Sample records for surrogate end-point studies

  1. Use of Surrogate end points in HTA

    Directory of Open Access Journals (Sweden)

    Mangiapane, Sandra


    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

  2. Levels of alkaline phosphatase and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis: an international follow-up study. (United States)

    Lammers, Willem J; van Buuren, Henk R; Hirschfield, Gideon M; Janssen, Harry L A; Invernizzi, Pietro; Mason, Andrew L; Ponsioen, Cyriel Y; Floreani, Annarosa; Corpechot, Christophe; Mayo, Marlyn J; Battezzati, Pier M; Parés, Albert; Nevens, Frederik; Burroughs, Andrew K; Kowdley, Kris V; Trivedi, Palak J; Kumagi, Teru; Cheung, Angela; Lleo, Ana; Imam, Mohamad H; Boonstra, Kirsten; Cazzagon, Nora; Franceschet, Irene; Poupon, Raoul; Caballeria, Llorenç; Pieri, Giulia; Kanwar, Pushpjeet S; Lindor, Keith D; Hansen, Bettina E


    Noninvasive surrogate end points of long-term outcomes of patients with primary biliary cirrhosis (PBC) are needed to monitor disease progression and evaluate potential treatments. We performed a meta-analysis of individual patient data from cohort studies to evaluate whether patients' levels of alkaline phosphatase and bilirubin correlate with their outcomes and can be used as surrogate end points. We performed a meta-analysis of data from 4845 patients included in 15 North American and European long-term follow-up cohort studies. Levels of alkaline phosphatase and bilirubin were analyzed in different settings and subpopulations at different time points relative to the clinical end point (liver transplantation or death). Of the 4845 patients, 1118 reached a clinical end point. The median follow-up period was 7.3 years; 77% survived for 10 years after study enrollment. Levels of alkaline phosphatase and bilirubin measured at study enrollment (baseline) and each year for 5 years were strongly associated with clinical outcomes (lower levels were associated with longer transplant-free survival). At 1 year after study enrollment, levels of alkaline phosphatase that were 2.0 times the upper limit of normal (ULN) best predicted patient outcome (C statistic, 0.71) but not significantly better than other thresholds. Of patients with alkaline phosphatase levels ≤ 2.0 times the ULN, 84% survived for 10 years compared with 62% of those with levels >2.0 times the ULN (P alkaline phosphatase 1 year after study enrollment predicted patient outcomes better than percentage change in level. One year after study enrollment, a bilirubin level 1.0 times the ULN best predicted patient transplant-free survival (C statistic, 0.79). Of patients with bilirubin levels ≤ 1.0 times the ULN, 86% survived for 10 years after study enrollment compared with 41% of those with levels >1.0 times the ULN (P alkaline phosphatase and bilirubin increased the ability to predict patient survival times

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

    DEFF Research Database (Denmark)

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


    . Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) is a 3-yr longitudinal study with four specific aims: 1) definition of clinically relevant COPD subtypes; 2) identification of parameters that predict disease progression in these subtypes; 3) examination of biomarkers...

  4. Surrogate end points in women's health research: science, protoscience, and pseudoscience. (United States)

    Grimes, David A; Schulz, Kenneth F; Raymond, Elizabeth G


    A surrogate end point (e.g., a laboratory test or image) serves as a proxy for a clinical end point of importance (e.g., fracture, thrombosis, or death). Adoption and use of surrogate end points lacking validation, especially in cardiovascular medicine, have caused thousands of patients' deaths, a serious violation of the ethical principle of beneficence. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  5. Early change in proteinuria as a surrogate end point for kidney disease progression

    DEFF Research Database (Denmark)

    Inker, Lesley A; Levey, Andrew S; Pandya, Kruti


    BACKGROUND: It is controversial whether proteinuria is a valid surrogate end point for randomized trials in chronic kidney disease. STUDY DESIGN: Meta-analysis of individual patient-level data. SETTING & POPULATION: Individual patient data for 9,008 patients from 32 randomized trials evaluating 5...... intervention types. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials of kidney disease progression until 2007 with measurements of proteinuria both at baseline and during the first year of follow-up, with at least 1 further year of follow-up for the clinical outcome. PREDICTOR: Early change...... in proteinuria. OUTCOMES: Doubling of serum creatinine level, end-stage renal disease, or death. RESULTS: Early decline in proteinuria was associated with lower risk of the clinical outcome (pooled HR, 0.74 per 50% reduction in proteinuria); this association was stronger at higher levels of baseline proteinuria...

  6. Estimated GFR Decline as a Surrogate End Point for Kidney Failure

    DEFF Research Database (Denmark)

    Lambers Heerspink, Hiddo J; Weldegiorgis, Misghina; Inker, Lesley A


    A doubling of serum creatinine value, corresponding to a 57% decline in estimated glomerular filtration rate (eGFR), is used frequently as a component of a composite kidney end point in clinical trials in type 2 diabetes. The aim of this study was to determine whether alternative end points defin...

  7. Physiological functions should be considered as true end points of nutritional intervention studies. (United States)

    Genton, L; van Gemert, W; Pichard, C; Soeters, P


    With the beginning of this millennium it has become fashionable to only follow 'evidence-based' practices. This generally-accepted approach cruelly negates experience or intelligent interpretation of pathophysiology. Another problem is that the great 'meta-analysts' of the present era only accept end points that they consider 'hard'. In the metabolic and nutritional field these end points are infection-related morbidity and mortality, and all other end points are considered 'surrogate'. The aim of this presentation is to prove that this claim greatly negates the contribution of more-fundamentally-oriented research, the fact that mortality has multifactorial causes, and that infection is a crude measure of immune function. The following problems should be considered: many populations undergoing intervention have low mortality, requiring studies with thousands of patients to demonstrate effects of intervention on mortality; nutrition is only in rare cases primary treatment, and in many populations is a prerequisite for survival rather than a therapeutic modality; once the effect of nutritional support is achieved, the extra benefit of modulation of the nutritional support regimen can only be modest; cost-benefit is not a valid end point, because the better it is done the more it will cost; morbidity and mortality are crude end points for the effect of nutritional intervention, and are influenced by many factors. In fact, it is a yes or no factor. In the literature the most important contributions include new insights into the pathogenesis of disease, the diminution of disease-related adverse events and/or functional improvement after therapy. In nutrition research the negligence of these end points has precluded the development and validation of functional end points, such as muscle, immune and cognitive functions. Disability, quality of life, morbidity and mortality are directly related to these functional variables. It is, therefore, of paramount importance to

  8. Using serum urate as a validated surrogate end point for flares in patients with gout

    DEFF Research Database (Denmark)

    Birger Morillon, Melanie; Stamp, L.; Taylor, E W


    Introduction: Gout is the most common inflammatory arthritis in men over 40 years of age. Long-term urate-lowering therapy is considered a key strategy for effective gout management. The primary outcome measure for efficacy in clinical trials of urate-lowering therapy is serum urate levels......, effectively acting as a surrogate for patient-centred outcomes such as frequency of gout attacks or pain. Yet it is not clearly demonstrated that the strength of the relationship between serum urate and clinically relevant outcomes is sufficiently strong for serum urate to be considered an adequate surrogate...

  9. Physiological functions should be considered as true end points of nutritional intervention studies


    Genton, L.; Gemert, W.van; Pichard, C.; Soeters, P.


    With the beginning of this millennium it has become fashionable to only follow ‘evidence-based' practices. This generally-accepted approach cruelly negates experience or intelligent interpretation of pathophysiology. Another problem is that the great ‘meta-analysts' of the present era only accept end points that they consider ‘hard'. In the metabolic and nutritional field these end points are infection-related morbidity and mortality, and all other end points are considered ‘surrogate'. The a...

  10. Surrogate End Points for Overall Survival in Loco-Regionally Advanced Nasopharyngeal Carcinoma: An Individual Patient Data Meta-analysis. (United States)

    Rotolo, Federico; Pignon, Jean-Pierre; Bourhis, Jean; Marguet, Sophie; Leclercq, Julie; Tong Ng, Wai; Ma, Jun; Chan, Anthony T C; Huang, Pei-Yu; Zhu, Guopei; Chua, Daniel T T; Chen, Yong; Mai, Hai-Qiang; Kwong, Dora L W; Soong, Yoke Lim; Moon, James; Tung, Yuk; Chi, Kwan-Hwa; Fountzilas, George; Zhang, Li; Hui, Edwin Pun; Lee, Anne W M; Blanchard, Pierre; Michiels, Stefan


    Our objective was to evaluate progression-free survival (PFS) and distant metastasis-free survival (DMFS) as surrogate end points for overall survival (OS) in randomized trials of chemotherapy in loco-regionally advanced nasopharyngeal carcinomas (NPCs). Individual patient data were obtained from 19 trials of the updated Meta-Analysis of Chemotherapy in Nasopharyngeal Carcinoma (MAC-NPC) plus one additional trial (total = 5144 patients). Surrogacy was evaluated at the individual level using a rank correlation coefficient ρ and at the trial level using a correlation coefficient R2 between treatment effects on the surrogate end point and OS. A sensitivity analysis was performed with two-year PFS/DMFS and five-year OS. PFS was strongly correlated with OS at the individual level (ρ = 0.93, 95% confidence interval [CI] = 0.93 to 0.94) and at the trial level (R2 = 0.95, 95% CI = 0.47 to 1.00). For DMFS, too, the individual-level correlation with OS was strong (ρ = 0.98, 95% CI = 0.98 to 0.98); at trial level, the correlation was high but the regression adjusted for measurement error could not be computed (unadjusted R2 = 0.96, 95% CI = 0.94 to 0.99). In the sensitivity analysis, two-year PFS was highly correlated with five-year OS at the individual level (ρ = 0.89, 95% CI = 0.88 to 0.90) and at the trial level (R2 = 0.85, 95% CI = 0.46 to 1.00); two-year DMFS was highly correlated with five-year OS at the individual level (ρ = 0.95, 95% CI = 0.94 to 0.95) and at the trial level (R2 = 0.78, 95% CI = 0.33 to 1.00). PFS and DMFS are valid surrogate end points for OS to assess treatment effect of chemotherapy in loco-regionally advanced NPC, while PFS can be measured earlier. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email:

  11. Thirty-Month Complete Response as a Surrogate End Point in First-Line Follicular Lymphoma Therapy: An Individual Patient-Level Analysis of Multiple Randomized Trials. (United States)

    Shi, Qian; Flowers, Christopher R; Hiddemann, Wolfgang; Marcus, Robert; Herold, Michael; Hagenbeek, Anton; Kimby, Eva; Hochster, Howard; Vitolo, Umberto; Peterson, Bruce A; Gyan, Emmanuel; Ghielmini, Michele; Nielsen, Tina; De Bedout, Sabine; Fu, Tommy; Valente, Nancy; Fowler, Nathan H; Hoster, Eva; Ladetto, Marco; Morschhauser, Franck; Zucca, Emanuele; Salles, Gilles; Sargent, Daniel J


    Purpose Follicular lymphoma (FL) is an indolent cancer, with effective but rarely curative treatment options. As a standard study end point for first-line FL therapy, progression-free survival (PFS) requires extended follow-up (median PFS, > 7 years). To provide patients with earlier access to newer therapies, an earlier end point to expedite clinical trials is needed. Our objective was to formally assess the complete response rate at 30 months (CR30) after initiation of induction therapy as a potential surrogate end point for PFS in first-line FL therapy. Patients and Methods We analyzed individual patient data from 13 randomized multicenter trials of induction and maintenance regimens in first-line FL therapy published after 1990 and with sufficient data to evaluate whether CR30 could predict treatment effects on PFS. Correlation of the CR30 odds ratio with the PFS hazard ratio was evaluated by both linear regression (R2WLS) and bivariate copula (R2Copula) models. Prespecified criteria for surrogacy required either R2WLS or R2Copula ≥ 0.80, with a lower-bound 95% CI > 0.60. Results Data from eight induction and five maintenance randomized trials in 3,837 evaluable patients were analyzed. The prespecified surrogacy threshold was met, with an R2WLS of 0.88 (95% CI, 0.77 to 0.96) and an R2Copula of 0.86 (95% CI, 0.72 to 1.00). Multiple sensitivity and supplemental analyses supported the robustness of the findings. A minimum 11% absolute improvement in CR30 from a 50% control rate predicted a significant treatment effect on PFS (hazard ratio, 0.69). Conclusion This large, prospective, pooled analysis of randomized chemotherapy, immunotherapy, and chemoimmunotherapy trials demonstrates that CR30 is a surrogate end point for PFS in first-line FL treatment trials. Use of this end point may expedite therapeutic development with the intent of bringing novel therapies to this patient population years before PFS results are mature.

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


    Erdman, L.K.; D'Acremont, V.; Hayford, K.; Rajwans, N.; Kilowoko, M.; Kyungu, E.; Hongoa, P.; Alamo, L.; Streiner, D.L.; Genton, B.; Kain, K.C.


    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 stud...

  13. Infant formula and neurocognitive outcomes: impact of study end-point selection. (United States)

    Sun, H; Como, P G; Downey, L C; Murphy, D; Ariagno, R L; Rodriguez, W


    Assessing validity and reliability of end points used in docosahexanoic and arachidonic acids (DHA and ARA) infant formula supplementation trials as an example for addressing the impact of end-point selection and critical need for well-defined, reliable and validated clinical outcome assessments for neurocognitive assessment in neonates and infants. We searched eight electronic databases and reviewed all randomized, controlled human trials using DHA/ARA supplements with neurodevelopment clinical outcomes. We systematically evaluated the validity and reliability of end-point measures based on the criteria for studying nutritional additives recommended by the Institute of Medicine, criteria described in the Food and Drug Administration guidance for clinical outcome assessment, development and literature review. We identified 29 articles that met the selection criteria. The end points that were used for neurodevelopment measures in 23 out of 29 original short-term studies included the Bayley Scale of Infant Development (BSID)-I and -II (n=12), Brunet-Lezine test (n=2), videotape infant's movements (n=1), record time to milestones including sitting, crawling, standing and walking (n=1), problem-solving test (n=2), brainstem auditory-evoked potential (n=1), Touwen examination (n=1), Fagan test of infant intelligence (n=2) and visual habituation protocol (n=1). None of these end points have a long-term predictive property for neurocognitive assessment. Compared with standard infant formula, the beneficial effects of DHA/ARA supplementation on neurodevelopment were reported in 2 out of 12 studies using BSID vs 8 out of 11 studies using other end-point measures. In addition, 6 out of 29 long-term follow-up studies used the end points including Stanford-Binet IQ test (n=1), Wechsler Preschool and Primary Scale of Intelligence (n=4) and Bracken Basic Concept Scale (n=1), which are generally scales of intellectual ability and typically do not change substantively in the short

  14. End points for validating early warning scores in the context of rapid response systems: a Delphi consensus study. (United States)

    Pedersen, N E; Oestergaard, D; Lippert, A


    When investigating early warning scores and similar physiology-based risk stratification tools, death, cardiac arrest and intensive care unit admission are traditionally used as end points. A large proportion of the patients identified by these end points cannot be saved, even with optimal treatment. This could pose a limitation to studies using these end points. We studied current expert opinion on end points for validating tools for the identification of patients in hospital wards at risk of imminent critical illness. The Delphi consensus methodology was used. We identified 22 experts based on objective criteria; 17 participated in the study. Each expert panel member's suggestions for end points were collected and distributed to the entire expert panel in anonymised form. The experts reviewed, rated and commented the suggested end points through the rounds in the Delphi process, and the experts' combined rating of the usefulness of each suggestion was established. A gross list of 86 suggestions for end points, relating to 13 themes, was produced. No items were uniformly recognised as ideal. The themes cardiac arrest, death, and level of care contained the items receiving highest ratings. End points relating to death, cardiac arrest and intensive care unit admission currently comprise the most obvious compromises for investigating early warning scores and similar risk stratification tools. Additional end points from the gross list of suggested end points could become feasible with the increased availability of large data sets with a multitude of recorded parameters. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  15. Definitions and End Points for Interventional Studies for Arteriovenous Dialysis Access. (United States)

    Beathard, Gerald A; Lok, Charmaine E; Glickman, Marc H; Al-Jaishi, Ahmed A; Bednarski, Donna; Cull, David L; Lawson, Jeffery H; Lee, Timmy C; Niyyar, Vandana D; Syracuse, Donna; Trerotola, Scott O; Roy-Chaudhury, Prabir; Shenoy, Surendra; Underwood, Margo; Wasse, Haimanot; Woo, Karen; Yuo, Theodore H; Huber, Thomas S


    This paper is part of the Clinical Trial Endpoints for Dialysis Vascular Access Project of the American Society of Nephrology Kidney Health Initiative. The purpose of this project is to promote research in vascular access by clarifying trial end points which would be best suited to inform decisions in those situations in which supportive clinical data are required. The focus of a portion of the project is directed toward arteriovenous access. There is a potential for interventional studies to be directed toward any of the events that may be associated with an arteriovenous access' evolution throughout its life cycle, which has been divided into five distinct phases. Each one of these has the potential for relatively unique problems. The first three of these correspond to three distinct stages of arteriovenous access development, each one of which has been characterized by objective direct and/or indirect criteria. These are characterized as: stage 1-patent arteriovenous access, stage 2-physiologically mature arteriovenous access, and stage 3-clinically functional arteriovenous access. Once the requirements of a stage 3-clinically functional arteriovenous access have been met, the fourth phase of its life cycle begins. This is the phase of sustained clinical use from which the arteriovenous access may move back and forth between it and the fifth phase, dysfunction. From this phase of its life cycle, the arteriovenous access requires a maintenance procedure to preserve or restore sustained clinical use. Using these definitions, clinical trial end points appropriate to the various phases that characterize the evolution of the arteriovenous access life cycle have been identified. It is anticipated that by using these definitions and potential end points, clinical trials can be designed that more closely correlate with the goals of the intervention and provide appropriate supportive data for clinical, regulatory, and coverage decisions. Copyright © 2017 by the American

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


    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

  17. Challenges in translating end points from trials to observational cohort studies in oncology

    Directory of Open Access Journals (Sweden)

    Ording AG


    Full Text Available Anne Gulbech Ording,1 Deirdre Cronin-Fenton,1 Vera Ehrenstein,1 Timothy L Lash,1,2 John Acquavella,1 Mikael Rørth,1 Henrik Toft Sørensen1 1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA Abstract: Clinical trials are considered the gold standard for examining drug efficacy and for approval of new drugs. Medical databases and population surveillance registries are valuable resources for post-approval observational research, which are increasingly used in studies of benefits and risk of new cancer drugs. Here, we address the challenges in translating endpoints from oncology trials to observational studies. Registry-based cohort studies can investigate real-world safety issues – including previously unrecognized concerns – by examining rare endpoints or multiple endpoints at once. In contrast to clinical trials, observational cohort studies typically do not exclude real-world patients from clinical practice, such as old and frail patients with comorbidity. The observational cohort study complements the clinical trial by examining the effectiveness of interventions applied in clinical practice and by providing evidence on long-term clinical outcomes, which are often not feasible to study in a clinical trial. Various endpoints can be included in clinical trials, such as hard endpoints, soft endpoints, surrogate endpoints, and patient-reported endpoints. Each endpoint has it strengths and limitations for use in research studies. Endpoints used in oncology trials are often not applicable in observational cohort studies which are limited by the setting of standard clinical practice and by non-standardized endpoint determination. Observational studies can be more helpful moving research forward if they restrict focus to appropriate and valid endpoints. Keywords: endpoint determination, medical oncology

  18. Prognostic importance of hemoglobin in hypertensive patients with electrocardiographic left ventricular hypertrophy: the Losartan Intervention For End point reduction in hypertension (LIFE) study

    DEFF Research Database (Denmark)

    Olsen, Michael Hecht; Wachtell, Kristian; Beevers, Gareth


    baseline hemoglobin measurements were randomized to losartan- or atenolol-based treatment and followed for 4.8 years for end points of all-cause mortality and composite of cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction. RESULTS: U-shaped relations were observed between deciles...... of baseline hemoglobin and all-cause mortality and the composite end point. In univariate Cox models, baseline hemoglobin in the lowest gender-specific decile (women/men: end point (HR 1......) and the composite end point (HR 1.36, 95% CI 1.08-1.71, P

  19. Estimating the Cost of Preeclampsia in the Healthcare System: Cross-Sectional Study Using Data From SCOPE Study (Screening for Pregnancy End Points). (United States)

    Fox, Aimée; McHugh, Sheena; Browne, John; Kenny, Louise C; Fitzgerald, Anthony; Khashan, Ali S; Dempsey, Eugene; Fahy, Ciara; O'Neill, Ciaran; Kearney, Patricia M


    To estimate the cost of preeclampsia from the national health payer's perspective using secondary data from the SCOPE study (Screening for Pregnancy End Points). SCOPE is an international observational prospective study of healthy nulliparous women with singleton pregnancies. Using data from the Irish cohort recruited between November 2008 and February 2011, all women with preeclampsia and a 10% random sample of women without preeclampsia were selected. Additional health service use data were extracted from the consenting participants' medical records for maternity services which were not included in SCOPE. Unit costs were based on estimates from 3 existing Irish studies. Costs were extrapolated to a national level using a prevalence rate of 5% to 7% among nulliparous pregnancies. Within the cohort of 1774 women, 68 developed preeclampsia (3.8%) and 171 women were randomly selected as controls. Women with preeclampsia used higher levels of maternity services. The average cost of a pregnancy complicated by preeclampsia was €5243 per case compared with €2452 per case for an uncomplicated pregnancy. The national cost of preeclampsia is between €6.5 and €9.1 million per annum based on the 5% to 7% prevalence rate. Postpartum care was the largest contributor to these costs (€4.9-€6.9 million), followed by antepartum care (€0.9-€1.3 million) and peripartum care (€0.6-€0.7 million). Women with preeclampsia generate significantly higher maternity costs than women without preeclampsia. These cost estimates will allow policy-makers to efficiently allocate resources for this pregnancy-specific condition. Moreover, these estimates are useful for future research assessing the cost-effectiveness of preeclampsia screening and treatment. © 2017 American Heart Association, Inc.

  20. Molecular recognition in a diverse set of protein-ligand interactions studied with molecular dynamics simulations and end-point free energy calculations. (United States)

    Wang, Bo; Li, Liwei; Hurley, Thomas D; Meroueh, Samy O


    End-point free energy calculations using MM-GBSA and MM-PBSA provide a detailed understanding of molecular recognition in protein-ligand interactions. The binding free energy can be used to rank-order protein-ligand structures in virtual screening for compound or target identification. Here, we carry out free energy calculations for a diverse set of 11 proteins bound to 14 small molecules using extensive explicit-solvent MD simulations. The structure of these complexes was previously solved by crystallography and their binding studied with isothermal titration calorimetry (ITC) data enabling direct comparison to the MM-GBSA and MM-PBSA calculations. Four MM-GBSA and three MM-PBSA calculations reproduced the ITC free energy within 1 kcal·mol(-1) highlighting the challenges in reproducing the absolute free energy from end-point free energy calculations. MM-GBSA exhibited better rank-ordering with a Spearman ρ of 0.68 compared to 0.40 for MM-PBSA with dielectric constant (ε = 1). An increase in ε resulted in significantly better rank-ordering for MM-PBSA (ρ = 0.91 for ε = 10), but larger ε significantly reduced the contributions of electrostatics, suggesting that the improvement is due to the nonpolar and entropy components, rather than a better representation of the electrostatics. The SVRKB scoring function applied to MD snapshots resulted in excellent rank-ordering (ρ = 0.81). Calculations of the configurational entropy using normal-mode analysis led to free energies that correlated significantly better to the ITC free energy than the MD-based quasi-harmonic approach, but the computed entropies showed no correlation with the ITC entropy. When the adaptation energy is taken into consideration by running separate simulations for complex, apo, and ligand (MM-PBSAADAPT), there is less agreement with the ITC data for the individual free energies, but remarkably good rank-ordering is observed (ρ = 0.89). Interestingly, filtering MD snapshots by prescoring

  1. Combustion Kinetic Studies of Gasolines and Surrogates

    KAUST Repository

    Javed, Tamour


    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

  2. End point behaviour of the pion distribution amplitude (United States)

    Szcepaniak, Adam; Mankiewicz, Lech


    We study the end point structure of the pion distribution amplitude and reexamine the perturbative analysis of the high-Q2 pion form factor in the factorization approach. Permanent address: Nicolaus Copernicus Astronomical Centre, Bartycka 18, PL-00-716 Warsaw, Poland.

