rosswog, Carolina; Shao, Susan; Shen, Jie; Theissen, Jessica; Tonini, Gian Paolo; Vandesompele, Jo; Wu, Po-Yen; Xiao, Wenzhong; Xu, Joshua; Xu, Weihong; Xuan, Jiekun; Yang, Yong; Ye, Zhan; Dong, Zirui; Zhang, Ke K; Yin, Ye; Zhao, Chen; Zheng, Yuanting; Wolfinger, Russell D; Shi, Tieliu; Malkas, Linda H; Berthold, Frank; Wang, Jun; Tong, Weida; Shi, Leming; Peng, Zhiyu; Fischer, Matthias

    2015-06-25

    Gene expression profiling is being widely applied in cancer research to identify biomarkers for clinical endpoint prediction. Since RNA-seq provides a powerful tool for transcriptome-based applications beyond the limitations of microarrays, we sought to systematically evaluate the performance of RNA-seq-based and microarray-based classifiers in this MAQC-III/SEQC study for clinical endpoint prediction using neuroblastoma as a model. We generate gene expression profiles from 498 primary neuroblastomas using both RNA-seq and 44 k microarrays. Characterization of the neuroblastoma transcriptome by RNA-seq reveals that more than 48,000 genes and 200,000 transcripts are being expressed in this malignancy. We also find that RNA-seq provides much more detailed information on specific transcript expression patterns in clinico-genetic neuroblastoma subgroups than microarrays. To systematically compare the power of RNA-seq and microarray-based models in predicting clinical endpoints, we divide the cohort randomly into training and validation sets and develop 360 predictive models on six clinical endpoints of varying predictability. Evaluation of factors potentially affecting model performances reveals that prediction accuracies are most strongly influenced by the nature of the clinical endpoint, whereas technological platforms (RNA-seq vs. microarrays), RNA-seq data analysis pipelines, and feature levels (gene vs. transcript vs. exon-junction level) do not significantly affect performances of the models. We demonstrate that RNA-seq outperforms microarrays in determining the transcriptomic characteristics of cancer, while RNA-seq and microarray-based models perform similarly in clinical endpoint prediction. Our findings may be valuable to guide future studies on the development of gene expression-based predictive models and their implementation in clinical practice.

  12. A systematic comparison of recurrent event models for application to composite endpoints.

    Science.gov (United States)

    Ozga, Ann-Kathrin; Kieser, Meinhard; Rauch, Geraldine

    2018-01-04

    Many clinical trials focus on the comparison of the treatment effect between two or more groups concerning a rarely occurring event. In this situation, showing a relevant effect with an acceptable power requires the observation of a large number of patients over a long period of time. For feasibility issues, it is therefore often considered to include several event types of interest, non-fatal or fatal, and to combine them within a composite endpoint. Commonly, a composite endpoint is analyzed with standard survival analysis techniques by assessing the time to the first occurring event. This approach neglects that an individual may experience more than one event which leads to a loss of information. As an alternative, composite endpoints could be analyzed by models for recurrent events. There exists a number of such models, e.g. regression models based on count data or Cox-based models such as the approaches of Andersen and Gill, Prentice, Williams and Peterson or, Wei, Lin and Weissfeld. Although some of the methods were already compared within the literature there exists no systematic investigation for the special requirements regarding composite endpoints. Within this work a simulation-based comparison of recurrent event models applied to composite endpoints is provided for different realistic clinical trial scenarios. We demonstrate that the Andersen-Gill model and the Prentice- Williams-Petersen models show similar results under various data scenarios whereas the Wei-Lin-Weissfeld model delivers effect estimators which can considerably deviate under commonly met data scenarios. Based on the conducted simulation study, this paper helps to understand the pros and cons of the investigated methods in the context of composite endpoints and provides therefore recommendations for an adequate statistical analysis strategy and a meaningful interpretation of results.

  13. Reducing sample size by combining superiority and non-inferiority for two primary endpoints in the Social Fitness study.

    Science.gov (United States)

    Donkers, Hanneke; Graff, Maud; Vernooij-Dassen, Myrra; Nijhuis-van der Sanden, Maria; Teerenstra, Steven

    2017-01-01

    In randomized controlled trials, two endpoints may be necessary to capture the multidimensional concept of the intervention and the objectives of the study adequately. We show how to calculate sample size when defining success of a trial by combinations of superiority and/or non-inferiority aims for the endpoints. The randomized controlled trial design of the Social Fitness study uses two primary endpoints, which can be combined into five different scenarios for defining success of the trial. We show how to calculate power and sample size for each scenario and compare these for different settings of power of each endpoint and correlation between them. Compared to a single primary endpoint, using two primary endpoints often gives more power when success is defined as: improvement in one of the two endpoints and no deterioration in the other. This also gives better power than when success is defined as: improvement in one prespecified endpoint and no deterioration in the remaining endpoint. When two primary endpoints are equally important, but a positive effect in both simultaneously is not per se required, the objective of having one superior and the other (at least) non-inferior could make sense and reduce sample size. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Radiometric titration of officinal radiopharmaceuticals using radioactive kryptonates as end-point indicators. I

    International Nuclear Information System (INIS)

    Toelgyessy, J.; Dillinger, P.; Harangozo, M.; Jombik, J.

    1980-01-01

    A method for the determination of salicylic, acetylsalicylic and benzoic acids in officinal pharmaceutical based on radiometric titration with 0.1 mol.l -1 NaOH was developed. The end-point was detected with the aid of radioactive glass kryptonate. After the end-point, the excess titrant attacks the glass surface layers and this results in releasing 85 Kr, and consequently, in decreasing the radioactivity of the kryptonate employed. The radioactive kryptonate used as an indicator was prepared by the bombardment of glass with accelerated 85 Kr ions. The developed method is simple, accurate and correct. (author)

  15. A duplex endpoint PCR assay for rapid detection and differentiation of Leptospira strains.

    Science.gov (United States)

    Benacer, Douadi; Zain, Siti Nursheena Mohd; Lewis, John W; Khalid, Mohd Khairul Nizam Mohd; Thong, Kwai Lin

    2017-01-01

    This study aimed to develop a duplex endpoint PCR assay for rapid detection and differentiation of Leptospira strains. Primers were designed to target the rrs (LG1/LG2) and ligB (LP1/LP2) genes to confirm the presence of the Leptospira genus and the pathogenic species, respectively. The assay showed 100% specificity against 17 Leptospira strains with a limit of detection of 23.1pg/µl of leptospiral DNA and sensitivity of 103 leptospires/ml in both spiked urine and water. Our duplex endpoint PCR assay is suitable for rapid early detection of Leptospira with high sensitivity and specificity.

  16. Comparison of methods for accurate end-point detection of potentiometric titrations

    International Nuclear Information System (INIS)

    Villela, R L A; Borges, P P; Vyskočil, L

    2015-01-01

    Detection of the end point in potentiometric titrations has wide application on experiments that demand very low measurement uncertainties mainly for certifying reference materials. Simulations of experimental coulometric titration data and consequential error analysis of the end-point values were conducted using a programming code. These simulations revealed that the Levenberg-Marquardt method is in general more accurate than the traditional second derivative technique used currently as end-point detection for potentiometric titrations. Performance of the methods will be compared and presented in this paper

  17. Comparison of methods for accurate end-point detection of potentiometric titrations

    Science.gov (United States)

    Villela, R. L. A.; Borges, P. P.; Vyskočil, L.

    2015-01-01

    Detection of the end point in potentiometric titrations has wide application on experiments that demand very low measurement uncertainties mainly for certifying reference materials. Simulations of experimental coulometric titration data and consequential error analysis of the end-point values were conducted using a programming code. These simulations revealed that the Levenberg-Marquardt method is in general more accurate than the traditional second derivative technique used currently as end-point detection for potentiometric titrations. Performance of the methods will be compared and presented in this paper.

  18. Verifying Elimination Programs with a Special Emphasis on Cysticercosis Endpoints and Postelimination Surveillance

    Directory of Open Access Journals (Sweden)

    Sukwan Handali

    2012-01-01

    Full Text Available Methods are needed for determining program endpoints or postprogram surveillance for any elimination program. Cysticercosis has the necessary effective strategies and diagnostic tools for establishing an elimination program; however, tools to verify program endpoints have not been determined. Using a statistical approach, the present study proposed that taeniasis and porcine cysticercosis antibody assays could be used to determine with a high statistical confidence whether an area is free of disease. Confidence would be improved by using secondary tests such as the taeniasis coproantigen assay and necropsy of the sentinel pigs.

  19. Federal Funding Accountability and Transparency Act frequently asked questions

    Science.gov (United States)

    One stop shop for Federal Funding Accountability and Transparency Act (FFATA) questions. This frequently asked document will assist with Federal Funding Accountability and Transparency Act (FFATA) related questions.

  20. Inconsistent approaches of the G-BA regarding acceptance of primary study endpoints as being relevant to patients - an analysis of three disease areas: oncological, metabolic, and infectious diseases

    Directory of Open Access Journals (Sweden)

    Thomas Staab

    2016-11-01

    Full Text Available Abstract Background Previous evaluations of oncological medicines in the German early benefit assessment (EBA procedure have demonstrated inconsistent acceptance of endpoints by regulatory authorities and the Federal Joint Committee (G-BA. Accepted standard endpoints for regulatory purposes are frequently not considered as patient-relevant in the German EBA system. In this study the acceptance of clinically acknowledged primary endpoints (PEPs from regulatory trials in EBAs conducted by the G-BA was evaluated across three therapeutic areas. Methods Medicines for oncological, metabolic and infectious diseases with EBAs finalised before 25 January 2016 were evaluated. Respective manufacturer’s dossiers, regulatory assessments, G-BA appraisals and oral hearing minutes were reviewed, and PEPs were examined to determine whether they were considered relevant to patients by the G-BA. Furthermore, the acceptance of symptomatic vs asymptomatic PEPs was also analysed. Results A total of 65 EBAs were evaluated. Mortality PEPs were widely accepted as patient-relevant but were only used in a minority of EBAs and exclusively in oncological diseases. Morbidity PEPs constituted around 72 % of assessed PEPs, but were excluded from the EBA in over half of the corresponding assessments as they were not considered patient-relevant. Symptomatic endpoints were largely deemed patient-relevant, whereas acceptance of asymptomatic endpoints varied between therapeutic areas. Conclusions This evaluation identified inconsistencies in patient relevance of morbidity-related PEPs as well as in acceptance of asymptomatic endpoints by the G-BA in all three disease areas examined. Better harmonisation between the regulatory authorities and the G-BA is still required after 5 years of AMNOG health technology assessment in Germany.

  1. A cross-cultural study on surrogate mother's empathy and maternal-foetal attachment.

    Science.gov (United States)

    Lorenceau, Ellen Schenkel; Mazzucca, Luis; Tisseron, Serge; Pizitz, Todd D

    2015-06-01

    Traditional and gestational surrogate mothers assist infertile couples by carrying their children. In 2005, a meta-analysis on surrogacy was conducted but no study had examined empathy and maternal-foetal attachment of surrogate mothers. Assessments of surrogate mothers show no sign of psychopathology, but one study showed differences on several MMPI-2 scales compared to a normative sample: surrogate mothers identified with stereotypically masculine traits such as assertiveness and competition. They had a higher self-esteem and lower levels of anxiety and depression. To determine if there is a difference in empathy and maternal-foetal attachment of surrogate mothers compared to a comparison group of mothers. Three groups of European traditional and gestational surrogate mothers (n=10), Anglo-Saxon traditional and gestational surrogate mothers (n=34) and a European normative sample of mothers (n=32) completed four published psychometric instruments: the Interpersonal Reactivity Index (empathy index), the Hospital Anxiety and Depressions Scale and the MC20, a social desirability scale. Pregnant surrogate mothers filled the Maternal Antenatal Attachment Scale (n=11). Statistical non-parametric analyses of variance were conducted. Depending on cultural background, surrogate mothers present differences in terms of empathy, anxiety and depression, social desirability and quality of attachment to the foetus compared to a normative sample. Environment plays a role for traditional and gestational surrogacy. Surrogate mothers of both groups are less anxious and depressed than normative samples. Maternal-foetal attachment is strong with a slightly lower quality of attachment. Surrogate mother's empathy indexes are similar to normative samples, sometimes higher. Copyright © 2014 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  2. Critical care physicians’ approaches to negotiating with surrogate decision makers: a qualitative study

    Science.gov (United States)

    Brush, David R.; Brown, Crystal E.; Alexander, G. Caleb

    2013-01-01

    Objective To describe how critical care physicians manage conflicts with surrogates about withdrawing or withholding patients’ life support. Design Qualitative analysis of key informant interviews with critical care physicians during 2010. We transcribed interviews verbatim and used grounded theory to code and revise a taxonomy of themes and to identify illustrative quotes. Setting 3 academic medical centers, 1 academic-affiliated medical center and 4 private practice groups or private hospitals in a large Midwestern city Subjects 14 critical care physicians Measurements and main results Physicians reported tailoring their approach to address specific reasons for disagreement with surrogates. Five common approaches were identified: (1) building trust, (2) educating and informing, (3) providing surrogates more time, (4) adjusting surrogate and physician roles, and (5) highlighting specific values. When mistrust was an issue, physicians endeavored to build a more trusting relationship with the surrogate before re-addressing decision making. Physicians also reported correcting misunderstandings by providing targeted education, and some reported highlighting specific patient, surrogate, or physician values that they hoped would guide surrogates to agree with them. When surrogates struggled with decision making roles, physicians attempted to reinforce the concept of substituted judgment. Physicians noted that some surrogates needed time to “come to terms” with the patent’s illness before agreeing with physicians. Many physicians had witnessed colleagues negotiate in ways they found objectionable, such as providing misleading information, injecting their own values into the negotiation, or behaving unprofessionally towards surrogates. While some physicians viewed their efforts to encourage surrogates’ agreement as persuasive, others strongly denied persuading surrogates and described their actions as “guiding” or “negotiating.” Conclusions Physicians

  3. Surrogate decision makers' perspectives on preventable breakdowns in care among critically ill patients: A qualitative study.

    Science.gov (United States)

    Fisher, Kimberly A; Ahmad, Sumera; Jackson, Madeline; Mazor, Kathleen M

    2016-10-01

    To describe surrogate decision makers' (SDMs) perspectives on preventable breakdowns in care among critically ill patients. We screened 70 SDMs of critically ill patients for those who identified a preventable breakdown in care, defined as an event where the SDM believes something "went wrong", that could have been prevented, and resulted in harm. In-depth interviews were conducted with SDMs who identified an eligible event. 32 of 70 participants (46%) identified at least one preventable breakdown in care, with a total of 75 discrete events. Types of breakdowns involved medical care (n=52), communication (n=59), and both (n=40). Four additional breakdowns were related to problems with SDM bedside access to the patient. Adverse consequences of breakdowns included physical harm, need for additional medical care, emotional distress, pain, suffering, loss of trust, life disruption, impaired decision making, and financial expense. 28 of 32 SDMs raised their concerns with clinicians, yet only 25% were satisfactorily addressed. SDMs of critically ill patients frequently identify preventable breakdowns in care which result in harm. An in-depth understanding of the types of events SDMs find problematic and the associated harms is an important step towards improving the safety and patient-centeredness of healthcare. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Focus Group Study Exploring Factors Related to Frequent Sickness Absence.

    Directory of Open Access Journals (Sweden)

    Annette Notenbomer

    Full Text Available Research investigating frequent sickness absence (3 or more episodes per year is scarce and qualitative research from the perspective of frequent absentees themselves is lacking. The aim of the current study is to explore awareness, determinants of and solutions to frequent sickness absence from the perspective of frequent absentees themselves.We performed a qualitative study of 3 focus group discussions involving a total of 15 frequent absentees. Focus group discussions were audiotaped and transcribed verbatim. Results were analyzed with the Graneheim method using the Job Demands Resources (JD-R model as theoretical framework.Many participants were not aware of their frequent sickness absence and the risk of future long-term sickness absence. As determinants, participants mentioned job demands, job resources, home demands, poor health, chronic illness, unhealthy lifestyles, and diminished feeling of responsibility to attend work in cases of low job resources. Managing these factors and improving communication (skills were regarded as solutions to reduce frequent sickness absence.The JD-R model provided a framework for determinants of and solutions to frequent sickness absence. Additional determinants were poor health, chronic illness, unhealthy lifestyles, and diminished feeling of responsibility to attend work in cases of low job resources. Frequent sickness absence should be regarded as a signal that something is wrong. Managers, supervisors, and occupational health care providers should advise and support frequent absentees to accommodate job demands, increase both job and personal resources, and improve health rather than express disapproval of frequent sickness absence and apply pressure regarding work attendance.

  5. Error modeling for surrogates of dynamical systems using machine learning: Machine-learning-based error model for surrogates of dynamical systems

    International Nuclear Information System (INIS)

    Trehan, Sumeet; Carlberg, Kevin T.; Durlofsky, Louis J.

    2017-01-01

    A machine learning–based framework for modeling the error introduced by surrogate models of parameterized dynamical systems is proposed. The framework entails the use of high-dimensional regression techniques (eg, random forests, and LASSO) to map a large set of inexpensively computed “error indicators” (ie, features) produced by the surrogate model at a given time instance to a prediction of the surrogate-model error in a quantity of interest (QoI). This eliminates the need for the user to hand-select a small number of informative features. The methodology requires a training set of parameter instances at which the time-dependent surrogate-model error is computed by simulating both the high-fidelity and surrogate models. Using these training data, the method first determines regression-model locality (via classification or clustering) and subsequently constructs a “local” regression model to predict the time-instantaneous error within each identified region of feature space. We consider 2 uses for the resulting error model: (1) as a correction to the surrogate-model QoI prediction at each time instance and (2) as a way to statistically model arbitrary functions of the time-dependent surrogate-model error (eg, time-integrated errors). We then apply the proposed framework to model errors in reduced-order models of nonlinear oil-water subsurface flow simulations, with time-varying well-control (bottom-hole pressure) parameters. The reduced-order models used in this work entail application of trajectory piecewise linearization in conjunction with proper orthogonal decomposition. Moreover, when the first use of the method is considered, numerical experiments demonstrate consistent improvement in accuracy in the time-instantaneous QoI prediction relative to the original surrogate model, across a large number of test cases. When the second use is considered, results show that the proposed method provides accurate statistical predictions of the time- and well

  6. 78 FR 73199 - Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs...

    Science.gov (United States)

    2013-12-05

    ... exposure measures is suitable for documenting BE (e.g., transdermal delivery systems and certain rectal and... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-D-1464] Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted...

  7. Baseline characteristics in the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE)

    DEFF Research Database (Denmark)

    Parving, Hans-Henrik; Brenner, Barry M; McMurray, John J V

    2012-01-01

    Patients with type 2 diabetes are at enhanced risk for macro- and microvascular complications. Albuminuria and/or reduced kidney function further enhances the vascular risk. We initiated the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE). Aliskiren, a novel direct renin...

  8. Can joint sound assess soft and hard endpoints of the Lachman test?: A preliminary study.

    Science.gov (United States)

    Hattori, Koji; Ogawa, Munehiro; Tanaka, Kazunori; Matsuya, Ayako; Uematsu, Kota; Tanaka, Yasuhito

    2016-05-12

    The Lachman test is considered to be a reliable physical examination for anterior cruciate ligament (ACL) injury. Patients with a damaged ACL demonstrate a soft endpoint feeling. However, examiners judge the soft and hard endpoints subjectively. The purpose of our study was to confirm objective performance of the Lachman test using joint auscultation. Human and porcine knee joints were examined. Knee joint sound during the Lachman test (Lachman sound) was analyzed by fast Fourier transformation. As quantitative indices of Lachman sound, the peak sound as the maximum relative amplitude (acoustic pressure) and its frequency were used. The mean Lachman peak sound for healthy volunteer knees was 86.9 ± 12.9 Hz in frequency and -40 ± 2.5 dB in acoustic pressure. The mean Lachman peak sound for intact porcine knees was 84.1 ± 9.4 Hz and -40.5 ± 1.7 dB. Porcine knees with ACL deficiency had a soft endpoint feeling during the Lachman test. The Lachman peak sounds of porcine knees with ACL deficiency were dispersed into four distinct groups, with center frequencies of around 40, 160, 450, and 1600. The Lachman peak sound was capable of assessing soft and hard endpoints of the Lachman test objectively.