  3. Small-Magnitude Effect Sizes in Epigenetic End Points are Important in Children's Environmental Health Studies: The Children's Environmental Health and Disease Prevention Research Center's Epigenetics Working Group. (United States)

    Breton, Carrie V; Marsit, Carmen J; Faustman, Elaine; Nadeau, Kari; Goodrich, Jaclyn M; Dolinoy, Dana C; Herbstman, Julie; Holland, Nina; LaSalle, Janine M; Schmidt, Rebecca; Yousefi, Paul; Perera, Frederica; Joubert, Bonnie R; Wiemels, Joseph; Taylor, Michele; Yang, Ivana V; Chen, Rui; Hew, Kinjal M; Freeland, Deborah M Hussey; Miller, Rachel; Murphy, Susan K


    Characterization of the epigenome is a primary interest for children's environmental health researchers studying the environmental influences on human populations, particularly those studying the role of pregnancy and early-life exposures on later-in-life health outcomes. Our objective was to consider the state of the science in environmental epigenetics research and to focus on DNA methylation and the collective observations of many studies being conducted within the Children's Environmental Health and Disease Prevention Research Centers, as they relate to the Developmental Origins of Health and Disease (DOHaD) hypothesis. We address the current laboratory and statistical tools available for epigenetic analyses, discuss methods for validation and interpretation of findings, particularly when magnitudes of effect are small, question the functional relevance of findings, and discuss the future for environmental epigenetics research. A common finding in environmental epigenetic studies is the small-magnitude epigenetic effect sizes that result from such exposures. Although it is reasonable and necessary that we question the relevance of such small effects, we present examples in which small effects persist and have been replicated across populations and across time. We encourage a critical discourse on the interpretation of such small changes and further research on their functional relevance for children's health. The dynamic nature of the epigenome will require an emphasis on future longitudinal studies in which the epigenome is profiled over time, over changing environmental exposures, and over generations to better understand the multiple ways in which the epigenome may respond to environmental stimuli.

  4. Surrogate for oropharyngeal cancer HPV status in cancer database studies. (United States)

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


    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.

  5. 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


    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.

  6. A Study of Colonial Surrogates and Indigenous Others. (United States)

    Willard, William


    Carlos Montezuma, an Apache, was raised by whites, graduated from medical school, and worked as physician for the Indian Service and Carlisle Indian School. Montezuma's life as colonial surrogate advocating "civilization" of the Indians is compared to Kafka's story of the ape who studied to become a passable European because it was "a way out" of…

  7. Influence of Clinical Trial Site Enrollment on Patient Characteristics, Protocol Completion, and End Points : Insights From the ASCEND-HF Trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure)

    NARCIS (Netherlands)

    Greene, Stephen J.; Hernandez, Adrian F.; Sun, Jie-Lena; Metra, Marco; Butler, Javed; Ambrosy, Andrew P.; Ezekowitz, Justin A.; Starling, Randall C.; Teerlink, John R.; Schulte, Phillip J.; Voors, Adriaan A.; Armstrong, Paul W.; O'Connor, Christopher M.; Mentz, Robert J.

    Background Most international acute heart failure trials have failed to show benefit with respect to key end points. The impact of site enrollment and protocol execution on trial performance is unclear. Methods and Results We assessed the impact of varying site enrollment volume among all 7141 acute

  8. Composite and multicomponent end points in clinical trials. (United States)

    Sankoh, Abdul J; Li, Haihong; D'Agostino, Ralph B


    In January 2017, the FDA released the draft guidance to industry on multiple end points in clinical trials. A class of multiplicity problems arise from the testing of individual or subset of components of a composite or multicomponent end point. This commentary attempts to further clarify these problems. Discussions include general consideration on the use of the composite and multicomponent end points, situations when multiplicity adjustments are needed, and the relevant multiple testing methods. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  9. Incidence Rate of Cardiovascular Disease End Points in the National Aeronautics and Space Administration Astronaut Corps. (United States)

    Ade, Carl J; Broxterman, Ryan M; Charvat, Jacqueline M; Barstow, Thomas J


    It is unknown whether the astronaut occupation or exposure to microgravity influences the risk of long-term cardiovascular disease (CVD). This study explored the effects of being a career National Aeronautics and Space Administration (NASA) astronaut on the risk for clinical CVD end points. During the Longitudinal Study of Astronaut Health, data were collected on 310 NASA astronauts and 981 nonastronaut NASA employees. The nonastronauts were matched to the astronauts on age, sex, and body mass index, to evaluate acute and chronic morbidity and mortality. The primary outcomes were composites of clinical CVD end points (myocardial infarction, congestive heart failure, stroke, and coronary artery bypass surgery) or coronary artery disease (CAD) end points (myocardial infarction and coronary artery bypass surgery). Of the astronauts, 5.2% had a clinical CVD end point and 2.9% had a CAD end point compared with the nonastronaut comparisons with 4.7% and 3.1% having CVD and CAD end points, respectively. In the multivariate models adjusted for traditional risk factors, astronauts had a similar risk of CVD compared with nonastronauts (adjusted hazard ratio, 1.08; 95% CI, 0.60-1.93; P=0.80). Risk of a CAD end point was similar between groups (hazard ratio, 0.97; CI, 0.45-2.08; P=0.93). In astronauts with early spaceflight experience, the risk of CVD (hazard ratio, 0.80; CI, 0.25-2.56; P=0.71) and CAD (hazard ratio, 1.23; CI: 0.27-5.61; P=0.79) compared with astronauts with no experience were not different. These findings suggest that being an astronaut is not associated with increased long-term risk of CVD development. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  10. Validation of Surrogates of Urine Osmolality in Population Studies. (United States)

    Youhanna, Sonia; Bankir, Lise; Jungers, Paul; Porteous, David; Polasek, Ozren; Bochud, Murielle; Hayward, Caroline; Devuyst, Olivier


    The importance of vasopressin and/or urine concentration in various kidney, cardiovascular, and metabolic diseases has been emphasized recently. Due to technical constraints, urine osmolality (Uosm), a direct reflect of urinary concentrating activity, is rarely measured in epidemiologic studies. We analyzed 2 possible surrogates of Uosm in 4 large population-based cohorts (total n = 4,247) and in patients with chronic kidney disease (CKD, n = 146). An estimated Uosm (eUosm) based on the concentrations of sodium, potassium, and urea, and a urine concentrating index (UCI) based on the ratio of creatinine concentrations in urine and plasma were compared to the measured Uosm (mUosm). eUosm is an excellent surrogate of mUosm, with a highly significant linear relationship and values within 5% of mUosm (r = 0.99 or 0.98 in each population cohort). Bland-Altman plots show a good agreement between eUosm and mUosm with mean differences between the 2 variables within ±24 mmol/L. This was verified in men and women, in day and night urine samples, and in CKD patients. The relationship of UCI with mUosm is also significant but is not linear and exhibits more dispersed values. Moreover, the latter index is no longer representative of mUosm in patients with CKD as it declines much more quickly with declining glomerular filtration rate than mUosm. The eUosm is a valid marker of urine concentration in population-based and CKD cohorts. The UCI can provide an estimate of urine concentration when no other measurement is available, but should be used only in subjects with normal renal function. © 2017 S. Karger AG, Basel.

  11. Use of Surrogate Outcomes in Nephrology Research. (United States)

    Samuels, Joshua


    Clinical trials are large and expensive and could require exceedingly long-term follow-up for subjects to reach clinically meaningful end points. To combat these methodologic issues, researchers sometimes use biomarkers as surrogate end points. A biomarker is an objectively measured characteristic that is indicative of some underlying phenomenon or process, while a surrogate is a biomarker that "takes the place" of a clinically meaningful outcome, usually earlier in the disease process. This paper reviews the history, strengths, and weaknesses of surrogate outcome use in clinical research and then discusses potential surrogate outcomes in nephrology research. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  12. Counterpoint—The End Point: Less Is More (United States)

    Fleming, G Alexander


    Improving the scientific and regulatory evaluation of therapies for metabolic disorders is a necessary ongoing process dependent on accruing knowledge and improving technology. The use of a composite primary efficacy outcome consisting of hemoglobin A1c (HbA1c) and hypoglycemia rates is alluring for evaluating glucose-lowering therapies. This composite, however, provides little advantage, if not some disadvantage, over HbA1c as the primary end point. Composite end points have traditionally been used as regulatory end points when a more straightforward approach is not available or feasible. The most well-known example is the composite of major adverse cardiac events (MACE), which has long been used for cardiac drug approvals by the Food and Drug Administration and has become a primary safety outcome for oral diabetes drugs. The MACE composite is widely accepted even though the cardiac death component would provide the most persuasive and near definitive reflection of benefit. Less definitive but more frequently occurring end points—myocardial infarction and stroke—are added to the composite only to enable outcome trials that can be completed in a reasonable time and with reasonable costs. Composite end points have inherent drawbacks and challenges, which may include undue dependence on assumptions, difficulty of validation, less sensitivity to detecting clinically important effects, and oversimplifying evidence for the prescribing physician and other therapeutic decision makers. The proposed efficacy end point composed of glycemic control and hypoglycemia carries all these drawbacks for diabetes drugs. Even insulin products, for which hypoglycemia is the chief safety concern, will more feasibly continue to be developed and evaluated under a treat to glycemic target design, with glycemic control as the sole primary efficacy outcome and rates of hypoglycemia as the prime adverse measure. PMID:22027331

  13. Capturing heterogeneity in gene expression studies by surrogate variable analysis.

    Directory of Open Access Journals (Sweden)

    Jeffrey T Leek


    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.

  14. A cross-cultural study on surrogate mother's empathy and maternal-foetal attachment. (United States)

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


    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.

  15. Speech Surrogates of Africa: A Study of the Fante Mmensuon ...

    African Journals Online (AJOL)

    Various forms of communication based on sounds produced by instruments are common in many African societies. Among these, the slit gong and drums are the most popular and the most widely used as speech surrogates in Africa (Nketia, 1971: 700). With the introduction of participant-observation research orientation to ...

  16. GFR Decline as an End Point for Clinical Trials in CKD : A Scientific Workshop Sponsored by the National Kidney Foundation and the US Food and Drug Administration

    NARCIS (Netherlands)

    Levey, Andrew S.; Inker, Lesley A.; Matsushita, Kunihiro; Greene, Tom; Willis, Kerry; Lewis, Edmund; de Zeeuw, Dick; Cheung, Alfred K.; Coresh, Josef


    The US Food and Drug Administration currently accepts halving of glomerular filtration rate (GFR), assessed as doubling of serum creatinine level, as a surrogate end point for the development of kidney failure in clinical trials of kidney disease progression. A doubling of serum creatinine level

  17. Neural predictor of the end point in a converter

    Directory of Open Access Journals (Sweden)

    Valentini, R.


    Full Text Available The paper presents a system based on neural networks which is capable of predicting the so-called End Point of a converter by exploiting the measurements of the oxygen content and of the temperature in order to predict the final carbon content. Due to several disadvantages of current LD algebraic model and the usage of modem process in steel plant, a new model based on neural network and knowledge base is designed. The new model allowed to obtain excellent simulation result and satisfied online testing report.

    La memoria presenta un sistema basado en redes neuronales capaz de predecir el llamado End Point de un convertidor, que utiliza la medida del contenido de oxígeno y de la temperatura para predecir el contenido de carbono final. A causa de las diversas desventajas del modelo algebraico normal LD, se han diseñado algunos modelos innovadores realizados mediante técnicas de soft-computing. El nuevo modelo permite obtener excelentes resultados en simulación y también en las pruebas on line.

  18. New supervised learning theory applied to cerebellar modeling for suppression of variability of saccade end points. (United States)

    Fujita, Masahiko


    A new supervised learning theory is proposed for a hierarchical neural network with a single hidden layer of threshold units, which can approximate any continuous transformation, and applied to a cerebellar function to suppress the end-point variability of saccades. In motor systems, feedback control can reduce noise effects if the noise is added in a pathway from a motor center to a peripheral effector; however, it cannot reduce noise effects if the noise is generated in the motor center itself: a new control scheme is necessary for such noise. The cerebellar cortex is well known as a supervised learning system, and a novel theory of cerebellar cortical function developed in this study can explain the capability of the cerebellum to feedforwardly reduce noise effects, such as end-point variability of saccades. This theory assumes that a Golgi-granule cell system can encode the strength of a mossy fiber input as the state of neuronal activity of parallel fibers. By combining these parallel fiber signals with appropriate connection weights to produce a Purkinje cell output, an arbitrary continuous input-output relationship can be obtained. By incorporating such flexible computation and learning ability in a process of saccadic gain adaptation, a new control scheme in which the cerebellar cortex feedforwardly suppresses the end-point variability when it detects a variation in saccadic commands can be devised. Computer simulation confirmed the efficiency of such learning and showed a reduction in the variability of saccadic end points, similar to results obtained from experimental data.

  19. A theoretical study of deuteron-induced surrogate reactions (United States)

    Carlson, B. V.; Capote, R.; Sin, M.


    We use the zero-range post-form DWBA approximation to calculate deuteron elastic and nonelastic breakup cross sections and estimate the breakup-fusion cross section that could serve as a surrogate for a neutron-induced reaction cross section. We compare the angular momentum dependence of the breakup-fusion compound nucleus formation cross section with that of the corresponding neutron-induced cross section.

  20. A theoretical study of deuteron-induced surrogate reactions

    Directory of Open Access Journals (Sweden)

    Carlson B.V.


    Full Text Available We use the zero-range post-form DWBA approximation to calculate deuteron elastic and nonelastic breakup cross sections and estimate the breakup-fusion cross section that could serve as a surrogate for a neutron-induced reaction cross section. We compare the angular momentum dependence of the breakup-fusion compound nucleus formation cross section with that of the corresponding neutron-induced cross section.

  1. Effectiveness of hydrochlorothiazide in combination with telmisartan and olmesartan in adults with moderate hypertension not controlled with monotherapy: a prospective, randomized, open-label, blinded end point (PROBE), parallel-arm study. (United States)

    Fogari, Roberto; Zoppi, Annalisa; Mugellini, Amedeo; Preti, Paola; Destro, Maurizio; Rinaldi, Andrea; Derosa, Giuseppe


    The potential combinations of antihypertensive agents are many, and making rational choices depends on the characteristics of each drug and on their complementary mechanisms of action. The aim of this study was to evaluate the effectiveness of adding hydrochlorothiazide (HCTZ) 12.5 mg to olmesartan 20 mg or telmisartan 80 mg on blood pressure (BP) in patients with moderate hypertension. Consecutive outpatients at the Centro per l'Ipertensione e la Fisiopatologia Cardiovascolare, University of Pavia, Pavia, Italy, of both sexes aged 39 to 75 years were considered eligible for enrollment if they had a sitting diastolic BP (DBP) ->99 mm Hg and 90 mm Hg) received HCTZ 12.5 mg QD for 8 additional weeks. Clinical and ambulatory BPs were measured at the end of the washout period and at the end of both treatment periods. Adverse events (AEs) were recorded from spontaneous reports and direct inquiry from investigators. One hundred forty-five patients, all of whom were white, were recruited for the study. After the initial washout period, 13 patients did not meet the inclusion criteria and 6 refused to continue. A total of 126 white patients (69 men, 57 women; mean [SD] age, 60.2 [11.6] years) were randomized to receive monotherapy. Of these, 35 patients (56%) in the olmesartan group and 33 (52%) in the telmisartan group had previously received antihypertensive therapy. At the end of monotherapy, the 52 patients in the olmesartan group and the 49 patients in the telmisartan treatment group who were still in the study and had their BP inadequately controlled by treatment had HCTZ 12.5 mg QD added to their treatment regimen. Both combinations induced a greater ambulatory mean (SD) systolic BP (SBP) and DBP reduction than monothera- py (SBP: 145.3 [6.1] in the olmesartan group and 140.1 [6.4] in the telmisartan group, P < 0.05; DBP: 88.1 [5.1] in the olmesartan group and 84.9 [4.9] in the telmisartan group, P < 0.05). The mean (SD) reduction from baseline in the telmisartan

  2. Regression calibration for classical exposure measurement error in environmental epidemiology studies using multiple local surrogate exposures. (United States)

    Bateson, Thomas F; Wright, J Michael


    Environmental epidemiologic studies are often hierarchical in nature if they estimate individuals' personal exposures using ambient metrics. Local samples are indirect surrogate measures of true local pollutant concentrations which estimate true personal exposures. These ambient metrics include classical-type nondifferential measurement error. The authors simulated subjects' true exposures and their corresponding surrogate exposures as the mean of local samples and assessed the amount of bias attributable to classical and Berkson measurement error on odds ratios, assuming that the logit of risk depends on true individual-level exposure. The authors calibrated surrogate exposures using scalar transformation functions based on observed within- and between-locality variances and compared regression-calibrated results with naive results using surrogate exposures. The authors further assessed the performance of regression calibration in the presence of Berkson-type error. Following calibration, bias due to classical-type measurement error, resulting in as much as 50% attenuation in naive regression estimates, was eliminated. Berkson-type error appeared to attenuate logistic regression results less than 1%. This regression calibration method reduces effects of classical measurement error that are typical of epidemiologic studies using multiple local surrogate exposures as indirect surrogate exposures for unobserved individual exposures. Berkson-type error did not alter the performance of regression calibration. This regression calibration method does not require a supplemental validation study to compute an attenuation factor.

  3. Comparative study of surrogate models for groundwater contamination source identification at DNAPL-contaminated sites (United States)

    Hou, Zeyu; Lu, Wenxi


    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.

  4. Detection of Bordetella pertussis from Clinical Samples by Culture and End-Point PCR in Malaysian Patients. (United States)

    Ting, Tan Xue; Hashim, Rohaidah; Ahmad, Norazah; Abdullah, Khairul Hafizi


    Pertussis or whooping cough is a highly infectious respiratory disease caused by Bordetella pertussis. In vaccinating countries, infants, adolescents, and adults are relevant patients groups. A total of 707 clinical specimens were received from major hospitals in Malaysia in year 2011. These specimens were cultured on Regan-Lowe charcoal agar and subjected to end-point PCR, which amplified the repetitive insertion sequence IS481 and pertussis toxin promoter gene. Out of these specimens, 275 were positive: 4 by culture only, 6 by both end-point PCR and culture, and 265 by end-point PCR only. The majority of the positive cases were from ≤3 months old patients (77.1%) (P 0.05). Our study showed that the end-point PCR technique was able to pick up more positive cases compared to culture method.

  5. Development of an instrumented spinal cord surrogate using optical fibers: A feasibility study. (United States)

    Facchinello, Yann; Wagnac, Éric; Ung, Bora; Petit, Yvan; Pradhan, Prabin; Peyrache, Louis-Marie; Mac-Thiong, Jean-Marc


    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.

  6. Motor Power Signal Analysis for End-Point Detection of Chemical Mechanical Planarization

    Directory of Open Access Journals (Sweden)

    Hongkai Li


    Full Text Available In the integrated circuit (IC manufacturing, in-situ end-point detection (EPD is an important issue in the chemical mechanical planarization (CMP process. In the paper, we chose the motor power signal of the polishing platen as the monitoring object. We then used the moving average method, which was appropriate for in-situ calculation process and made it easy to code for software development, to smooth the signal curve, and then studied the signal variation during the actual CMP process. The results demonstrated that the motor power signal contained the end-point feature of the metal layer removal, and the processed signal curve facilitated the feature extraction and it was relatively steady before and after the layer transition stage. In addition, the motor power signal variation of the polishing head was explored and further analysis of time delay was performed.

  7. End-point impedance measurements across dominant and nondominant hands and robotic assistance with directional damping. (United States)

    Erden, Mustafa Suphi; Billard, Aude


    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.

  8. Serum Bicarbonate and Kidney Disease Progression and Cardiovascular Outcome in Patients With Diabetic Nephropathy: A Post Hoc Analysis of the RENAAL (Reduction of End Points in Non-Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan) Study and IDNT (Irbesartan Diabetic Nephropathy Trial). (United States)

    Schutte, Elise; Lambers Heerspink, Hiddo J; Lutgers, Helen L; Bakker, Stephan J L; Vart, Priya; Wolffenbuttel, Bruce H R; Umanath, Kausik; Lewis, Julia B; de Zeeuw, Dick; Gansevoort, Ron T


    Low serum bicarbonate level has been reported to be an independent predictor of kidney function decline and mortality in patients with chronic kidney disease. Mechanisms underlying low serum bicarbonate levels may differ in patients with and without diabetes. We aimed to specifically investigate the association of serum bicarbonate level with kidney disease progression and cardiovascular outcome in a cohort of patients with type 2 diabetes and nephropathy. Post hoc analysis of 2 multicenter randomized controlled trials. 2,628 adults with type 2 diabetes and nephropathy. Serum bicarbonate level. Incidence of: (1) end-stage renal disease (ESRD), (2) ESRD or doubling of serum creatinine level, (3) all-cause mortality, (4) cardiovascular events (fatal/nonfatal stroke/myocardial infarction), and (5) heart failure. Serum bicarbonate was measured at baseline as total carbon dioxide. Associations of baseline serum bicarbonate level with end points were investigated using Cox regression models. Serum bicarbonate levels were studied as a continuous variable and stratified in quartiles. Follow-up was 2.8±1.0 (SD) years. Cox regression analyses showed that serum bicarbonate level had inverse associations with incident ESRD (HR, 0.91; 95% CI, 0.89-0.93; P0.05). Analysis of bicarbonate quartiles showed similar results for the quartile with the lowest bicarbonate (≤21 mEq/L) versus the quartile with normal bicarbonate levels (24-26 mEq/L). There was no association of bicarbonate level with cardiovascular events and heart failure. Post hoc analysis and single measurement of serum bicarbonate. In this cohort of patients with type 2 diabetes with nephropathy, serum bicarbonate level associations with kidney disease end points were not retained after adjustment for estimated glomerular filtration rate, which is in contrast to results of earlier studies in nondiabetic populations. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  9. Business Administration Students as Surrogates for IT Professionals: Summary of a Study (United States)

    Cline, Melinda; St. John, Jeremy; Guynes, Carl S.


    The purpose of this paper is to report a summary of the results of a study which examined the appropriateness of using business school students as surrogates for IT professionals by comparing cognitive styles, physiological characteristics, and basic demographic data among the two groups. Cognitive style refers to the way individuals think,…

  10. Analysis of Clinical End Points of Randomised Trials Including Bevacizumab and Chemotherapy versus Chemotherapy as First-line Treatment of Metastatic Colorectal Cancer. (United States)

    Colloca, G; Venturino, A; Guarneri, D


    Progression-free survival is recognised as an appropriate end point for randomised clinical trials of chemotherapy of patients with metastatic colorectal cancer, although it is not clear if it is reliable after chemotherapy plus bevacizumab. A literature search of randomised trials of systemic treatment including chemotherapy plus bevacizumab versus chemotherapy in patients with metastatic colorectal cancer was undertaken. For each trial the differences in overall survival and in either time-to-event or response-related end points were calculated. A Spearman test was carried out between the difference in each end point and the difference in survival. For the end points with the higher relationships with overall survival a regression analysis was carried out and R(2) (proportion of variability explained) was reported. Progression-free survival is closely related to overall survival (r=0.817; R(2)=0.706) and this relationship does not seem to be changed by the discontinuation of bevacizumab. The response-related end points have a better overall performance than the other time-to-event end points, even when only phase III trials are considered. In phase III trials, the disease control rate seems to be strongly related to overall survival (r=0.975; R(2)=0.889) and the overall response rate reports a good performance (r=0.866; R(2)=0.484). An open-label design and the timing of disease radiological evaluation do not seem to interfere with the correlation of differences of progression-free survival and overall survival. A validation of the disease control rate and the overall response rate as a surrogate end point of survival at a patient level and a standardised definition of the timing for their measurement are strongly recommended in trials of chemotherapy plus bevacizumab. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  11. Comparative Numerical Study of Four Biodiesel Surrogates for Application on Diesel 0D Phenomenological Modeling

    Directory of Open Access Journals (Sweden)

    Claude Valery Ngayihi Abbe


    Full Text Available To meet more stringent norms and standards concerning engine performances and emissions, engine manufacturers need to develop new technologies enhancing the nonpolluting properties of the fuels. In that sense, the testing and development of alternative fuels such as biodiesel are of great importance. Fuel testing is nowadays a matter of experimental and numerical work. Researches on diesel engine’s fuel involve the use of surrogates, for which the combustion mechanisms are well known and relatively similar to the investigated fuel. Biodiesel, due to its complex molecular configuration, is still the subject of numerous investigations in that area. This study presents the comparison of four biodiesel surrogates, methyl-butanoate, ethyl-butyrate, methyl-decanoate, and methyl-9-decenoate, in a 0D phenomenological combustion model. They were investigated for in-cylinder pressure, thermal efficiency, and NOx emissions. Experiments were performed on a six-cylinder turbocharged DI diesel engine fuelled by methyl ester (MEB and ethyl ester (EEB biodiesel from wasted frying oil. Results showed that, among the four surrogates, methyl butanoate presented better results for all the studied parameters. In-cylinder pressure and thermal efficiency were predicted with good accuracy by the four surrogates. NOx emissions were well predicted for methyl butanoate but for the other three gave approximation errors over 50%.

  12. Nasal epithelial cells can act as a physiological surrogate for paediatric asthma studies.

    Directory of Open Access Journals (Sweden)

    Surendran Thavagnanam

    Full Text Available INTRODUCTION: Differentiated paediatric epithelial cells can be used to study the role of epithelial cells in asthma. Nasal epithelial cells are easier to obtain and may act as a surrogate for bronchial epithelium in asthma studies. We assessed the suitability of nasal epithelium from asthmatic children to be a surrogate for bronchial epithelium using air-liquid interface cultures. METHODS: Paired nasal and bronchial epithelial cells from asthmatic children (n = 9 were differentiated for 28 days under unstimulated and IL-13-stimulated conditions. Morphological and physiological markers were analysed using immunocytochemistry, transepithelial-electrical-resistance, Quantitative Real-time-PCR, ELISA and multiplex cytokine/chemokine analysis. RESULTS: Physiologically, nasal epithelial cells from asthmatic children exhibit similar cytokine responses to stimulation with IL-13 compared with paired bronchial epithelial cells. Morphologically however, nasal epithelial cells differed significantly from bronchial epithelial cells from asthmatic patients under unstimulated and IL-13-stimulated conditions. Nasal epithelial cells exhibited lower proliferation/differentiation rates and lower percentages of goblet and ciliated cells when unstimulated, while exhibiting a diminished and varied response to IL-13. CONCLUSIONS: We conclude that morphologically, nasal epithelial cells would not be a suitable surrogate due to a significantly lower rate of proliferation and differentiation of goblet and ciliated cells. Physiologically, nasal epithelial cells respond similarly to exogenous stimulation with IL-13 in cytokine production and could be used as a physiological surrogate in the event that bronchial epithelial cells are not available.

  13. Old model organisms and new behavioral end-points: Swimming alteration as an ecotoxicological response. (United States)

    Faimali, Marco; Gambardella, Chiara; Costa, Elisa; Piazza, Veronica; Morgana, Silvia; Estévez-Calvar, Noelia; Garaventa, Francesca


    Behavioral responses of aquatic organisms have received much less attention than developmental or reproductive ones due to the scarce presence of user-friendly tools for their acquisition. The technological development of data acquisition systems for quantifying behavior in the aquatic environment and the increase of studies on the understanding the relationship between the behavior of aquatic organisms and the physiological/ecological activities have generated renewed interest in using behavioral responses also in marine ecotoxicology. Recent reviews on freshwater environment show that behavioral end-points are comparatively fast and sensitive, and warrant further attention as tools for assessing the toxicological effects of environmental contaminants. In this mini-review, we perform a systematic analysis of the most recent works that have used marine invertebrate swimming alteration as behavioral end-point in ecotoxicological studies by assessing the differences between behavioral and acute responses in a wide range of species, in order to compare their sensitivity. Copyright © 2016. Published by Elsevier Ltd.

  14. Marine and estuarine porewater toxicity testing -- species and end point comparisons

    Energy Technology Data Exchange (ETDEWEB)

    Carr, R.S.; Chapman, D.C.; Biedenbach, J.M.; Robertson, L. [NBS, Corpus Christi, TX (United States). NFCR Field Research Station


    As part of their continuing development and evaluation of the porewater toxicity test approach for assessing the quality of marine and estuarine sediments, a variety of studies involving species and endpoint comparisons as well as validation studies have recently been conducted. The results from numerous extensive sediment quality assessment surveys have demonstrated that porewater toxicity tests are considerably more sensitive than the standard solid-phase tests and invariably exhibit a higher degree of concordance with sediment quality assessment guidelines than the standard tests. Species that have been evaluated for use in testing marine and estuarine pore water include a life-cycle test with the polychaete Dinophilus gyrociliatus, survival and hatching success with embryo-larval stages of red drum Sciaaenops ocellatus, survival of nauplii stages of the harpacticoid copepod Longipedia sp., and three different assays (fertilization, embryological development, and cytogenetic) with the sea urchin Arbacia punctulata. The different species and end points have been compared using sediment pore water from a variety of contaminated sites. Although the results of tests with the different species and end points were often comparable, in general, the sea urchin embryological development assay appears to be the most sensitive porewater test evaluated thus far in their laboratory.

  15. Reliability of environmental and occupational exposure data provided by surrogate respondents in a case-control study of Parkinson's disease. (United States)

    Wang, F L; Semchuk, K M; Love, E J


    This study used data provided by 40 non-demented Parkinson's disease patients and 101 community controls, and by their 110 spouses and 31 adult children to assess the reliability of surrogate-provided rural environmental and occupational exposure information on the index subjects. The level of overall raw agreement between the index subjects and the spouse or adult child surrogates varied from 50.0 to 100.0% for the case-surrogate group and from 80.6 to 96.0% for the control-surrogate group. We did not detect significant differences in overall raw agreement between the case-surrogate and control-surrogate groups or between the spouse-surrogate and adult child-surrogate groups, for any of the variables studied. Considering all index subjects and their surrogates, the level of overall raw agreement was 80.3% for well water consumption, 82.3% for farm living, 85.8% for agricultural work, 87.1% for use of pesticides, 87.9% for field crop farming and 91.9% for use of fertilizers. However, the kappa estimates were lower, varying from 0.48 (SE = 0.20) for fertilizer use to 0.66 (SE = 0.11) for crop farming. The level of specific agreement was 52.2% for fertilizer use, 64.0% for pesticide use, 71.4% for agricultural work, 73.9% for crop farming, 80.9% for farm living, and 83.6% for well water consumption. The overall findings of this study support the use, if necessary, of spouses and adult children of index subjects as surrogate respondents in case-control studies of rural environment and occupational exposures and Parkinson's disease and, possibly, other neurologic diseases. Specific agreement seems to be a better index of reliability than overall agreement in studies where exposure is rare.

  16. An empirical assessment and comparison of species-based and habitat-based surrogates: a case study of forest vertebrates and large old trees. (United States)

    Lindenmayer, David B; Barton, Philip S; Lane, Peter W; Westgate, Martin J; McBurney, Lachlan; Blair, David; Gibbons, Philip; Likens, Gene E


    A holy grail of conservation is to find simple but reliable measures of environmental change to guide management. For example, particular species or particular habitat attributes are often used as proxies for the abundance or diversity of a subset of other taxa. However, the efficacy of such kinds of species-based surrogates and habitat-based surrogates is rarely assessed, nor are different kinds of surrogates compared in terms of their relative effectiveness. We use 30-year datasets on arboreal marsupials and vegetation structure to quantify the effectiveness of: (1) the abundance of a particular species of arboreal marsupial as a species-based surrogate for other arboreal marsupial taxa, (2) hollow-bearing tree abundance as a habitat-based surrogate for arboreal marsupial abundance, and (3) a combination of species- and habitat-based surrogates. We also quantify the robustness of species-based and habitat-based surrogates over time. We then use the same approach to model overall species richness of arboreal marsupials. We show that a species-based surrogate can appear to be a valid surrogate until a habitat-based surrogate is co-examined, after which the effectiveness of the former is lost. The addition of a species-based surrogate to a habitat-based surrogate made little difference in explaining arboreal marsupial abundance, but altered the co-occurrence relationship between species. Hence, there was limited value in simultaneously using a combination of kinds of surrogates. The habitat-based surrogate also generally performed significantly better and was easier and less costly to gather than the species-based surrogate. We found that over 30 years of study, the relationships which underpinned the habitat-based surrogate generally remained positive but variable over time. Our work highlights why it is important to compare the effectiveness of different broad classes of surrogates and identify situations when either species- or habitat-based surrogates are likely

  17. Mobility and cognition: End points for dietary interventions in aging (United States)

    BACKGROUND: Healthy aging is associated with functional declines in mobility and cognition among both humans and non-human animals. OBJECTIVE: This study combines human measures of mobility and cognition to develop a test battery for evaluating the effects of dietary supplements among older adults....

  18. The Hot and Energetic Universe: End points of stellar evolution

    NARCIS (Netherlands)

    Motch, Christian; Wilms, Jörn; Barret, Didier; Becker, Werner; Bogdanov, Slavko; Boirin, Laurence; Corbel, Stéphane; Cackett, Ed; Campana, Sergio; de Martino, Domitilla; Haberl, Frank; in't Zand, Jean; Méndez, Mariano; Mignani, Roberto; Miller, Jon; Orio, Marina; Psaltis, Dimitrios; Rea, Nanda; Rodriguez, Jérôme; Rozanska, Agata; Schwope, Axel; Steiner, Andrew; Webb, Natalie; Zampieri, Luca; Zane, Silvia


    White dwarfs, neutron stars and stellar mass black holes are key laboratories to study matter in most extreme conditions of gravity and magnetic field. The unprecedented effective area of Athena+ will allow us to advance our understanding of emission mechanisms and accretion physics over a wide

  19. Tumble Graphs: Avoiding Misleading End Point Extrapolation When Graphing Interactions From a Moderated Multiple Regression Analysis (United States)

    Bodner, Todd E.


    This article revisits how the end points of plotted line segments should be selected when graphing interactions involving a continuous target predictor variable. Under the standard approach, end points are chosen at ±1 or 2 standard deviations from the target predictor mean. However, when the target predictor and moderator are correlated or the…

  20. End points for validating early warning scores in the context of rapid response systems

    DEFF Research Database (Denmark)

    Pedersen, N. E.; Oestergaard, D.; Lippert, A.


    INTRODUCTION: When investigating early warning scores and similar physiology-based risk stratification tools, death, cardiac arrest and intensive care unit admission are traditionally used as end points. A large proportion of the patients identified by these end points cannot be saved, even with ...

  1. Response rate as a potential surrogate for survival and efficacy in patients treated with novel immune checkpoint inhibitors: A meta-regression of randomised prospective studies. (United States)

    Roviello, Giandomenico; Andre, Fabrice; Venturini, Sergio; Pistilli, Barbara; Curigliano, Giuseppe; Cristofanilli, Massimo; Rosellini, Pietro; Generali, Daniele


    To assess the role of the tumour response rate (RR) after immune checkpoint inhibitors-based therapy as a potential surrogate end-point of progression-free survival (PFS) and overall survival (OS) in patients with solid tumours, we performed a trial-based meta-regression of randomised studies comparing different immune checkpoint inhibitors-based treatments. The systematic literature search included the electronic databases and the proceedings of oncologic meetings. Treatment effects on PFS and OS were expressed as hazard ratios (HRs); treatment effects on RR were expressed as odds ratios (ORs). A weighted regression analysis was performed on log-transformed treatment effect estimates to test the association between treatment effects on the surrogate outcome and treatment effects on the clinical outcome. Twenty-four trials, for a total of 11,894 patients, were included in the analysis. Using the complete set of data, the regression of either the log(HR) for PFS or the log(HR) for OS on the log(OR) for RR demonstrated weak associations (R2 = 0.47; 95% confidence interval [CI], 0.03-0.77; P = 0.001; and R2 = 0.32; 95% CI, 0.02-0.76; P = 0.01, respectively). The pre-planned analyses stratifying trials according to different type of disease and different mechanism of action of immune checkpoint inhibitors showed a very weak association of the RR with the OS for non-small cell lung cancer indicated and a modest association of the RR with the PFS for cytotoxic T lymphocyte-associated antigen 4 checkpoint inhibitors. The results of the trial-based meta-regression analysis indicated a weak correlation between RR and OS, supporting future investigations to assess the surrogacy of RR in the patient treated with immune checkpoint inhibitors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. End-point variability is not noise in saccade adaptation.

    Directory of Open Access Journals (Sweden)

    James P Herman

    Full Text Available When each of many saccades is made to overshoot its target, amplitude gradually decreases in a form of motor learning called saccade adaptation. Overshoot is induced experimentally by a secondary, backwards intrasaccadic target step (ISS triggered by the primary saccade. Surprisingly, however, no study has compared the effectiveness of different sizes of ISS in driving adaptation by systematically varying ISS amplitude across different sessions. Additionally, very few studies have examined the feasibility of adaptation with relatively small ISSs. In order to best understand saccade adaptation at a fundamental level, we addressed these two points in an experiment using a range of small, fixed ISS values (from 0° to 1° after a 10° primary target step. We found that significant adaptation occurred across subjects with an ISS as small as 0.25°. Interestingly, though only adaptation in response to 0.25° ISSs appeared to be complete (the magnitude of change in saccade amplitude was comparable to size of the ISS, further analysis revealed that a comparable proportion of the ISS was compensated for across conditions. Finally, we found that ISS size alone was sufficient to explain the magnitude of adaptation we observed; additional factors did not significantly improve explanatory power. Overall, our findings suggest that current assumptions regarding the computation of saccadic error may need to be revisited.

  3. End-point variability is not noise in saccade adaptation. (United States)

    Herman, James P; Cloud, C Phillip; Wallman, Josh


    When each of many saccades is made to overshoot its target, amplitude gradually decreases in a form of motor learning called saccade adaptation. Overshoot is induced experimentally by a secondary, backwards intrasaccadic target step (ISS) triggered by the primary saccade. Surprisingly, however, no study has compared the effectiveness of different sizes of ISS in driving adaptation by systematically varying ISS amplitude across different sessions. Additionally, very few studies have examined the feasibility of adaptation with relatively small ISSs. In order to best understand saccade adaptation at a fundamental level, we addressed these two points in an experiment using a range of small, fixed ISS values (from 0° to 1° after a 10° primary target step). We found that significant adaptation occurred across subjects with an ISS as small as 0.25°. Interestingly, though only adaptation in response to 0.25° ISSs appeared to be complete (the magnitude of change in saccade amplitude was comparable to size of the ISS), further analysis revealed that a comparable proportion of the ISS was compensated for across conditions. Finally, we found that ISS size alone was sufficient to explain the magnitude of adaptation we observed; additional factors did not significantly improve explanatory power. Overall, our findings suggest that current assumptions regarding the computation of saccadic error may need to be revisited.

  4. [Research on whole blending end-point evaluation method of Angong Niuhuang Wan based on QbD concept]. (United States)

    Liu, Xiao-Na; Zheng, Qiu-Sheng; Che, Xiao-Qing; Wu, Zhi-Sheng; Qiao, Yan-Jiang


    The blending end-point determination of Angong Niuhuang Wan (AGNH) is a key technology problem. The control strategy based on quality by design (QbD) concept proposes a whole blending end-point determination method, and provides a methodology for blending the Chinese materia medica containing mineral substances. Based on QbD concept, the laser induced breakdown spectroscopy (LIBS) was used to assess the cinnabar, realgar and pearl powder blending of AGNH in a pilot-scale experiment, especially the whole blending end-point in this study. The blending variability of three mineral medicines including cinnabar, realgar and pearl powder, was measured by moving window relative standard deviation (MWRSD) based on LIBS. The time profiles of realgar and pearl powder did not produce consistent results completely, but all of them reached even blending at the last blending stage, so that the whole proposal blending end point was determined. LIBS is a promising Process Analytical Technology (PAT) for process control. Unlike other elemental determination technologies such ICP-OES, LIBS does not need an elaborate digestion procedure, which is a promising and rapid technique to understand the blending process of Chinese materia medica (CMM) containing cinnabar, realgar and other mineral traditional Chinese medicine. This study proposed a novel method for the research of large varieties of traditional Chinese medicines.. Copyright© by the Chinese Pharmaceutical Association.

  5. Blend uniformity end-point determination using near-infrared spectroscopy and multivariate calibration. (United States)

    Sulub, Yusuf; Konigsberger, Michele; Cheney, James


    A multivariate calibration approach using near-infrared (NIR) spectroscopy for determining blend uniformity end-point of a pharmaceutical solid dosage form containing 29.4% (w/w) drug load with three major excipients (crospovidone, lactose, and microcrystalline cellulose) is presented. A set of 21 off-line, static calibration samples were used to develop a multivariate partial least-squares (PLS) calibration model for on-line predictions of the API content during the blending process. The concentrations of the API and the three major excipients were varied randomly to minimize correlations between the components. A micro-electrical-mechanical-system (MEMS) based NIR spectrometer was used for this study. To minimize spectral differences between the static and dynamic measurement modes, the acquired NIR spectra were preprocessed using standard normal variate (SNV) followed by second derivative Savitsky-Golay using 21 points. The performance of the off-line PLS calibration model were evaluated in real-time on 67 production scale (750L bin size) blend experiments conducted over 3 years. The real-time API-NIR (%) predictions of all batches ranged from 93.7% to 104.8% with standard deviation ranging from 0.5% to 1.8%. These results showed the attainment of blend homogeneity and were confirmed with content uniformity by HPLC of respective manufactured tablets values ranging from 95.4% to 101.3% with standard deviation ranging from 0.5% to 2.1%. Furthermore, the performance of the PLS calibration model was evaluated against off-target batches manufactured with high and low amounts of water during the granulation phase of production. This approach affects the particle size and hence blending. All the off-target batches exhibited API-NIR (%) predictions of 94.6% to 103.5% with standard deviation ranging from 0.7% to 1.9%. Using off-target data, a systematic approach was developed to determine blend uniformity end-point. This was confirmed with 3 production scale batches

  6. A systematic approach to deep caries removal end points: the peripheral seal concept in adhesive dentistry. (United States)

    Alleman, David S; Magne, Pascal


    The objective of this article is to present evidence-based protocols for the diagnosis and treatment of deep caries lesions in vital teeth. These protocols combine caries-detecting dye with anatomical and histologic knowledge to arrive at ideal caries removal end points for adhesive restorations. DIAGNOdent laser fluorescence technology can also be used to confirm these end points. These ideal caries removal end points generate a peripheral seal zone that can support long-term biomimetic restorations. A review of the published literature since 1980 on caries, caries diagnosis, and caries treatments and their relationships to adhesive bonding techniques was carried out. Combining anatomical measurements and pathologic and histologic knowledge with caries-detecting dye and DIAGNOdent laser fluorescence technologies can produce ideal caries removal end points for adhesive dentistry without exposing vital pulps.

  7. Information resources and the correlation of response patterns between biological end points

    Energy Technology Data Exchange (ETDEWEB)

    Malling, H.V. [National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States); Wassom, J.S. [Oak Ridge National Laboratory, TN (United States)


    This paper focuses on the analysis of information for mutagenesis, a biological end point that is important in the overall process of assessing possible adverse health effects from chemical exposure. 17 refs.

  8. End-point controller design for an experimental two-link flexible manipulator using convex optimization (United States)

    Oakley, Celia M.; Barratt, Craig H.


    Recent results in linear controller design are used to design an end-point controller for an experimental two-link flexible manipulator. A nominal 14-state linear-quadratic-Gaussian (LQG) controller was augmented with a 528-tap finite-impulse-response (FIR) filter designed using convex optimization techniques. The resulting 278-state controller produced improved end-point trajectory tracking and disturbance rejection in simulation and experimentally in real time.

  9. Experimental Study on Surrogate Nuclear Fuel Rods under Reversed Cyclic Bending

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hong [ORNL; Wang, Jy-An John [ORNL


    The mechanical behavior of spent nuclear fuel (SNF) rods under reversed cyclic bending or bending fatigue must be understood to evaluate their vibration integrity in a transportation environment. This is especially important for high-burnup fuels (>45 GWd/MTU), which have the potential for increased structural damage. It has been demonstrated that the bending fatigue of SNF rods can be effectively studied using surrogate rods. In this investigation, surrogate rods made of stainless steel (SS) 304 cladding and aluminum oxide pellets were tested under load or moment control at a variety of amplitude levels at 5 Hz using the Cyclic Integrated Reversible-Bending Fatigue Tester developed at Oak Ridge National Laboratory. The behavior of the rods was further characterized using flexural rigidity and hysteresis data, and fractography was performed on the failed rods. The proposed surrogate rods captured many of the characteristics of deformation and failure mode observed in SNF, including the linear-to-nonlinear deformation transition and large residual curvature in static tests, PPI and PCMI failure mechanisms, and large variation in the initial structural condition. Rod degradation was measured and characterized by measuring the flexural rigidity; the degradation of the rigidity depended on both the moment amplitude applied and the initial structural condition of the rods. It was also shown that a cracking initiation site can be located on the internal surface or the external surface of cladding. Finally, fatigue damage to the bending rods can be described in terms of flexural rigidity, and the fatigue life of rods can be predicted once damage model parameters are properly evaluated. The developed experimental approach, test protocol, and analysis method can be used to study the vibration integrity of SNF rods in the future.