  9. Coulometric Titration of Ethylenediaminetetraacetate (EDTA) with Spectrophotometric Endpoint Detection: An Experiment for the Instrumental Analysis Laboratory

    Science.gov (United States)

    Williams, Kathryn R.; Young, Vaneica Y.; Killian, Benjamin J.

    2011-01-01

    Ethylenediaminetetraacetate (EDTA) is commonly used as an anticoagulant in blood-collection procedures. In this experiment for the instrumental analysis laboratory, students determine the quantity of EDTA in commercial collection tubes by coulometric titration with electrolytically generated Cu[superscript 2+]. The endpoint is detected…

  10. A covariant open bosonic string field theory including the endpoint and middlepoint interaction

    International Nuclear Information System (INIS)

    Liu, B.G.; Northwest Univ., Xian; Chen, Y.X.

    1988-01-01

    Extending the usual endpoint and midpoint interactions, we introduce numerous kinds of interactions, labelled by a parameter λ and obtain a non-commutative and associative string field algebra by adding up all interactions. With this algebra we develop a covariant open bosonic string field theory, which reduces to Witten's open bosonic string field theory under a special string length choice. (orig.)

  11. Using an Ecosystem Approach to complement protection schemes based on organism-level endpoints

    International Nuclear Information System (INIS)

    Bradshaw, Clare; Kapustka, Lawrence; Barnthouse, Lawrence; Brown, Justin; Ciffroy, Philippe; Forbes, Valery; Geras'kin, Stanislav; Kautsky, Ulrik; Bréchignac, François

    2014-01-01

    Radiation protection goals for ecological resources are focussed on ecological structures and functions at population-, community-, and ecosystem-levels. The current approach to radiation safety for non-human biota relies on organism-level endpoints, and as such is not aligned with the stated overarching protection goals of international agencies. Exposure to stressors can trigger non-linear changes in ecosystem structure and function that cannot be predicted from effects on individual organisms. From the ecological sciences, we know that important interactive dynamics related to such emergent properties determine the flows of goods and services in ecological systems that human societies rely upon. A previous Task Group of the IUR (International Union of Radioecology) has presented the rationale for adding an Ecosystem Approach to the suite of tools available to manage radiation safety. In this paper, we summarize the arguments for an Ecosystem Approach and identify next steps and challenges ahead pertaining to developing and implementing a practical Ecosystem Approach to complement organism-level endpoints currently used in radiation safety. - Highlights: • An Ecosystem Approach to radiation safety complements the organism-level approach. • Emergent properties in ecosystems are not captured by organism-level endpoints. • The proposed Ecosystem Approach better aligns with management goals. • Practical guidance with respect to system-level endpoints is needed. • Guidance on computational model selection would benefit an Ecosystem Approach

  12. Impact of confinement housing on study end-points in the calf model of cryptosporidiosis.

    Science.gov (United States)

    Graef, Geneva; Hurst, Natalie J; Kidder, Lance; Sy, Tracy L; Goodman, Laura B; Preston, Whitney D; Arnold, Samuel L M; Zambriski, Jennifer A

    2018-04-01

    Diarrhea is the second leading cause of death in children confinement housing, and Interval Collection (IC), which permits use of box stalls. CFC mimics human challenge model methodology but it is unknown if confinement housing impacts study end-points and if data gathered via this method is suitable for generalization to human populations. Using a modified crossover study design we compared CFC and IC and evaluated the impact of housing on study end-points. At birth, calves were randomly assigned to confinement (n = 14) or box stall housing (n = 9), or were challenged with 5 x 107 C. parvum oocysts, and followed for 10 days. Study end-points included fecal oocyst shedding, severity of diarrhea, degree of dehydration, and plasma cortisol. Calves in confinement had no significant differences in mean log oocysts enumerated per gram of fecal dry matter between CFC and IC samples (P = 0.6), nor were there diurnal variations in oocyst shedding (P = 0.1). Confinement housed calves shed significantly more oocysts (P = 0.05), had higher plasma cortisol (P = 0.001), and required more supportive care (P = 0.0009) than calves in box stalls. Housing method confounds study end-points in the calf model of cryptosporidiosis. Due to increased stress data collected from calves in confinement housing may not accurately estimate the efficacy of chemotherapeutics targeting C. parvum.

  13. Deep vadose zone remediation: technical and policy challenges, opportunities, and progress in achieving cleanup endpoints

    International Nuclear Information System (INIS)

    Wellman, D.M.; Freshley, M.D.; Truex, M.J.; Lee, M.H.

    2013-01-01

    Current requirements for site remediation and closure are standards-based and are often overly conservative, costly, and in some cases, technically impractical. Use of risk-informed alternate endpoints provides a means to achieve remediation goals that are permitted by regulations and are protective of human health and the environment. Alternate endpoints enable the establishment of a path for cleanup that may include intermediate remedial milestones and transition points and/or regulatory alternatives to standards-based remediation. A framework is presented that is centered around developing and refining conceptual models in conjunction with assessing risks and potential endpoints as part of a system-based assessment that integrates site data with scientific understanding of processes that control the distribution and transport of contaminants in the subsurface and pathways to receptors. This system-based assessment and subsequent implementation of the remediation strategy with appropriate monitoring are targeted at providing a holistic approach to addressing risks to human health and the environment. This holistic approach also enables effective predictive analysis of contaminant behavior to provide defensible criteria and data for making long-term decisions. Developing and implementing an alternate endpoint-based approach for remediation and waste site closure presents a number of challenges and opportunities. Categories of these challenges include scientific and technical, regulatory, institutional, and budget and resource allocation issues. Opportunities exist for developing and implementing systems-based approaches with respect to supportive characterization, monitoring, predictive modeling, and remediation approaches. (authors)

  14. Alternate Endpoints for Deep Vadose Zone Environments: Challenges, Opportunities, and Progress - 13036

    International Nuclear Information System (INIS)

    Wellman, Dawn M.; Freshley, Mark D.; Truex, Michael J.; Lee, M. Hope

    2013-01-01

    Current requirements for site remediation and closure are standards-based and are often overly conservative, costly, and in some cases, technically impractical to achieve. Use of risk-informed alternate endpoints provide a means to achieve remediation goals that are permitted by regulations and are protective of human health and the environment. Alternate endpoints enable establishing a path for cleanup that may include intermediate remedial milestones and transition points and/or regulatory alternatives to standards-based remediation. A framework is presented that is centered around developing and refining conceptual models in conjunction with assessing risks and potential endpoints as part of a system-based assessment that integrates site data with scientific understanding of processes that control the distribution and transport of contaminants in the subsurface and pathways to receptors. This system-based assessment and subsequent implementation of the remediation strategy with appropriate monitoring are targeted at providing a holistic approach to addressing risks to human health and the environment. This holistic approach also enables effective predictive analysis of contaminant behavior to provide defensible criteria and data for making long-term decisions. Developing and implementing an alternate endpoint-based approach for remediation and waste site closure presents a number of challenges and opportunities. Categories of these challenges include scientific and technical, regulatory, institutional, and budget and resource allocation issues. Opportunities exist for developing and implementing systems-based approaches with respect to supportive characterization, monitoring, predictive modeling, and remediation approaches. (authors)

  15. Alternate Endpoints for Deep Vadose Zone Environments: Challenges, Opportunities, and Progress - 13036

    Energy Technology Data Exchange (ETDEWEB)

    Wellman, Dawn M.; Freshley, Mark D.; Truex, Michael J.; Lee, M. Hope [Pacific Northwest National Laboratory, 902 Battelle Blvd, Richland, WA, 99352 (United States)

    2013-07-01

    Current requirements for site remediation and closure are standards-based and are often overly conservative, costly, and in some cases, technically impractical to achieve. Use of risk-informed alternate endpoints provide a means to achieve remediation goals that are permitted by regulations and are protective of human health and the environment. Alternate endpoints enable establishing a path for cleanup that may include intermediate remedial milestones and transition points and/or regulatory alternatives to standards-based remediation. A framework is presented that is centered around developing and refining conceptual models in conjunction with assessing risks and potential endpoints as part of a system-based assessment that integrates site data with scientific understanding of processes that control the distribution and transport of contaminants in the subsurface and pathways to receptors. This system-based assessment and subsequent implementation of the remediation strategy with appropriate monitoring are targeted at providing a holistic approach to addressing risks to human health and the environment. This holistic approach also enables effective predictive analysis of contaminant behavior to provide defensible criteria and data for making long-term decisions. Developing and implementing an alternate endpoint-based approach for remediation and waste site closure presents a number of challenges and opportunities. Categories of these challenges include scientific and technical, regulatory, institutional, and budget and resource allocation issues. Opportunities exist for developing and implementing systems-based approaches with respect to supportive characterization, monitoring, predictive modeling, and remediation approaches. (authors)

  16. Deep vadose zone remediation: technical and policy challenges, opportunities, and progress in achieving cleanup endpoints

    Energy Technology Data Exchange (ETDEWEB)

    Wellman, D.M.; Freshley, M.D.; Truex, M.J.; Lee, M.H. [Pacific Northwest National Laboratory, Richland, Washington (United States)

    2013-07-01

    Current requirements for site remediation and closure are standards-based and are often overly conservative, costly, and in some cases, technically impractical. Use of risk-informed alternate endpoints provides a means to achieve remediation goals that are permitted by regulations and are protective of human health and the environment. Alternate endpoints enable the establishment of a path for cleanup that may include intermediate remedial milestones and transition points and/or regulatory alternatives to standards-based remediation. A framework is presented that is centered around developing and refining conceptual models in conjunction with assessing risks and potential endpoints as part of a system-based assessment that integrates site data with scientific understanding of processes that control the distribution and transport of contaminants in the subsurface and pathways to receptors. This system-based assessment and subsequent implementation of the remediation strategy with appropriate monitoring are targeted at providing a holistic approach to addressing risks to human health and the environment. This holistic approach also enables effective predictive analysis of contaminant behavior to provide defensible criteria and data for making long-term decisions. Developing and implementing an alternate endpoint-based approach for remediation and waste site closure presents a number of challenges and opportunities. Categories of these challenges include scientific and technical, regulatory, institutional, and budget and resource allocation issues. Opportunities exist for developing and implementing systems-based approaches with respect to supportive characterization, monitoring, predictive modeling, and remediation approaches. (authors)

  17. Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative

    DEFF Research Database (Denmark)

    Myles, P S; Boney, O; Botti, M

    2018-01-01

    Medicine initiative was established to derive a set of standardised endpoints for use in perioperative clinical trials. METHODS: We undertook a systematic review to identify measures of patient comfort used in the anaesthetic, surgical, and other perioperative literature. A multi-round Delphi consensus...

  18. End-point construction and systematic titration error in linear titration curves-complexation reactions

    NARCIS (Netherlands)

    Coenegracht, P.M.J.; Duisenberg, A.J.M.

    The systematic titration error which is introduced by the intersection of tangents to hyperbolic titration curves is discussed. The effects of the apparent (conditional) formation constant, of the concentration of the unknown component and of the ranges used for the end-point construction are

  19. Transmission assessment surveys (TAS) to define endpoints for lymphatic filariasis mass drug administration

    DEFF Research Database (Denmark)

    Chu, Brian K.; Deming, Michael; Biritwum, Nana-Kwadwo

    2013-01-01

    Lymphatic filariasis (LF) is targeted for global elimination through treatment of entire at-risk populations with repeated annual mass drug administration (MDA). Essential for program success is defining and confirming the appropriate endpoint for MDA when transmission is presumed to have reached...

  20. Iron Deficiency In Frequent And First Time Female Blood Donors ...

    African Journals Online (AJOL)

    Aim of the study: This study was conducted to evaluate the frequency of iron deficiency and relevant factors in frequent and first time female blood donors at Casablanca blood transfusion centre, Morocco. Methods: Between November 2005 and April 2006, twenty-one female first time and twenty-one frequent female blood ...

  1. Emergency Department Frequent Users for Acute Alcohol Intoxication.

    Science.gov (United States)

    Klein, Lauren R; Martel, Marc L; Driver, Brian E; Reing, Mackenzie; Cole, Jon B

    2018-03-01

    A subset of frequent users of emergency services are those who use the emergency department (ED) for acute alcohol intoxication. This population and their ED encounters have not been previously described. This was a retrospective, observational, cohort study of patients presenting to the ED for acute alcohol intoxication between 2012 and 2016. We collected all data from the electronic medical record. Frequent users for alcohol intoxication were defined as those with greater than 20 visits for acute intoxication without additional medical chief complaints in the previous 12 months. We used descriptive statistics to evaluate characteristics of frequent users for alcohol intoxication, as well as their ED encounters. We identified 32,121 patient encounters. Of those, 325 patients were defined as frequent users for alcohol intoxication, comprising 11,370 of the encounters during the study period. The median maximum number of encounters per person for alcohol intoxication in a one-year period was 47 encounters (range 20 to 169). Frequent users were older (47 years vs. 39 years), and more commonly male (86% vs. 71%). Frequent users for alcohol intoxication had higher rates of medical and psychiatric comorbidities including liver disease, chronic kidney disease, ischemic vascular disease, dementia, chronic obstructive pulmonary disease, history of traumatic brain injury, schizophrenia, and bipolar disorder. In this study, we identified a group of ED frequent users who use the ED for acute alcohol intoxication. This population had higher rates of medical and psychiatric comorbidities compared to non-frequent users.

  2. Classification and Target Group Selection Based Upon Frequent Patterns

    NARCIS (Netherlands)

    W.H.L.M. Pijls (Wim); R. Potharst (Rob)

    2000-01-01

    textabstractIn this technical report , two new algorithms based upon frequent patterns are proposed. One algorithm is a classification method. The other one is an algorithm for target group selection. In both algorithms, first of all, the collection of frequent patterns in the training set is

  3. Social environment and frequent attendance in Danish general practice

    DEFF Research Database (Denmark)

    Vedsted, Peter; Olesen, Frede

    2005-01-01

    of 1423 (73.7%) frequent attenders and 1103 (74.9%) infrequent attenders responded. Male frequent attendance was associated, with statistical significance, with living alone and being without work or on a disability pension. Among women, lack of professional education or being without work tended...

  4. Emergency Department Frequent Users for Acute Alcohol Intoxication

    Directory of Open Access Journals (Sweden)

    Marc L. Martel

    2018-02-01

    Full Text Available Introduction: A subset of frequent users of emergency services are those who use the emergency department (ED for acute alcohol intoxication. This population and their ED encounters have not been previously described. Methods: This was a retrospective, observational, cohort study of patients presenting to the ED for acute alcohol intoxication between 2012 and 2016. We collected all data from the electronic medical record. Frequent users for alcohol intoxication were defined as those with greater than 20 visits for acute intoxication without additional medical chief complaints in the previous 12 months. We used descriptive statistics to evaluate characteristics of frequent users for alcohol intoxication, as well as their ED encounters. Results: We identified 32,121 patient encounters. Of those, 325 patients were defined as frequent users for alcohol intoxication, comprising 11,370 of the encounters during the study period. The median maximum number of encounters per person for alcohol intoxication in a one-year period was 47 encounters (range 20 to 169. Frequent users were older (47 years vs. 39 years, and more commonly male (86% vs. 71%. Frequent users for alcohol intoxication had higher rates of medical and psychiatric comorbidities including liver disease, chronic kidney disease, ischemic vascular disease, dementia, chronic obstructive pulmonary disease, history of traumatic brain injury, schizophrenia, and bipolar disorder. Conclusion: In this study, we identified a group of ED frequent users who use the ED for acute alcohol intoxication. This population had higher rates of medical and psychiatric comorbidities compared to non-frequent users.

  5. Population modelling to compare chronic external radiotoxicity between individual and population endpoints in four taxonomic groups.

    Science.gov (United States)

    Alonzo, Frédéric; Hertel-Aas, Turid; Real, Almudena; Lance, Emilie; Garcia-Sanchez, Laurent; Bradshaw, Clare; Vives I Batlle, Jordi; Oughton, Deborah H; Garnier-Laplace, Jacqueline

    2016-02-01

    In this study, we modelled population responses to chronic external gamma radiation in 12 laboratory species (including aquatic and soil invertebrates, fish and terrestrial mammals). Our aim was to compare radiosensitivity between individual and population endpoints and to examine how internationally proposed benchmarks for environmental radioprotection protected species against various risks at the population level. To do so, we used population matrix models, combining life history and chronic radiotoxicity data (derived from laboratory experiments and described in the literature and the FREDERICA database) to simulate changes in population endpoints (net reproductive rate R0, asymptotic population growth rate λ, equilibrium population size Neq) for a range of dose rates. Elasticity analyses of models showed that population responses differed depending on the affected individual endpoint (juvenile or adult survival, delay in maturity or reduction in fecundity), the considered population endpoint (R0, λ or Neq) and the life history of the studied species. Among population endpoints, net reproductive rate R0 showed the lowest EDR10 (effective dose rate inducing 10% effect) in all species, with values ranging from 26 μGy h(-1) in the mouse Mus musculus to 38,000 μGy h(-1) in the fish Oryzias latipes. For several species, EDR10 for population endpoints were lower than the lowest EDR10 for individual endpoints. Various population level risks, differing in severity for the population, were investigated. Population extinction (predicted when radiation effects caused population growth rate λ to decrease below 1, indicating that no population growth in the long term) was predicted for dose rates ranging from 2700 μGy h(-1) in fish to 12,000 μGy h(-1) in soil invertebrates. A milder risk, that population growth rate λ will be reduced by 10% of the reduction causing extinction, was predicted for dose rates ranging from 24 μGy h(-1) in mammals to 1800 μGy h(-1) in

  6. Selection of Surrogate Bacteria for Use in Food Safety Challenge Studies: A Review.

    Science.gov (United States)

    Hu, Mengyi; Gurtler, Joshua B

    2017-09-01

    Nonpathogenic surrogate bacteria are prevalently used in a variety of food challenge studies in place of foodborne pathogens such as Listeria monocytogenes, Salmonella, Escherichia coli O157:H7, and Clostridium botulinum because of safety and sanitary concerns. Surrogate bacteria should have growth characteristics and/or inactivation kinetics similar to those of target pathogens under given conditions in challenge studies. It is of great importance to carefully select and validate potential surrogate bacteria when verifying microbial inactivation processes. A validated surrogate responds similar to the targeted pathogen when tested for inactivation kinetics, growth parameters, or survivability under given conditions in agreement with appropriate statistical analyses. However, a considerable number of food studies involving putative surrogate bacteria lack convincing validation sources or adequate validation processes. Most of the validation information for surrogates in these studies is anecdotal and has been collected from previous publications but may not be sufficient for given conditions in the study at hand. This review is limited to an overview of select studies and discussion of the general criteria and approaches for selecting potential surrogate bacteria under given conditions. The review also includes a list of documented bacterial pathogen surrogates and their corresponding food products and treatments to provide guidance for future studies.

  7. Making fire and fire surrogate science available: a summary of regional workshops with clients

    Science.gov (United States)

    Andrew Youngblood; Heidi Bigler-Cole; Christopher J. Fettig; Carl Fiedler; Eric E. Knapp; John F. Lehmkuhl; Kenneth W. Outcalt; Carl N. Skinner; Scott L. Stephens; Thomas A. Waldrop

    2007-01-01

    Operational-scale experiments that evaluate the consequences of fire and mechanical "surrogates" for natural disturbance events are essential to better understand strategies for reducing the incidence and severity of wildfire. The national Fire and Fire Surrogate (FFS) study was initiated in 1999 to establish an integrated network of long-term studies...

  8. Use of surrogate travel to lower training costs and reduce person-rems

    International Nuclear Information System (INIS)

    Scully, M.C.; Porter, N.J.; Scott, J.W.

    1985-01-01

    In the commercial nuclear power industry where access on site may be prohibited by regulations, procedures, or the potential of extremely high radiation levels, a surrogate travel system has potential for the reduction of both exposure and personnel training time. A prototype surrogate travel system using a microcomputer-assisted laser optical video disc has been developed by Southern California Edison and Combustion Engineering

  9. Someone to Lean on: Assessment and Implications of Social Surrogate Use in Childhood

    Science.gov (United States)

    Arbeau, Kimberley A.; Coplan, Robert J.; Matheson, Adrienne

    2012-01-01

    A social surrogate is a person who helps a shy individual deal with the stresses of a social situation. Previous research has only investigated social surrogate use in adults. The purpose of the current study was to develop and evaluate a new self-report measure of social surrogacy in middle childhood and to explore the implications of this…

  10. Outcomes for Gestational Carriers Versus Traditional Surrogates in the United States.

    Science.gov (United States)

    Fuchs, Erika L; Berenson, Abbey B

    2018-05-01

    Little is known about the obstetric and procedural outcomes of traditional surrogates and gestational carriers. Participants included 222 women living in the United States who completed a brief online survey between November 2015 and February 2016. Differences between gestational carriers (n = 204) and traditional surrogates (n = 18) in demographic characteristics, pregnancy outcomes, and procedural outcomes were examined using chi-squared tests, Fisher's exact tests, and t-tests. Out of 248 eligible respondents, 222 surveys were complete, for a response rate of 89.5%. Overall, obstetric outcomes were similar among gestational carriers and traditional surrogates. Traditional surrogates were more likely than gestational carriers to have a Center for Epidemiologic Studies Depression Scale Revised score of 16 or higher (37.5% vs. 4.0%). Gestational carriers reported higher mean compensation ($27,162.80 vs. $17,070.07) and were more likely to travel over 400 miles (46.0% vs. 0.0%) than traditional surrogates. Procedural differences, but not differences in obstetric outcomes, emerged between gestational carriers and traditional surrogates. To ensure that both traditional surrogates and gestational carriers receive optimal medical care, it may be necessary to extend practice guidelines to ensure that traditional surrogates are offered the same level of care offered to gestational carriers.

  11. A fast surrogate model tailor-made for real time control

    DEFF Research Database (Denmark)

    Borup, Morten; Thrysøe, Cecilie; Arnbjerg-Nielsen, Karsten

    A surrogate model of a detailed hydraulic urban drainage model is created for supplying inflow forecasts to an MPC model for 31 separate locations. The original model is subdivided into 66 relationships extracted from the original model. The surrogate model is 9000 times faster than the original...... model, with just a minor deviation from the original model results....

  12. A Global Online Handwriting Recognition Approach Based on Frequent Patterns

    Directory of Open Access Journals (Sweden)

    C. Gmati

    2018-06-01

    Full Text Available In this article, the handwriting signals are represented based on geometric and spatio-temporal characteristics to increase the feature vectors relevance of each object. The main goal was to extract features in the form of a numeric vector based on the extraction of frequent patterns. We used two types of frequent motifs (closed frequent patterns and maximal frequent patterns that can represent handwritten characters pertinently. These common features patterns are generated from a raw data transformation method to achieve high relevance. A database of words consisting of two different letters was created. The proposed application gives promising results and highlights the advantages that frequent pattern extraction algorithms can achieve, as well as the central role played by the “minimum threshold” parameter in the overall description of the characters.

  13. XML documents cluster research based on frequent subpatterns

    Science.gov (United States)

    Ding, Tienan; Li, Wei; Li, Xiongfei

    2015-12-01

    XML data is widely used in the information exchange field of Internet, and XML document data clustering is the hot research topic. In the XML document clustering process, measure differences between two XML documents is time costly, and impact the efficiency of XML document clustering. This paper proposed an XML documents clustering method based on frequent patterns of XML document dataset, first proposed a coding tree structure for encoding the XML document, and translate frequent pattern mining from XML documents into frequent pattern mining from string. Further, using the cosine similarity calculation method and cohesive hierarchical clustering method for XML document dataset by frequent patterns. Because of frequent patterns are subsets of the original XML document data, so the time consumption of XML document similarity measure is reduced. The experiment runs on synthetic dataset and the real datasets, the experimental result shows that our method is efficient.

  14. Population modelling to compare chronic external radiotoxicity between individual and population endpoints in four taxonomic groups

    International Nuclear Information System (INIS)

    Alonzo, Frédéric; Hertel-Aas, Turid; Real, Almudena; Lance, Emilie; Garcia-Sanchez, Laurent; Bradshaw, Clare; Vives i Batlle, Jordi; Oughton, Deborah H.; Garnier-Laplace, Jacqueline

    2016-01-01

    In this study, we modelled population responses to chronic external gamma radiation in 12 laboratory species (including aquatic and soil invertebrates, fish and terrestrial mammals). Our aim was to compare radiosensitivity between individual and population endpoints and to examine how internationally proposed benchmarks for environmental radioprotection protected species against various risks at the population level. To do so, we used population matrix models, combining life history and chronic radiotoxicity data (derived from laboratory experiments and described in the literature and the FREDERICA database) to simulate changes in population endpoints (net reproductive rate R_0, asymptotic population growth rate λ, equilibrium population size N_e_q) for a range of dose rates. Elasticity analyses of models showed that population responses differed depending on the affected individual endpoint (juvenile or adult survival, delay in maturity or reduction in fecundity), the considered population endpoint (R_0, λ or N_e_q) and the life history of the studied species. Among population endpoints, net reproductive rate R_0 showed the lowest EDR_1_0 (effective dose rate inducing 10% effect) in all species, with values ranging from 26 μGy h"−"1 in the mouse Mus musculus to 38,000 μGy h"−"1 in the fish Oryzias latipes. For several species, EDR_1_0 for population endpoints were lower than the lowest EDR_1_0 for individual endpoints. Various population level risks, differing in severity for the population, were investigated. Population extinction (predicted when radiation effects caused population growth rate λ to decrease below 1, indicating that no population growth in the long term) was predicted for dose rates ranging from 2700 μGy h"−"1 in fish to 12,000 μGy h"−"1 in soil invertebrates. A milder risk, that population growth rate λ will be reduced by 10% of the reduction causing extinction, was predicted for dose rates ranging from 24 μGy h"−"1

  15. Predictors of Frequent Emergency Room Visits among a Homeless Population.

    Directory of Open Access Journals (Sweden)

    Kinna Thakarar

    Full Text Available Homelessness, HIV, and substance use are interwoven problems. Furthermore, homeless individuals are frequent users of emergency services. The main purpose of this study was to identify risk factors for frequent emergency room (ER visits and to examine the effects of housing status and HIV serostatus on ER utilization. The second purpose was to identify risk factors for frequent ER visits in patients with a history of illicit drug use.A retrospective analysis was performed on 412 patients enrolled in a Boston-based health care for the homeless program (HCH. This study population was selected as a 2:1 HIV seronegative versus HIV seropositive match based on age, sex, and housing status. A subgroup analysis was performed on 287 patients with history of illicit drug use. Chart data were analyzed to compare demographics, health characteristics, and health service utilization. Results were stratified by housing status. Logistic models using generalized estimating equations were used to predict frequent ER visits.In homeless patients, hepatitis C was the only predictor of frequent ER visits (OR 4.49, p<0.01. HIV seropositivity was not predictive of frequent ER visits. In patients with history of illicit drug use, mental health (OR 2.53, 95% CI 1.07-5.95 and hepatitis C (OR 2.85, 95% CI 1.37-5.93 were predictors of frequent ER use. HIV seropositivity did not predict ER use (OR 0.45, 95% CI 0.21 - 0.97.In a HCH population, hepatitis C predicted frequent ER visits in homeless patients. HIV seropositivity did not predict frequent ER visits, likely because HIV seropositive HCH patients are engaged in care. In patients with history of illicit drug use, hepatitis C and mental health disorders predicted frequent ER visits. Supportive housing for patients with mental health disorders and hepatitis C may help prevent unnecessary ER visits in this population.

  16. Comparative study of different surrogate markers for individual radiation sensitivity

    International Nuclear Information System (INIS)

    Hoffmann, Nele Julia

    2013-01-01

    Radiotherapy is an important part of therapeutic tumor treatment concept. The applied total dose is limited by the unavoidable radiation effect on the surrounding normal tissue and the risk of radiation induced acute or chronic side effects. The clinical radiation sensitivity, i.e. the risk of radiogenic side effects is strongly coupled to the cellular radiation sensitivity. The contribution is focused on the development of a predictive tool for the individual radiation sensitivity for individual radiotherapeutic planning using lymphocytes. Residual foci, i.e. accumulated repair associated proteins at the residual double strand break are supposed to be surrogate markers of the cellular radiation sensitivity. No relation between the foci detection and the G(0)/G(1) was found assay with respect to the individual radiation sensitivity.

  17. Optimization of inlet plenum of A PBMR using surrogate modeling

    International Nuclear Information System (INIS)

    Lee, Sang-Moon; Kim, Kwang-Yong

    2009-01-01

    The purpose of present work is to optimize the design of inlet plenum of PBMR type gas cooled nuclear reactor numerically using a combining of three-dimensional Reynolds-averaged Navier-Stokes (RANS) analysis and surrogate modeling technique. Shear stress transport (SST) turbulence model is used as a turbulence closure. Three geometric design variables are selected, namely, rising channel diameter to plenum height ratio, aspect ratio of the plenum cross section, and inlet port angle. The objective function is defined as a linear combination of uniformity of three-dimensional flow distribution term and pressure drop in the inlet plenum and rising channels of PBMR term with a weighting factor. Twenty design points are selected using Latin-hypercube method of design of experiment and objective function values are obtained at each design point using RANS solver. (author)

  18. Development of parietal bone surrogates for parietal graft lift training

    Directory of Open Access Journals (Sweden)

    Hollensteiner Marianne

    2016-09-01

    Full Text Available Currently the surgical training of parietal bone graft techniques is performed on patients or specimens. Commercially available bone models do not deliver realistic haptic feedback. Thus customized parietal skull surrogates were developed for surgical training purposes. Two human parietal bones were used as reference. Based on the measurement of insertion forces of drilling, milling and saw procedures suitable material compositions for molding cortical and cancellous calvarial layers were found. Artificial skull caps were manufactured and tested. Additionally microtomograpy images of human and artificial parietal bones were performed to analyze outer table and diploe thicknesses. Significant differences between human and artificial skulls were not detected with the mechanical procedures tested. Highly significant differences were found for the diploe thickness values. In conclusion, an artificial bone has been created, mimicking the properties of human parietal bone thus being suitable for tabula externa graft lift training.

  19. Surrogate motherhood, rights and duties: a reply to Campbell.

    Science.gov (United States)

    McLachlan, H V; Swales, J K

    2001-01-01

    In a recent article in Health Care Analysis (Vol. 8, No. 1), Campbell misrepresents our specific arguments about commercial surrogate motherhood (C.S.M.) and our general philosophical and political views by saying or suggesting that we are 'Millsian' liberals and consequentialists. He gives too the false impression that we do not oppose, in principle, slavery and child purchase. Here our position on C.S.M. is re-expressed and elaborated upon in order to eliminate possible confusion. Our general ethical and philosophical framework is also outlined and shown to be other than Campbell says that it is. In particular, a moral philosophy that is based on neither consequentialism nor Kantianism is presented. C.S.M., it is argued, is not child purchase. It is like it in some respects and unlike it in others. It is unlike it in the respects which, relative to the present discussion, matter.

  20. Surrogate mothers: aboriginal grandmothers raising grandchildren in Taiwan.

    Science.gov (United States)

    Chang, Yu-Ting; Hayter, Mark

    2011-05-01

    The purpose of this qualitative study was to understand the experiences of Taiwanese aboriginal grandmothers when raising their grandchildren. Adopting a phenomenological approach, interviews were conducted with 15 Taiwanese aboriginal grandmothers who served as primary caregiver to a grandchild or grandchildren. Data were analyzed using Giorgi's phenomenological method. Four themes emerged from the data analysis, reflecting the parenting experience of grandmothers: using aged bodies to do energetic work: represented the physical effects of raising grandchildren; conflicting emotions: reflected the psychological effects of raising grandchildren; lifelong and privative obligation: described the cultural and societal beliefs of raising grandchildren; and coping strategies for raising grandchildren outlined methods the grandmothers used to cope with parenting their grandchildren. The results of this study offers insights into surrogate parenting within an underresearched group in Taiwan and will enable health care providers to be more aware of the physical, emotional, and social effects of the role of grandparent parenting.

  1. Effectiveness of biodiversity surrogates for conservation planning: different measures of effectiveness generate a kaleidoscope of variation.

    Directory of Open Access Journals (Sweden)

    Hedley S Grantham

    Full Text Available Conservation planners represent many aspects of biodiversity by using surrogates with spatial distributions readily observed or quantified, but tests of their effectiveness have produced varied and conflicting results. We identified four factors likely to have a strong influence on the apparent effectiveness of surrogates: (1 the choice of surrogate; (2 differences among study regions, which might be large and unquantified (3 the test method, that is, how effectiveness is quantified, and (4 the test features that the surrogates are intended to represent. Analysis of an unusually rich dataset enabled us, for the first time, to disentangle these factors and to compare their individual and interacting influences. Using two data-rich regions, we estimated effectiveness using five alternative methods: two forms of incidental representation, two forms of species accumulation index and irreplaceability correlation, to assess the performance of 'forest ecosystems' and 'environmental units' as surrogates for six groups of threatened species-the test features-mammals, birds, reptiles, frogs, plants and all of these combined. Four methods tested the effectiveness of the surrogates by selecting areas for conservation of the surrogates then estimating how effective those areas were at representing test features. One method measured the spatial match between conservation priorities for surrogates and test features. For methods that selected conservation areas, we measured effectiveness using two analytical approaches: (1 when representation targets for the surrogates were achieved (incidental representation, or (2 progressively as areas were selected (species accumulation index. We estimated the spatial correlation of conservation priorities using an index known as summed irreplaceability. In general, the effectiveness of surrogates for our taxa (mostly threatened species was low, although environmental units tended to be more effective than forest ecosystems

  2. The Impact of Chemoembolization Endpoints on Survival in Hepatocellular Carcinoma Patients

    Science.gov (United States)

    Jin, Brian; Wang, Dingxin; Lewandowski, Robert J.; Riaz, Ahsun; Ryu, Robert K.; Sato, Kent T.; Larson, Andrew C.; Salem, Riad; Omary, Reed A.

    2010-01-01

    OBJECTIVE To investigate the relationship between angiographic embolic endpoints of transarterial chemoembolization (TACE) and survival in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS This study retrospectively assessed 105 patients with surgically unresectable HCC who underwent TACE. Patients were classified according to a previously established subjective angiographic chemoembolization endpoint (SACE) scale. Only one patient was classified as SACE level 1 and thus excluded from all subsequent analysis. Survival was evaluated with Kaplan-Meier analysis. Multivariate analysis with Cox’s proportional hazard regression model was used to determine independent prognostic risk factors of survival. RESULTS Overall median survival was 21.1 months (95% confidence interval [CI], 15.9–26.4). Patients embolized to SACE levels 2 and 3 were aggregated and had a significantly higher median survival (25.6 months; 95% CI, 16.2–35.0) than patients embolized to SACE level 4 (17.1 months; 95% CI, 13.3–20.9) (p = 0.035). Multivariate analysis indicated that SACE level 4 (Hazard ratio [HR], 2.49; 95% CI, 1.41–4.42; p = 0.002), European Cooperative Oncology Group performance status > 0 (HR, 1.97; 95% CI, 1.15–3.37; p = 0.013), American Joint Committee on Cancer stage 3 or 4 (HR, 2.42; 95% CI, 1.27–4.60; p = 0.007), and Child-Pugh class B (HR, 1.94; 95% CI, 1.09–3.46; p = 0.025) were all independent negative prognostic indicators of survival. CONCLUSION Embolization to an intermediate, sub-stasis endpoint (SACE levels 2 and 3) during TACE improves survival compared to embolization to a higher, stasis endpoint (SACE level 4). Interventional oncologists should consider targeting these intermediate, sub-stasis angiographic endpoints during TACE. PMID:21427346

  3. LVAD patients' and surrogates' perspectives on SPIRIT-HF: An advance care planning discussion.

    Science.gov (United States)

    Metzger, Maureen; Song, Mi-Kyung; Devane-Johnson, Stephanie

    2016-01-01

    To describe LVAD patients' and surrogates' experiences with, and perspectives on SPIRIT-HF, an advance care planning (ACP) intervention. ACP is important for patients with LVAD, yet little is known about their experiences or those of their surrogates who have participated in ACP discussions. We used qualitative content analysis techniques to conduct a secondary analysis of 28 interviews with patients with LVAD (n = 14) and their surrogates (n = 14) who had participated in an RCT pilot study of SPIRIT-HF. Main themes from the data include: 1) sharing their HF stories was very beneficial; 2) participating in SPIRIT-HF led to greater peace of mind for patients and surrogates; 3) "one size does not fit all" when it comes to timing of ACP discussions. An understanding patient and surrogate perspectives may inform clinicians' approach to ACP discussions. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. A computational methodology for formulating gasoline surrogate fuels with accurate physical and chemical kinetic properties

    KAUST Repository

    Ahmed, Ahfaz

    2015-03-01

    Gasoline is the most widely used fuel for light duty automobile transportation, but its molecular complexity makes it intractable to experimentally and computationally study the fundamental combustion properties. Therefore, surrogate fuels with a simpler molecular composition that represent real fuel behavior in one or more aspects are needed to enable repeatable experimental and computational combustion investigations. This study presents a novel computational methodology for formulating surrogates for FACE (fuels for advanced combustion engines) gasolines A and C by combining regression modeling with physical and chemical kinetics simulations. The computational methodology integrates simulation tools executed across different software platforms. Initially, the palette of surrogate species and carbon types for the target fuels were determined from a detailed hydrocarbon analysis (DHA). A regression algorithm implemented in MATLAB was linked to REFPROP for simulation of distillation curves and calculation of physical properties of surrogate compositions. The MATLAB code generates a surrogate composition at each iteration, which is then used to automatically generate CHEMKIN input files that are submitted to homogeneous batch reactor simulations for prediction of research octane number (RON). The regression algorithm determines the optimal surrogate composition to match the fuel properties of FACE A and C gasoline, specifically hydrogen/carbon (H/C) ratio, density, distillation characteristics, carbon types, and RON. The optimal surrogate fuel compositions obtained using the present computational approach was compared to the real fuel properties, as well as with surrogate compositions available in the literature. Experiments were conducted within a Cooperative Fuels Research (CFR) engine operating under controlled autoignition (CAI) mode to compare the formulated surrogates against the real fuels. Carbon monoxide measurements indicated that the proposed surrogates

  5. Predictors of Frequent Emergency Room Visits among a Homeless Population.

    Science.gov (United States)

    Thakarar, Kinna; Morgan, Jake R; Gaeta, Jessie M; Hohl, Carole; Drainoni, Mari-Lynn

    2015-01-01

    Homelessness, HIV, and substance use are interwoven problems. Furthermore, homeless individuals are frequent users of emergency services. The main purpose of this study was to identify risk factors for frequent emergency room (ER) visits and to examine the effects of housing status and HIV serostatus on ER utilization. The second purpose was to identify risk factors for frequent ER visits in patients with a history of illicit drug use. A retrospective analysis was performed on 412 patients enrolled in a Boston-based health care for the homeless program (HCH). This study population was selected as a 2:1 HIV seronegative versus HIV seropositive match based on age, sex, and housing status. A subgroup analysis was performed on 287 patients with history of illicit drug use. Chart data were analyzed to compare demographics, health characteristics, and health service utilization. Results were stratified by housing status. Logistic models using generalized estimating equations were used to predict frequent ER visits. In homeless patients, hepatitis C was the only predictor of frequent ER visits (OR 4.49, phomeless patients. HIV seropositivity did not predict frequent ER visits, likely because HIV seropositive HCH patients are engaged in care. In patients with history of illicit drug use, hepatitis C and mental health disorders predicted frequent ER visits. Supportive housing for patients with mental health disorders and hepatitis C may help prevent unnecessary ER visits in this population.

  6. Frequent Pairs in Data Streams: Exploiting Parallelism and Skew

    DEFF Research Database (Denmark)

    Campagna, Andrea; Kutzkow, Konstantin; Pagh, Rasmus

    2011-01-01

    We introduce the Pair Streaming Engine (PairSE) that detects frequent pairs in a data stream of transactions. Our algorithm finds the most frequent pairs with high probability, and gives tight bounds on their frequency. It is particularly space efficient for skewed distribution of pair supports...... items mining in data streams. We show how to efficiently scale these approaches to handle large transactions. We report experimental results showcasing precision and recall of our method. In particular, we find that often our method achieves excellent precision, returning identical upper and lower...... bounds on the supports of the most frequent pairs....

  7. Frequently Asked Questions for Parents of Children with PH

    Science.gov (United States)

    ... Frequently Asked Questions for Parents of Children with PH What causes pulmonary hypertension in children? I’ve ... of what I read is about adults with PH. What are the primary differences between PH in ...

  8. Frequently Asked Questions about Measles in the U.S.

    Science.gov (United States)

    ... Pan American Health Organization Frequently Asked Questions about Measles in the U.S. Language: English (US) Español (Spanish) ... I’ve been exposed to someone who has measles. What should I do? A: Immediately call your ...