  10. Enumerating Microorganism Surrogates for Groundwater Transport Studies Using Solid-Phase Cytometry. (United States)

    Stevenson, Margaret E; Blaschke, A Paul; Schauer, Sonja; Zessner, Matthias; Sommer, Regina; Farnleitner, Andreas H; Kirschner, Alexander K T


    Investigations on the pollution of groundwater with pathogenic microorganisms, e.g. tracer studies for groundwater transport, are constrained by their potential health risk. Thus, microspheres are often used in groundwater transport studies as non-hazardous surrogates for pathogenic microorganisms. Even though pathogenic microorganisms occur at low concentrations in groundwater, current detection methods of microspheres (spectrofluorimetry, flow cytometry and epifluorescence microscopy) have rather high detection limits and are unable to detect rare events. Solid-phase cytometry (SPC) offers the unique capability of reliably quantifying extremely low concentrations of fluorescently labelled microorganisms or microspheres in natural waters, including groundwater. Until now, microspheres have been used in combination with SPC only for instrument calibration purposes and not for environmental applications. In this study, we explored the limits of the SPC methodology for its applicability to groundwater transport studies. The SPC approach proved to be a highly sensitive and reliable enumeration system for microorganism surrogates down to a minimum size of 0.5 μm, in up to 500 ml of groundwater, and 0.75 μm, in up to 1 ml of turbid surface water. Hence, SPC is proposed to be a useful method for enumerating microspheres for groundwater transport studies in the laboratory, as well as in the field when non-toxic, natural products are used.

  11. Survival End Points for Huntington Disease Trials Prior to a Motor Diagnosis. (United States)

    Long, Jeffrey D; Mills, James A; Leavitt, Blair R; Durr, Alexandra; Roos, Raymund A; Stout, Julie C; Reilmann, Ralf; Landwehrmeyer, Bernhard; Gregory, Sarah; Scahill, Rachael I; Langbehn, Douglas R; Tabrizi, Sarah J


    Predictive genetic testing in Huntington disease (HD) enables therapeutic trials in HTT gene expansion mutation carriers prior to a motor diagnosis. Progression-free survival (PFS) is the composite of a motor diagnosis or a progression event, whichever comes first. To determine if PFS provides feasible sample sizes for trials with mutation carriers who have not yet received a motor diagnosis. This study uses data from the 2-phase, longitudinal cohort studies called Track and from a longitudinal cohort study called the Cooperative Huntington Observational Research Trial (COHORT). Track had 167 prediagnosis mutation carriers and 156 noncarriers, whereas COHORT had 366 prediagnosis mutation carriers and noncarriers. Track studies were conducted at 4 sites in 4 countries (Canada, France, England, and the Netherlands) from which data were collected from January 17, 2008, through November 17, 2014. The COHORT was conducted at 38 sites in 3 countries (Australia, Canada, and the United States) from which data were collected from February 14, 2006, through December 31, 2009. Results from the Track data were externally validated with data from the COHORT. The required sample size was estimated for a 2-arm prediagnosis clinical trial. Data analysis took place from May 1, 2016, to June 10, 2017. The primary end point is PFS. Huntington disease progression events are defined for the Unified Huntington's Disease Rating Scale total motor score, total functional capacity, symbol digit modalities test, and Stroop word test. Of Track's 167 prediagnosis mutation carriers, 93 (55.6%) were women, and the mean (SD) age was 40.06 (8.92) years; of the 156 noncarriers, 87 (55.7%) were women, and the mean (SD) age was 45.58 (10.30) years. Of the 366 COHORT participants, 229 (62.5%) were women and the mean (SD) age was 42.21 (12.48) years. The PFS curves of the Track mutation carriers showed good external validity with the COHORT mutation carriers after adjusting for initial progression. For

  12. Validation of Laboratory Animal and Surrogate Human Models in Primary Blast Injury Studies. (United States)

    Chandra, Namas; Sundaramurthy, Aravind; Gupta, Raj K


    Blast-induced neurotrauma has affected more than 300,000 service members. It is important to understand the effect of single and repeated shock-blast wave exposures on the neuropsychological behavior of soldiers, to offer them better protection, diagnostics, and treatment. Preclinical animal models and helmet design studies on human surrogate models have relied on the use of compression gas-driven shock tubes. Traditional shock tubes are so simple that if not carefully designed and operated, the test results can easily introduce detrimental artifacts clouding the conclusions. In this work, we present live-fire test results of an instrumented human surrogate head-neck model and compare with the data obtained in a carefully designed shock tube. We present various features incorporated in the shock tube design that led to better fidelity between live-fire and laboratory shock-blast conditions. The effect of specimen placement, choice of driver gas, pressure and volume of driver, end-plate conditions, and measurement techniques all determine the successful replication of live-fire loading conditions. These parameters become more important when conducting animal testing as the totality of loading will dictate the injury severity and type which ultimately will determine the mechanisms of blast-induced neurotrauma and hence their prevention and treatment strategies. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

  13. Changes in the Skin Conductance Monitor as an End Point for Sympathetic Nerve Blocks. (United States)

    Gungor, Semih; Rana, Bhumika; Fields, Kara; Bae, James J; Mount, Lauren; Buschiazzo, Valeria; Storm, Hanne


    There is a lack of objective methods for determining the achievement of sympathetic block. This study validates the skin conductance monitor (SCM) as an end point indicator of successful sympathetic blockade as compared with traditional monitors. This interventional study included 13 patients undergoing 25 lumbar sympathetic blocks to compare time to indication of successful blockade between the SCM indices and traditional measures, clinically visible hyperemia, clinically visible engorgement of veins, subjective skin temperature difference, unilateral thermometry monitoring, bilateral comparative thermometry monitoring, and change in waveform amplitude in pulse oximetry plethysmography, within a 30-minute observation period. Differences in the SCM indices were studied pre- and postblock to validate the SCM. SCM showed substantially greater odds of indicating achievement of sympathetic block in the next moment (i.e., hazard rate) compared with all traditional measures (clinically visible hyperemia, clinically visible engorgement of veins, subjective temperature difference, unilateral thermometry monitoring, bilateral comparative thermometry monitoring, and change in waveform amplitude in pulse oximetry plethysmography; P ≤ 0.011). SCM indicated successful block for all (100%) procedures, while the traditional measures failed to indicate successful blocks in 16-84% of procedures. The SCM indices were significantly higher in preblock compared with postblock measurements (P SCM is a more reliable and rapid response indicator of a successful sympathetic blockade when compared with traditional monitors.

  14. Critical care physicians’ approaches to negotiating with surrogate decision makers: a qualitative study (United States)

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


    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

  15. Meta-analyses of randomized controlled trials show suboptimal validity of surrogate outcomes for overall survival in advanced colorectal cancer. (United States)

    Ciani, Oriana; Buyse, Marc; Garside, Ruth; Peters, Jaime; Saad, Everardo D; Stein, Ken; Taylor, Rod S


    To quantify and compare the treatment effects on three surrogate end points, progression-free survival (PFS), time to progression (TTP), and tumor response rate (TR) vs. overall survival (OS) based on a meta-analysis of randomized controlled trials (RCTs) of drug interventions in advanced colorectal cancer (aCRC). We systematically searched for RCTs of pharmacologic therapies in aCRC between 2003 and 2013. Trial characteristics, risk of bias, and outcomes were recorded based on a predefined form. Univariate and multivariate random-effects meta-analyses were used to estimate pooled summary treatment effects. The ratio of hazard ratios (HRs)/odds ratios (ORs) and difference in medians were used to quantify the degree of difference in treatment effects on the surrogate end points and OS. Spearman ρ, surrogate threshold effect (STE), and R(2) were also estimated across predefined trial-level covariates. We included 101 RCTs. In univariate and multivariate meta-analyses, we found larger treatment effects for the surrogates than for OS. Compared with OS, treatment effects were on average 13% higher when HRs were measured and 3% to 45% higher when ORs were considered; differences in median PFS/TTP were higher than on OS by an average of 0.5 month. Spearman ρ ranged from 0.39 to 0.80, mean R(2) from 0.06 to 0.65, and STE was 0.8 for HRPFS, 0.64 for HRTTP, or 0.28 for ORTR. The stratified analyses revealed high variability across all strata. None of the end points in this study were found to achieve the level of evidence (ie, mean R(2)trial > 0.60) that has been set to select high or excellent correlation levels by common surrogate evaluation tools. Previous surrogacy relationships observed between PFS and TTP vs. OS in selected settings may not apply across other classes or lines of therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Systematic adjudication of myocardial infarction end-points in an international clinical trial

    Directory of Open Access Journals (Sweden)

    Lee Kerry L


    Full Text Available Abstract Background Clinical events committees (CEC are used routinely to adjudicate suspected end-points in cardiovascular trials, but little information has been published about the various processes used. We reviewed results of the CEC process used to identify and adjudicate suspected end-point (post-enrolment myocardial infarction (MI in the large Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide Therapy (PURSUIT trial. Methods The PURSUIT trial randomised 10,948 patients with acute coronary syndromes to receive eptifibatide or placebo. A central adjudication process was established prospectively to identify all suspected MIs and adjudicate events based on protocol definitions of MI. Suspected MIs were identified by systematic review of data collection forms, cardiac enzyme results, and electrocardiograms. Two physicians independently reviewed all suspected events. If they disagreed whether a MI had occurred, a committee of cardiologists adjudicated the case. Results The CEC identified 5005 patients with suspected infarction (46%, of which 1415 (28% were adjudicated as end-point infarctions. As expected, the process identified more end-point events than did the site investigators. Absolute and relative treatment effects of eptifibatide were smaller when using CEC-determined MI rates rather than site investigator-determined rates. The site-investigator reporting of MI and the CEC assessment of MI disagreed in 20% of the cases reviewed by the CEC. Conclusions End-point adjudication by a CEC is important, to provide standardised, systematic, independent, and unbiased assessment of end-points, particularly in trials that span geographic regions and clinical practice settings. Understanding the CEC process used is important in the interpretation of trial results and event rates.

  17. An end-point method based on graphene oxide for RNase H analysis and inhibitors screening. (United States)

    Zhao, Chuan; Fan, Jialong; Peng, Lan; Zhao, Lijian; Tong, Chunyi; Wang, Wei; Liu, Bin


    As a highly conserved damage repair protein, RNase H can hydrolysis DNA-RNA heteroduplex endonucleolytically and cleave RNA-DNA junctions as well. In this study, we have developed an accurate and sensitive RNase H assay based on fluorophore-labeled chimeric substrate hydrolysis and the differential affinity of graphene oxide on RNA strand with different length. This end-point measurement method can detect RNase H in a range of 0.01 to 1 units /mL with a detection limit of 5.0×10 -3 units/ mL under optimal conditions. We demonstrate the utility of the assay by screening antibiotics, resulting in the identification of gentamycin, streptomycin and kanamycin as inhibitors with IC 50 of 60±5µM, 70±8µM and 300±20µM, respectively. Furthermore, the assay was reliably used to detect RNase H in complicated biosamples and found that RNase H activity in tumor cells was inhibited by gentamycin and streptomycin sulfate in a concentration-dependent manner. The average level of RNase H in serums of HBV infection group was similar to that of control group. In summary, the assay provides an alternative tool for biochemical analysis for this enzyme and indicates the feasibility of high throughput screening inhibitors of RNase H in vitro and in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Ozonation of diesel-fuel contaminated sand and the implications for remediation end-points. (United States)

    Li, Xingang; Cao, Xingtao; Wu, Guozhong; Temple, Tracey; Coulon, Frédéric; Sui, Hong


    In this study, we investigate specifically the influence of soil grain size and water content on the degradation of n-alkane fractions and the formation of aldehydes and carboxylic acid during ozonation. 15 g of quartz sand spiked with diesel (25 g kg(-1)) were exposed to ozone for 20 h at concentrations of 10, 30 and 50 mg L(-1), respectively. Results indicated that ozonation of the n-alkanes in fine grain size sand (0.15-0.25 mm) was 1.2 times faster than coarse sand due to higher surface contact area between O3 and sand particles. Soil moisture below 18% w/w did not influence the ozonation efficiency. In contrast the ozonation led to an increase of acidity of the sand samples (pH=3.0) after 20 h treatment. This was due to the formation of carboxylic acid. Formaldehyde, one of the key by-products of ozonation, was always sand during the process. Overall the findings demonstrated that not only the alkanes but also aldehydes and carboxylic acid should be considered when defining remediation end-points. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Leveraging Data Fusion Strategies in Multireceptor Lead Optimization MM/GBSA End-Point Methods. (United States)

    Knight, Jennifer L; Krilov, Goran; Borrelli, Kenneth W; Williams, Joshua; Gunn, John R; Clowes, Alec; Cheng, Luciano; Friesner, Richard A; Abel, Robert


    Accurate and efficient affinity calculations are critical to enhancing the contribution of in silico modeling during the lead optimization phase of a drug discovery campaign. Here, we present a large-scale study of the efficacy of data fusion strategies to leverage results from end-point MM/GBSA calculations in multiple receptors to identify potent inhibitors among an ensemble of congeneric ligands. The retrospective analysis of 13 congeneric ligand series curated from publicly available data across seven biological targets demonstrates that in 90% of the individual receptor structures MM/GBSA scores successfully identify subsets of inhibitors that are more potent than a random selection, and data fusion strategies that combine MM/GBSA scores from each of the receptors significantly increase the robustness of the predictions. Among nine different data fusion metrics based on consensus scores or receptor rankings, the SumZScore (i.e., converting MM/GBSA scores into standardized Z-Scores within a receptor and computing the sum of the Z-Scores for a given ligand across the ensemble of receptors) is found to be a robust and physically meaningful metric for combining results across multiple receptors. Perhaps most surprisingly, even with relatively low to modest overall correlations between SumZScore and experimental binding affinities, SumZScore tends to reliably prioritize subsets of inhibitors that are at least as potent as those that are prioritized from a "best" single receptor identified from known compounds within the congeneric series.

  20. Drug release into hydrogel-based subcutaneous surrogates studied by UV imaging

    DEFF Research Database (Denmark)

    Ye, Fengbin; Larsen, Susan Weng; Yaghmur, Anan


    of the performance of drug delivery systems based on in vitro experiments. The objective of this study was to evaluate a UV imaging-based method for real-time characterization of the release and transport of piroxicam in hydrogel-based subcutaneous tissue mimics/surrogates. Piroxicam partitioning from medium chain...... triglyceride (MCT) into 0.5% (w/v) agarose or 25% (w/v) F127-based hydrogels was investigated by monitoring the concentration profiles of the drug in the gels. The effect of pH on piroxicam distribution and diffusion coefficients was studied. For both hydrogel systems, the diffusion of piroxicam in the gels...... upon the injection of aqueous or MCT solutions into an agarose-based hydrogel were investigated by UV imaging. The spatial distribution of piroxicam around the injection site in the gel matrix was monitored in real-time. The disappearance profiles of piroxicam from the injected aqueous solution were...

  1. 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


    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.

  2. Atherosclerotic Surrogate Markers in Adults With Down Syndrome: A Case-Control Study. (United States)

    Parra, Pedro; Costa, Ramón; de Asúa, Diego Real; Moldenhauer, Fernando; Suárez, Carmen


    The authors aimed to compare surrogate markers of atherosclerosis (pulse wave velocity, intima-media thickness) between adults with and without Down syndrome (DS) and to assess the impact of parathyroid hormone levels and classic cardiovascular risk factors on arterial stiffness. After comparing 51 adults with DS and 51 healthy adults (siblings of DS individuals), the authors found that adults with DS seem to have lower arterial stiffness, as a result of chronic hypotension. Subclinical atherosclerosis parameters do not correlate with traditional cardiovascular risk factors in adults with DS, thus raising the hypothesis that classic predictive models for cardiovascular disease are not valid in this population. Hyperparathyroidism could play an important role in arterial damage in these individuals. The lower than expected prevalence of obesity and dyslipidemia could be explained by better eating habits, with this study being the first to address the anthropometric and clinical profile of a Mediterranean cohort of adults with DS. ©2016 Wiley Periodicals, Inc.

  3. Systematic adjudication of myocardial infarction end-points in an international clinical trial.

    NARCIS (Netherlands)

    K.W. Mahaffey (Kenneth); R.A. Harrington (Robert Alex); N.S. Kleiman (Neal); L.G. Berdan (Lisa); B.S. Crenshaw (Brian); B.E. Tardiff (Barbara); C.B. Granger (Christopher); I. DeJong (Ingrid); M. Bhapkar (Manju); P. Widimsky (Petr); R. Corbalon (Ramón); K.L. Lee (Kerry); J.W. Deckers (Jaap); M.L. Simoons (Maarten); E.J. Topol (Eric); R.M. Califf (Robert); K.M. Akkerhuis (Martijn)


    textabstractBACKGROUND: Clinical events committees (CEC) are used routinely to adjudicate suspected end-points in cardiovascular trials, but little information has been published about the various processes used. We reviewed results of the CEC process used to identify and adjudicate suspected

  4. Systematic adjudication of myocardial infarction end-points in an international clinical trial

    NARCIS (Netherlands)

    K.W. Mahaffey (Kenneth); R.A. Harrington (Robert Alex); K.M. Akkerhuis (Martijn); N.S. Kleiman (Neal); L.G. Berdan (Lisa); B.S. Crenshaw (Brian); B.E. Tardiff (Barbara); C.B. Granger (Christopher); I. DeJong (Ingrid); M. Bhapkar (Manju); P. Widimsky (Petr); R. Corbalon (Ramón); K.L. Lee (Kerry); J.W. Deckers (Jaap); M.L. Simoons (Maarten); E.J. Topol (Eric); R.M. Califf (Robert)


    textabstractBackground. Clinical events committees (CEC) are used routinely to adjudicate suspected end-points in cardiovascular trials, but little information has been published about the various processes used. We reviewed results of the CEC process used to identify and adjudicate suspected

  5. Is Chronic Dialysis the Right Hard Renal End Point To Evaluate Renoprotective Drug Effects?

    NARCIS (Netherlands)

    Weldegiorgis, Misghina; de Zeeuw, Dick; Dwyer, Jamie P.; Mol, Peter; Heerspink, Hiddo J. L.


    Background and objectives: RRT and doubling of serum creatinine are considered the objective hard end points in nephrology intervention trials. Because both are assumed to reflect changes in the filtration capacity of the kidney, drug effects, if present, are attributed to kidney protection.

  6. 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

  7. End-of-Life Decisions: A Cross-National Study of Treatment Preference Discussions and Surrogate Decision-Maker Appointments (United States)

    Evans, Natalie; Pasman, H. Roeline; Vega Alonso, Tomás; Van den Block, Lieve; Miccinesi, Guido; Van Casteren, Viviane; Donker, Gé; Bertolissi, Stefano; Zurriaga, Oscar; Deliens, Luc; Onwuteaka-Philipsen, Bregje; EUROIMPACT, on behalf of


    Background Making treatment decisions in anticipation of possible future incapacity is an important part of patient participation in end-of-life decision-making. This study estimates and compares the prevalence of GP-patient end-of-life treatment discussions and patients’ appointment of surrogate decision-makers in Italy, Spain, Belgium and the Netherlands and examines associated factors. Methods A cross-sectional, retrospective survey was conducted with representative GP networks in four countries. GPs recorded the health and care characteristics in the last three months of life of 4,396 patients who died non-suddenly. Prevalences were estimated and logistic regressions were used to examine between country differences and country-specific associated patient and care factors. Results GP-patient discussion of treatment preferences occurred for 10%, 7%, 25% and 47% of Italian, Spanish, Belgian and of Dutch patients respectively. Furthermore, 6%, 5%, 16% and 29% of Italian, Spanish, Belgian and Dutch patients had a surrogate decision-maker. Despite some country-specific differences, previous GP-patient discussion of primary diagnosis, more frequent GP contact, GP provision of palliative care, the importance of palliative care as a treatment aim and place of death were positively associated with preference discussions or surrogate appointments. A diagnosis of dementia was negatively associated with preference discussions and surrogate appointments. Conclusions The study revealed a higher prevalence of treatment preference discussions and surrogate appointments in the two northern compared to the two southern European countries. Factors associated with preference discussions and surrogate appointments suggest that delaying diagnosis discussions impedes anticipatory planning, whereas early preference discussions, particularly for dementia patients, and the provision of palliative care encourage participation. PMID:23472122

  8. End-of-life decisions: a cross-national study of treatment preference discussions and surrogate decision-maker appointments.

    Directory of Open Access Journals (Sweden)

    Natalie Evans

    Full Text Available BACKGROUND: Making treatment decisions in anticipation of possible future incapacity is an important part of patient participation in end-of-life decision-making. This study estimates and compares the prevalence of GP-patient end-of-life treatment discussions and patients' appointment of surrogate decision-makers in Italy, Spain, Belgium and the Netherlands and examines associated factors. METHODS: A cross-sectional, retrospective survey was conducted with representative GP networks in four countries. GPs recorded the health and care characteristics in the last three months of life of 4,396 patients who died non-suddenly. Prevalences were estimated and logistic regressions were used to examine between country differences and country-specific associated patient and care factors. RESULTS: GP-patient discussion of treatment preferences occurred for 10%, 7%, 25% and 47% of Italian, Spanish, Belgian and of Dutch patients respectively. Furthermore, 6%, 5%, 16% and 29% of Italian, Spanish, Belgian and Dutch patients had a surrogate decision-maker. Despite some country-specific differences, previous GP-patient discussion of primary diagnosis, more frequent GP contact, GP provision of palliative care, the importance of palliative care as a treatment aim and place of death were positively associated with preference discussions or surrogate appointments. A diagnosis of dementia was negatively associated with preference discussions and surrogate appointments. CONCLUSIONS: The study revealed a higher prevalence of treatment preference discussions and surrogate appointments in the two northern compared to the two southern European countries. Factors associated with preference discussions and surrogate appointments suggest that delaying diagnosis discussions impedes anticipatory planning, whereas early preference discussions, particularly for dementia patients, and the provision of palliative care encourage participation.

  9. End-point disease investigation for virus strains of intermediate virulence as illustrated by flavivirus infections. (United States)

    Suen, Willy W; Prow, Natalie A; Setoh, Yin X; Hall, Roy A; Bielefeldt-Ohmann, Helle


    Viruses of intermediate virulence are defined as isolates causing an intermediate morbidity/mortality rate in a specific animal model system, involving specific host and inoculation parameters (e.g. dose and route). Therefore, variable disease phenotype may exist between animals that develop severe disease or die and those that are asymptomatic or survive after infection with these isolates. There may also be variability amongst animals within each of these subsets. Such potential variability may confound the use of time-point sacrifice experiments to investigate pathogenesis of this subset of virus strains, as uniformity in disease outcome is a fundamental assumption for time-course sacrifice experiments. In the current study, we examined the disease phenotype, neuropathology, neural infection and glial cell activity in moribund/dead and surviving Swiss white (CD-1) mice after intraperitoneal infection with various Australian flaviviruses, including West Nile virus (WNV) strains of intermediate virulence (WNVNSW2011 and WNVNSW2012), and highly virulent Murray Valley encephalitis virus (MVEV) isolates. We identified notable intragroup variation in the end-point disease in mice infected with either WNVNSW strain, but to a lesser extent in mice infected with MVEV strains. The variable outcomes associated with WNVNSW infection suggest that pathogenesis investigations using time-point sacrifice of WNVNSW-infected mice may not be the best approach, as the assumption of uniformity in outcomes is violated. Our study has therefore highlighted a previously unacknowledged challenge to investigating pathogenesis of virus isolates of intermediate virulence. We have also set a precedent for routine examination of the disease phenotype in moribund/dead and surviving mice during survival challenge experiments.