  9. Stability of the frequent COPD exacerbator in the general population

    DEFF Research Database (Denmark)

    Reilev, Mette; Lykkegaard, Jesper; Halling, Anders

    2017-01-01

    Exacerbation frequency is central in treatment strategies for chronic obstructive pulmonary disease. However, whether chronic obstructive pulmonary disease patients from the general population with frequent exacerbations continue to have frequent exacerbations over an extended period of time is c...... considerably over time. This could hold implications for COPD treatment and challenge assumptions made about disease progression....... is currently unknown. In this study, we aimed to investigate the stability of the frequent exacerbator in a population-based setting. To this end, we conducted a nationwide register-based descriptive study with a 10-year follow-up period of chronic obstructive pulmonary disease patients with at least one...... obstructive pulmonary disease treatment guidelines and their practical application. CHRONIC OBSTRUCTIVE LUNG DISEASE: VARIATIONS IN DISEASE PROGRESSION: Patients with chronic obstructive pulmonary disease (COPD) who suffer from frequent exacerbations do not necessarily persist with such severity over time...

  10. Incremental Frequent Subgraph Mining on Large Evolving Graphs

    KAUST Repository

    Abdelhamid, Ehab; Canim, Mustafa; Sadoghi, Mohammad; Bhatta, Bishwaranjan; Chang, Yuan-Chi; Kalnis, Panos

    2017-01-01

    , such as social networks, utilize large evolving graphs. Mining these graphs using existing techniques is infeasible, due to the high computational cost. In this paper, we propose IncGM+, a fast incremental approach for continuous frequent subgraph mining problem

  11. THE FREQUENT SKIN DISEASES DIAGNOSED AT UNIVERSITY STUDENTS

    Directory of Open Access Journals (Sweden)

    Yesim KAYMAK

    2005-12-01

    Full Text Available The incidence of some skin diseases are increasing at adolescent and early adulthood period. The most frequent disease at this period is acne vulgaris whereas fungal diseases, dermatitis, dermatosis which are due to stress and other reasons, oral mucosal lesions and herpetic lesions of perioral region are also frequent. In this research we aim to determine the frequent dermatologic diseases of university students and 147 female, 74 male, a total of 221 students are included. We questioned the dermatologic complaints of students, then examined dermatologically in detail and registered ages, sexes, findings of the dermatological examination and dermatological diagnostic informations. As a result it is found out that the most frequent diseases are acne vulgaris (34.1%, allergic and pruritic dermatosis (16.6%, fungal diseases ( 13.0%, and eritamatous-squamous disease (8.3%. [TAF Prev Med Bull 2005; 4(6.000: 313-320

  12. Personalized privacy-preserving frequent itemset mining using randomized response.

    Science.gov (United States)

    Sun, Chongjing; Fu, Yan; Zhou, Junlin; Gao, Hui

    2014-01-01

    Frequent itemset mining is the important first step of association rule mining, which discovers interesting patterns from the massive data. There are increasing concerns about the privacy problem in the frequent itemset mining. Some works have been proposed to handle this kind of problem. In this paper, we introduce a personalized privacy problem, in which different attributes may need different privacy levels protection. To solve this problem, we give a personalized privacy-preserving method by using the randomized response technique. By providing different privacy levels for different attributes, this method can get a higher accuracy on frequent itemset mining than the traditional method providing the same privacy level. Finally, our experimental results show that our method can have better results on the frequent itemset mining while preserving personalized privacy.

  13. Long-Term Stability Testing Results Using Surrogates And Sorbents For Savannah River Site Organic And Aqueous Wastestreams - 10016

    International Nuclear Information System (INIS)

    Burns, H.

    2009-01-01

    The U.S. Department of Energy (DOE) has tasked MSE Technology Applications, Inc. (MSE) with evaluating the long-term stability of various commercially available sorbent materials to solidify two organic surrogate wastestreams (both volatile and nonvolatile), a volatile organic surrogate with a residual aqueous phase, an aqueous surrogate, and an aqueous surrogate with a residual organic phase. The Savannah River Site (SRS) Legacy and F-Canyon plutonium/uranium extraction (PUREX) process waste surrogates constituted the volatile organic surrogates, and various oils constituted the nonvolatile organic surrogates. The aqueous surrogates included a rainwater surrogate and an aqueous organic surrogate. MSE also evaluated the PUREX surrogate with a residual aqueous component with and without aqueous type sorbent materials. Solidification of the various surrogate wastestreams listed above was performed from 2004 to 2006 at the MSE Test Facility located in Butte, Montana. This paper summarizes the comparison of the initial liquid release test (LRT) values with LRT results obtained during subsequent sampling events in an attempt to understand and define the long-term stability characteristics for the solidified wastestreams.

  14. Perceived Quality of Social Relations and Frequent Drunkenness

    DEFF Research Database (Denmark)

    Kjærulff, Thora M; Rivera, Francisco; Jiménez-Iglesias, Antonia

    2014-01-01

    in School-aged Children Study (HBSC) 2010 survey were used including 1177 female and 1126 male students aged between 15 and 16 years. RESULTS: For both genders, students reporting low school satisfaction had increased odds of frequent drunkenness. Among females, low and medium levels of classmate support...... predictors of frequent drunkenness among female than male students and that other factors than social relations may contribute to explain excessive alcohol use among Spanish adolescents....

  15. The Impact of Frequent Shopper Programs in Grocery Retailing

    OpenAIRE

    David Bell; Rajiv Lal

    2002-01-01

    Frequent Shopper programs are becoming ubiquitous in retailing. Retailers seem unsure however about whether these programs are leading to higher loyalty, or to higher profits. In this paper we analyze data from a US supermarket chain that has used a number of frequent shopper rewards to improve sales and profitability. We find that while these programs are profitable, this is only because substantial incremental sales to casual shoppers (cherry pickers) oset subsidies to already loyal custome...

  16. Enumerating all maximal frequent subtrees in collections of phylogenetic trees.

    Science.gov (United States)

    Deepak, Akshay; Fernández-Baca, David

    2014-01-01

    A common problem in phylogenetic analysis is to identify frequent patterns in a collection of phylogenetic trees. The goal is, roughly, to find a subset of the species (taxa) on which all or some significant subset of the trees agree. One popular method to do so is through maximum agreement subtrees (MASTs). MASTs are also used, among other things, as a metric for comparing phylogenetic trees, computing congruence indices and to identify horizontal gene transfer events. We give algorithms and experimental results for two approaches to identify common patterns in a collection of phylogenetic trees, one based on agreement subtrees, called maximal agreement subtrees, the other on frequent subtrees, called maximal frequent subtrees. These approaches can return subtrees on larger sets of taxa than MASTs, and can reveal new common phylogenetic relationships not present in either MASTs or the majority rule tree (a popular consensus method). Our current implementation is available on the web at https://code.google.com/p/mfst-miner/. Our computational results confirm that maximal agreement subtrees and all maximal frequent subtrees can reveal a more complete phylogenetic picture of the common patterns in collections of phylogenetic trees than maximum agreement subtrees; they are also often more resolved than the majority rule tree. Further, our experiments show that enumerating maximal frequent subtrees is considerably more practical than enumerating ordinary (not necessarily maximal) frequent subtrees.

  17. Enumerating all maximal frequent subtrees in collections of phylogenetic trees

    Science.gov (United States)

    2014-01-01

    Background A common problem in phylogenetic analysis is to identify frequent patterns in a collection of phylogenetic trees. The goal is, roughly, to find a subset of the species (taxa) on which all or some significant subset of the trees agree. One popular method to do so is through maximum agreement subtrees (MASTs). MASTs are also used, among other things, as a metric for comparing phylogenetic trees, computing congruence indices and to identify horizontal gene transfer events. Results We give algorithms and experimental results for two approaches to identify common patterns in a collection of phylogenetic trees, one based on agreement subtrees, called maximal agreement subtrees, the other on frequent subtrees, called maximal frequent subtrees. These approaches can return subtrees on larger sets of taxa than MASTs, and can reveal new common phylogenetic relationships not present in either MASTs or the majority rule tree (a popular consensus method). Our current implementation is available on the web at https://code.google.com/p/mfst-miner/. Conclusions Our computational results confirm that maximal agreement subtrees and all maximal frequent subtrees can reveal a more complete phylogenetic picture of the common patterns in collections of phylogenetic trees than maximum agreement subtrees; they are also often more resolved than the majority rule tree. Further, our experiments show that enumerating maximal frequent subtrees is considerably more practical than enumerating ordinary (not necessarily maximal) frequent subtrees. PMID:25061474

  18. Health information-seeking on behalf of others: characteristics of "surrogate seekers".

    Science.gov (United States)

    Cutrona, Sarah L; Mazor, Kathleen M; Vieux, Sana N; Luger, Tana M; Volkman, Julie E; Finney Rutten, Lila J

    2015-03-01

    Understanding the behaviors of surrogate seekers (those who seek health information for others) may guide efforts to improve health information transmission. We used 2011-2012 data from the Health Information National Trends Survey to describe behaviors of online surrogate seekers. Respondents were asked about use of the Internet for surrogate-seeking over the prior 12 months. Data were weighted to calculate population estimates. Two thirds (66.6%) reported surrogate-seeking. Compared to those who sought health information online for only themselves, surrogate seekers were more likely to live in households with others (weighted percent 89.4 vs. 82.5% of self-seekers; p user-generated content: email communication with healthcare providers; visits to social networking sites to read and share about medical topics and participation in online health support groups. On multivariate analysis, those who had looked online for healthcare providers were more likely to be surrogate seekers (OR 1.67, 95% CI 1.08-2.59). In addition to seeking health information, surrogate seekers create and pass along communications that may influence medical care decisions. Research is needed to identify ways to facilitate transmission of accurate health information.

  19. Surrogate mobility and orientation affect the early neurobehavioral development of infant rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Dettmer, Amanda M; Ruggiero, Angela M; Novak, Melinda A; Meyer, Jerrold S; Suomi, Stephen J

    2008-05-01

    A biological mother's movement appears necessary for optimal development in infant monkeys. However, nursery-reared monkeys are typically provided with inanimate surrogate mothers that move very little. The purpose of this study was to evaluate the effects of a novel, highly mobile surrogate mother on motor development, exploration, and reactions to novelty. Six infant rhesus macaques (Macaca mulatta) were reared on mobile hanging surrogates (MS) and compared to six infants reared on standard stationary rocking surrogates (RS) and to 9-15 infants reared with their biological mothers (MR) for early developmental outcome. We predicted that MS infants would develop more similarly to MR infants than RS infants. In neonatal assessments conducted at Day 30, both MS and MR infants showed more highly developed motor activity than RS infants on measures of grasping (p = .009), coordination (p = .038), spontaneous crawl (p = .009), and balance (p = .003). At 2-3 months of age, both MS and MR infants displayed higher levels of exploration in the home cage than RS infants (p = .016). In a novel situation in which only MS and RS infants were tested, MS infants spent less time near their surrogates in the first five minutes of the test session than RS infants (p = .05), indicating a higher level of comfort. Collectively, these results suggest that when nursery-rearing of infant monkeys is necessary, a mobile hanging surrogate may encourage more normative development of gross motor skills and exploratory behavior and may serve as a useful alternative to stationary or rocking surrogates.

  20. Narrative Interest Standard: A Novel Approach to Surrogate Decision-Making for People With Dementia.

    Science.gov (United States)

    Wilkins, James M

    2017-06-17

    Dementia is a common neurodegenerative process that can significantly impair decision-making capacity as the disease progresses. When a person is found to lack capacity to make a decision, a surrogate decision-maker is generally sought to aid in decision-making. Typical bases for surrogate decision-making include the substituted judgment standard and the best interest standard. Given the heterogeneous and progressive course of dementia, however, these standards for surrogate decision-making are often insufficient in providing guidance for the decision-making for a person with dementia, escalating the likelihood of conflict in these decisions. In this article, the narrative interest standard is presented as a novel and more appropriate approach to surrogate decision-making for people with dementia. Through case presentation and ethical analysis, the standard mechanisms for surrogate decision-making for people with dementia are reviewed and critiqued. The narrative interest standard is then introduced and discussed as a dementia-specific model for surrogate decision-making. Through incorporation of elements of a best interest standard in focusing on the current benefit-burden ratio and elements of narrative to provide context, history, and flexibility for values and preferences that may change over time, the narrative interest standard allows for elaboration of an enriched context for surrogate decision-making for people with dementia. More importantly, however, a narrative approach encourages the direct contribution from people with dementia in authoring the story of what matters to them in their lives.

  1. Public’s Approach to Surrogate Consent for Dementia Research: Cautious Pragmatism

    Science.gov (United States)

    De Vries, Raymond; Ryan, Kerry A.; Stanczyk, Aimee; Appelbaum, Paul S.; Damschroder, Laura; Knopman, David S.; Kim, Scott Y. H.

    2011-01-01

    Objectives To describe how members of the older general public deliberate with one another in finding solutions to the dilemma of involving decisionally incapable persons in dementia research. Design, Setting, and Participants 160 persons aged 50+ who participated in an all-day deliberative democracy (DD) session on the ethics of surrogate consent for dementia research. The DD day consisted of both extensive, interactive education with experts in clinical research and ethics, as well as small group deliberations. Measurements Audiotaped small group deliberations were transcribed and analyzed, and the main thematic elements were coded. Results During deliberation, participants acknowledged the limitations of advanced research directives and discussed ways to improve their use. Although there was consensus about the necessity of surrogate consent, the participants recognized potential pitfalls and looked for ways to safeguard the process. Participants supporting surrogate consent for research emphasized societal and individual benefit, the importance of assent, and trust in surrogates and the oversight system. Other participants felt that the high risk of some research scenarios was not sufficiently offset by benefits to patients or society. Conclusions Members of the older general public are able to make use of in-depth education and peer deliberation to provide reasoned and informed opinions on the ethical use of surrogate consent for dementia research. The public’s approach to surrogate consent is one of cautious pragmatism: an overall trust in science and future surrogates with awareness of the potential pitfalls, suggesting that their trust cannot be taken for granted. PMID:23498383

  2. Attachment and Detachment Behavior of Human Adenovirus and Surrogates in Fine Granular Limestone Aquifer Material.

    Science.gov (United States)

    Stevenson, Margaret E; Sommer, Regina; Lindner, Gerhard; Farnleitner, Andreas H; Toze, Simon; Kirschner, Alexander K T; Blaschke, Alfred P; Sidhu, Jatinder P S

    2015-09-01

    The transport of human adenovirus, nanoparticles, and PRD1 and MS2 bacteriophages was tested in fine granular limestone aquifer material taken from a borehole at a managed aquifer recharge site in Adelaide, South Australia. Comparison of transport and removal of virus surrogates with the pathogenic virus is necessary to understand the differences between the virus and surrogate. Because experiments using pathogenic viruses cannot be done in the field, laboratory tests using flow-through soil columns were used. Results show that PRD1 is the most appropriate surrogate for adenovirus in an aquifer dominated by calcite material but not under high ionic strength or high pH conditions. It was also found that straining due to size and the charge of the colloid were not dominant removal mechanisms in this system. Implications of this study indicate that a certain surrogate may not represent a specific pathogen solely based on similar size, morphology, and/or surface charge. Moreover, if a particular surrogate is representative of a pathogen in one aquifer system, it may not be the most appropriate surrogate in another porous media system. This was apparent in the inferior performance of MS2 as a surrogate, which is commonly used in virus transport studies. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  3. Laboratory Testing of Waste Isolation Pilot Plant Surrogate Waste Materials

    Science.gov (United States)

    Broome, S.; Bronowski, D.; Pfeifle, T.; Herrick, C. G.

    2011-12-01

    The Waste Isolation Pilot Plant (WIPP) is a U.S. Department of Energy geological repository for the permanent disposal of defense-related transuranic (TRU) waste. The waste is emplaced in rooms excavated in the bedded Salado salt formation at a depth of 655 m below the ground surface. After emplacement of the waste, the repository will be sealed and decommissioned. WIPP Performance Assessment modeling of the underground material response requires a full and accurate understanding of coupled mechanical, hydrological, and geochemical processes and how they evolve with time. This study was part of a broader test program focused on room closure, specifically the compaction behavior of waste and the constitutive relations to model this behavior. The goal of this study was to develop an improved waste constitutive model. The model parameters are developed based on a well designed set of test data. The constitutive model will then be used to realistically model evolution of the underground and to better understand the impacts on repository performance. The present study results are focused on laboratory testing of surrogate waste materials. The surrogate wastes correspond to a conservative estimate of the degraded containers and TRU waste materials after the 10,000 year regulatory period. Testing consists of hydrostatic, uniaxial, and triaxial tests performed on surrogate waste recipes that were previously developed by Hansen et al. (1997). These recipes can be divided into materials that simulate 50% and 100% degraded waste by weight. The percent degradation indicates the anticipated amount of iron corrosion, as well as the decomposition of cellulosics, plastics, and rubbers. Axial, lateral, and volumetric strain and axial and lateral stress measurements were made. Two unique testing techniques were developed during the course of the experimental program. The first involves the use of dilatometry to measure sample volumetric strain under a hydrostatic condition. Bulk

  4. Free Energy, Enthalpy and Entropy from Implicit Solvent End-Point Simulations.

    Science.gov (United States)

    Fogolari, Federico; Corazza, Alessandra; Esposito, Gennaro

    2018-01-01

    Free energy is the key quantity to describe the thermodynamics of biological systems. In this perspective we consider the calculation of free energy, enthalpy and entropy from end-point molecular dynamics simulations. Since the enthalpy may be calculated as the ensemble average over equilibrated simulation snapshots the difficulties related to free energy calculation are ultimately related to the calculation of the entropy of the system and in particular of the solvent entropy. In the last two decades implicit solvent models have been used to circumvent the problem and to take into account solvent entropy implicitly in the solvation terms. More recently outstanding advancement in both implicit solvent models and in entropy calculations are making the goal of free energy estimation from end-point simulations more feasible than ever before. We review briefly the basic theory and discuss the advancements in light of practical applications.

  5. Adaptive endpoint detection of seismic signal based on auto-correlated function

    International Nuclear Information System (INIS)

    Fan Wanchun; Shi Ren

    2000-01-01

    There are certain shortcomings for the endpoint detection by time-waveform envelope and/or by checking the travel table (both labelled as the artificial detection method). Based on the analysis of the auto-correlation function, the notion of the distance between auto-correlation functions was quoted, and the characterizations of the noise and the signal with noise were discussed by using the distance. Then, the method of auto-adaptable endpoint detection of seismic signal based on auto-correlated similarity was summed up. The steps of implementation and determining of the thresholds were presented in detail. The experimental results that were compared with the methods based on artificial detecting show that this method has higher sensitivity even in a low SNR circumstance

  6. Free Energy, Enthalpy and Entropy from Implicit Solvent End-Point Simulations

    Directory of Open Access Journals (Sweden)

    Federico Fogolari

    2018-02-01

    Full Text Available Free energy is the key quantity to describe the thermodynamics of biological systems. In this perspective we consider the calculation of free energy, enthalpy and entropy from end-point molecular dynamics simulations. Since the enthalpy may be calculated as the ensemble average over equilibrated simulation snapshots the difficulties related to free energy calculation are ultimately related to the calculation of the entropy of the system and in particular of the solvent entropy. In the last two decades implicit solvent models have been used to circumvent the problem and to take into account solvent entropy implicitly in the solvation terms. More recently outstanding advancement in both implicit solvent models and in entropy calculations are making the goal of free energy estimation from end-point simulations more feasible than ever before. We review briefly the basic theory and discuss the advancements in light of practical applications.

  7. The Different Moral Bases of Patient and Surrogate Decision-Making.

    Science.gov (United States)

    Brudney, Daniel

    2018-01-01

    My topic is a problem with our practice of surrogate decision-making in health care, namely, the problem of the surrogate who is not doing her job-the surrogate who cannot be reached or the surrogate who seems to refuse to understand or to be unable to understand the clinical situation. The analysis raises a question about the surrogate who simply disagrees with the medical team. One might think that such a surrogate is doing her job-the team just doesn't like how she is doing it. My analysis raises the question of whether (or perhaps when) she should be overridden. In approaching this problem, I focus not on the range of difficulties in practice but on the underlying moral conceptual issue. My concern will be to show that the moral values that underpin patient decision-making are fundamentally different from those that underpin surrogate decision-making. Identifying the distinctions will set parameters for any successful solution to the "Who should decide?" A patient has a specific kind of moral right to make her own medical decisions. A surrogate has no analogous moral right to decide for someone else. We want the surrogate to make the decision because we believe that she has a relevant epistemological advantage over anyone else on the scene. If and when she has no such advantage or if she refuses or is unable to use it, then there might not be sufficient reason to let her be the decision-maker. © 2018 The Hastings Center.

  8. Muscle Synergies Heavily Influence the Neural Control of Arm Endpoint Stiffness and Energy Consumption.

    Science.gov (United States)

    Inouye, Joshua M; Valero-Cuevas, Francisco J

    2016-02-01

    Much debate has arisen from research on muscle synergies with respect to both limb impedance control and energy consumption. Studies of limb impedance control in the context of reaching movements and postural tasks have produced divergent findings, and this study explores whether the use of synergies by the central nervous system (CNS) can resolve these findings and also provide insights on mechanisms of energy consumption. In this study, we phrase these debates at the conceptual level of interactions between neural degrees of freedom and tasks constraints. This allows us to examine the ability of experimentally-observed synergies--correlated muscle activations--to control both energy consumption and the stiffness component of limb endpoint impedance. In our nominal 6-muscle planar arm model, muscle synergies and the desired size, shape, and orientation of endpoint stiffness ellipses, are expressed as linear constraints that define the set of feasible muscle activation patterns. Quadratic programming allows us to predict whether and how energy consumption can be minimized throughout the workspace of the limb given those linear constraints. We show that the presence of synergies drastically decreases the ability of the CNS to vary the properties of the endpoint stiffness and can even preclude the ability to minimize energy. Furthermore, the capacity to minimize energy consumption--when available--can be greatly affected by arm posture. Our computational approach helps reconcile divergent findings and conclusions about task-specific regulation of endpoint stiffness and energy consumption in the context of synergies. But more generally, these results provide further evidence that the benefits and disadvantages of muscle synergies go hand-in-hand with the structure of feasible muscle activation patterns afforded by the mechanics of the limb and task constraints. These insights will help design experiments to elucidate the interplay between synergies and the mechanisms

  9. Comparison of mammalian and fish cell line cytotoxicity: impact of endpoint and exposure duration

    International Nuclear Information System (INIS)

    Guelden, Michael; Moerchel, Sabine; Seibert, Hasso

    2005-01-01

    Comparisons of acute toxic concentrations of chemicals to fish in vivo and cytotoxic concentrations to fish cell lines in vitro reveal rather good correlations of the toxic potencies in vitro and in vivo, but a clearly lower sensitivity of the fish cells. To examine whether the low sensitivity is specific for fish cells, cytotoxic potencies of reference chemicals from the Multicenter Evaluation of In Vitro Cytotoxicity program (MEIC) reported for the fish cell lines R1 and RTG-2 were compared with those obtained with the mouse Balb/c 3T3 cell line. Cytotoxic potencies (EC 50 values) for MEIC reference chemicals were determined with exponentially growing Balb/c 3T3 cells using three different test protocols. To assess both endpoints, cell proliferation and cell survival, EC 50 values were measured for the decrease in final cell protein after 24 and 72 h of exposure and for the reduction of cell protein increase during 24 h of exposure. EC 50 values obtained with the fish cell lines R1 and RTG-2 using cell survival as endpoint were taken from the MEIC data base. The comparison of cytotoxic potencies shows that, in general, the fish cell lines and the mammalian cell line are almost equally sensitive towards the cytotoxic action of chemicals. The mammalian cell line assay, however, becomes considerably more sensitive, by factors of 3.4-8.5, than the fish cell line assays, if cell growth instead of cell survival is used as endpoint. It is concluded, that cell proliferation might be a better endpoint than cell survival and that mammalian cell lines might be suited to assess fish acute toxicity

  10. Energy metabolism and biotransformation as endpoints to pre-screen hepatotoxicity using a liver spheroid model

    International Nuclear Information System (INIS)

    Xu Jinsheng; Purcell, Wendy M.

    2006-01-01

    The current study investigated liver spheroid culture as an in vitro model to evaluate the endpoints relevant to the status of energy metabolism and biotransformation after exposure to test toxicants. Mature rat liver spheroids were exposed to diclofenac, galactosamine, isoniazid, paracetamol, m-dinitrobenzene (m-DNB) and 3-nitroaniline (3-NA) for 24 h. Pyruvate uptake, galactose biotransformation, lactate release and glucose secretion were evaluated after exposure. The results showed that pyruvate uptake and lactate release by mature liver spheroids in culture were maintained at a relatively stable level. These endpoints, together with glucose secretion and galactose biotransformation, were related to and could reflect the status of energy metabolism and biotransformation in hepatocytes. After exposure, all of the test agents significantly reduced glucose secretion, which was shown to be the most sensitive endpoint of those evaluated. Diclofenac, isoniazid, paracetamol and galactosamine reduced lactate release (P < 0.01), but m-DNB increased lactate release (P < 0.01). Diclofenac, isoniazid and paracetamol also reduced pyruvate uptake (P < 0.01), while galactosamine had little discernible effect. Diclofenac, galactosamine, paracetamol and m-DNB also reduced galactose biotransformation (P < 0.01), by contrast, isoniazid did not. The metabolite of m-DNB, 3-NA, which served as a negative control, did not cause significant changes in lactate release, pyruvate uptake or galactose biotransformation. It is concluded that pyruvate uptake, galactose biotransformation, lactate release and glucose secretion can be used as endpoints for evaluating the status of energy metabolism and biotransformation after exposure to test agents using the liver spheroid model to pre-screen hepatotoxicity

  11. Kinetic titration with differential thermometric determination of the end-point.

    Science.gov (United States)

    Sajó, I

    1968-06-01

    A method has been described for the determination of concentrations below 10(-4)M by applying catalytic reactions and using thermometric end-point determination. A reference solution, identical with the sample solution except for catalyst, is titrated with catalyst solution until the rates of reaction become the same, as shown by a null deflection on a galvanometer connected via bridge circuits to two opposed thermistors placed in the solutions.

  12. Quantitative 4D Transcatheter Intraarterial Perfusion MR Imaging as a Method to Standardize Angiographic Chemoembolization Endpoints

    Science.gov (United States)

    Jin, Brian; Wang, Dingxin; Lewandowski, Robert J.; Ryu, Robert K.; Sato, Kent T.; Larson, Andrew C.; Salem, Riad; Omary, Reed A.

    2011-01-01

    PURPOSE We aimed to test the hypothesis that subjective angiographic endpoints during transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) exhibit consistency and correlate with objective intraprocedural reductions in tumor perfusion as determined by quantitative four dimensional (4D) transcatheter intraarterial perfusion (TRIP) magnetic resonance (MR) imaging. MATERIALS AND METHODS This prospective study was approved by the institutional review board. Eighteen consecutive patients underwent TACE in a combined MR/interventional radiology (MR-IR) suite. Three board-certified interventional radiologists independently graded the angiographic endpoint of each procedure based on a previously described subjective angiographic chemoembolization endpoint (SACE) scale. A consensus SACE rating was established for each patient. Patients underwent quantitative 4D TRIP-MR imaging immediately before and after TACE, from which mean whole tumor perfusion (Fρ) was calculated. Consistency of SACE ratings between observers was evaluated using the intraclass correlation coefficient (ICC). The relationship between SACE ratings and intraprocedural TRIP-MR imaging perfusion changes was evaluated using Spearman’s rank correlation coefficient. RESULTS The SACE rating scale demonstrated very good consistency among all observers (ICC = 0.80). The consensus SACE rating was significantly correlated with both absolute (r = 0.54, P = 0.022) and percent (r = 0.85, P SACE rating scale demonstrates very good consistency between raters, and significantly correlates with objectively measured intraprocedural perfusion reductions during TACE. These results support the use of the SACE scale as a standardized alternative method to quantitative 4D TRIP-MR imaging to classify patients based on embolic endpoints of TACE. PMID:22021520

  13. Risk factors associated with incidence and persistence of frequent headaches.

    Science.gov (United States)

    Marklund, Susanna; Häggman-Henrikson, Birgitta; Wänman, Anders

    2014-11-01

    Headaches represent a significant public health problem, but the knowledge of factors specifically related to incidence and persistence of headaches is still limited. The aim of this study was to evaluate whether gender, self-reported bruxism and variations in the dental occlusion contribute to onset and persistence of frequent headaches. The study population comprised 280 dental students, examined annually in a 2-year prospective study with a questionnaire and a clinical examination of the jaw function. In the analysis subjects were dichotomized into cases with frequent (once a week or more) or without frequent headaches (controls). The 2-year cumulative incidence was based on subjects without frequent headaches at baseline. Cases with 2-year persistent headaches reported such symptoms at all three examinations. Self-reported bruxism and factors in the dental occlusion at baseline were used as independent variables in logistic regression analyses. The 2-year cumulative incidence of frequent headaches was 21%. Female gender (OR = 2.6; CI = 1.3-5.4), self-reported bruxism (OR = 2.3; CI = 1.2-4.4) and mandibular instability in intercuspal position (OR = 3.2; CI = 1.4-7.5) were associated with incidence of frequent headaches. Persistent headaches during the observation period were present in 12 individuals (4%) and significantly related to mandibular instability in intercuspal position (OR = 6.1; CI = 1.6-22.6). The results indicate that female gender, self-reported bruxism and mandibular instability in intercuspal position are of importance in the development of frequent headaches. In management of these patients a multidisciplinary approach including dentists may be important and, thus, advocated.

  14. The bedding environment, sleep position, and frequent wheeze in childhood.

    Science.gov (United States)

    Ponsonby, Anne-Louise; Dwyer, Terence; Trevillian, Leigh; Kemp, Andrew; Cochrane, Jennifer; Couper, David; Carmichael, Allan

    2004-05-01

    Synthetic quilt use has been associated with increased childhood wheeze in previous studies. Our aim was to examine whether the adverse effect of synthetic quilt use on frequent wheeze differed by usual sleep position. A population-based cross-sectional study of 6378 (92% of those eligible) 7-year-olds in Tasmania, Australia, was conducted in 1995. Exercise-challenge lung function was obtained on a subset of 414 children from randomly selected schools. Child bedding including pillow and overbedding composition and usual sleep position by parental questionnaire. Frequent wheeze (>12 wheeze episodes over the past year), using the International Study of Asthma and Allergies in Childhood parental questionnaire, and baseline and postexercise forced expiratory volume in 1 second lung-function measures. Frequent wheeze (n = 117) was positively associated with synthetic quilts, synthetic pillows, electric blankets, and sleeping in a bottom bunk bed but did not vary by sleep position. In a nested case-control analysis, the association between synthetic quilt use and frequent wheeze differed by sleep position. Among children who slept supine, synthetic (versus feather) quilt use was associated with frequent wheeze (adjusted odds ratio: 2.37 [1.08, 5.23]). However, among nonsupine sleepers, overlying synthetic quilt use was not associated with frequent wheeze (adjusted odds ratio: 1.06 [0.60, 1.88]). This difference in quilt effect by sleep position was highly significant. Similarly, synthetic quilt use was associated with lower postexercise forced expiratory volume in 1 second measures among supine but not nonsupine sleeping children. An increasing focus on the bedding environment immediately adjacent to the nose and mouth is required for respiratory disorders provoked by bedding, such as child asthma characterized by frequent wheeze.

  15. A New Test Unit for Disintegration End-Point Determination of Orodispersible Films.

    Science.gov (United States)

    Low, Ariana; Kok, Si Ling; Khong, Yuet Mei; Chan, Sui Yung; Gokhale, Rajeev

    2015-11-01

    No standard time or pharmacopoeia disintegration test method for orodispersible films (ODFs) exists. The USP disintegration test for tablets and capsules poses significant challenges for end-point determination when used for ODFs. We tested a newly developed disintegration test unit (DTU) against the USP disintegration test. The DTU is an accessory to the USP disintegration apparatus. It holds the ODF in a horizontal position, allowing top-view of the ODF during testing. A Gauge R&R study was conducted to assign relative contributions of the total variability from the operator, sample or the experimental set-up. Precision was compared using commercial ODF products in different media. Agreement between the two measurement methods was analysed. The DTU showed improved repeatability and reproducibility compared to the USP disintegration system with tighter standard deviations regardless of operator or medium. There is good agreement between the two methods, with the USP disintegration test giving generally longer disintegration times possibly due to difficulty in end-point determination. The DTU provided clear end-point determination and is suitable for quality control of ODFs during product developmental stage or manufacturing. This may facilitate the development of a standardized methodology for disintegration time determination of ODFs. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  16. End-point impedance measurements across dominant and nondominant hands and robotic assistance with directional damping.

    Science.gov (United States)

    Erden, Mustafa Suphi; Billard, Aude

    2015-06-01

    The goal of this paper is to perform end-point impedance measurements across dominant and nondominant hands while doing airbrush painting and to use the results for developing a robotic assistance scheme. We study airbrush painting because it resembles in many ways manual welding, a standard industrial task. The experiments are performed with the 7 degrees of freedom KUKA lightweight robot arm. The robot is controlled in admittance using a force sensor attached at the end-point, so as to act as a free-mass and be passively guided by the human. For impedance measurements, a set of nine subjects perform 12 repetitions of airbrush painting, drawing a straight-line on a cartoon horizontally placed on a table, while passively moving the airbrush mounted on the robot's end-point. We measure hand impedance during the painting task by generating sudden and brief external forces with the robot. The results show that on average the dominant hand displays larger impedance than the nondominant in the directions perpendicular to the painting line. We find the most significant difference in the damping values in these directions. Based on this observation, we develop a "directional damping" scheme for robotic assistance and conduct a pilot study with 12 subjects to contrast airbrush painting with and without robotic assistance. Results show significant improvement in precision with both dominant and nondominant hands when using robotic assistance.

  17. Using quantitative structure-activity relationships (QSAR) to predict toxic endpoints for polycyclic aromatic hydrocarbons (PAH).

    Science.gov (United States)

    Bruce, Erica D; Autenrieth, Robin L; Burghardt, Robert C; Donnelly, K C; McDonald, Thomas J

    2008-01-01

    Quantitative structure-activity relationships (QSAR) offer a reliable, cost-effective alternative to the time, money, and animal lives necessary to determine chemical toxicity by traditional methods. Additionally, humans are exposed to tens of thousands of chemicals in their lifetimes, necessitating the determination of chemical toxicity and screening for those posing the greatest risk to human health. This study developed models to predict toxic endpoints for three bioassays specific to several stages of carcinogenesis. The ethoxyresorufin O-deethylase assay (EROD), the Salmonella/microsome assay, and a gap junction intercellular communication (GJIC) assay were chosen for their ability to measure toxic endpoints specific to activation-, induction-, and promotion-related effects of polycyclic aromatic hydrocarbons (PAH). Shape-electronic, spatial, information content, and topological descriptors proved to be important descriptors in predicting the toxicity of PAH in these bioassays. Bioassay-based toxic equivalency factors (TEF(B)) were developed for several PAH using the quantitative structure-toxicity relationships (QSTR) developed. Predicting toxicity for a specific PAH compound, such as a bioassay-based potential potency (PP(B)) or a TEF(B), is possible by combining the predicted behavior from the QSTR models. These toxicity estimates may then be incorporated into a risk assessment for compounds that lack toxicity data. Accurate toxicity predictions are made by examining each type of endpoint important to the process of carcinogenicity, and a clearer understanding between composition and toxicity can be obtained.

  18. Individuals versus organisms versus populations in the definition of ecological assessment endpoints.

    Science.gov (United States)

    Suter, Glenn W; Norton, Susan B; Fairbrother, Anne

    2005-11-01

    Discussions and applications of the policies and practices of the U.S. Environmental Protection Agency (USEPA) in ecological risk assessment will benefit from continued clarification of the concepts of assessment endpoints and of levels of biological organization. First, assessment endpoint entities and attributes can be defined at different levels of organization. Hence, an organism-level attribute, such as growth or survival, can be applied collectively to a population-level entity such as the brook trout in a stream. Second, assessment endpoints for ecological risk assessment are often mistakenly described as "individual level," which leads to the idea that such assessments are intended to protect individuals. Finally, populations play a more important role in risk assessments than is generally recognized. Organism-level attributes are used primarily for population-level assessments. In addition, the USEPA and other agencies already are basing management decisions on population or community entities and attributes such as production of fisheries, abundance of migratory bird populations, and aquatic community composition.

  19. Reduction of animal suffering in rabies vaccine potency testing by introduction of humane endpoints.

    Science.gov (United States)

    Takayama-Ito, Mutsuyo; Lim, Chang-Kweng; Nakamichi, Kazuo; Kakiuchi, Satsuki; Horiya, Madoka; Posadas-Herrera, Guillermo; Kurane, Ichiro; Saijo, Masayuki

    2017-03-01

    Potency controls of inactivated rabies vaccines for human use are confirmed by the National Institutes of Health challenge test in which lethal infection with severe neurological symptoms should be observed in approximately half of the mice inoculated with the rabies virus. Weight loss, decreased body temperature, and the presence of rabies-associated neurological signs have been proposed as humane endpoints. The potential for reduction of animal suffering by introducing humane endpoints in the potency test for inactivated rabies vaccine for human use was investigated. The clinical signs were scored and body weight was monitored. The average times to death following inoculation were 10.49 and 10.99 days post-inoculation (dpi) by the potency and challenge control tests, respectively, whereas the average times to showing Score-2 signs (paralysis, trembling, and coma) were 6.26 and 6.55 dpi, respectively. Body weight loss of more than 15% appeared at 5.82 and 6.42 dpi. The data provided here support the introduction of obvious neuronal signs combined with a body weight loss of ≥15% as a humane endpoint to reduce the time of animal suffering by approximately 4 days. Copyright © 2017 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  20. First Trimester Hemolysis, Elevated Liver Enzymes, Low Platelets Syndrome in a Surrogate Pregnancy

    OpenAIRE

    Myer, Emily; Hill, James

    2015-01-01

    Background The occurrence of hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome before 20 weeks of gestation is rare. HELLP is a possible but rare syndrome in gestational surrogate pregnancies for surrogates with risk factors for development of preeclampsia. Case A 32-year-old patient with chronic hypertension and positive antinuclear antibody presented for prenatal care at 13 weeks and 1 day. She was a surrogate for the embryo of a 43-year-old couple. By 15 weeks she developed...

  1. Children of surrogate mothers: psychological well-being, family relationships and experiences of surrogacy.

    Science.gov (United States)

    Jadva, V; Imrie, S

    2014-01-01

    What impact does surrogacy have on the surrogates' own children? The children of surrogate mothers do not experience any negative consequences as a result of their mother's decision to be a surrogate, irrespective of whether or not the surrogate uses her own egg. Participants were recruited as part of a study of the long-term effects of surrogacy for surrogates and their family members. Data were collected from 36 children of surrogates at a single time point. Participants whose mother had been a surrogate 5-15 years prior to interview and who were aged over 12 years were eligible to take part. Thirty-six participants (14 male and 22 female) aged 12-25 years were interviewed (response rate = 52%). Questionnaires assessing psychological health and family functioning were administered. Forty-four per cent (15) of participants' mothers had undergone gestational surrogacy, 39% (14) had used their own egg (genetic surrogacy) and 19% (7) had completed both types of surrogacy. Most surrogates' children (86%, 31) had a positive view of their mother's surrogacy. Forty-seven per cent (17) of children were in contact with the surrogacy child and all reported good relationships with him/her. Forty per cent (14) of children referred to the child as a sibling or half-sibling and this did not differ between genetic and gestational surrogacy. Most children (89%, 32), reported a positive view of family life, with all enjoying spending time with their mother. Mean scores on the questionnaire assessments of psychological health and self-esteem were within the normal range and did not differ by surrogacy type. The sample size for this study was relatively small and not all children chose to take part, therefore their views cannot be known. Nevertheless, this is the first study to assess the experiences of surrogacy from the perspective of the surrogates' own children. There may be some bias from the inclusion of siblings from the same family. Findings of this study show that family

  2. Methylene blue as a lignin surrogate in manganese peroxidase reaction systems.

    Science.gov (United States)

    Goby, Jeffrey D; Penner, Michael H; Lajoie, Curtis A; Kelly, Christine J

    2017-11-15

    Manganese peroxidase (MnP) is associated with lignin degradation and is thus relevant to lignocellulosic-utilization technologies. Technological applications require reaction mixture optimization. A surrogate substrate can facilitate this if its susceptibility to degradation is easily monitored and mirrors that of lignin. The dye methylene blue (MB) was evaluated in these respects as a surrogate substrate by testing its reactivity in reaction mixtures containing relevant redox mediators (dicarboxylic acids, fatty acids). Relative rates of MB degradation were compared to available literature reports of lignin degradation under similar conditions, and suggest that MB can be a useful lignin surrogate in MnP systems. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Results from Second Round of Remediated Nitrate Salt Surrogate Formulation and Testing

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Geoffrey Wayne [Los Alamos National Laboratory; Leonard, Philip [Los Alamos National Laboratory; Hartline, Ernest Leon [Los Alamos National Laboratory; Tian, Hongzhao [Los Alamos National Laboratory

    2016-04-04

    High Explosives and Technology (M-7) completed the second round of formulation and testing of Remediated Nitrate Salt (RNS) surrogates on March 17, 2016. This report summarizes the results of the work and also includes additional documentation required under test plan PLAN-TA9-2443 Rev B, "Remediated Nitrate Salt (RNS) Surrogate Formulation and Testing Standard Procedure", released February 16, 2016. All formulation and testing was carried out according to PLAN-TA9-2443 Rev B. Results from the first round of formulation and testing were documented in memorandum M7-16-6042, "Results from First Round of Remediated Nitrate Salt Surrogate Formulation and Testing."