  10. Effectiveness of Fire and Fire Surrogate Treatments For Controlling Wildfire Behavior in Piedmont Forests: A Simulation Study (United States)

    Helen H. Mohr; Thomas A. Waldrop; Sandra Rideout; Ross J. Phillips; Charles T. Flint


    The need for fuel reduction has increased in United States forests due to decades of fire exclusion. Excessive fuel buildup has led to uncharacteristically severe fires in areas with historically short-interval, low-to-moderate-intensity fire regimes. The National Fire and Fire Surrogate (NFFS) Study compared the impacts of three fuel-reduction treatments on numerous...

  11. End-of-life decisions: a cross-national study of treatment preference discussions and surrogate decision-maker appointments.

    NARCIS (Netherlands)

    Evans, N.; Pasman, H.R.W.; Vega Alonso, T.; Block, L. van den; Miccinesi, G.; Viviane, V.C.; Donker, G.; Bertolissi, S.; Zurriaga, O.; Deliens, L.


    Aim: Making decisions in anticipation of possible future incapacity is part of patient participation in end-of-life decision-making. This study estimates and compares the prevalence of GP-patient end-of-life treatment preference discussions and appointments of surrogate decision-makers in Italy,

  12. Overview of the "epigenetic end points in toxicologic pathology and relevance to human health" session of the 2014 Society Of Toxicologic Pathology Annual Symposium. (United States)

    Hoenerhoff, Mark J; Hartke, James


    The theme of the Society of Toxicologic Pathology 2014 Annual Symposium was "Translational Pathology: Relevance of Toxicologic Pathology to Human Health." The 5th session focused on epigenetic end points in biology, toxicity, and carcinogenicity, and how those end points are relevant to human exposures. This overview highlights the various presentations in this session, discussing integration of epigenetics end points in toxicologic pathology studies, investigating the role of epigenetics in product safety assessment, epigenetic changes in cancers, methodologies to detect them, and potential therapies, chromatin remodeling in development and disease, and epigenomics and the microbiome. The purpose of this overview is to discuss the application of epigenetics to toxicologic pathology and its utility in preclinical or mechanistic based safety, efficacy, and carcinogenicity studies. © 2014 by The Author(s).

  13. Free Energy, Enthalpy and Entropy from Implicit Solvent End-Point Simulations

    Directory of Open Access Journals (Sweden)

    Federico Fogolari


    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.

  14. A Development of a Human Cranial Bone Surrogate for Impact Studies

    Directory of Open Access Journals (Sweden)

    Jack C Roberts


    Full Text Available 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 3-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 seen in pendulum impacts of intact human skulls. 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.

  15. The Experience of Surrogate Decision Makers on Being Approached for Consent for Patient Participation in Research. A Multicenter Study. (United States)

    Burns, Karen E A; Prats, Clara Juando; Maione, Maria; Lanceta, Mary; Zubrinich, Celia; Jeffs, Lianne; Smith, Orla M


    Recruitment in critical care research differs from other contexts in important ways: patients lack decision-making capacity, uncertainty exists regarding patient prognosis, and critical illnesses are often associated with appreciable morbidity and mortality. We aimed to describe the experiences of surrogate decision makers (SDMs) in being approached for consent for critically ill patients to participate in research. A multicenter, qualitative study involving semistructured interviews with 26 SDMs, who provided or declined surrogate consent for research participation, at 5 Canadian centers nested within a multicenter observational study of research recruitment practices. Transcripts were reviewed by three qualitative researchers, and data were analyzed using grounded theory and a narrative critical analysis. SDMs were guided by an overarching desire for the patient to live. Surrogate research decision-making involved three sequential stages: (1) being approached; (2) reflecting on participation; and (3) making a decision. In stage 1, SDMs identified factors (their expectations, how they were approached, the attributes of the person approaching, and study risks and benefits) that characterized their consent encounter and affirmed a preference to be approached in person. If SDMs perceived the risk of participation to be too high or felt patients may not benefit from participation, they did not contemplate further. In stage 2, SDMs who knew the patient's wishes or had a deeper understanding of research prioritized the patient's wishes and the perceived benefits of participation. Without this information, SDMs prioritized obtaining more and better care for the patient, considered what was in their mutual best interests, and valued healthcare professional's knowledge. Trust in healthcare professionals was essential to proceeding further. In stage 3, SDMs considered six factors in rendering decisions. SDMs engaged in three sequential stages and considered six factors in

  16. Cuff filling volumes for pediatric classic laryngeal mask airways: comparison of clinical end points versus adjusted cuff pressure. (United States)

    Ghai, Babita; Sethi, Sameer; Ram, Jagat; Wig, Jyotsna


    Clinical end points are often used to guide inflation and adequacy of cuff seal after laryngeal mask airway placement. However, clinical end points for cuff inflation have been shown to have significantly higher intracuff pressure. The adjusted cuff pressure between 55 and 60 cm H(2)O causes significantly better seal of laryngeal mask airway. We prospectively assessed the cuff pressures generated by cuff inflation guided by clinical end points, and the actual volume of air required to achieve cuff pressures between 55 and 60 cm H(2)O for sizes 1-2.5 reusable classic laryngeal mask airway. Two hundred and three ASA I and II children undergoing elective cataract surgery requiring general anesthesia receiving laryngeal mask airway sizes 1-2.5 were recruited to this study. The laryngeal mask airway was placed using standard technique. After insertion of laryngeal mask airway, the cuff was slowly inflated until a slight outward shift of device was noted. Cuff pressures were measured using calibrated hand held Portex Cuff Inflator Pressure Gauge (Portex Limited, Hythe, Kent, UK). If the cuff pressure was >60 cm H(2)O, the cuff was deflated to achieve a cuff pressure of 55-60 cm H(2)O. The volume of air required to achieve this pressure was recorded. The volume of air required to achieve the pressure between 55 and 60 cm H(2)O in laryngeal mask airway size 1, 1.5, 2.0, and 2.5 were 2.750 ± 0.2565, 4.951 ± 0.5378, 6.927 ± 0.6328, and 10.208 ± 1.4535 ml, respectively. The difference between the initial and the final cuff volumes and pressures in all laryngeal mask airway sizes were statistically significant(P = 0.000). Lower cuff volumes are required to achieve a pressure of 60 cm H(2)O than those required if clinical end points are used as a sole guide for determining cuff inflation for patients receiving pediatric laryngeal mask airways. © 2012 Blackwell Publishing Ltd.

  17. Liquid tissue surrogates for X-ray and CT phantom studies. (United States)

    FitzGerald, Paul F; Colborn, Robert E; Edic, Peter M; Lambert, Jack W; Bonitatibus, Peter J; Yeh, Benjamin M


    kVp were -104 HU (-113 HU) for adipose #3, -87 HU (-90 HU) for adipose #2, 59 HU (55 HU) for liver tissue, and 33 HU (31 HU) for pancreatic tissue; at 120 kVp, these were -83 HU (-83 HU) for adipose #3, -68 HU (-63 HU) for adipose #2, 55 HU (52 HU) for liver tissue, and 35 HU (33 HU) for pancreatic tissue. Our method for formulating tissue surrogates allowed straightforward production of solutions with CT attenuation that closely matched the target tissues' expected CT attenuation values and trends with kVp. The LTSs' inexpensive and widely available constituent chemicals, combined with their liquid state, should enable rapid production and versatile use among different phantom and experiment types. Further study is warranted, such as the inclusion of contrast agents. These liquid tissue surrogates may potentially accelerate development and testing of advanced CT imaging techniques and technologies. © 2017 American Association of Physicists in Medicine.

  18. The effects of Cannabis sativa L. seed (hemp seed) on reproductive and neurobehavioral end points in rats. (United States)

    Yousofi, Másume; Saberivand, Adel; Becker, Lora A; Karimi, Isaac


    This study determined the effects of maternal dietary intake of hemp seed on reproductive and neurobehavioral end points of Wistar rats. Time-mated rats were fed 100% hemp seed (n  =  15), 50% hemp seed (n  =  15) or basal diet (n  =  15) once a day. The amount of food made available was based on control feed consumption records. All dams remained on their respective diets from premating (14 days) throughout gestation and lactation. After weaning, all pups were given their maternal diet until puberty. Mating and delivery weights of dams in all groups did not show significant changes. Number of pregnancies, number and post-natal survival rate of total rat pups, litter size and milk yield were lower in the group that received 100% hemp seed. Offspring that received 50% hemp seed diet expressed reproductive and neurobehavioral end points from a modified Fox battery earlier than rats on 100% hemp seed or basal diet, except acoustic startle results where no differences appeared. In conclusion, this study shows that hemp seed supplementation does not improve the reproductive and neurobehavioral performances of rats. Pregnant women and nursing mothers should be cautious about the using of Cannabis sativa L. byproducts in their diets. Copyright © 2011 Wiley Periodicals, Inc.

  19. Criteria for use of composite end points for competing risks-a systematic survey of the literature with recommendations. (United States)

    Manja, Veena; AlBashir, Siwar; Guyatt, Gordon


    Composite end points are frequently used in reports of clinical trials. One rationale for the use of composite end points is to account for competing risks. In the presence of competing risks, the event rate of a specific event depends on the rates of other competing events. One proposed solution is to include all important competing events in one composite end point. Clinical trialists require guidance regarding when this approach is appropriate. To identify publications describing criteria for use of composite end points for competing risk and to offer guidance regarding when a composite end point is appropriate on the basis of competing risks. We searched MEDLINE, CINAHL, EMBASE, The Cochrane's Central & Systematic Review databases including the Health Technology Assessment database, and the Cochrane's Methodology register from inception to April 2015, and candidate textbooks, to identify all articles providing guidance on this issue. Eligible publications explicitly addressed the issue of a composite outcome to address competing risks. Two reviewers independently screened the titles and abstracts for full-text review; independently reviewed full-text publications; and abstracted specific criteria authors offered for use of composite end points to address competing risks. Of 63,645 titles and abstracts, 166 proved potentially relevant of which 43 publications were included in the final review. Most publications note competing risks as a reason for using composite end points without further elaboration. None of the articles or textbook chapters provide specific criteria for use of composite end points for competing risk. Some advocate using composite end points to avoid bias due to competing risks and others suggest that composite end points seldom or never be used for this purpose. We recommend using composite end points for competing risks only if the competing risk is plausible and if it occurs with sufficiently high frequency to influence the interpretation

  20. Rapid end-point quantitation of prion seeding activity with sensitivity comparable to bioassays.

    Directory of Open Access Journals (Sweden)

    Jason M Wilham


    Full Text Available A major problem for the effective diagnosis and management of prion diseases is the lack of rapid high-throughput assays to measure low levels of prions. Such measurements have typically required prolonged bioassays in animals. Highly sensitive, but generally non-quantitative, prion detection methods have been developed based on prions' ability to seed the conversion of normally soluble protease-sensitive forms of prion protein to protease-resistant and/or amyloid fibrillar forms. Here we describe an approach for estimating the relative amount of prions using a new prion seeding assay called real-time quaking induced conversion assay (RT-QuIC. The underlying reaction blends aspects of the previously described quaking-induced conversion (QuIC and amyloid seeding assay (ASA methods and involves prion-seeded conversion of the alpha helix-rich form of bacterially expressed recombinant PrP(C to a beta sheet-rich amyloid fibrillar form. The RT-QuIC is as sensitive as the animal bioassay, but can be accomplished in 2 days or less. Analogous to end-point dilution animal bioassays, this approach involves testing of serial dilutions of samples and statistically estimating the seeding dose (SD giving positive responses in 50% of replicate reactions (SD(50. Brain tissue from 263K scrapie-affected hamsters gave SD(50 values of 10(11-10(12/g, making the RT-QuIC similar in sensitivity to end-point dilution bioassays. Analysis of bioassay-positive nasal lavages from hamsters affected with transmissible mink encephalopathy gave SD(50 values of 10(3.5-10(5.7/ml, showing that nasal cavities release substantial prion infectivity that can be rapidly detected. Cerebral spinal fluid from 263K scrapie-affected hamsters contained prion SD(50 values of 10(2.0-10(2.9/ml. RT-QuIC assay also discriminated deer chronic wasting disease and sheep scrapie brain samples from normal control samples. In principle, end-point dilution quantitation can be applied to many types of

  1. Imputation of a true endpoint from a surrogate: application to a cluster randomized controlled trial with partial information on the true endpoint

    Directory of Open Access Journals (Sweden)

    Duffy Stephen W


    Full Text Available Abstract Background The Anglia Menorrhagia Education Study (AMES is a randomized controlled trial testing the effectiveness of an education package applied to general practices. Binary data are available from two sources; general practitioner reported referrals to hospital, and referrals to hospital determined by independent audit of the general practices. The former may be regarded as a surrogate for the latter, which is regarded as the true endpoint. Data are only available for the true end point on a sub set of the practices, but there are surrogate data for almost all of the audited practices and for most of the remaining practices. Methods The aim of this paper was to estimate the treatment effect using data from every practice in the study. Where the true endpoint was not available, it was estimated by three approaches, a regression method, multiple imputation and a full likelihood model. Results Including the surrogate data in the analysis yielded an estimate of the treatment effect which was more precise than an estimate gained from using the true end point data alone. Conclusions The full likelihood method provides a new imputation tool at the disposal of trials with surrogate data.

  2. A study of friction mechanisms between a surrogate skin (Lorica soft) and nonwoven fabrics. (United States)

    Cottenden, David J; Cottenden, Alan M


    Hygiene products such as incontinence pads bring nonwoven fabrics into contact with users' skin, which can cause damage in various ways, including the nonwoven abrading the skin by friction. The aim of the work described here was to develop and use methods for understanding the origin of friction between nonwoven fabrics and skin by relating measured normal and friction forces to the nature and area of the contact (fibre footprint) between them. The method development work reported here used a skin surrogate (Lorica Soft) in place of skin for reproducibility. The work was primarily experimental in nature, and involved two separate approaches. In the first, a microscope with a shallow depth of field was used to determine the length of nonwoven fibre in contact with a facing surface as a function of pressure, from which the contact area could be inferred; and, in the second, friction between chosen nonwoven fabrics and Lorica Soft was measured at a variety of anatomically relevant pressures (0.25-32.1kPa) and speeds (0.05-5mms(-1)). Both techniques were extensively validated, and showed reproducibility of about 5% in length and force, respectively. Straightforward inspection of the data for Lorica Soft against the nonwovens showed that Amontons' law (with respect to load) was obeyed to high precision (R(2)>0.999 in all cases), though there was the suggestion of sub-linearity at low loads. More detailed consideration of the friction traces suggested that two different friction mechanisms are important, and comparison with the contact data suggests tentatively that they may correspond to adhesion between two different populations of contacts, one "rough" and one "smooth". This additional insight is a good illustration of how these techniques may prove valuable in studying other, similar interfaces. In particular, they could be used to investigate interfaces between nonwovens and skin, which was the primary motivation for developing them. Copyright © 2013 Elsevier Ltd

  3. Composite End Points in Acute Heart Failure Research: Data Simulations Illustrate the Limitations. (United States)

    Brown, Paul M; Anstrom, Kevin J; Felker, G Michael; Ezekowitz, Justin A


    Composite end points are frequently used in clinical trials of investigational treatments for acute heart failure, eg, to boost statistical power and reduce the overall sample size. By incorporating multiple and varying types of clinical outcomes they provide a test for the overall efficacy of the treatment. Our objective is to compare the performance of popular composite end points in terms of statistical power and describe the uncertainty in these power estimates and issues concerning implementation. We consider several composites that incorporate outcomes of varying types (eg, time to event, categorical, and continuous). Data are simulated for 5 outcomes, and the composites are derived and compared. Power is evaluated graphically while varying the size of the treatment effects, thus describing the sensitivity of power to varying circumstances and eventualities such as opposing effects. The average z score offered the most power, although caution should be exercised when opposing effects are anticipated. Results emphasize the importance of an a priori assessment of power and scientific basis for construction, including the weighting of individual outcomes deduced from data simulations. The interpretation of a composite should be made alongside results from the individual components. The average z score offers the most power, but this should be considered in the research context and is not without its limitations. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  4. Centrifugal multiplexing fixed-volume dispenser on a plastic lab-on-a-disk for parallel biochemical single-end-point assays. (United States)

    La, Moonwoo; Park, Sang Min; Kim, Dong Sung


    In this study, a multiple sample dispenser for precisely metered fixed volumes was successfully designed, fabricated, and fully characterized on a plastic centrifugal lab-on-a-disk (LOD) for parallel biochemical single-end-point assays. The dispenser, namely, a centrifugal multiplexing fixed-volume dispenser (C-MUFID) was designed with microfluidic structures based on the theoretical modeling about a centrifugal circumferential filling flow. The designed LODs were fabricated with a polystyrene substrate through micromachining and they were thermally bonded with a flat substrate. Furthermore, six parallel metering and dispensing assays were conducted at the same fixed-volume (1.27 μl) with a relative variation of ±0.02 μl. Moreover, the samples were metered and dispensed at different sub-volumes. To visualize the metering and dispensing performances, the C-MUFID was integrated with a serpentine micromixer during parallel centrifugal mixing tests. Parallel biochemical single-end-point assays were successfully conducted on the developed LOD using a standard serum with albumin, glucose, and total protein reagents. The developed LOD could be widely applied to various biochemical single-end-point assays which require different volume ratios of the sample and reagent by controlling the design of the C-MUFID. The proposed LOD is feasible for point-of-care diagnostics because of its mass-producible structures, reliable metering/dispensing performance, and parallel biochemical single-end-point assays, which can identify numerous biochemical.

  5. Surrogate variable analysis using partial least squares (SVA-PLS) in gene expression studies. (United States)

    Chakraborty, Sutirtha; Datta, Somnath; Datta, Susmita


    In a typical gene expression profiling study, our prime objective is to identify the genes that are differentially expressed between the samples from two different tissue types. Commonly, standard analysis of variance (ANOVA)/regression is implemented to identify the relative effects of these genes over the two types of samples from their respective arrays of expression levels. But, this technique becomes fundamentally flawed when there are unaccounted sources of variability in these arrays (latent variables attributable to different biological, environmental or other factors relevant in the context). These factors distort the true picture of differential gene expression between the two tissue types and introduce spurious signals of expression heterogeneity. As a result, many genes which are actually differentially expressed are not detected, whereas many others are falsely identified as positives. Moreover, these distortions can be different for different genes. Thus, it is also not possible to get rid of these variations by simple array normalizations. This both-way error can lead to a serious loss in sensitivity and specificity, thereby causing a severe inefficiency in the underlying multiple testing problem. In this work, we attempt to identify the hidden effects of the underlying latent factors in a gene expression profiling study by partial least squares (PLS) and apply ANCOVA technique with the PLS-identified signatures of these hidden effects as covariates, in order to identify the genes that are truly differentially expressed between the two concerned tissue types. We compare the performance of our method SVA-PLS with standard ANOVA and a relatively recent technique of surrogate variable analysis (SVA), on a wide variety of simulation settings (incorporating different effects of the hidden variable, under situations with varying signal intensities and gene groupings). In all settings, our method yields the highest sensitivity while maintaining relatively

  6. End-Point Contact Force Control with Quantitative Feedback Theory for Mobile Robots

    Directory of Open Access Journals (Sweden)

    Shuhuan Wen


    Full Text Available Robot force control is an important issue for intelligent mobile robotics. The end-point stiffness of a robot is a key and open problem in the research community. The control strategies are mostly dependent on both the specifications of the task and the environment of the robot. Due to the limited stiffness of the end-effector, we may adopt inherent torque to feedback the oscillations of the controlled force. This paper proposes an effective control strategy which contains a controller using quantitative feedback theory. The nested loop controllers take into account the physical limitation of the system's inner variables and harmful interference. The biggest advantage of the method is its simplicity in both the design process and the implementation of the control algorithm in engineering practice. Taking the one-link manipulator as an example, numerical experiments are carried out to verify the proposed control method. The results show the satisfactory performance.

  7. Infrared interference patterns for new capabilities in laser end point detection

    CERN Document Server

    Heason, D J


    Standard laser interferometry is used in dry etch fabrication of semiconductor and MEMS devices to measure etch depth, rate and to detect the process end point. However, many wafer materials, such as silicon are absorbing at probing wavelengths in the visible, severely limiting the amount of information that can be obtained using this technique. At infrared (IR) wavelengths around 1500 nm and above, silicon is highly transparent. In this paper we describe an instrument that can be used to monitor etch depth throughout a thru-wafer etch. The provision of this information could eliminate the requirement of an 'etch stop' layer and improve the performance of fabricated devices. We have added a further new capability by using tuneable lasers to scan through wavelengths in the near IR to generate an interference pattern. Fitting a theoretical curve to this interference pattern gives in situ measurement of film thickness. Whereas conventional interferometry would only allow etch depth to be monitored in real time, ...

  8. Initial experiments on the end-point control of a flexible one-link robot (United States)

    Cannon, R. H., Jr.; Schmitz, E.


    The present investigation is concerned with initial experiments regarding a specific unsolved control problem which appeared to be central to advances in the art of robotics. This problem involves the control of a flexible member (one link of a robot system). The position of the end-effector, called the end point or tip, is controlled by measuring that position and using the measurement as a basis for applying control torque to the other end of the flexible member, as for instance, the robot's elbow joint. A description is presented of the features of the first experimental arm which has been made, and an outline is provided of the general strategy for controlling it using its tip sensor and shoulder torquer.

  9. The Japanese Quail as an avian model for testing endocrine disrupting chemicals: endocrine and behavioral end points (United States)

    Ottinger, M.A.; Abdelnabi, M.A.; Thompson, N.; Wu, J.; Henry, K.; Humphries, E.; Henry, P.F.P.


    Birds have extremely varied reproductive strategies. As such, the impact of endocrine disrupting chemicals (EDCs) can greatly differ across avian species. Precocial species, such as Japanese quail appear to be most sensitive to EDC effects during embryonic development, particularly sexual differentiation. A great deal is known about the ontogeny of Japanese quail (Coturnix japonica) relative to endocrine, neuro-endocrine, and behavioral components of reproduction. Therefore, this species provides an excellent model for understanding effects of EDCs on reproductive biology with exposure at specific stages of the life cycle. The purpose of these experiments was to conduct a 1- or 2- generation experiment with positive or negative control chemicals and to determine changes in selected end points. Japanese quail embryos were exposed to estradiol benzoate (EB; positive control) in a 2-generation design or to fadrozole (FAD; negative control) in a 1-generation design. Embryonic EB treatment resulted in significant reductions (pbehaviors as well as increased lag time (26 vs 148 sec; control vs EB) in behavioral tests. Fadrozole exposure resulted in reduced hatchability of fertile eggs, particularly at higher doses. There were no significant effects on courtship and mating behavior of males although males showed an increased lag time in their responses, nally, a behavioral test for studying motor and fear responses in young chicks was used; chicks exposed to an estrogenic pesticide (methoxychlor) showed some deficits. In summary, the use of appropriate and reliable end points that are responsive to endocrine disruption are critical for assessment of EDCs. Supported in part by EPA grant R826134.

  10. Surrogate alcohol drinking in Estonia. (United States)

    Pärna, Kersti; Leon, David A


    Surrogate, nonbeverage alcohols, provide a cheap and concentrated source of ethanol for drinking that has been associated with premature mortality. The aim of this study was to provide the first estimate of the prevalence of surrogate alcohol consumption in a national population sample of Estonia. The Estonian Health Interview Survey conducted in 2006 to 2007 was a nationally representative sample of the population aged 15 to 84 years (N = 6,370). The age-standardized percentage prevalences of ever having drunk surrogates were estimated. The association of age, ethnicity, and education with the prevalence of surrogate drinking was estimated using logistic regression. Of all respondents who reported drinking at least once in their lifetime (N = 5,423), 65% had consumed alcohol during the previous 4 weeks. In this group (N = 3,525), the age-standardized prevalence rate of surrogate drinking was 1.4% (2.3% men, 0.3% women). Among men, surrogate drinking was rare under the age of 35 years (0.3%). Ethnicity and education were both related to surrogate drinking: relative to Estonian men, non-Estonians (mainly Russians) had an odds ratio (OR) for surrogate drinking (adjusted for age and education) of 2.58 (95% CI 1.41, 4.72), while relative to those with higher education those with secondary education had an OR (adjusted for age and ethnicity) of 2.28 (0.78, 6.67) and those with basic education an OR of 3.91 (1.29, 11.84). Surrogate alcohols are drunk in Estonia, particularly among men. This behavior shows pronounced variation in prevalence by ethnicity and education. Reducing consumption of these substances needs to be part of any strategy to reduce the burden of alcohol-related problems in Estonia today. Copyright © 2011 by the Research Society on Alcoholism.

  11. Reporting Clinical End Points and Safety Events in an Acute Coronary Syndrome Trial: Results With Integrated Collection. (United States)

    Guimarães, Patrícia O; Lopes, Renato D; Stevens, Susanna R; Zimerman, André; Wruck, Lisa; James, Stefan K; Haque, Ghazala; Giraldez, Roberto Rocha C V; Alexander, John H; Alexander, Karen P


    End points and adverse events (AEs) are collected separately in clinical trials, yet regulatory requirements for serious AE reporting vary across regions, so classifying end points according to seriousness criteria can be useful in global trials. In the Apixaban for Prevention of Acute Ischemic Events 2 (APPRAISE-2) trial, patients with a recent acute coronary syndrome were randomized to apixaban or placebo for the prevention of recurrent ischemic events. Suspected end points (myocardial infarction, stroke, or bleeding) were adjudicated by an independent clinical events classification committee. Safety criteria were collected for suspected end points and AEs. Patient-level event rates per 100 patient-days of follow-up, modeled using Poisson regression, explored the influence of region and patient characteristics on event reporting. Overall, 13 909 events were reported by 858 sites in 39 countries; 8.4% (n=1166) were suspected end points, and 91.6% (n=12 743) were AEs. Overall, 66.0% of suspected end points were confirmed by the clinical events classification committee. Most clinical events classification committee-confirmed end points met criteria to be classified as serious (94.0%); many clinical events classification committee-negated end points also did (63.2%), but fewer AEs met seriousness criteria (17.9%). The most common seriousness criterion was hospitalization (79.9%, n=2594). Region explained 28.7% of end point- and 26.4% of serious AE-reporting variation, and patient characteristics explained an additional 25.4% of end point and 13.4% of serious AE variation. Nonserious AE-reporting variation was not explained by adjustment. An integrated collection of end points and serious AEs is feasible in a multinational trial and illustrates the shared characteristics of events. Tailoring event collection to fit the phase and purpose of the trial is achievable and informative. URL: Unique identifier: NCT00831441. © 2017 The

  12. Regression with Small Data Sets: A Case Study using Code Surrogates in Additive Manufacturing

    Energy Technology Data Exchange (ETDEWEB)

    Kamath, C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Fan, Y. J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)


    There has been an increasing interest in recent years in the mining of massive data sets whose sizes are measured in terabytes. While it is easy to collect such large data sets in some application domains, there are others where collecting even a single data point can be very expensive, so the resulting data sets have only tens or hundreds of samples. For example, when complex computer simulations are used to understand a scientific phenomenon, we want to run the simulation for many different values of the input parameters and analyze the resulting output. The data set relating the simulation inputs and outputs is typically quite small, especially when each run of the simulation is expensive. However, regression techniques can still be used on such data sets to build an inexpensive \\surrogate" that could provide an approximate output for a given set of inputs. A good surrogate can be very useful in sensitivity analysis, uncertainty analysis, and in designing experiments. In this paper, we compare different regression techniques to determine how well they predict melt-pool characteristics in the problem domain of additive manufacturing. Our analysis indicates that some of the commonly used regression methods do perform quite well even on small data sets.

  13. Modeling study of impact of water on carbon monoxide, PAH and nitrogen oxide emissions from combustion of surrogate fuel (United States)

    Elsinawi, Abdulaziz H.

    Methods for reducing emissions are required to meet the new and increasingly stringent emission regulations for diesel engines. Water-emulsified fuel is one of the few promising emission reduction techniques with the potential to simultaneously reduce NOX and soot in diesel engines. Even though a better understanding could be obtained by modeling the processes involved, little effort has been directed toward modeling the combustion of water-in-fuel emulsion. This dissertation provides a better understanding of the effects of the presence of water in fuel in the form of emulsion on spray combustion and pollutant emissions, namely NOX, soot, and carbon monoxide by modeling the relevant processes and focusing on the variables behind the emission reduction and performance. The modeling study was performed using the commercially available software package CFD-ACE+ to simulate spray combustion at conditions relevant to diesel engines. Surrogate fuel (80% n-heptane and 20% toluene) was used instead of the conventional diesel fuel because the detailed kinetic and thermodynamic data needed for modeling is available for this surrogate fuel but not available for diesel. An emulsified fuel with 3, 5, 8 and 15% water by volume was used as an engine feed for each separate run and the results are compared with that of the dry surrogate fuel with 0% water. The modeling results are also validated against experimental data for 2-stroke diesel engines available in the literature [1]. The modeling results show that water had a significant effect on reducing engine operating temperature, NOX and the formation of soot precursors. However, the reduction of NOX and soot formation is at the expense of an increase in carbon monoxide (CO) emissions and elongated ignition delay time, which is disadvantageous for the steady running of diesel engines.

  14. CaFE: a tool for binding affinity prediction using end-point free energy methods. (United States)

    Liu, Hui; Hou, Tingjun


    Accurate prediction of binding free energy is of particular importance to computational biology and structure-based drug design. Among those methods for binding affinity predictions, the end-point approaches, such as MM/PBSA and LIE, have been widely used because they can achieve a good balance between prediction accuracy and computational cost. Here we present an easy-to-use pipeline tool named Calculation of Free Energy (CaFE) to conduct MM/PBSA and LIE calculations. Powered by the VMD and NAMD programs, CaFE is able to handle numerous static coordinate and molecular dynamics trajectory file formats generated by different molecular simulation packages and supports various force field parameters. CaFE source code and documentation are freely available under the GNU General Public License via GitHub at It is a VMD plugin written in Tcl and the usage is platform-independent. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail:

  15. Can in vitro assessment provide relevant end points for cognitive drug programs? (United States)

    Albensi, Benedict C


    Several start-up biotechnology companies have been created with the primary intent of developing cognitive enhancers. In addition, established pharmaceutical companies also frequently focus their efforts on cognitive drug discovery. In many instances, the rationale and evidence for these endeavors are based largely on in vitro assessments. In particular, the experimental paradigm, know as long-term potentiation (LTP), a cellular model of synaptic plasticity and memory encoding, is being increasing used preclinically for assessing potential nootropic drugs in vitro. Central to this thinking is the idea that the modulation of LTP and/or glutamate receptors are the key criteria that must be met for the development of cognitive enhancers. However, programs targeting the NMDA receptor, a glutamate receptor subtype, over the years have been less than fruitful. In addition, skeptics criticize the relevance of some in vitro tests such as LTP for simulating human cognitive function. Given these considerations, one may wonder if in vitro assessments in general, and the LTP paradigm in particular, provide relevant end points for cognitive drug discovery and development programs. The focus of this article is to address this question and to present evidence as to why in vitro assessment is still critical to the success of any cognitive drug program.

  16. Fish fins as non-lethal surrogates for muscle tissues in freshwater food web studies using stable isotopes. (United States)

    Hette Tronquart, Nicolas; Mazeas, Laurent; Reuilly-Manenti, Liana; Zahm, Amandine; Belliard, Jérôme


    Dorsal white muscle is the standard tissue analysed in fish trophic studies using stable isotope analyses. However, sampling white muscle often implies the sacrifice of fish. Thus, we examined whether the non-lethal sampling of fin tissue can substitute muscle sampling in food web studies. Analysing muscle and fin δ(15)N and δ(13)C values of 466 European freshwater fish (14 species) with an elemental analyser coupled with an isotope ratio mass spectrometer, we compared the isotope values of the two tissues. Correlations between fin and muscle isotope ratios were examined for all fish together and specifically for 12 species. We further proposed four methods of assessing muscle from fin isotope ratios and estimated the errors made using these muscle surrogates. Despite significant differences between isotope values of the two tissues, fin and muscle isotopic signals are strongly correlated. Muscle values, estimated with raw fin isotope ratios (1st method), induce an error of ca. 1‰ for both isotopes. In comparison, specific (2nd method) or general (3rd method) correlations provide meaningful corrections of fin isotope ratios (errors muscle estimates (errors >0.8‰). There is little chance that a global model can be created. However, the 2nd and 3rd methods of estimating muscle values from fin isotope ratios should provide an acceptable level of error for the studies of European freshwater food web. We thus recommend that future studies use fin tissue as a non-lethal surrogate for muscle. Copyright © 2012 John Wiley & Sons, Ltd.

  17. The Teratogenic Potencies of Valproic Acid Derivatives and Their Effects on Biological End-points are Related to Changes in Histone Deacetylase and Erk1/2 Activities

    DEFF Research Database (Denmark)

    Gotfryd, Kamil; Hansen, Maria; Kawa, Anna


    Valproic acid (VPA) is a known teratogen. In the present study, the effects of VPA and seven VPA derivatives with different teratogenic potencies (isobutyl-, 5-methyl-, ethyl-, propyl-, butyl-, pentyl- and hexyl-4-yn-VPA) were investigated in L929 cells in vitro. Evaluated end-points included...... associated with the teratogenic potencies of the VPA derivatives. However, in contrast to changes in Erk1/2 phosphorylation and H3 acetylation, significant changes in GSK-3ß phosphorylation could only be obtained in response to prolonged incubation at high drug concentration. There was an association between...... changes in H3 acetylation and GSK-3ß-Tyr216 phosphorylation, whereas none of these end-points were associated with changes in Erk1/2 phosphorylation. These results suggest that the teratogenic potencies of VPA and VPA derivatives are related to effects on both Erk1/2 and histone deacetylase activities...

  18. Using a gel/plastic surrogate to study the biomechanical response of the head under air shock loading: a combined experimental and numerical investigation. (United States)

    Zhu, Feng; Wagner, Christina; Dal Cengio Leonardi, Alessandra; Jin, Xin; Vandevord, Pamela; Chou, Clifford; Yang, King H; King, Albert I


    A combined experimental and numerical study was conducted to determine a method to elucidate the biomechanical response of a head surrogate physical model under air shock loading. In the physical experiments, a gel-filled egg-shaped skull/brain surrogate was exposed to blast overpressure in a shock tube environment, and static pressures within the shock tube and the surrogate were recorded throughout the event. A numerical model of the shock tube was developed using the Eulerian approach and validated against experimental data. An arbitrary Lagrangian-Eulerian (ALE) fluid-structure coupling algorithm was then utilized to simulate the interaction of the shock wave and the head surrogate. After model validation, a comprehensive series of parametric studies was carried out on the egg-shaped surrogate FE model to assess the effect of several key factors, such as the elastic modulus of the shell, bulk modulus of the core, head orientation, and internal sensor location, on pressure and strain responses. Results indicate that increasing the elastic modulus of the shell within the range simulated in this study led to considerable rise of the overpressures. Varying the bulk modulus of the core from 0.5 to 2.0 GPa, the overpressure had an increase of 7.2%. The curvature of the surface facing the shock wave significantly affected both the peak positive and negative pressures. Simulations of the head surrogate with the blunt end facing the advancing shock front had a higher pressure compared to the simulations with the pointed end facing the shock front. The influence of an opening (possibly mimicking anatomical apertures) on the peak pressures was evaluated using a surrogate head with a hole on the shell of the blunt end. It was revealed that the presence of the opening had little influence on the positive pressures but could affect the negative pressure evidently.

  19. AUA White Paper on Nonneurogenic Chronic Urinary Retention: Consensus Definition, Treatment Algorithm, and Outcome End Points. (United States)

    Stoffel, John T; Peterson, Andrew C; Sandhu, Jaspreet S; Suskind, Anne M; Wei, John T; Lightner, Deborah J


    The AUA (American Urological Association) QIPS (Quality Improvement and Patient Safety) committee created a white paper on the diagnosis and management of nonneurogenic chronic urinary retention. Recommendations for the white paper were based on a review of the literature and consensus expert opinion from the workgroup. The workgroup defined nonneurogenic chronic urinary retention as an elevated post-void residual of greater than 300 mL that persisted for at least 6 months and documented on 2 or more separate occasions. It is proposed that chronic urinary retention should be categorized by risk (high vs low) and symptomatology (symptomatic versus asymptomatic). High risk chronic urinary retention was defined as hydronephrosis on imaging, stage 3 chronic kidney disease or recurrent culture proven urinary tract infection or urosepsis. Symptomatic chronic urinary retention was defined as subjectively moderate to severe urinary symptoms impacting quality of life and/or a recent history of catheterization. A treatment algorithm was developed predicated on stratifying patients with chronic urinary retention first by risk and then by symptoms. The proposed 4 primary outcomes that should be assessed to determine effectiveness of retention treatment are 1) symptom improvement, 2) risk reduction, 3) successful trial of voiding without catheterization, and 4) stability of symptoms and risk over time. Defining and categorizing nonneurogenic chronic urinary retention, creating a treatment algorithm and proposing treatment end points will hopefully spur comparative research that will ultimately lead to a better understanding of this challenging condition. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  20. In vitro study of thimerosal reactions in human whole blood and plasma surrogate samples. (United States)

    Trümpler, Stefan; Meermann, Björn; Nowak, Sascha; Buscher, Wolfgang; Karst, Uwe; Sperling, Michael


    Because of its bactericidal and fungicidal properties, thimerosal is used as a preservative in drugs and vaccines and is thus deliberately injected into the human body. In aqueous environment, it decomposes into thiosalicylic acid and the ethylmercury cation. This organomercury fragment is a potent neurotoxin and is suspected to have similar toxicity and bioavailability like the methylmercury cation. In this work, human whole blood and physiological simulation solutions were incubated with thimerosal to investigate its behaviour and binding partners in the blood stream. Inductively coupled plasma with optical emission spectrometry (ICP-OES) was used for total mercury determination in different blood fractions, while liquid chromatography (LC) coupled to electrospray ionisation time-of-flight (ESI-TOF) and inductively coupled plasma-mass spectrometry (ICP-MS) provided information on the individual mercury species in plasma surrogate samples. Analogous behaviour of methylmercury and ethylmercury species in human blood was shown and an ethylmercury-glutathione adduct was identified. Copyright © 2014 Elsevier GmbH. All rights reserved.

  1. Using serum urate as a validated surrogate end point for flares in patients with gout: protocol for a systematic review and meta-regression analysis

    NARCIS (Netherlands)

    Morillon, M.B.; Stamp, L.; Taylor, W.; Fransen, J.; Dalbeth, N.; Singh, J.A.; Christensen, R.; Lassere, M.


    INTRODUCTION: Gout is the most common inflammatory arthritis in men over 40 years of age. Long-term urate-lowering therapy is considered a key strategy for effective gout management. The primary outcome measure for efficacy in clinical trials of urate-lowering therapy is serum urate levels,

  2. A two-step experimental design for a sediment bioassay using growth of the amphipod Hyalella azteca for the test end point (United States)

    Kubitz, Jody A.; Besser, John M.; Giesy, John P.


    We designed a sediment bioassay using 25% growth inhibition of Hyalella azteca as the end point.Hyalella azteca exhibits size-specific fecundity, so growth is a surrogate of reproductive production. We investigated density effects on growth to address whether crowding could affect test interpretation; amphipods in 14,000/m2 exposures were 16 to 20% smaller than those at 7,000/m2. Using power analysis, we found that 20 to 25 samples are required to determine significance when α = 0.10 and 1 − β = 0.90. To minimize the need for laboratory resources, we designed a two-step (screening and confirmatory) bioassay, which we tested with field-collected sediments. The screening bioassay compared 11 sediments to a reference. Three sediments were “toxic” (significant growth inhibition when 1 − β = 0.66 and n = 5), five sediments were “nontoxic” (>90% of reference), and three sediments were “possibly toxic” (growth inhibition was insignificant). In the confirmatory bioassay, three possibly toxic and two nontoxic samples were reevaluated. Two were toxic (1 − β = 0.91 and n = 20), and the remaining four samples were nontoxic. In summary, five sediments were toxic and six sediments were nontoxic. The two-step analysis used minimal laboratory resources but maximized statistical power, where needed, to discriminate growth effects.

  3. Experimental study of thermo-mechanical behavior of SiC composite tubing under high temperature gradient using solid surrogate

    Energy Technology Data Exchange (ETDEWEB)

    Alva, Luis; Shapovalov, Kirill [University of South Carolina, Mechanical Engineering Department (United States); Jacobsen, George M.; Back, Christina A. [General Atomics (United States); Huang, Xinyu, E-mail: [University of South Carolina, Mechanical Engineering Department (United States)


    Nuclear grade silicon carbide fiber (SiC{sub f}) reinforced silicon carbide matrix (SiC{sub m}) composite is a promising candidate material for accident tolerance fuel (ATF) cladding. A major challenge is ensuring the mechanical robustness of the ceramic cladding under accident conditions. In this work the high temperature mechanical response of a SiC{sub f}–SiC{sub m} composite tubing is studied using a novel thermo-mechanical test method. A solid surrogate tube is placed within and bonded to the SiC{sub f}–SiC{sub m} sample tube using a ceramic adhesive. The bonded tube pair is heated from the center using a ceramic glower. During testing, the outer surface temperature of the SiC sample tube rises up to 1274 K, and a steep temperature gradient develops through the thickness of the tube pair. Due to CTE mismatch and the temperature gradient, the solid surrogate tube induces high tensile stress in the SiC sample. During testing, 3D digital image correlation (DIC) method is used to map the strains on the outer surface of the SiC-composite, and acoustic emissions (AE) are monitored to detect the onset and progress of material damage. The thermo-mechanical behavior of SiC-composite sample is compared with that of monolithic SiC samples. Finite element models are developed to estimate stress–strain distribution within the tube assembly. Model predicted surface strain matches the measured surface strain using the DIC method. AE activities indicated a progressive damage process for SiC{sub f}–SiC{sub m} composite samples. For the composites tested in this study, the threshold mechanical hoop strain for matrix micro-cracking to initiate in SiC{sub f}–SiC{sub m} sample is found to be ∼300 microstrain.

  4. Validity of early MRI structural damage end points and potential impact on clinical trial design in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Baker, Joshua F; Conaghan, Philip G; Emery, Paul


    OBJECTIVE: To evaluate the construct validity of the rheumatoid arthritis MRI score (RAMRIS) erosion evaluation as structural damage end point and to assess the potential impact of incorporation in clinical trials. METHODS: In a randomised trial of early methotrexate-naïve RA (GO-BEFORE), RAMRIS ...

  5. Page 1 88 K. C. MoHAN RAO AND P. R. NAIDU exact end-point was ...

    Indian Academy of Sciences (India)

    exact end-point was determined either by calculation method” or by locating the maxima on first derivative curve. Amounts of acridine ranging from. 45–90 mg were estimated by this method and the results are presented in. Table I. TABLE I. Potentiometric titration of acridine. Amount (X 10-4 gm). SAASAASAASAA ...

  6. Surrogate Model Application to the Identification of Optimal Groundwater Exploitation Scheme Based on Regression Kriging Method-A Case Study of Western Jilin Province. (United States)

    An, Yongkai; Lu, Wenxi; Cheng, Weiguo


    This paper introduces a surrogate model to identify an optimal exploitation scheme, while the western Jilin province was selected as the study area. A numerical simulation model of groundwater flow was established first, and four exploitation wells were set in the Tongyu county and Qian Gorlos county respectively so as to supply water to Daan county. Second, the Latin Hypercube Sampling (LHS) method was used to collect data in the feasible region for input variables. A surrogate model of the numerical simulation model of groundwater flow was developed using the regression kriging method. An optimization model was established to search an optimal groundwater exploitation scheme using the minimum average drawdown of groundwater table and the minimum cost of groundwater exploitation as multi-objective functions. Finally, the surrogate model was invoked by the optimization model in the process of solving the optimization problem. Results show that the relative error and root mean square error of the groundwater table drawdown between the simulation model and the surrogate model for 10 validation samples are both lower than 5%, which is a high approximation accuracy. The contrast between the surrogate-based simulation optimization model and the conventional simulation optimization model for solving the same optimization problem, shows the former only needs 5.5 hours, and the latter needs 25 days. The above results indicate that the surrogate model developed in this study could not only considerably reduce the computational burden of the simulation optimization process, but also maintain high computational accuracy. This can thus provide an effective method for identifying an optimal groundwater exploitation scheme quickly and accurately.

  7. Single strain isolation method for cell culture-adapted hepatitis C virus by end-point dilution and infection.

    Directory of Open Access Journals (Sweden)

    Nao Sugiyama

    Full Text Available The hepatitis C virus (HCV culture system has enabled us to clarify the HCV life cycle and essential host factors for propagation. However, the virus production level of wild-type JFH-1 (JFH-1/wt is limited, and this leads to difficulties in performing experiments that require higher viral concentrations. As the cell culture-adapted JFH-1 has been reported to have robust virus production, some mutations in the viral genome may play a role in the efficiency of virus production. In this study, we obtained cell culture-adapted virus by passage of full-length JFH-1 RNA-transfected Huh-7.5.1 cells. The obtained virus produced 3 log-fold more progeny viruses as compared with JFH-1/wt. Several mutations were identified as being responsible for robust virus production, but, on reverse-genetics analysis, the production levels of JFH-1 with these mutations did not reach the level of cell culture-adapted virus. By using the single strain isolation method by end-point dilution and infection, we isolated two strains with additional mutations, and found that these strains have the ability to produce more progeny viruses. On reverse-genetics analysis, the strains with these additional mutations were able to produce robust progeny viruses at comparable levels as cell culture-adapted JFH-1 virus. The strategy used in this study will be useful for identifying strains with unique characteristics, such as robust virus production, from a diverse population, and for determining the responsible mutations for these characteristics.

  8. UST-ID robotics: Wireless communication and minimum conductor technology, and end-point tracking technology surveys

    Energy Technology Data Exchange (ETDEWEB)

    Holliday, M.A.