  4. Defining frequent use of an urban emergency department

    Science.gov (United States)

    Locker, Thomas E; Baston, Simon; Mason, Suzanne M; Nicholl, Jon

    2007-01-01

    Objective This study aimed to develop a definition of frequent use of an emergency department (ED) by comparing differences in the observed frequency distribution with that of a theoretical frequency distribution. Methods A retrospective analysis of attendance of ED and minor injury unit attendances in one city over 1 year was conducted. From these data, the expected frequency distribution was determined based upon a Poisson distribution. Results During the period studied, 75 141 people attended on 98 908 occasions. The theoretical frequency distribution showed that there were 2764 (3.7%) “frequent users” presenting repeatedly due to non‐random events. These patients made 12 316 (12.4%) attendances. Frequent users were older than chance users (mean age 49.7 vs 44.5 years). A greater proportion arrived by ambulance (55.3% vs 27.5%), presented with psychiatric problems (5.8% vs 1.1%) or alcohol intoxication (1.3% vs 0.5%), and were admitted to hospital (37.4% vs 19.6%). Conclusion We have identified that there is a group of patients who present repeatedly due to non‐random events, confirming the existence of “frequent users”. Their characteristics are clearly different to other patients in the ED. We propose that “frequent users” be defined as any patient who makes more than four attendances per year. PMID:17513534

  5. Effects of angiotensin II blockade on intermediate cardiovascular endpoints in haemodialysis patients: a randomised double-blind placebo-controlled one-year intervention trial (SAFIR study)

    DEFF Research Database (Denmark)

    Peters, Christian Daugaard; Kjærgaard, Krista Dybtved; Jensen, Jens Dam

    Agents blocking the renin-angiotensin-aldosterone system are frequently used in end-stage renal disease patients, but whether they exert beneficial cardiovascular (CV) effects is unclear. The long-term effects of the angiotensin II receptor blocker irbesartan was investigated in 82 haemodialysis...... renal function. Brachial BP decreased significantly in both groups, but there was no significant difference between placebo and irbesartan treated. Use of additional antihypertensive medication, ultrafiltration volume, and dialysis dosage were not different in the two groups. Intermediate CV endpoints...... such as central aortic BP, carotid-femoral pulse wave velocity, left ventricular mass index, N-terminal prohormone of brain natriuretic peptide, heart rate variability, and plasma catecholamines were not significantly affected by irbesartan treatment. Changes in systolic BP during the study period correlated...

  6. The Use of Tools, Modelling Methods, Data Types, and Endpoints in Systems Medicine: A Survey on Projects of the German e:Med-Programme.

    Science.gov (United States)

    Gietzelt, Matthias; Höfer, Thomas; Knaup-Gregori, Petra; König, Rainer; Löpprich, Martin; Poos, Alexandra; Ganzinger, Matthias

    2016-01-01

    Systems medicine is the consequent continuation of research efforts on the road to an individualized medicine. Thereby, systems medicine tries to offer a holistic view on the patient by combining different data sources to highlight different perspectives on the patient's health. Our research question was to identify the main data types, modelling methods, analysis tools, and endpoints currently used and studied in systems medicine. Therefore, we conducted a survey on projects with a systems medicine background. Fifty participants completed this survey. The results of the survey were analyzed using histograms and cross tables, and finally compared to results of a former literature review with the same research focus. The data types reported in this survey were widely diversified. As expected, genomic and phenotype data were used most frequently. In contrast, environmental and behavioral data were rarely used in the projects. Overall, the cross tables of the data types in the survey and the literature review showed overlapping results.

  7. The development of radioactive sample surrogates for training and exercises

    International Nuclear Information System (INIS)

    Kevin Carney; Martha Finck; Christopher McGrath; Bevin Brush; Dick Jansen; Donald Dry; George Brooks; David Chamberlain

    2013-01-01

    Source term information is required for to reconstruct a device used in a dispersed radiological dispersal device. Simulating a radioactive environment to train and exercise sampling and sample characterization methods with suitable sample materials is a continued challenge. The Idaho National Laboratory has developed and permitted a radioactive response training range (RRTR), an 800 acre test range that is approved for open air dispersal of activated KBr, for training first responders in the entry and exit from radioactively contaminated areas, and testing protocols for environmental sampling and field characterization. Members from the Department of Defense, Law Enforcement, and the Department of Energy participated in the first contamination exercise that was conducted at the RRTR in the July 2011. The range was contaminated using a short lived radioactive 82 Br isotope (activated KBr). Soil samples contaminated with KBr (dispersed as a solution) and glass particles containing activated potassium bromide that emulated dispersed radioactive materials (such as ceramic-based sealed source materials) were collected to assess environmental sampling and characterization techniques. This presentation summarizes the performance of a radioactive materials surrogate for use as a training aide for nuclear forensics. (author)

  8. Effectiveness of amphibians as biodiversity surrogates in pond conservation.

    Science.gov (United States)

    Ilg, Christiane; Oertli, Beat

    2017-04-01

    Amphibian decline has led to worldwide conservation efforts, including the identification and designation of sites for their protection. These sites could also play an important role in the conservation of other freshwater taxa. In 89 ponds in Switzerland, we assessed the effectiveness of amphibians as a surrogate for 4 taxonomic groups that occur in the same freshwater ecosystems as amphibians: dragonflies, aquatic beetles, aquatic gastropods, and aquatic plants. The ponds were all of high value for amphibian conservation. Cross-taxon correlations were tested for species richness and conservation value, and Mantel tests were used to investigate community congruence. Species richness, conservation value, and community composition of amphibians were weakly congruent with these measures for the other taxonomic groups. Paired comparisons for the 5 groups considered showed that for each metric, amphibians had the lowest degree of congruence. Our results imply that site designation for amphibian conservation will not necessarily provide protection for freshwater biodiversity as a whole. To provide adequate protection for freshwater species, we recommend other taxonomic groups be considered in addition to amphibians in the prioritization and site designation process. © 2016 Society for Conservation Biology.

  9. Capturing heterogeneity in gene expression studies by surrogate variable analysis.

    Directory of Open Access Journals (Sweden)

    Jeffrey T Leek

    2007-09-01

    Full Text Available It has unambiguously been shown that genetic, environmental, demographic, and technical factors may have substantial effects on gene expression levels. In addition to the measured variable(s of interest, there will tend to be sources of signal due to factors that are unknown, unmeasured, or too complicated to capture through simple models. We show that failing to incorporate these sources of heterogeneity into an analysis can have widespread and detrimental effects on the study. Not only can this reduce power or induce unwanted dependence across genes, but it can also introduce sources of spurious signal to many genes. This phenomenon is true even for well-designed, randomized studies. We introduce "surrogate variable analysis" (SVA to overcome the problems caused by heterogeneity in expression studies. SVA can be applied in conjunction with standard analysis techniques to accurately capture the relationship between expression and any modeled variables of interest. We apply SVA to disease class, time course, and genetics of gene expression studies. We show that SVA increases the biological accuracy and reproducibility of analyses in genome-wide expression studies.

  10. The composition of surrogate and illegal alcohol products in Estonia.

    Science.gov (United States)

    Lang, Katrin; Väli, Marika; Szucs, Sándor; Adány, Róza; McKee, Martin

    2006-01-01

    To identify the composition of illegal and surrogate alcohol products consumed in Estonia. The initial source of information was a series of visits made in August 2005 to a soup kitchen in central Tartu, Estonia. Individuals were asked for brief details of their personal circumstances, what they normally drank, and in addition they were asked to bring samples of the substances they usually consumed. In other cases, the substances identified were purchased by the investigators or from informal contacts in north-eastern part of Estonia, an area that is well known for illegal alcohol consumption. Samples were tested for chemical contents. We identified a range of alcohol-containing substances that are consumed, although, not intended for consumption. These comprised medicinal products, aftershaves, illegally produced spirits, and fire-lighting fuel. The medicinal compounds contained, on average, 67% ethanol by volume; the aftershaves contained slightly less. Both were typically pure, with a few containing detectable quantities of isoamyl alcohol. The illegally produced alcohol contained, on average, 43% ethanol by volume, ranging from 32 to 53%. However, many also contained detectable quantities of long chain alcohols. These substances are half the price or less of commercial vodka, with fire lighting fuels especially inexpensive. There is in Estonia a range of alcohol-containing substances easily available at low cost. Some contain substantially higher concentrations of ethanol than commercial spirits and others also contain toxic long chain alcohols.

  11. Black-hole kicks from numerical-relativity surrogate models

    Science.gov (United States)

    Gerosa, Davide; Hébert, François; Stein, Leo C.

    2018-05-01

    Binary black holes radiate linear momentum in gravitational waves as they merge. Recoils imparted to the black-hole remnant can reach thousands of km /s , thus ejecting black holes from their host galaxies. We exploit recent advances in gravitational waveform modeling to quickly and reliably extract recoils imparted to generic, precessing, black-hole binaries. Our procedure uses a numerical-relativity surrogate model to obtain the gravitational waveform given a set of binary parameters; then, from this waveform we directly integrate the gravitational-wave linear momentum flux. This entirely bypasses the need for fitting formulas which are typically used to model black-hole recoils in astrophysical contexts. We provide a thorough exploration of the black-hole kick phenomenology in the parameter space, summarizing and extending previous numerical results on the topic. Our extraction procedure is made publicly available as a module for the Python programming language named surrkick. Kick evaluations take ˜0.1 s on a standard off-the-shelf machine, thus making our code ideal to be ported to large-scale astrophysical studies.

  12. Social capital and frequent attenders in general practice

    DEFF Research Database (Denmark)

    Pasgaard, Alexander A.; Mæhlisen, Maiken H.; Overgaard, Charlotte

    2018-01-01

    weeks. RESULTS: Using multiple logistic regression, we found that frequent attendance was associated with a lower score in interpersonal trust [OR 0.86 (0.79-0.94)] and social network [OR 0.88 (0.79-0.98)] for women, when adjusted for age, education, income and SF12 health scores. Norms of reciprocity...... at the individual level, and includes cognitive (interpersonal trust and norms of reciprocity) as well as structural (social network and civic engagement) dimensions. Frequent attendance is defined as the upper-quartile of the total number of measured consultations with a general practitioner over a period of 148...... and civic engagement were not significantly associated with frequent attendance for women [OR 1.05 (0.99-1.11) and OR 1.01 (0.92-1.11) respectively]. None of the associations were statistically significant for men. CONCLUSION: This study suggests that for women, some aspects of social capital are associated...

  13. Social environment and frequent attendance in Danish general practice

    DEFF Research Database (Denmark)

    Vedsted, Peter; Olesen, Frede

    2005-01-01

    inequalities in health or whether social factors in themselves determine the use of general practice. AIM: To examine if social factors are associated with frequent attendance in general practice after adjusting for physical and psychological health variables. DESIGN OF STUDY: Population-based cross......BACKGROUND: A lack of social support is associated with increased morbidity and mortality and a decreased effect of prevention. Frequent attenders to primary care are characterised by poorer social conditions than other patients in general practice, but we do not know whether this is due to social...... during the period November 1997-October 1998. A questionnaire about physical, psychological and social factors was sent to the patients. The associations between social factors and frequent attendance were adjusted for physical and psychological health and tendency towards somatisation. RESULTS: A total...

  14. Frequently Used Coping Scales: A Meta-Analysis.

    Science.gov (United States)

    Kato, Tsukasa

    2015-10-01

    This article reports the frequency of the use of coping scales in academic journals published from 1998 to 2010. Two thousand empirical journal articles were selected from the EBSCO database. The COPE, Ways of Coping Questionnaire, Coping Strategies Questionnaire, Coping Inventory for Stressful Situations, Religious-COPE and Coping Response Inventory were frequently mentioned. In particular, the COPE (20.2%) and Ways of Coping Questionnaire (13.6%) were used the most frequently. In this literature reviewed, coping scales were most often used to assess coping with health issues (e.g. illness, pain and medical diagnoses) over other types of stressors, and patients were the most frequent participants. Further, alpha coefficients were estimated for the COPE subscales, and correlations between the COPE subscales and coping outcomes were calculated, including depressive symptoms, anxiety, negative affect, psychological distress, physical symptoms and well-being. Copyright © 2013 John Wiley & Sons, Ltd.

  15. Examination of Operation Quality for High-frequent Railway Operation

    DEFF Research Database (Denmark)

    Landex, Alex; Kaas, Anders H.

    2009-01-01

    take the first train in their direction. The article examines four different approaches to examine operation quality for high-frequent operation that are based on the experiences of the passengers. These approaches are the service frequency of the operation, travel time extension, a combination......The examination of operation quality for high-frequent operation requires other approaches than the typical evaluation of punctuality (trains on time) and reliability (operated trains). This is because passengers in high-frequent railway systems do not necessarily notice train delays as they just...... of the service frequency and travel time approaches, and passenger delays. The service frequency and travel time approaches are simple measurements with low complexity and complement each other. Therefore, the article recommends combining the service frequency and travel time approaches to get a more accurate...

  16. Comparison of burrowing and stimuli-evoked pain behaviors as end-points in rat models of inflammatory pain and peripheral neuropathic pain

    Directory of Open Access Journals (Sweden)

    Arjun eMuralidharan

    2016-05-01

    Full Text Available Establishment and validation of ethologically-relevant, non-evoked behavioral end-points as surrogate measures of spontaneous pain in rodent pain models has been proposed as a means to improve preclinical to clinical research translation in the pain field. Here, we compared the utility of burrowing behavior with hypersensitivity to applied mechanical stimuli for pain assessment in rat models of chronic inflammatory and peripheral neuropathic pain. Briefly, groups of male Sprague-Dawley rats were habituated to the burrowing environment and trained over a 5-day period. Rats that burrowed ≤450g of gravel on any two days of the individual training phase were excluded from the study. The remaining rats received either a unilateral intraplantar injection of Freund’s complete adjuvant (FCA or saline, or underwent unilateral chronic constriction injury (CCI of the sciatic nerve- or sham-surgery. Baseline burrowing behavior and evoked pain behaviors were assessed prior to model induction, and twice-weekly until study completion on day 14. For FCA- and CCI-rats, but not the corresponding groups of sham-rats, evoked mechanical hypersensitivity developed in a temporal manner in the ipsilateral hindpaws. Although burrowing behavior also decreased in a temporal manner for both FCA- and CCI-rats, there was considerable inter-animal variability. By contrast, mechanical hyperalgesia and mechanical allodynia in the ipsilateral hindpaws of FCA- and CCI-rats respectively, exhibited minimal inter-animal variability. Our data collectively show that burrowing behavior is altered in rodent models of chronic inflammatory pain and peripheral neuropathic pain. However, large group sizes are needed to ensure studies are adequately powered due to considerable inter-animal variability.

  17. A Review of Clinical Trial Endpoints of Patients with Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension and How They Relate to Patient Outcomes in the United States.

    Science.gov (United States)

    Divers, Christine; Platt, David; Wang, Edward; Lin, Jay; Lingohr-Smith, Melissa; Mathai, Stephen C

    2017-01-01

    Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are subgroups of pulmonary hypertension and are considered rare diseases. Understanding how endpoints of clinical trials (and patient registry studies) of patients with PAH and CTEPH are associated with patient outcomes is important in order to address the concerns of patients, health care providers, decision makers, and payers. The purpose of this review was to examine how endpoints used in clinical trials and patient registry studies are associated with outcomes of patients with PAH and CTEPH. A PubMed literature search was conducted to retrieve published studies, including randomized phase III clinical trials and observational studies, from years 2000 to May 2015 that evaluated the associations between change in 6-minute walking distance (6MWD), 6MWD thresholds, change in World Health Organization functional class (WHO-FC), and time to clinical worsening with outcomes of patients with PAH and CTEPH. Based on this review of published literature, a reduction in 6MWD as a criterion for PAH worsening, a deterioration in WHO-FC, and delay in the time to clinical worsening are clinically meaningful trial endpoints and are associated with outcomes of patients with PAH and CTEPH. Utilization and standardization of these endpoints will be useful for comparing interventions of clinical trials and therapies. Hospitalizations are frequent among patients with PAH and CTEPH, and total health care costs are high. From a U.S. payer perspective, clinical worsening is an important composite endpoint in that it includes hospitalization, which can be transformed into a preventative cost value associated with efficacious treatment of patients with PAH and CTEPH. In view of the greater number of medications available to treat PAH, the introduction of the first approved therapy to treat CTEPH, and the increasing use of combination pharmacotherapy, reliable prognostic markers of treatment

  18. Energetic endpoints provide early indicators of life history effects in a freshwater gastropod exposed to the fungicide, pyraclostrobin

    International Nuclear Information System (INIS)

    Fidder, Bridgette N.; Reátegui-Zirena, Evelyn G.; Olson, Adric D.; Salice, Christopher J.

    2016-01-01

    Organismal energetics provide important insights into the effects of environmental toxicants. We aimed to determine the effects of pyraclostrobin on Lymnaea stagnalis by examining energy allocation patterns and life history traits. Juvenile snails exposed to pyraclostrobin decreased feeding rate and increased apparent avoidance behaviors at environmentally relevant concentrations. In adults, we found that sublethal concentrations of pyraclostrobin did not affect reproductive output, however, there were significant effects on developmental endpoints with longer time to hatch and decreased hatching success in pyraclostrobin-exposed egg masses. Further, there were apparent differences in developmental effects depending on whether mothers were also exposed to pyraclostrobin suggesting this chemical can exert intergenerational effects. Pyraclostrobin also affected protein and carbohydrate content of eggs in mothers that were exposed to pyraclostrobin. Significant effects on macronutrient content of eggs occurred at lower concentrations than effects on gross endpoints such as hatching success and time to hatch suggesting potential value for these endpoints as early indicators of ecologically relevant stress. These results provide important insight into the effects of a common fungicide on important endpoints for organismal energetics and life history. - Highlights: • We exposed a freshwater snail to relevant concentrations of pyraclostrobin. • We monitored energetic and life history endpoints. • Pyraclostrobin affected feeding, hatching success and egg macronutrient content. • Energetic-based endpoints may provide valuable insight to toxic effects. - The fungicide pyraclostrobin at environmentally relevant concentrations effects a range of life history and energetic endpoints in the freshwater snail, Lymnaea stagnalis.

  19. adapta~k>n -11 of the surrogate memods for linear programming ...

    African Journals Online (AJOL)

    2005-08-02

    Aug 2, 2005 ... inequality problem is made uj~ of the primal and dual optimal solutions for the given primal ... KEYWORDS: Linear Programming, Duality Theory, Surrogate Methods. ..... replaces x and the process IS repeated with the new x.

  20. Spot Sampling and Exposure Surrogate Selection as Sources of Bias in Environmental Epidemiology Studies

    Science.gov (United States)

    Spot measurements of chemical biomarkers are often used as quantitative exposure surrogates in environmental epidemiology studies. These measures can be expressed a number of different ways – for example, urinary biomarkers can be expressed in units of concentration (&micr...