    This report is a technology review of the current state-of-the-art in two technologies applicable to the Underground Storage Tank (UST) program at the Hanford Nuclear Reservation. The first review is of wireless and minimal conductor technologies for in-tank communications. The second review is of advanced concepts for independent tool-point tracking. This study addresses the need to provide wireless transmission media or minimum conductor technology for in-tank communications and robot control. At present, signals are conducted via contacting transmission media, i.e., cables. Replacing wires with radio frequencies or invisible light are commonplace in the communication industry. This technology will be evaluated for its applicability to the needs of robotics. Some of these options are radio signals, leaky coax, infrared, microwave, and optical fiber systems. Although optical fiber systems are contacting transmission media, they will be considered because of their ability to reduce the number of conductors. In this report we will identify, evaluate, and recommend the requirements for wireless and minimum conductor technology to replace the present cable system. The second section is a technology survey of concepts for independent end-point tracking (tracking the position of robot end effectors). The position of the end effector in current industrial robots is determined by computing that position from joint information, which is basically a problem of locating a point in three-dimensional space. Several approaches are presently being used in industrial robotics, including: stereo-triangulation with a theodolite network and electrocamera system, photogrammetry, and multiple-length measurement with laser interferometry and wires. The techniques that will be evaluated in this survey are advanced applications of the aforementioned approaches. These include laser tracking (3-D and 5-D), ultrasonic tracking, vision-guided servoing, and adaptive robotic visual tracking.

  9. Comparison of first, last, and longest-held jobs as surrogates for all jobs in estimating cumulative exposure in cross-sectional studies of work-related asthma

    NARCIS (Netherlands)

    Benke, Geza; Sim, Malcolm R.; McKenzie, Dean P.; Macfarlane, Ewan; del Monaco, Anthony; Hoving, Jan L.; Fritschi, Lin


    BACKGROUND: Previous occupational studies have used exposure in most recent job as a Surrogate for all jobs or "total work history" exposure. This method may not be valid for diseases in which disability brought on by one job may influence later work history, such as asthma. We investigated

  10. Total Acid Value Titration of Hydrotreated Biomass Fast Pyrolysis Oil: Determination of Carboxylic Acids and Phenolics with Multiple End-Point Detection

    Energy Technology Data Exchange (ETDEWEB)

    Christensen, E.; Alleman, T. L.; McCormick, R. L.


    Total acid value titration has long been used to estimate corrosive potential of petroleum crude oil and fuel oil products. The method commonly used for this measurement, ASTM D664, utilizes KOH in isopropanol as the titrant with potentiometric end point determination by pH sensing electrode and Ag/AgCl reference electrode with LiCl electrolyte. A natural application of the D664 method is titration of pyrolysis-derived bio-oil, which is a candidate for refinery upgrading to produce drop in fuels. Determining the total acid value of pyrolysis derived bio-oil has proven challenging and not necessarily amenable to the methodology employed for petroleum products due to the different nature of acids present. We presented an acid value titration for bio-oil products in our previous publication which also utilizes potentiometry using tetrabutylammonium hydroxide in place of KOH as the titrant and tetraethylammonium bromide in place of LiCl as the reference electrolyte to improve the detection of these types of acids. This method was shown to detect numerous end points in samples of bio-oil that were not detected by D664. These end points were attributed to carboxylic acids and phenolics based on the results of HPLC and GC-MS studies. Additional work has led to refinement of the method and it has been established that both carboxylic acids and phenolics can be determined accurately. Use of pH buffer calibration to determine half-neutralization potentials of acids in conjunction with the analysis of model compounds has allowed us to conclude that this titration method is suitable for the determination of total acid value of pyrolysis oil and can be used to differentiate and quantify weak acid species. The measurement of phenolics in bio-oil is subject to a relatively high limit of detection, which may limit the utility of titrimetric methodology for characterizing the acidic potential of pyrolysis oil and products.

  11. Birds as biodiversity surrogates

    DEFF Research Database (Denmark)

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


    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....

  12. Surrogates of Long-Term Vitamin D Exposure and Ovarian Cancer Risk in Two Prospective Cohort Studies

    Directory of Open Access Journals (Sweden)

    Jennifer Prescott


    Full Text Available Experimental evidence and ecologic studies suggest a protective role of vitamin D in ovarian carcinogenesis. However, epidemiologic studies using individual level data have been inconsistent. We evaluated ultraviolet (UV-B radiation, vitamin D intake, and predicted plasma 25-hydroxyvitamin D [25(OHD] levels as long-term surrogates of vitamin D exposure within the Nurses’ Health Study (NHS and NHSII. We estimated incidence rate ratios (RRs and 95% confidence intervals (CIs for risk of overall ovarian cancer and by histologic subtype using Cox proportional hazards models. Between 1976 and 2010 in NHS and 1989 and 2011 in NHSII, we identified a total of 1,225 incident epithelial ovarian cancer cases (NHS: 970, NHSII: 255 over 4,628,648 person-years of follow-up. Cumulative average UV-B exposure was not associated with ovarian cancer risk in NHS (Ptrend = 0.08, but was associated with reduced risk in NHSII (highest vs. lowest category RR = 0.67; 95% CI: 0.50, 0.89; Ptrend < 0.01. When stratified by histologic subtype, UV-B flux was positively associated with risk of serous tumors in NHS (Ptrend < 0.01, but inversely associated in NHSII (Ptrend = 0.01. Adjusted for confounders, ovarian cancer risk was not associated with vitamin D intake from food or supplements or with predicted 25(OHD levels. Our study does not strongly support a protective role for vitamin D in ovarian cancer risk.

  13. End-point energy measurements of field emission current in a continuous-wave normal-conducting rf injector (United States)

    Nguyen, D. C.; Moody, N. A.; Andrews, H. L.; Bolme, G.; Castellano, L. J.; Heath, C. E.; Krawczyk, F. L.; Kwon, S. I.; McCrady, R.; Martinez, F. A.; Marroquin, P.; Prokop, M.; Renneke, R. M.; Roybal, P.; Roybal, W. T.; Tomei, T. L.; Torrez, P. A.; Tuzel, W. M.; Zaugg, T.


    The LANL/AES normal-conducting radio-frequency injector has been tested at cw cathode gradients up to 10MV/m. Field-emission electrons from a roughened copper cathode are accelerated to beam energy as high as 2.5 MeV and impinge on a stainless steel target. The energies of the resulting bremsstrahlung photons are measured at varying levels of injector cavity rf power corresponding to different accelerating gradients. At low cavity power, the bremsstrahlung spectra exhibit well-defined end-point energies at the positions where the number of single-photon events decreases to one (S/Nratio=1). Increasing the cavity power raises the probability of two-photon events in which two photons simultaneously arrive at the detector and register counts at twice the photon energy. The end-point energies at high cavity power are recorded at positions where the single-photon events transition to two-photon events. The measured end-point energies using this method are in excellent agreement with PARMELA calculations based on the cavity gradients deduced from the cavity rf power measurements.

  14. A novel surrogate index for hepatic insulin resistance.

    LENUS (Irish Health Repository)

    Vangipurapu, J


    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.

  15. Evaluation of kidney size in children: a pilot study of renal length as a surrogate of organ growth

    Directory of Open Access Journals (Sweden)

    Boo Won Kim


    Full Text Available Purpose : Somatic growth is an important indicator of health in children. Adequate organ growth is essential in growth and directly related to body growth. We consider renal length as a surrogate of organ growth in growing children. Measurement of weight, height, and many anthropometric indices, such as body surface area (BSA, body mass index (BMI, and Rohrer and Kaup indices, are used to evaluate growth status. The aim of this study was to evaluate the association between renal length and somatic parameters and analyze the affecting factors for renal size during growth. Methods : The data for renal length in 66 children (age, 12.9¡?#?5.6; months; male/female, 34/32 were obtained. Each kidney was measured with ultrasonography and dimercaptosuccinic acid scan. The data on age, sex, height, and weight were obtained from the medical records. BSA, BMI, and Rohrer and Kaup indices were calculated from measured height and weight. BSA was calculated by 2 methods, and is expressed as BSA I and BSA II. Results : There were significant correlations between renal size and age, weight, height, BSA I, BSA II, and Rohrer index. In the regression analysis, the most significant contributing factor to renal growth was height (R2=0.636, P&lt;0.001. Conclusion : Height seems to be the most important factor associated with organ growth in growing children. Further studies to evaluate adequate organ growth should be carried out.

  16. Effects of Cooking End-point Temperature and Muscle Part on Sensory ‘Hardness’ and ‘Chewiness’ Assessed Using Scales Presented in ISO11036:1994

    Directory of Open Access Journals (Sweden)

    Keisuke Sasaki


    Full Text Available Texture and ‘tenderness’ in particular, is an important sensory characteristic for consumers’ satisfaction of beef. Objective and detailed sensory measurements of beef texture have been needed for the evaluation and management of beef quality. This study aimed to apply the sensory scales defined in ISO11036:1994 to evaluate the texture of beef. Longissimus and Semitendinosus muscles of three Holstein steers cooked to end-point temperatures of 60°C and 72°C were subjected to sensory analyses by a sensory panel with expertise regarding the ISO11036 scales. For the sensory analysis, standard scales of ‘chewiness’ (9-points and ‘hardness’ (7-points were presented to the sensory panel with reference materials defined in ISO11036. As a result, both ‘chewiness’ and ‘hardness’ assessed according to the ISO11036 scales increased by increasing the cooking end-point temperature, and were different between Longissimus and Semitendinosus muscles. The sensory results were in good agreement with instrumental texture measurements. However, both texture ratings in this study were in a narrower range than the full ISO scales. For beef texture, ISO11036 scales for ‘chewiness’ and ‘hardness’ are useful for basic studies, but some alterations are needed for practical evaluation of muscle foods.

  17. The application of lichens as ecological surrogates of air pollution in the subtropics: a case study in South Brazil. (United States)

    Koch, Natália M; Branquinho, Cristina; Matos, Paula; Pinho, Pedro; Lucheta, Fabiane; Martins, Suzana M A; Vargas, Vera M F


    The use of lichens as ecological surrogates has been an important tool to evaluate the impact of air pollution in both ecosystem and human health but remains underused in the subtropics due to lack of knowledge. Aiming to support the application of lichen as ecological surrogates of the effects of air pollution in the subtropics, we hypothesized that urbanization was an important driver of changes on lichen diversity, composition, and vitality. For that, we quantified several lichen diversity metrics (richness, cover, and community composition) and photobiont vitality in relation to atmospheric pollution or its surrogates (modeled pollutant gases, pollutants in lichen thallus, and land cover). We confirmed that air pollution was a key driver for lichen diversity. Changes in lichen community composition and vitality were very significantly related to air pollution and integrated the effect of multiple stressors (particulate matter, NOx, and Cu), thus being powerful ecological indicators of air pollution in the subtropics.

  18. The accuracy of surrogate decision makers: a systematic review. (United States)

    Shalowitz, David I; Garrett-Mayer, Elizabeth; Wendler, David


    Clinicians currently rely on patient-designated and next-of-kin surrogates to make end-of-life treatment decisions for incapacitated patients. Surrogates are instructed to use the substituted judgment standard, which directs them to make the treatment decision that the patient would have made if he or she were capacitated. However, commentators have questioned the accuracy with which surrogates predict patients' treatment preferences. A systematic literature search was conducted using PubMed, the Cochrane Library, and manuscript references, to identify published studies that provide empirical data on how accurately surrogates predict patients' treatment preferences and on the efficacy of commonly proposed methods to improve surrogate accuracy. Two of us (D.I.S. and D.W.) reviewed all articles and extracted data on the hypothetical scenarios used to assess surrogate accuracy and the percentage of agreement between patients and surrogates. The search identified 16 eligible studies, involving 151 hypothetical scenarios and 2595 surrogate-patient pairs, which collectively analyzed 19 526 patient-surrogate paired responses. Overall, surrogates predicted patients' treatment preferences with 68% accuracy. Neither patient designation of surrogates nor prior discussion of patients' treatment preferences improved surrogates' predictive accuracy. Patient-designated and next-of-kin surrogates incorrectly predict patients' end-of-life treatment preferences in one third of cases. These data undermine the claim that reliance on surrogates is justified by their ability to predict incapacitated patients' treatment preferences. Future studies should assess whether other mechanisms might predict patients' end-of-life treatment preferences more accurately. Also, they should assess whether reliance on patient-designated and next-of-kin surrogates offers patients and/or their families benefits that are independent of the accuracy of surrogates' decisions.

  19. Surrogates of Long-Term Vitamin D Exposure and Ovarian Cancer Risk in Two Prospective Cohort Studies

    Energy Technology Data Exchange (ETDEWEB)

    Prescott, Jennifer, E-mail:; Bertrand, Kimberly A.; Poole, Elizabeth M.; Rosner, Bernard A.; Tworoger, Shelley S. [Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, 181 Longwood Ave. Boston, MA 02115 (United States)


    Experimental evidence and ecologic studies suggest a protective role of vitamin D in ovarian carcinogenesis. However, epidemiologic studies using individual level data have been inconsistent. We evaluated ultraviolet (UV)-B radiation, vitamin D intake, and predicted plasma 25-hydroxyvitamin D [25(OH)D] levels as long-term surrogates of vitamin D exposure within the Nurses’ Health Study (NHS) and NHSII. We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) for risk of overall ovarian cancer and by histologic subtype using Cox proportional hazards models. Between 1976 and 2010 in NHS and 1989 and 2011 in NHSII, we identified a total of 1,225 incident epithelial ovarian cancer cases (NHS: 970, NHSII: 255) over 4,628,648 person-years of follow-up. Cumulative average UV-B exposure was not associated with ovarian cancer risk in NHS (P{sub trend} = 0.08), but was associated with reduced risk in NHSII (highest vs. lowest category RR = 0.67; 95% CI: 0.50, 0.89; P{sub trend} < 0.01). When stratified by histologic subtype, UV-B flux was positively associated with risk of serous tumors in NHS (P{sub trend} < 0.01), but inversely associated in NHSII (P{sub trend} = 0.01). Adjusted for confounders, ovarian cancer risk was not associated with vitamin D intake from food or supplements or with predicted 25(OH)D levels. Our study does not strongly support a protective role for vitamin D in ovarian cancer risk.

  20. Saliva as a surrogate to explore the association between lipid profiles and chronic periodontitis: A case-control study

    Directory of Open Access Journals (Sweden)

    Veena Kalburgi


    Conclusion: Increased salivary lipids in chronic periodontitis patients suggest an association between hyperlipidemia and periodontitis. The relatively easy and non-invasive nature of saliva can be used as a diagnostic tool to assess the lipid status. Further research is needed to determine its specificity as a surrogate to serum lipid profiles.

  1. Cardiorenal end points in a trial of aliskiren for type 2 diabetes

    DEFF Research Database (Denmark)

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


    This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both....

  2. Artificial neural network surrogate development of equivalence models for nuclear data uncertainty propagation in scenario studies

    Directory of Open Access Journals (Sweden)

    Krivtchik Guillaume


    Full Text Available Scenario studies simulate the whole fuel cycle over a period of time, from extraction of natural resources to geological storage. Through the comparison of different reactor fleet evolutions and fuel management options, they constitute a decision-making support. Consequently uncertainty propagation studies, which are necessary to assess the robustness of the studies, are strategic. Among numerous types of physical model in scenario computation that generate uncertainty, the equivalence models, built for calculating fresh fuel enrichment (for instance plutonium content in PWR MOX so as to be representative of nominal fuel behavior, are very important. The equivalence condition is generally formulated in terms of end-of-cycle mean core reactivity. As this results from a physical computation, it is therefore associated with an uncertainty. A state-of-the-art of equivalence models is exposed and discussed. It is shown that the existing equivalent models implemented in scenario codes, such as COSI6, are not suited to uncertainty propagation computation, for the following reasons: (i existing analytical models neglect irradiation, which has a strong impact on the result and its uncertainty; (ii current black-box models are not suited to cross-section perturbations management; and (iii models based on transport and depletion codes are too time-consuming for stochastic uncertainty propagation. A new type of equivalence model based on Artificial Neural Networks (ANN has been developed, constructed with data calculated with neutron transport and depletion codes. The model inputs are the fresh fuel isotopy, the irradiation parameters (burnup, core fractionation, etc., cross-sections perturbations and the equivalence criterion (for instance the core target reactivity in pcm at the end of the irradiation cycle. The model output is the fresh fuel content such that target reactivity is reached at the end of the irradiation cycle. Those models are built and

  3. Removal of oxides from alkali metal melts by reductive titration to electrical resistance-change end points (United States)

    Tsang, Floris Y.


    Alkali metal oxides dissolved in alkali metal melts are reduced with soluble metals which are converted to insoluble oxides. The end points of the reduction is detected as an increase in electrical resistance across an alkali metal ion-conductive membrane interposed between the oxide-containing melt and a material capable of accepting the alkali metal ions from the membrane when a difference in electrical potential, of the appropriate polarity, is established across it. The resistance increase results from blocking of the membrane face by ions of the excess reductant metal, to which the membrane is essentially non-conductive.

  4. The patient-reported outcome (PRO) consortium: filling measurement gaps for PRO end points to support labeling claims. (United States)

    Coons, S J; Kothari, S; Monz, B U; Burke, L B


    The importance of appropriately and effectively incorporating the patient's voice into the evaluation of new medical products has been recognized and affirmed by regulators.(1,2,3) Patient-reported outcomes (PROs) are increasingly being assessed in clinical trials to quantify treatment benefits such as symptom relief and improved functioning. Translating PRO-based treatment benefits into labeling claims can provide information to physicians and patients and assist in prescribing decisions.(4,5) Hence, standardizing the valid and reliable measurement of PRO end points is critical.

  5. Black smoke as a surrogate for PM 10 in health studies? (United States)

    Muir, David; Laxen, Duncan P. H.

    There is a rapidly growing interest in health implications of airborne fine particles. The focus of attention is on particulate matter less than 10 μm aerodynamic diameter (PM 10). In the U.K. there are few PM 10 measurements and this is potentially hampering health effect studies. There is however a wide body of black smoke data using the British Standard smoke stain method. Black smoke may indeed be a better indicator of health impacts. It is therefore timely to examine the relationship between black smoke and PM 10. This has been done using recent monitoring results for Bristol, a moderate sized U.K. city. Daily average black smoke (averaged over six urban background sites) is shown to be a reasonable predictor of daily average PM 10 and of daily peak 1 h PM 10. However, different relationships apply to winter and summer periods showing that these methods are measuring different components of fine airborne particles.

  6. Is human blood a good surrogate for brain tissue in transcriptional studies?

    Directory of Open Access Journals (Sweden)

    van den Berg Leonard H


    Full Text Available Abstract Background Since human brain tissue is often unavailable for transcriptional profiling studies, blood expression data is frequently used as a substitute. The underlying hypothesis in such studies is that genes expressed in brain tissue leave a transcriptional footprint in blood. We tested this hypothesis by relating three human brain expression data sets (from cortex, cerebellum and caudate nucleus to two large human blood expression data sets (comprised of 1463 individuals. Results We found mean expression levels were weakly correlated between the brain and blood data (r range: [0.24,0.32]. Further, we tested whether co-expression relationships were preserved between the three brain regions and blood. Only a handful of brain co-expression modules showed strong evidence of preservation and these modules could be combined into a single large blood module. We also identified highly connected intramodular "hub" genes inside preserved modules. These preserved intramodular hub genes had the following properties: first, their expression levels tended to be significantly more heritable than those from non-preserved intramodular hub genes (p -90; second, they had highly significant positive correlations with the following cluster of differentiation genes: CD58, CD47, CD48, CD53 and CD164; third, a significant number of them were known to be involved in infection mechanisms, post-transcriptional and post-translational modification and other basic processes. Conclusions Overall, we find transcriptome organization is poorly preserved between brain and blood. However, the subset of preserved co-expression relationships characterized here may aid future efforts to identify blood biomarkers for neurological and neuropsychiatric diseases when brain tissue samples are unavailable.

  7. Cardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes

    NARCIS (Netherlands)

    Parving, Hans-Henrik; Brenner, Barry M.; McMurray, John J. V.; de Zeeuw, Dick; Haffner, Steven M.; Solomon, Scott D.; Chaturvedi, Nish; Persson, Frederik; Desai, Akshay S.; Nicolaides, Maria; Richard, Alexia; Xiang, Zhihua; Brunel, Patrick; Pfeffer, Marc A.; Juncos, Luis; Orias, Marcelo; Kuschnir, Emilio; Rusculleda, Marcelo; Garcia, Sergio; Farias, Eduardo; Lema, Luis; Hominal, Miguel; Montana, Oscar; Sala, Jorgelina; Diaz, Monica; Piskorz, Daniel; Vita, Nestor; Litwak, Leon; Sinay, Isaac; Marin, Marcos; Massari, Pablo; Majul, Claudio; Aizemberg, D.; Azize, Guillermo Moises; Bartolacci, Ines; Reboredo, Ana; Vico, Marisa; Milesi, Ricardo; Sessa, Horacio; Wassermann, Alfredo; Margulis, Fernando; Zangroniz, Pedro; Watschinger, B.; Prager, R.; Toplak, H.; Paulweber, B.; Drexel, H.; Francesconi, C.; Foeger, B.; Mayer, G.; Braun, R.K.; Brath, H.; Gaal, L.V.; Niepen, P.V.D.; Persu, A.; Vercammen, C.; Vriese, A.D.; Coucke, F.; Mathieu, C.; Fery, F.; Treille, S.; Meeus, G.; Acker, K.V.; Scheen, A.; Tits, J.; Ruige, J.; Krzesinski, J.M.; Hollanders, G.; Lienart, F.; Dendale, P.; Quinonez, M.; Arnouts, P.; Vanuytsel, J.; Zanella, M.; Mion, D; Forti, A.; Almeida, F.; Cunha, R.; de Paula, R.B.; Brandao, A.; Rocha, J.; Krieger, E.; Feitosa, G.; Saraiva, J.; Martin, J.; Hissa, M.N.; Schmid, H.; Felicio, J.; Sgarbi, J.; Oigman, W.; Bowering, K.; Garceau, C.; Berlingieri, J.C.; Weisnagel, S.J.; Hardin, P.; Powell, C.; Turcot, R.; Muirhead, N.; Aronson, R.; Barima, Y.T.; Steele, A.W.; Pandey, S.; Woo, V.; Cha, J.; Dattani, D.; Godin, C.; Gupta, M.; Leiter, L.; Saunders, K.; Tellier, G.; Ting, R; Tobe, S.; Chouinard, G.; Schlosser, R.; Khandwala, H.; Ekoe, J.M.; Harris, S.B.; Pichette, V.; Lachance, P.; Ooi, TC; Tildesley, H.; Barrett, B.; Cournoyer, S.; Lu, J; Zhang, J.; Liu, X.; Yan, S.; Qi, X.; Li, Q.; Li, H.; Lv, X.; Yang, J.; Sun, N.; Xia, W.; Wang, Yumei; Tong, N.; Mei, C.; Gu, S.; Zhang, J.; Chen, X.; Li, L.; Su, B.; Wang, L.; Qiu, M.; Wu, X.; Liu, Z.; Jia, W.; Xu, G.; Dong, J.; Zhu, D.; Mei, C.; Gu, S.; Zhang, J.; Chen, X.; Li, L.; Su, B.; Wang, L.; Qiu, M.; Wu, X.; Liu, Z.; Jia, W.; Xu, G.; Dong, J.; Zhu, D.; Zhang, M.; Yan, J.; Liu, B.; Chen, J.; Fu, J.; Yan, L.; Zhan, X.; Zhong, L.; yang, T.; Ma, J.; Xu, M.; Xu, X.; Shi, B.; Ji, Q.; Zhong, H.; He, R.; Yuan, Z.; Zhou, Z.; Lin, H.; Yang, W.; Ke, Y.; Li, Q.; Hong, T.; Franco, C.; Casas, L.; Triana, A.; Botero, R.; Jaramillo, C.; Hernandez, E.; Barrera, C.; Blanco, D.; Stipal, R.; Widimsky, P.; Dohnalova, L.; Komroskova, M.; Kvapil, M.; Belobradkova, J.; Tesar, V.; Cifkova, R.; Vodnansky, P.; Kocourkova, B.; Christiansen, J.S.; Lervang, H-H; Perrild, H.; Rossing, P.; Oestergaard, O.; Juhl, H.; Thorsteinsson, B.; Snorgaard, O.; Urhammer, S.; Egstrup, K.; Tikkanen, T; Helin, K.; Rinne, J.; Lahtela, J.; Strand, J.; Valtonen, E.; Saari, M.; Kananen, K.; Savela, K.; Marre, M.; Blacher, J.; Aldigier, J-C; Zaoui, P.; Fauvel, J-P; Gouet, D.; Valensi, P-E; Charpentier, G.; Marechaud, R.; Penfornis, A.; Ovize, M; Kovalchuck, A.A.; Haller, H.; Dellanna, F.