  1. An improved and explicit surrogate variable analysis procedure by coefficient adjustment.

    Science.gov (United States)

    Lee, Seunggeun; Sun, Wei; Wright, Fred A; Zou, Fei

    2017-06-01

    Unobserved environmental, demographic, and technical factors can negatively affect the estimation and testing of the effects of primary variables. Surrogate variable analysis, proposed to tackle this problem, has been widely used in genomic studies. To estimate hidden factors that are correlated with the primary variables, surrogate variable analysis performs principal component analysis either on a subset of features or on all features, but weighting each differently. However, existing approaches may fail to identify hidden factors that are strongly correlated with the primary variables, and the extra step of feature selection and weight calculation makes the theoretical investigation of surrogate variable analysis challenging. In this paper, we propose an improved surrogate variable analysis using all measured features that has a natural connection with restricted least squares, which allows us to study its theoretical properties. Simulation studies and real data analysis show that the method is competitive to state-of-the-art methods.

  2. A reaction mechanism for gasoline surrogate fuels for large polycyclic aromatic hydrocarbons

    KAUST Repository

    Raj, Abhijeet; Charry Prada, Iran David; Amer, Ahmad Amer; Chung, Suk-Ho

    2012-01-01

    This work aims to develop a reaction mechanism for gasoline surrogate fuels (n-heptane, iso-octane and toluene) with an emphasis on the formation of large polycyclic aromatic hydrocarbons (PAHs). Starting from an existing base mechanism for gasoline

  3. Acylation-stimulating protein is a surrogate biomarker for acute myocardial infarction: Role of statins

    Directory of Open Access Journals (Sweden)

    Hayder M Al-Kuraishy

    2017-01-01

    Conclusion: ASP levels are elevated in patients with acute MI and regarded as surrogate biomarker for acute MI also; therapy with statins leads to significant reduction in ASP levels compared to nonstatins-treated patients that presented with acute MI.

  4. First Trimester Hemolysis, Elevated Liver Enzymes, Low Platelets Syndrome in a Surrogate Pregnancy.

    Science.gov (United States)

    Myer, Emily; Hill, James

    2015-10-01

    Background The occurrence of hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome before 20 weeks of gestation is rare. HELLP is a possible but rare syndrome in gestational surrogate pregnancies for surrogates with risk factors for development of preeclampsia. Case A 32-year-old patient with chronic hypertension and positive antinuclear antibody presented for prenatal care at 13 weeks and 1 day. She was a surrogate for the embryo of a 43-year-old couple. By 15 weeks she developed uncontrolled hypertension requiring hospitalization. She was expectantly managed until her condition deteriorated. At 16 weeks and 1 day she developed hemolysis, elevated liver enzymes, thrombocytopenia, and fetal demise. Conclusions HELLP syndrome is rare and carries a significant morbidity and mortality for the mother and fetus. Clinicians should encourage the surrogate to share her medical history with the embryo donor for appropriate counseling on pregnancy risks.

  5. Surrogate Models for Online Monitoring and Process Troubleshooting of NBR Emulsion Copolymerization

    Directory of Open Access Journals (Sweden)

    Chandra Mouli R. Madhuranthakam

    2016-03-01

    Full Text Available Chemical processes with complex reaction mechanisms generally lead to dynamic models which, while beneficial for predicting and capturing the detailed process behavior, are not readily amenable for direct use in online applications related to process operation, optimisation, control, and troubleshooting. Surrogate models can help overcome this problem. In this research article, the first part focuses on obtaining surrogate models for emulsion copolymerization of nitrile butadiene rubber (NBR, which is usually produced in a train of continuous stirred tank reactors. The predictions and/or profiles for several performance characteristics such as conversion, number of polymer particles, copolymer composition, and weight-average molecular weight, obtained using surrogate models are compared with those obtained using the detailed mechanistic model. In the second part of this article, optimal flow profiles based on dynamic optimisation using the surrogate models are obtained for the production of NBR emulsions with the objective of minimising the off-specification product generated during grade transitions.

  6. Experimental Validation of Surrogate Models for Predicting the Draping of Physical Interpolating Surfaces

    DEFF Research Database (Denmark)

    Christensen, Esben Toke; Lund, Erik; Lindgaard, Esben

    2018-01-01

    This paper concerns the experimental validation of two surrogate models through a benchmark study involving two different variable shape mould prototype systems. The surrogate models in question are different methods based on kriging and proper orthogonal decomposition (POD), which were developed...... to the performance of the studied surrogate models. By comparing surrogate model performance for the two variable shape mould systems, and through a numerical study involving simple finite element models, the underlying cause of this effect is explained. It is concluded that for a variable shape mould prototype...... hypercube approach. This sampling method allows for generating a space filling and high-quality sample plan that respects mechanical constraints of the variable shape mould systems. Through the benchmark study, it is found that mechanical freeplay in the modeled system is severely detrimental...

  7. Surrogate Plant Data Base : Volume 4. Appendix E : Medium and Heavy Truck Manufacturing

    Science.gov (United States)

    1983-05-01

    This four volume report consists of a data base describing "surrogate" automobile and truck manufacturing plants developed as part of a methodology for evaluating capital investment requirements in new manufacturing facilities to build new fleets of ...

  8. Surrogate Plant Data Base : Volume 2. Appendix C : Facilities Planning Baseline Data

    Science.gov (United States)

    1983-05-01

    This four volume report consists of a data base describing "surrogate" automobile and truck manufacturing plants developed as part of a methodology for evaluating capital investment requirements in new manufacturing facilities to build new fleets of ...

  9. An Efficient Constraint Boundary Sampling Method for Sequential RBDO Using Kriging Surrogate Model

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jihoon; Jang, Junyong; Kim, Shinyu; Lee, Tae Hee [Hanyang Univ., Seoul (Korea, Republic of); Cho, Sugil; Kim, Hyung Woo; Hong, Sup [Korea Research Institute of Ships and Ocean Engineering, Busan (Korea, Republic of)

    2016-06-15

    Reliability-based design optimization (RBDO) requires a high computational cost owing to its reliability analysis. A surrogate model is introduced to reduce the computational cost in RBDO. The accuracy of the reliability depends on the accuracy of the surrogate model of constraint boundaries in the surrogated-model-based RBDO. In earlier researches, constraint boundary sampling (CBS) was proposed to approximate accurately the boundaries of constraints by locating sample points on the boundaries of constraints. However, because CBS uses sample points on all constraint boundaries, it creates superfluous sample points. In this paper, efficient constraint boundary sampling (ECBS) is proposed to enhance the efficiency of CBS. ECBS uses the statistical information of a kriging surrogate model to locate sample points on or near the RBDO solution. The efficiency of ECBS is verified by mathematical examples.

  10. Developing the role of the social worker as coordinator of services at the surrogate parenting center.

    Science.gov (United States)

    Gagin, Roni; Cohen, Miri; Greenblatt, Lee; Solomon, Hanah; Itskovitz-Eldor, Joseph

    2004-01-01

    A law permitting couples to conceive biological children through surrogacy was legislated in Israel in March 1996. The Rambam Medical Center has established the only nonprofit Surrogate Parenting Center at a public hospital in Israel. The multidisciplinary teamwork at the Center is case managed by a social worker. An important role of the social work intervention is consultation and support for the couple and the surrogate at all stages of the process. The case study presented in the article illustrates the need for sensitive and professional intervention due to the complexity of the surrogacy process and the crisis it involves for both the surrogate and the couple. In light of the growing parenting surrogacy cases in the United States, Europe, and Israel, a structured social work intervention model is described, which may be implemented at public or private surrogate parenting centers.

  11. Single-site Lennard-Jones models via polynomial chaos surrogates of Monte Carlo molecular simulation

    KAUST Repository

    Kadoura, Ahmad Salim; Siripatana, Adil; Sun, Shuyu; Knio, Omar; Hoteit, Ibrahim

    2016-01-01

    In this work, two Polynomial Chaos (PC) surrogates were generated to reproduce Monte Carlo (MC) molecular simulation results of the canonical (single-phase) and the NVT-Gibbs (two-phase) ensembles for a system of normalized structureless Lennard

  12. Soot formation characteristics of gasoline surrogate fuels in counterflow diffusion flames

    KAUST Repository

    Choi, Byungchul; Choi, Sangkyu; Chung, Suk-Ho

    2011-01-01

    The characteristics of polycyclic aromatic hydrocarbon (PAH) and soot for gasoline surrogate fuels have been investigated in counterflow diffusion flames by adopting laser-induced fluorescence (LIF) and laser-induced incandescence (LII) techniques

  13. Plutonium and surrogate fission products in a composite ceramic waste form

    International Nuclear Information System (INIS)

    Esh, D. W.; Frank, S. M.; Goff, K. M.; Johnson, S. G.; Moschetti, T. L.; O'Holleran, T.

    1999-01-01

    Argonne National Laboratory is developing a ceramic waste form to immobilize salt containing fission products and transuranic elements. Preliminary results have been presented for ceramic waste forms containing surrogate fission products such as cesium and the lanthanides. In this work results from scanning electron microscopy/energy dispersive spectroscopy and x-ray diffraction are presented in greater detail for ceramic waste forms containing surrogate fission products. Additionally, results for waste forms containing plutonium and surrogate fission products are presented. Most of the surrogate fission products appear to be silicates or aluminosilicates whereas the plutonium is usually found in an oxide form. There is also evidence for the presence of plutonium within the sodalite phase although the chemical speciation of the plutonium is not known

  14. Associations between maternal lifestyle factors and neonatal body composition in the Screening for Pregnancy Endpoints (Cork) cohort study.

    Science.gov (United States)

    Dahly, Darren L; Li, Xia; Smith, Hazel A; Khashan, Ali S; Murray, Deirdre M; Kiely, Mairead E; O'B Hourihane, Jonathan; McCarthy, Fergus P; Kenny, Louise C; Kearney, Patricia M

    2018-02-01

    Neonatal body composition likely mediates fetal influences on life long chronic disease risk. A better understanding of how maternal lifestyle is related to newborn body composition could thus inform intervention efforts. Using Cork participant data (n = 1754) from the Screening for Pregnancy Endpoints (SCOPE) cohort study [ECM5(10)05/02/08], we estimated how pre-pregnancy body size, gestational weight gain, exercise, alcohol, smoking and diet were related to neonatal fat and fat-free mass, as well as length and gestational age at birth, using quantile regression. Maternal factors were measured by a trained research midwife at 15 gestational weeks, in addition to a 3rd trimester weight measurement used to calculate weight gain. Infant body composition was measured using air-displacement plethysmography. Healthy (versus excess) gestational weight gain was associated with lower median fat-free mass [-112 g, 95% confidence interval (CI): -47 to -176) and fat mass (-33 g, 95% CI: -1 to -65) in the offspring; and a 103 g decrease in the 95th centile of fat mass (95% CI: -33 to -174). Maternal normal weight status (versus obesity) was associated with lower median fat mass (-48 g, 95% CI: -12 to -84). At the highest centiles, fat mass was lower among infants of women who engaged in frequent moderate-intensity exercise early in the pregnancy (-92 g at the 95th centile, 95% CI: -168 to -16). Lastly, women who never smoked tended to have longer babies with more fat mass and fat-free mass. No other lifestyle factors were strongly related to infant body composition. These results suggest that supporting healthy maternal lifestyles could reduce the risk of excess fat accumulation in the offspring, without adversely affecting fat-free mass development, length or gestational age. © The Author 2017; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

  15. Surrogate in vitro fertilization outcome in typical and atypical forms of Mayer-Rokitansky-Kuster-Hauser syndrome.

    Science.gov (United States)

    Raziel, A; Friedler, S; Gidoni, Y; Ben Ami, I; Strassburger, D; Ron-El, R

    2012-01-01

    The genital malformations in Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) are frequently accompanied by associated malformations whose forms were recently classified as typical (isolated uterovaginal aplasia/hypoplasia) and atypical (the addition of malformations in the ovary or renal system). The aim of this study was to compare the surrogate IVF performance of women with typical and atypical forms including their chances of achieving pregnancy. The follow-up data on a total of 102 cycles of surrogate IVF in 27 MRKH patients treated in our department between 2000 and 2010 were analysed. Twenty patients with the typical form who underwent 72 IVF cycles were compared with seven patients with the atypical form who underwent 30 IVF cycles. The various examined parameters of these intended mothers were age, hormonal profile during controlled ovarian hyperstimulation and laboratory outcome. The mean number of gonadotrophin ampoules needed for stimulation and treatment duration was significantly higher in the atypical form (3600 ± 1297IU for 13 ± 2.3 days versus 2975 ± 967 IU for 11.6 ± 1.6 days, P≤ 0.01). Serum estradiol and progesterone levels measured on the hCG administration day were similar. A significantly higher mean number of follicles 12.6 ± 6 versus 8.9 ± 5.4, P≤ 0.03, metaphase II (MII) oocytes 8.7 ± 5.1 versus 6.7 ± 4.8, P≤ 0.05, fertilizations 6 ± 3.6 versus 4.4 ± 3.3, P≤ 0.03 and cleaving embryos 5.7 ± 3.8 versus 4.1 ± 3.3, P≤ 0.01 were available in patients with the typical form compared with those with the atypical form, respectively. There was no significant difference in fertilization rate, cleavage rate or the mean number of transferred embryos. Embryo quality of the transferred ones and pregnancy rate per cycle were also similar between the two groups. Women with the typical form of MRKH needed fewer gonadotrophins and for a shorter duration for ovarian hyperstimulation. The mean number of follicles, oocytes, MII oocytes

  16. Distinguishing the relevant features of frequent suicide attempters.

    Science.gov (United States)

    Lopez-Castroman, Jorge; Perez-Rodriguez, Maria de las Mercedes; Jaussent, Isabelle; Alegria, Analucia A; Artes-Rodriguez, Antonio; Freed, Peter; Guillaume, Sébastien; Jollant, Fabrice; Leiva-Murillo, Jose Miguel; Malafosse, Alain; Oquendo, Maria A; de Prado-Cumplido, Mario; Saiz-Ruiz, Jeronimo; Baca-Garcia, Enrique; Courtet, Philippe

    2011-05-01

    In spite of the high prevalence of suicide behaviours and the magnitude of the resultant burden, little is known about why individuals reattempt. We aim to investigate the relationships between clinical risk factors and the repetition of suicidal attempts. 1349 suicide attempters were consecutively recruited in the Emergency Room (ER) of two academic hospitals in France and Spain. Patients were extensively assessed and demographic and clinical data obtained. Data mining was used to determine the minimal number of variables that blinded the rest in relation to the number of suicide attempts. Using this set, a probabilistic graph ranking relationships with the target variable was constructed. The most common diagnoses among suicide attempters were affective disorders, followed by anxiety disorders. Risk of frequent suicide attempt was highest among middle-aged subjects, and diminished progressively with advancing age of onset at first attempt. Anxiety disorders significantly increased the risk of presenting frequent suicide attempts. Pathway analysis also indicated that frequent suicide attempts were linked to greater odds for alcohol and substance abuse disorders and more intensive treatment. Novel statistical methods found several clinical features that were associated with a history of frequent suicide attempts. The identified pathways may promote new hypothesis-driven studies of suicide attempts and preventive strategies. Copyright © 2010 Elsevier Ltd. All rights reserved.

  17. Competence-Based Education and Training– about Frequently Asked Questions

    NARCIS (Netherlands)

    Mulder, M.

    2012-01-01

    This article follows the author's previous piece on practical guidelines for the development of comprehensive competence-based education and training (Mulder, 2012). It is about the questions that have been and are still frequently asked in presentations, workshops and classes about the introduction

  18. Injury patterns in children with frequent emergency department visits

    DEFF Research Database (Denmark)

    Laursen, B

    2006-01-01

    -14 years. Information on all ED visits was obtained from the Danish National Patient Registry. Injury type, place of accident, injury mechanism, admission, and distance to ED were compared between children with frequent ED visits (five or more during the three years) and children with only one visit...... less severe injuries and more dislocations, sprains, and strains....

  19. Hybrid Recommendation System Memanfaatkan Penggalian Frequent Itemset dan Perbandingan Keyword

    OpenAIRE

    Suka Parwita, Wayan Gede; Winarko, Edi

    2015-01-01

    Abstrak Recommendation system sering dibangun dengan memanfaatkan data peringkat item dan data identitas pengguna. Data peringkat item merupakan data yang langka pada sistem yang baru dibangun. Sedangkan, pemberian data identitas pada recommendation system dapat menimbulkan kekhawatiran penyalahgunaan data identitas. Hybrid recommendation system memanfaatkan algoritma penggalian frequent itemset dan perbandingan keyword dapat memberikan daftar rekomendasi tanpa menggunakan data identi...

  20. Vaginal microbiota of women with frequent vulvovaginal candidiasis.

    Science.gov (United States)

    Zhou, Xia; Westman, Rachel; Hickey, Roxana; Hansmann, Melanie A; Kennedy, Colleen; Osborn, Thomas W; Forney, Larry J

    2009-09-01

    Vulvovaginal candidiasis (VVC) is an insidious infection that afflicts a large proportion of women of all ages, and 5 to 8% of affected women experience recurrent VVC (RVVC). The aim of this study was to explore the possible importance of vaginal bacterial communities in reducing the risk of RVVC. The species composition and diversity of microbial communities were evaluated for 42 women with and without frequent VVC based on profiles of terminal restriction fragment polymorphisms of 16S rRNA genes and phylogenetic analysis of cloned 16S rRNA gene sequences from the numerically dominant microbial populations. The data showed that there were no significant differences between the vaginal microbial communities of women in the two groups (likelihood score, 5.948; bootstrap P value, 0.26). Moreover, no novel bacteria were found in the communities of women with frequent VVC. The vaginal communities of most women in both groups (38/42; 90%) were dominated by species of Lactobacillus. The results of this study failed to provide evidence for the existence of altered or unusual vaginal bacterial communities in women who have frequent VVC compared to women who do not have frequent VVC. The findings suggest that commensal vaginal bacterial species may not be able to prevent VVC.

  1. Ban the Book Report: Promoting Frequent and Enthusiastic Reading

    Science.gov (United States)

    Foster, Graham

    2012-01-01

    Teachers recognize that frequent independent reading increases student knowledge on a wide range of topics, enhances vocabulary, and improves comprehension. "Ban the Book Report" inspires teachers to go beyond narrow and analytical book reports by exploring the potential of book talks, alternate book covers, identifying features of informational…

  2. An Adaptive Algorithm for Finding Frequent Sets in Landmark Windows

    DEFF Research Database (Denmark)

    Dang, Xuan-Hong; Ong, Kok-Leong; Lee, Vincent

    2012-01-01

    We consider a CPU constrained environment for finding approximation of frequent sets in data streams using the landmark window. Our algorithm can detect overload situations, i.e., breaching the CPU capacity, and sheds data in the stream to “keep up”. This is done within a controlled error threshold...

  3. Frequent visitors at the psychiatric emergency room - A literature review.

    Science.gov (United States)

    Schmidt, Manuela

    2018-03-01

    Frequent visitors at the psychiatric emergency room (PER) constitute a small subgroup of patients, yet they are responsible for a disproportionate number of visits and thus claim considerable resources. Their needs are often left unmet and their repetitive visits reflect their dissatisfaction as well as that of PERs' staff. Motivated by these dilemmas, this study systematically reviews the literature about frequent visitors at PER and seeks to answer two questions: What characterizes frequent visitors at PER in the literature? and What characterizes PER in the literature? Based on 29 studies, this paper offers answers to the two questions based on a strength weakness opportunities and threats (SWOT) analysis. The results of the review and subsequent analysis of the literature revealed the multiplicity and complexity of frequent visitors' characteristics and how they appear to converge. Commonalities were more difficult to identify in PER characteristics. In some cases, this happened because the characteristics were poorly described or were context specific. As a result, it was not easy to compare the studies on PER. Based on SWOT and the findings of the analysis, the paper proposes new venues of research and suggests how the field of mental health might develop by taking into account its opportunities and threats.

  4. Frequent epigenetic inactivation of Wnt antagonist genes in breast cancer

    Science.gov (United States)

    Suzuki, H; Toyota, M; Caraway, H; Gabrielson, E; Ohmura, T; Fujikane, T; Nishikawa, N; Sogabe, Y; Nojima, M; Sonoda, T; Mori, M; Hirata, K; Imai, K; Shinomura, Y; Baylin, S B; Tokino, T

    2008-01-01

    Although mutation of APC or CTNNB1 (β-catenin) is rare in breast cancer, activation of Wnt signalling is nonetheless thought to play an important role in breast tumorigenesis, and epigenetic silencing of Wnt antagonist genes, including the secreted frizzled-related protein (SFRP) and Dickkopf (DKK) families, has been observed in various tumours. In breast cancer, frequent methylation and silencing of SFRP1 was recently documented; however, altered expression of other Wnt antagonist genes is largely unknown. In the present study, we found frequent methylation of SFRP family genes in breast cancer cell lines (SFRP1, 7 out of 11, 64%; SFRP2, 11 out of 11, 100%; SFRP5, 10 out of 11, 91%) and primary breast tumours (SFRP1, 31 out of 78, 40%; SFRP2, 60 out of 78, 77%; SFRP5, 55 out of 78, 71%). We also observed methylation of DKK1, although less frequently, in cell lines (3 out of 11, 27%) and primary tumours (15 out of 78, 19%). Breast cancer cell lines express various Wnt ligands, and overexpression of SFRPs inhibited cancer cell growth. In addition, overexpression of a β-catenin mutant and depletion of SFRP1 using small interfering RNA synergistically upregulated transcriptional activity of T-cell factor/lymphocyte enhancer factor. Our results confirm the frequent methylation and silencing of Wnt antagonist genes in breast cancer, and suggest that their loss of function contributes to activation of Wnt signalling in breast carcinogenesis. PMID:18283316

  5. GRAMI: Generalized Frequent Subgraph Mining in Large Graphs

    KAUST Repository

    El Saeedy, Mohammed El Sayed

    2011-07-24

    Mining frequent subgraphs is an important operation on graphs. Most existing work assumes a database of many small graphs, but modern applications, such as social networks, citation graphs or protein-protein interaction in bioinformatics, are modeled as a single large graph. Interesting interactions in such applications may be transitive (e.g., friend of a friend). Existing methods, however, search for frequent isomorphic (i.e., exact match) subgraphs and cannot discover many useful patterns. In this paper we propose GRAMI, a framework that generalizes frequent subgraph mining in a large single graph. GRAMI discovers frequent patterns. A pattern is a graph where edges are generalized to distance-constrained paths. Depending on the definition of the distance function, many instantiations of the framework are possible. Both directed and undirected graphs, as well as multiple labels per vertex, are supported. We developed an efficient implementation of the framework that models the frequency resolution phase as a constraint satisfaction problem, in order to avoid the costly enumeration of all instances of each pattern in the graph. We also implemented CGRAMI, a version that supports structural and semantic constraints; and AGRAMI, an approximate version that supports very large graphs. Our experiments on real data demonstrate that our framework is up to 3 orders of magnitude faster and discovers more interesting patterns than existing approaches.

  6. A Successful Induction of Lactation in Surrogate Pregnancy with Metoclopramide and Review of Lactation Induction

    OpenAIRE

    Elahe Mirzaaga; Arezoo Arabipoor; Mitra Frotan; Marzieh Shiva

    2010-01-01

    In surrogate pregnancies genetic parents have little opportunity for early bonding with their infants,either prenatally (in utero) or during the immediate postnatal period. Procedures commonlyused to induce lactation include both pharmacologic and nonpharmacologic methods, often incombination. Studies reporting induced lactation are sparse, due to the rarity of augmentedlactation. Here we report a case of lactation induction following a surrogate pregnancy. Othermethods that can be used to au...

  7. Induction of lactation in the intended mother of a surrogate pregnancy: case report.

    Science.gov (United States)

    Biervliet, F P; Maguiness, S D; Hay, D M; Killick, S R; Atkin, S L

    2001-03-01

    A case of a successful induction of lactation in a commissioning mother of a surrogate pregnancy is reported. Induction of lactation was achieved with oral metoclopramide which was well tolerated. Alternative methods to induce lactation are reviewed. The advantages of breast-feeding and the relative ease with which lactation can be induced after a surrogate pregnancy would suggest that this could be offered to all commissioning mothers.

  8. Using multiscale spatial models to assess potential surrogate habitat for an imperiled reptile.

    Directory of Open Access Journals (Sweden)

    Jennifer M Fill

    Full Text Available In evaluating conservation and management options for species, practitioners might consider surrogate habitats at multiple scales when estimating available habitat or modeling species' potential distributions based on suitable habitats, especially when native environments are rare. Species' dependence on surrogates likely increases as optimal habitat is degraded and lost due to anthropogenic landscape change, and thus surrogate habitats may be vital for an imperiled species' survival in highly modified landscapes. We used spatial habitat models to examine a potential surrogate habitat for an imperiled ambush predator (eastern diamondback rattlesnake, Crotalus adamanteus; EDB at two scales. The EDB is an apex predator indigenous to imperiled longleaf pine ecosystems (Pinus palustris of the southeastern United States. Loss of native open-canopy pine savannas and woodlands has been suggested as the principal cause of the species' extensive decline. We examined EDB habitat selection in the Coastal Plain tidewater region to evaluate the role of marsh as a potential surrogate habitat and to further quantify the species' habitat requirements at two scales: home range (HR and within the home range (WHR. We studied EDBs using radiotelemetry and employed an information-theoretic approach and logistic regression to model habitat selection as use vs.We failed to detect a positive association with marsh as a surrogate habitat at the HR scale; rather, EDBs exhibited significantly negative associations with all landscape patches except pine savanna. Within home range selection was characterized by a negative association with forest and a positive association with ground cover, which suggests that EDBs may use surrogate habitats of similar structure, including marsh, within their home ranges. While our HR analysis did not support tidal marsh as a surrogate habitat, marsh may still provide resources for EDBs at smaller scales.

  9. Fabrication and Characterization of Surrogate Glasses Aimed to Validate Nuclear Forensic Techniques

    Science.gov (United States)

    2017-12-01

    the glass formed during a nuclear event, trinitite [14]. The SiO2 composition is generally greater than 50% for trinitite and can vary appreciably...CHARACTERIZATION OF SURROGATE GLASSES AIMED TO VALIDATE NUCLEAR FORENSIC TECHNIQUES by Ken G. Foos December 2017 Thesis Advisor: Claudia...December 2017 3. REPORT TYPE AND DATES COVERED Master’s thesis 4. TITLE AND SUBTITLE FABRICATION AND CHARACTERIZATION OF SURROGATE GLASSES AIMED TO

  10. Engagement in Advance Care Planning and Surrogates' Knowledge of Patients' Treatment Goals.

    Science.gov (United States)

    Fried, Terri R; Zenoni, Maria; Iannone, Lynne; O'Leary, John; Fenton, Brenda T

    2017-08-01

    A key objective of advance care planning (ACP) is improving surrogates' knowledge of patients' treatment goals. Little is known about whether ACP outside of a trial accomplishes this. The objective was to examine patient and surrogate reports of ACP engagement and associations with surrogate knowledge of goals. Cohort study SETTING: Primary care in a Veterans Affairs Medical Center. 350 community-dwelling veterans age ≥55 years and the individual they would choose to make medical decisions on their behalf, interviewed separately. Treatment goals were assessed by veterans' ratings of 3 health states: severe physical disability, cognitive disability, and pain, as an acceptable or unacceptable result of treatment for severe illness. Surrogates had knowledge if they correctly predicted all 3 responses. Veterans and surrogates were asked about living will and health care proxy completion and communication about life-sustaining treatment and quality versus quantity of life (QOL). Over 40% of dyads agreed that the veteran had not completed a living will or health care proxy and that there was no QOL communication. For each activity, sizeable proportions (18-34%) disagreed about participation. In dyads who agreed QOL communication had occurred, 30% of surrogates had knowledge, compared to 21% in dyads who agreed communication had not occurred and 15% in dyads who disagreed (P = .01). This relationship persisted in multivariable analysis. Agreement about other ACP activities was not associated with knowledge. Disagreement about ACP participation was common. Agreement about communication regarding QOL was modestly associated with surrogate knowledge of treatment goals. Eliciting surrogates' perspectives is critical to ACP. Even dyads who agree about participation may need additional support for successful engagement. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

  11. Test procedures for polyester immobilized salt-containing surrogate mixed wastes

    International Nuclear Information System (INIS)

    Biyani, R.K.; Hendrickson, D.W.

    1997-01-01

    These test procedures are written to meet the procedural needs of the Test Plan for immobilization of salt containing surrogate mixed waste using polymer resins, HNF-SD-RE-TP-026 and to ensure adequacy of conduct and collection of samples and data. This testing will demonstrate the use of four different polyester vinyl ester resins in the solidification of surrogate liquid and dry wastes, similar to some mixed wastes generated by DOE operations

  12. Stochastic rat lung dosimetry for inhaled radon progeny: a surrogate for the human lung for lung cancer risk assessment

    Energy Technology Data Exchange (ETDEWEB)

    Winkler-Heil, R.; Hofmann, W. [University of Salzburg, Division of Physics and Biophysics, Department of Materials Research and Physics, Salzburg (Austria); Hussain, M. [University of Salzburg, Division of Physics and Biophysics, Department of Materials Research and Physics, Salzburg (Austria); Higher Education Commission of Pakistan, Islamabad (Pakistan)

    2015-05-15

    Laboratory rats are frequently used in inhalation studies as a surrogate for human exposures. The objective of the present study was therefore to develop a stochastic dosimetry model for inhaled radon progeny in the rat lung, to predict bronchial dose distributions and to compare them with corresponding dose distributions in the human lung. The most significant difference between human and rat lungs is the branching structure of the bronchial tree, which is relatively symmetric in the human lung, but monopodial in the rat lung. Radon progeny aerosol characteristics used in the present study encompass conditions typical for PNNL and COGEMA rat inhalation studies, as well as uranium miners and human indoor exposure conditions. It is shown here that depending on exposure conditions and modeling assumptions, average bronchial doses in the rat lung ranged from 5.4 to 7.3 mGy WLM{sup -1}. If plotted as a function of airway generation, bronchial dose distributions exhibit a significant maximum in large bronchial airways. If, however, plotted as a function of airway diameter, then bronchial doses are much more uniformly distributed throughout the bronchial tree. Comparisons between human and rat exposures indicate that rat bronchial doses are slightly higher than human bronchial doses by about a factor of 1.3, while lung doses, averaged over the bronchial (BB), bronchiolar (bb) and alveolar-interstitial (AI) regions, are higher by about a factor of about 1.6. This supports the current view that the rat lung is indeed an appropriate surrogate for the human lung in case of radon-induced lung cancers. Furthermore, airway diameter seems to be a more appropriate morphometric parameter than airway generations to relate bronchial doses to bronchial carcinomas. (orig.)

  13. A surrogate fuel formulation to characterize heating and evaporation of light naphtha droplets

    KAUST Repository

    Kabil, I.

    2018-03-08

    Light naphtha (LN) is gaining interest in internal combustion (IC) engine applications due to its low refining cost and higher heating values compared to commercial gasoline. To properly describe the chemical and physical behavior of the LN fuel under IC engine conditions, a systematic procedure to develop unified physical and chemical surrogates is described. The reduced component models to describe the chemical characteristics of LN are combined with the effective thermal conductivity/effective diffusivity (ETC/ED) model to represent the accurate evaporation behavior. Three surrogate fuels consisting of three to five components are presented and their performance in heating and evaporation of a single LN droplet is compared against the conventional primary reference fuel (PRF65) surrogate which is based on chemical aspects only. Unlike the previous approaches, the new surrogates also target matching the hydrogen-to-carbon ratio and research octane number in order to accurately describe the chemical behavior of the fuel. Subsequently, the performance of the surrogates in describing spray characteristics is tested by computational simulations compared with experimental measurements. The simulations were carried out using CONVERGE CFD package. The ETC/ED model was implemented into CONVERGE using user-defined functions. The predicted spray penetration length for the developed surrogates shows good agreement with the experimental data. At engine-like conditions, the ETC/ED model predicts higher vapor mass than the infinite thermal conductivity/infinite diffusivity model, hence showing the expected trend by incorporating the realistic droplet heating process.

  14. One mum too few: maternal status in host surrogate motherhood arrangements.

    Science.gov (United States)

    Oultram, Stuart

    2015-06-01

    In a host surrogate motherhood arrangement, the surrogate agrees to be implanted with, and carry to term, an embryo created from the commissioning couple's gametes. When the surrogate child is born, it is the surrogate mother who, according to UK law, holds the legal status of mother. By contrast, the commissioning mother possesses no maternal status and she can only attain it once the surrogate agrees to the completion of the arrangement. One consequence of this is that, in the event that a host arrangement fails, the commissioning mother is left without maternal status. In this paper, I argue that this denial of maternal status misrepresents the commissioning mother's role in the host arrangement and her relationship with the surrogate child. Consequently, I suggest that commissioning mothers participating in host surrogacy arrangements ought to be granted the status of mother in the event that the arrangement fails. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  15. Surrogate alcohol containing methanol, social deprivation and public health in Novosibirsk, Russia.

    Science.gov (United States)

    Neufeld, Maria; Lachenmeier, Dirk; Hausler, Thomas; Rehm, Jürgen

    2016-11-01

    Surrogate alcohol, i.e. alcohol not intended or not officially intended for human consumption, continues to play an important role in alcohol consumption in Russia, especially for people with alcohol dependence. Among the different types of surrogate alcohol, there are windshield washer antifreeze liquids; these products are the cheapest kinds of non-beverage alcohol available and thus likely to be used by the most deprived and marginalised groups such as homeless people with alcohol dependence. Although it is well known, that non-beverage alcohol is used for consumption by various groups in Russia, and although there are laws to prohibit the use of methanol as part of windshield washer antifreeze liquids for the very reason that such products could be used as surrogate alcohol, we detected products in retail sale which were a mix of water and methanol only. Methanol poses serious health threats including blindness and death, and there had been repeated methanol deaths from surrogate alcohol in Russia over the last years. If law-enforcement does not change for surrogate products, we can expect more methanol-resulting deaths in the most deprived and marginalized groups of people with alcohol dependence in Russia. In addition, ingredients with questionable safety profiles such as formic acid should also be prohibited in non-beverage alcohol products that are likely to be consumed as surrogate alcohol. Copyright © 2016. Published by Elsevier B.V.

  16. Concordance Between Veterans' Self-Report and Documentation of Surrogate Decision Makers: Implications for Quality Measurement.

    Science.gov (United States)

    Garner, Kimberly K; Dubbert, Patricia; Lensing, Shelly; Sullivan, Dennis H

    2017-01-01

    The Measuring What Matters initiative of the American Academy of Hospice and Palliative Medicine and the Hospice and Palliative Nurses Association identified documentation of a surrogate decision maker as one of the top 10 quality indicators in the acute hospital and hospice settings. To better understand the potential implementation of this Measuring What Matters quality measure #8, Documentation of Surrogate in outpatient primary care settings by describing primary care patients' self-reported identification and documentation of a surrogate decision maker. Examination of patient responses to self-assessment questions from advance health care planning educational groups conducted in one medical center primary care clinic and seven community-based outpatient primary care clinics. We assessed the concordance between patient reports of identifying and naming a surrogate decision maker and having completed an advance directive (AD) with presence of an AD in the electronic medical record. Of veterans without a documented AD on file, more than half (66%) reported that they had talked with someone they trusted and nearly half (52%) reported that they had named someone to communicate their preferences. Our clinical project data suggest that many more veterans may have initiated communications with surrogate decision makers than is evident in the electronic medical record. System changes are needed to close the gap between veterans' plans for a surrogate decision maker and the documentation available to acute care health care providers. Published by Elsevier Inc.

  17. Comparative study of surrogate models for groundwater contamination source identification at DNAPL-contaminated sites

    Science.gov (United States)

    Hou, Zeyu; Lu, Wenxi

    2018-05-01

    Knowledge of groundwater contamination sources is critical for effectively protecting groundwater resources, estimating risks, mitigating disaster, and designing remediation strategies. Many methods for groundwater contamination source identification (GCSI) have been developed in recent years, including the simulation-optimization technique. This study proposes utilizing a support vector regression (SVR) model and a kernel extreme learning machine (KELM) model to enrich the content of the surrogate model. The surrogate model was itself key in replacing the simulation model, reducing the huge computational burden of iterations in the simulation-optimization technique to solve GCSI problems, especially in GCSI problems of aquifers contaminated by dense nonaqueous phase liquids (DNAPLs). A comparative study between the Kriging, SVR, and KELM models is reported. Additionally, there is analysis of the influence of parameter optimization and the structure of the training sample dataset on the approximation accuracy of the surrogate model. It was found that the KELM model was the most accurate surrogate model, and its performance was significantly improved after parameter optimization. The approximation accuracy of the surrogate model to the simulation model did not always improve with increasing numbers of training samples. Using the appropriate number of training samples was critical for improving the performance of the surrogate model and avoiding unnecessary computational workload. It was concluded that the KELM model developed in this work could reasonably predict system responses in given operation conditions. Replacing the simulation model with a KELM model considerably reduced the computational burden of the simulation-optimization process and also maintained high computation accuracy.

  18. Development of an instrumented spinal cord surrogate using optical fibers: A feasibility study.

    Science.gov (United States)

    Facchinello, Yann; Wagnac, Éric; Ung, Bora; Petit, Yvan; Pradhan, Prabin; Peyrache, Louis-Marie; Mac-Thiong, Jean-Marc

    2017-10-01

    In vitro replication of traumatic spinal cord injury is necessary to understand its biomechanics and to improve animal models. During a traumatic spinal cord injury, the spinal cord withstands an impaction at high velocity. In order to fully assess the impaction, the use of spinal canal occlusion sensor is necessary. A physical spinal cord surrogate is also often used to simulate the presence of the spinal cord and its surrounding structures. In this study, an instrumented physical spinal cord surrogate is presented and validated. The sensing is based on light transmission loss observed in embedded bare optical fibers subjected to bending. The instrumented surrogate exhibits similar mechanical properties under static compression compared to fresh porcine spinal cords. The instrumented surrogate has a compression sensing threshold of 40% that matches the smallest compression values leading to neurological injuries. The signal obtained from the sensor allows calculating the compression of the spinal cord surrogate with a maximum of 5% deviation. Excellent repeatability was also observed under repetitive loading. The proposed instrumented spinal cord surrogate is promising with satisfying mechanical properties and good sensing capability. It is the first attempt at proposing a method to assess the internal loads sustained by the spinal cord during a traumatic injury. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

  19. A conceptual model of the role of communication in surrogate decision making for hospitalized adults.

    Science.gov (United States)

    Torke, Alexia M; Petronio, Sandra; Sachs, Greg A; Helft, Paul R; Purnell, Christianna

    2012-04-01

    To build a conceptual model of the role of communication in decision making, based on literature from medicine, communication studies and medical ethics. We proposed a model and described each construct in detail. We review what is known about interpersonal and patient-physician communication, described literature about surrogate-clinician communication, and discussed implications for our developing model. The communication literature proposes two major elements of interpersonal communication: information processing and relationship building. These elements are composed of constructs such as information disclosure and emotional support that are likely to be relevant to decision making. We propose these elements of communication impact decision making, which in turn affects outcomes for both patients and surrogates. Decision making quality may also mediate the relationship between communication and outcomes. Although many elements of the model have been studied in relation to patient-clinician communication, there is limited data about surrogate decision making. There is evidence of high surrogate distress associated with decision making that may be alleviated by communication-focused interventions. More research is needed to test the relationships proposed in the model. Good communication with surrogates may improve both the quality of medical decisions and outcomes for the patient and surrogate. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  20. Modeling of Heating and Evaporation of FACE I Gasoline Fuel and its Surrogates

    KAUST Repository

    Elwardani, Ahmed Elsaid

    2016-04-05

    The US Department of Energy has formulated different gasoline fuels called \\'\\'Fuels for Advanced Combustion Engines (FACE)\\'\\' to standardize their compositions. FACE I is a low octane number gasoline fuel with research octane number (RON) of approximately 70. The detailed hydrocarbon analysis (DHA) of FACE I shows that it contains 33 components. This large number of components cannot be handled in fuel spray simulation where thousands of droplets are directly injected in combustion chamber. These droplets are to be heated, broken-up, collided and evaporated simultaneously. Heating and evaporation of single droplet FACE I fuel was investigated. The heating and evaporation model accounts for the effects of finite thermal conductivity, finite liquid diffusivity and recirculation inside the droplet, referred to as the effective thermal conductivity/effective diffusivity (ETC/ED) model. The temporal variations of the liquid mass fractions of the droplet components were used to characterize the evaporation process. Components with similar evaporation characteristics were merged together. A representative component was initially chosen based on the highest initial mass fraction. Three 6 components surrogates, Surrogate 1-3, that match evaporation characteristics of FACE I have been formulated without keeping same mass fractions of different hydrocarbon types. Another two surrogates (Surrogate 4 and 5) were considered keeping same hydrocarbon type concentrations. A distillation based surrogate that matches measured distillation profile was proposed. The calculated molar mass, hydrogen-to-carbon (H/C) ratio and RON of Surrogate 4 and distillation based one are close to those of FACE I.