    BACKGROUND This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both. METHODS In a double-blind fashion, we randomly assigned


    Studies of biochemical homeostasis and/or body growth have been included as outcome variables in most nutrition trials in paediatric patients. Moreover, these outcome variables have provided important insights into the nutrient requirements of infants and children, and continue to do so. Examples ...

  9. Longitudinal study of surrogate aging measures during human immunodeficiency virus seroconversion. (United States)

    Leung, Janice M; Fishbane, Nick; Jones, Meaghan; Morin, Alexander; Xu, Stella; Liu, Joseph Cy; MacIsaac, Julie; Milloy, M-J; Hayashi, Kanna; Montaner, Julio; Horvath, Steve; Kobor, Michael; Sin, Don D; Harrigan, P Richard; Man, S F Paul


    Persons living with human immunodeficiency virus (HIV) harbor an increased risk of age-related conditions. We measured changes in telomere length and DNA methylation in the peripheral blood of 31 intravenous drug users, who were followed longitudinally with blood samples pre-HIV (T1), immediately post-HIV (T2; 1.9±1 year from T1), and at a later follow-up time (T3; 2.2±1 year from T2). Absolute telomere length measurements were performed using polymerase chain reaction methods. Methylation profiles were obtained using the Illumina Human Methylation450 platform. Methylation aging was assessed using the Horvath method. Telomere length significantly decreased between T1 and T2 (227±46 at T1 vs. 201±48 kbp/genome at T2, p=0.045), while no differences were observed between T2 and T3 (201±48 at T2 vs. 186±27 kbp/genome at T3, p=0.244). Methylation aging as measured by the age acceleration residual increased over the time course of HIV infection (p=0.035). CpG sites corresponding to PCBP2 and CSRNP1 were differentially methylated between T1 and T2 at a q-value <0.05. Telomere shortening and methylation changes can therefore be observed in the short-term period immediately following HIV seroconversion. Further studies to confirm these results in larger sample sizes and to compare these results to non-HIV and non-injection drug users are warranted.

  10. Spatial surrogate for domestic combustion's air emissions: A case study from Silesian Metropolis, Poland. (United States)

    Zasina, Damian; Zawadzki, Jaroslaw


    The aim of this study is improving currently applied methodology for spatial disaggregation, as well as mapping air emission inventories by taking into account the auxiliary spatial data on population density. District heating infrastructure occurring in more populated areas changes distinctly the spatial distribution of estimated air emission; however, it does not change the initial estimate. That means the total, disaggregated value is constant. Considered sources of domestic combustion are located in the central part of the Silesian Metropolis, in the southern part of Poland. A large part of this area is strongly urbanized and supplied with heat (hot water) from the district heating system. Data on population density help to determine the area within which the dwellers use heat energy and hot water supplied by the heating infrastructure, apart from heating with small domestic boilers and stoves. This causes the domestic combustion's emission impact within the distinguished area to be significantly lower in comparison to the official guidelines on air emission inventories. The important differences in spatial air emissions distributions calculated using a top-down approach are found for strongly urbanized areas supplied partly with heat and hot water from the district heating network. This fact should be taken into account when preparing detailed, high-resolution emission inventories for air regional and local quality modeling. The spatial issues connected with elaboration of the high-resolution emission inventories are presented for the example of the populated area of the Silesian Metropolis (Poland). Spatial distribution of the population density is used to determine the area supplied with heat and hot water from the district heating system. It changes distinctly the spatial distribution of the air emission from small residential combustion sources.

  11. Development of Pain End Point Models for Use in Prostate Cancer Clinical Trials and Drug Approval (United States)


    6) IN PROGRESS 2a. Develop IVRS platform (Months 1 – 3) Completed 2b. Develop study databases on secure, password-protected server (Months 3...mode of administration.31 To optimally represent patients’ experiences at a given time point of interest during a trial, pain and analge- sic ...the improvement. Pain intensity and analge- sic use are assessed at baseline and at each preselected follow-up time point to calculate the percentage of

  12. Large deflection analysis of cantilever beam under end point and distributed load

    DEFF Research Database (Denmark)

    Kimiaeifar, Amin; Tolou, N; Barari, Amin


    Although the deflection of beams has been studied for decades, the solutions were either linearized (i.e. small deflection) or based on elliptic integrals or functions (large deflection). The latter one includes the geometric nonlinearity but calculation of the deflection along the beam length...... distributed loads. Direct nonlinear solution by use of homotopy analysis method was implemented to drive the semi-exact solution of trajectory position of any point along the beam length. For the purpose of comparison, the deflections were calculated and compared to those of finite element method which...

  13. Influences of end-point heating temperature on the quality attributes of chicken meat. (United States)

    Chumngoen, W; Chen, C F; Chen, H Y; Tan, F J


    This study aimed to evaluate the changes in physicochemical, textural and sensory characteristics of broiler (BR) and Taiwan native chicken (TNC) pectoralis muscle heated at temperatures of 50-95°C. With increasing temperature, cooking loss, collagen solubility, shear force value and hardness, of samples increased in both chicken breeds. Rapid decreases in protein solubility were observed when the meat was heated to 50°C and gradually decreased thereafter. Meat from BRs and native chickens performed differently upon heating in certain characteristics. TNC meat had longer cooking time and lower myofibrillar fragmentation index than BR meat did. TNC meat had higher collagen content, shear force values and springiness but lower collagen solubility than BR meat did. BR meat had significantly higher onset and end transition temperatures than TNC meat did. In BR meat, a sensory analysis revealed that moisture release decreased and chicken flavour increased with increasing temperature. Protein solubility, cooking loss and the texture of heated meat were highly correlated. This study scientifically assessed the performances of the two breeds of chickens with different thermal treatments; producers could utilise the information to produce poultry products with more desirable qualities.

  14. Clinical end points for drug treatment trials in BCR-ABL1-negative classic myeloproliferative neoplasms: consensus statements from European LeukemiaNET (ELN) and Internation Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT). (United States)

    Barosi, G; Tefferi, A; Besses, C; Birgegard, G; Cervantes, F; Finazzi, G; Gisslinger, H; Griesshammer, M; Harrison, C; Hehlmann, R; Hermouet, S; Kiladjian, J-J; Kröger, N; Mesa, R; Mc Mullin, M F; Pardanani, A; Passamonti, F; Samuelsson, J; Vannucchi, A M; Reiter, A; Silver, R T; Verstovsek, S; Tognoni, G; Barbui, T


    The discovery of somatic mutations, primarily JAK2V617F and CALR, in classic BCR-ABL1-negative myeloproliferative neoplasms (MPNs) has generated interest in the development of molecularly targeted therapies, whose accurate assessment requires a standardized framework. A working group, comprised of members from European LeukemiaNet (ELN) and International Working Group for MPN Research and Treatment (IWG-MRT), prepared consensus-based recommendations regarding trial design, patient selection and definition of relevant end points. Accordingly, a response able to capture the long-term effect of the drug should be selected as the end point of phase II trials aimed at developing new drugs for MPNs. A time-to-event, such as overall survival, or progression-free survival or both, as co-primary end points, should measure efficacy in phase III studies. New drugs should be tested for preventing disease progression in myelofibrosis patients with early disease in randomized studies, and a time to event, such as progression-free or event-free survival should be the primary end point. Phase III trials aimed at preventing vascular events in polycythemia vera and essential thrombocythemia should be based on a selection of the target population based on new prognostic factors, including JAK2 mutation. In conclusion, we recommended a format for clinical trials in MPNs that facilitates communication between academic investigators, regulatory agencies and drug companies.

  15. The effect of statins on average survival in randomised trials, an analysis of end point postponement

    DEFF Research Database (Denmark)

    Kristensen, Malene Lopez; Christensen, Palle Mark; Hallas, Jesper


    OBJECTIVE: To estimate the average postponement of death in statin trials. SETTING: A systematic literature review of all statin trials that presented all-cause survival curves for treated and untreated. INTERVENTION: Statin treatment compared to placebo. PRIMARY OUTCOME MEASURES: The average...... postponement of death as represented by the area between the survival curves. RESULTS: 6 studies for primary prevention and 5 for secondary prevention with a follow-up between 2.0 and 6.1 years were identified. Death was postponed between -5 and 19 days in primary prevention trials and between -10 and 27 days...... in secondary prevention trials. The median postponement of death for primary and secondary prevention trials were 3.2 and 4.1 days, respectively. CONCLUSIONS: Statin treatment results in a surprisingly small average gain in overall survival within the trials' running time. For patients whose life expectancy...

  16. A damper driven robotic end-point manipulator for functional rehabilitation exercises after stroke. (United States)

    Westerveld, Ard J; Aalderink, Bernard Johan; Hagedoorn, Wouter; Buijze, Martijn; Schouten, Alfred C; Kooij, Herman van der


    Stroke survivors may benefit from robotic assistance for relearning of functional movements. Current assistive devices are either passive, limited to only two dimensions or very powerful. However, for reach training, weight compensation and a little assistance with limited power is sufficient. We designed and evaluated a novel three-dimensional robotic manipulator, which is able to support the arm weight and assist functional reaching movements. Key points of the design are a damper-based drive train, giving an inherently safe system and its compact and lightweight design. The system is force actuated with a bandwidth of up to 2.3 Hz, which is sufficient for functional arm movements. Maximal assistive forces are 15 N for the up/down and forward/backward directions and 10 N for the left/right direction. Force tracking errors are smaller than 1.5 N for all axes and the total weight of the robot is 25 kg. Furthermore, the device has shown its benefit for increasing reaching distance in a single-case study with a stroke subject. The newly developed system has the technical ability to assist the arm during movement, which is a prerequisite for successful training of stroke survivors. Therapeutic effects of the applied assistance need to be further evaluated. However, with its inherent safety and ease of use, this newly developed system even has the potential for home-based therapeutic training after stroke.

  17. The effect of statins on average survival in randomised trials, an analysis of end point postponement. (United States)

    Kristensen, Malene Lopez; Christensen, Palle Mark; Hallas, Jesper


    To estimate the average postponement of death in statin trials. A systematic literature review of all statin trials that presented all-cause survival curves for treated and untreated. Statin treatment compared to placebo. The average postponement of death as represented by the area between the survival curves. 6 studies for primary prevention and 5 for secondary prevention with a follow-up between 2.0 and 6.1 years were identified. Death was postponed between -5 and 19 days in primary prevention trials and between -10 and 27 days in secondary prevention trials. The median postponement of death for primary and secondary prevention trials were 3.2 and 4.1 days, respectively. Statin treatment results in a surprisingly small average gain in overall survival within the trials' running time. For patients whose life expectancy is limited or who have adverse effects of treatment, withholding statin therapy should be considered. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

  18. Towards free 3D end-point control for robotic-assisted human reaching using binocular eye tracking. (United States)

    Maimon-Dror, Roni O; Fernandez-Quesada, Jorge; Zito, Giuseppe A; Konnaris, Charalambos; Dziemian, Sabine; Faisal, A Aldo


    Eye-movements are the only directly observable behavioural signals that are highly correlated with actions at the task level, and proactive of body movements and thus reflect action intentions. Moreover, eye movements are preserved in many movement disorders leading to paralysis (or amputees) from stroke, spinal cord injury, Parkinson's disease, multiple sclerosis, and muscular dystrophy among others. Despite this benefit, eye tracking is not widely used as control interface for robotic interfaces in movement impaired patients due to poor human-robot interfaces. We demonstrate here how combining 3D gaze tracking using our GT3D binocular eye tracker with custom designed 3D head tracking system and calibration method enables continuous 3D end-point control of a robotic arm support system. The users can move their own hand to any location of the workspace by simple looking at the target and winking once. This purely eye tracking based system enables the end-user to retain free head movement and yet achieves high spatial end point accuracy in the order of 6 cm RMSE error in each dimension and standard deviation of 4 cm. 3D calibration is achieved by moving the robot along a 3 dimensional space filling Peano curve while the user is tracking it with their eyes. This results in a fully automated calibration procedure that yields several thousand calibration points versus standard approaches using a dozen points, resulting in beyond state-of-the-art 3D accuracy and precision.

  19. The StartReact effect in tasks requiring end-point accuracy. (United States)

    Castellote, J M; Valls-Solé, J


    Fast and accurate movements are often performed in response to a sensory signal. In reaction time tasks, execution of open loop movements is speeded up when a startling auditory stimulus (SAS) is applied together with the imperative signal (IS). In this study, we examined the effects of a SAS on the performance of a task that demands accuracy. Nine subjects were asked to move a monitored pen to a target point located in a table at a fixed angular distance of 30 degrees from a start point. The target was a spot of three possible diameters: 5, 10, and 20mm. Finger force for pen holding, pen tip pressure against the table and kinematic variables of the forearm movement were measured for three conditions: control, SAS delivered at IS (SAS-IS trials) and SAS delivered during movement execution (SAS-MOV trials). Two movement phases could be identified in the movement trajectory and force profile. The first phase, ballistic, was significantly shortened in SAS-MOV trials, with earlier and larger peak velocity and peak force with respect to control trials. The second phase, slow approach to target, was longer in SAS-IS trials but not in SAS-MOV trials. Accuracy was maintained throughout all conditions and stimulation modes. A SAS speeds up only the first (ballistic) part of the movement in an accuracy task. Slower target approach compensates for the accelerated initial movement. No changes in the last part of the movement are seen when a SAS is delivered after movement onset. The StartReact effect is restricted to the onset of a complex movement, when muscles are activated in a ballistic mode, without feedback. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  20. The effect of aborting ongoing movements on end point position estimation. (United States)

    Itaguchi, Yoshihiro; Fukuzawa, Kazuyoshi


    The present study investigated the impact of motor commands to abort ongoing movement on position estimation. Participants carried out visually guided reaching movements on a horizontal plane with their eyes open. By setting a mirror above their arm, however, they could not see the arm, only the start and target points. They estimated the position of their fingertip based solely on proprioception after their reaching movement was stopped before reaching the target. The participants stopped reaching as soon as they heard an auditory cue or were mechanically prevented from moving any further by an obstacle in their path. These reaching movements were carried out at two different speeds (fast or slow). It was assumed that additional motor commands to abort ongoing movement were required and that their magnitude was high, low, and zero, in the auditory-fast condition, the auditory-slow condition, and both the obstacle conditions, respectively. There were two main results. (1) When the participants voluntarily stopped a fast movement in response to the auditory cue (the auditory-fast condition), they showed more underestimates than in the other three conditions. This underestimate effect was positively related to movement velocity. (2) An inverted-U-shaped bias pattern as a function of movement distance was observed consistently, except in the auditory-fast condition. These findings indicate that voluntarily stopping fast ongoing movement created a negative bias in the position estimate, supporting the idea that additional motor commands or efforts to abort planned movement are involved with the position estimation system. In addition, spatially probabilistic inference and signal-dependent noise may explain the underestimate effect of aborting ongoing movement.

  1. Practical surrogate marker of pulmonary dysanapsis by simple spirometry: an observational case-control study in primary care. (United States)

    Shiota, Satomi; Ichikawa, Masako; Suzuki, Kazuhiro; Fukuchi, Yoshinosuke; Takahashi, Kazuhisa


    We see patients who present with spirometry airflow limitation despite their forced expiratory volume in one second (FEV1) as well as forced vital capacity (FVC) to be supernormal (FEV1/FVC spirometry conditions (results measured with spirometry) could be suitably used as a practical surrogate marker of pulmonary dysanapsis: the condition of disproportionate but physiologically normal growth between airways and lung parenchyma. We compared the conventional surrogate marker of dysanapsis, maximum mid-expiratory flow to FVC (MMF/FVC), in SUBJECTS (FEV1/FVC spirometry results with SUBJECTS) (n = 55), and in CONTROLS (age- and height- matched, normal spirometry results) (n = 25). Next we added imaging analysis to evaluate the relationship between the cross sectional airway luminal area (X-Ai) and the lung volume results among the three groups. The MMF/FVC was significantly lower in SUBJECTS and in EMPHYSEMA compared to CONTROLS. However, percent predicted peak expiratory flow (%PEFR) was significantly lower only in SUBJECTS and not in EMPHYSEMA compared to CONTROLS. The ratio of the X-Ai of the trachea and right apical bronchus to lung volume was significantly lower in SUBJECTS compared to CONTROLS. The simple spirometry conditions in SUBJECTS are highly suggestive of practical surrogate marker of pulmonary dysanapsis. Awareness of this concept would help to attenuate the risk of overdiagnosis of obstructive pulmonary disease.

  2. Plutonium radiation surrogate (United States)

    Frank, Michael I [Dublin, CA


    A self-contained source of gamma-ray and neutron radiation suitable for use as a radiation surrogate for weapons-grade plutonium is described. The source generates a radiation spectrum similar to that of weapons-grade plutonium at 5% energy resolution between 59 and 2614 keV, but contains no special nuclear material and emits little .alpha.-particle radiation. The weapons-grade plutonium radiation surrogate also emits neutrons having fluxes commensurate with the gamma-radiation intensities employed.

  3. Circulating oxysterol metabolites as potential new surrogate markers in patients with hormone receptor-positive breast cancer: Results of the OXYTAM study. (United States)

    Dalenc, Florence; Iuliano, Luiggi; Filleron, Thomas; Zerbinati, Chiara; Voisin, Maud; Arellano, Cécile; Chatelut, Etienne; Marquet, Pierre; Samadi, Mohammad; Roché, Henri; Poirot, Marc; Silvente-Poirot, Sandrine


    Accumulating evidence indicates that cholesterol oxygenation products, also known as oxysterols (OS), are involved in breast cancer (BC) promotion. The impact of Tam, as well as aromatase inhibitors (AI), an alternative BC endocrine therapy (ET), on OS metabolism in patients is currently unknown. We conducted a prospective clinical study in BC patients receiving Tam (n=15) or AI (n=14) in adjuvant or in metastatic settings. The primary end point was the feasibility of detecting and quantifying 11 different OS in the circulation of patients before and after 28days of treatment with Tam or AI. Key secondary end points were the measurements of variations in the concentrations of OS according to differences between patients and treatments. OS profiling in the serum of patients was determined by gas chromatography coupled to mass spectrometry. OS profiling was conducted in all patients both at baseline and during treatment regimens. An important inter-individual variability was observed for each OS. Interestingly 5,6β-epoxycholesterol relative concentrations significantly increased in the entire population (p=0.0109), while no increase in Cholestane-triol (CT) levels was measured. Interestingly, we found that, in contrast to AI, Tam therapy significantly decreased blood levels of 24-hydroxycholesterol (24-HC), 7α-HC and 25-HC (a tumor promoter) (p=0.0007, p=0.0231 and p=0.0231, respectively), whereas 4β-HC levels increased (p=0.0010). Interestingly, levels of 27-HC (a tumor promoter) significantly increased in response to AI (p=0.0342), but not Tam treatment. According to these results, specific OS are promising candidate markers of Tam and AI efficacy. Thus, further clinical investigations are needed to confirm the use of oxysterols as biomarkers of both prognosis and/or the efficacy of ET. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Voltammetric iodometric titration of ascorbic acid with dead-stop end-point detection in fresh vegetables and fruit samples. (United States)

    Verdini, R A; Lagier, C M


    The present work describes a method for determining ascorbic acid, which combines iodometry with a voltammetric technique to detect the end point of the titration. In addition, the validity of the method applied to natural vegetable or fruit samples was assessed. The results were compared with those obtained by an accurate method such as HPLC using UV detection. Similar values of ascorbic acid for different natural samples were obtained by means of this approach (p > 0.05). The limit of quantification was 0.1 mg. This technique presents the advantage of other electroanalytical methods such as avoiding filtration or ultracentrifugation steps, with the additional benefit of using the platinum electrodes, which are routinely used in the laboratory. These facts allow a rapid and efficient quantification of ascorbic acid with very low cost of reagents and equipment.

  5. Sagittal Abdominal Diameter as a Surrogate Marker of Insulin Resistance in an Admixtured Population--Brazilian Metabolic Syndrome Study (BRAMS). (United States)

    Vasques, Ana Carolina J; Cassani, Roberta S L; Forti, Adriana C e; Vilela, Brunna S; Pareja, José Carlos; Tambascia, Marcos Antonio; Geloneze, Bruno


    Sagittal abdominal diameter (SAD) has been proposed as a surrogate marker of insulin resistance (IR). However, the utilization of SAD requires specific validation for each ethnicity. We aimed to investigate the potential use of SAD, compared with classical anthropometrical parameters, as a surrogate marker of IR and to establish the cutoff values of SAD for screening for IR. A multicenter population survey on metabolic disorders was conducted. A race-admixtured sample of 824 adult women was assessed. The anthropometric parameters included: BMI, waist circumference (WC), waist-to-hip ratio and SAD. IR was determined by a hyperglycemic clamp and the HOMA-IR index. After adjustments for age and total body fat mass, SAD (r = 0.23 and r = -0.70) and BMI (r = 0.20 and r = -0.71) were strongly correlated with the IR measured by the HOMA-IR index and the clamp, respectively (p < 0.001). In the ROC analysis, the optimal cutoff for SAD in women was 21.0 cm. The women with an increased SAD presented 3.2 (CI 95%: 2.1-5.0) more likelihood of having IR, assessed by the HOMA-IR index compared with those with normal SAD (p < 0.001); whereas women with elevated BMI and WC were 2.1 (95% CI: 1.4-3.3) and 2.8 (95% CI: 1.7-4.5) more likely to have IR (p < 0.001), respectively. No statistically significant results were found for waist-to-hip ratio. SAD can be a suitable surrogate marker of IR. Understanding and applying routine and simplified methods is essential because IR is associated with an increased risk of obesity-related diseases even in the presence of normal weight, slight overweight, as well as in obesity. Further prospective analysis will need to verify SAD as a determinant of clinical outcomes, such as type 2 diabetes and cardiovascular events, in the Brazilian population.

  6. Surrogate versus couple therapy in vaginismus. (United States)

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


    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.

  7. A comparative study of the oxidation characteristics of two gasoline fuels and an n-heptane/iso-octane surrogate mixture

    KAUST Repository

    Javed, Tamour


    Ignition delay times and CO, H2O, OH and CO2 time-histories were measured behind reflected shock waves for two FACE (Fuels for Advanced Combustion Engines) gasolines and one PRF (Primary Reference Fuel) blend. The FACE gasolines chosen for this work are primarily paraffinic and have the same octane rating (∼RON = 84) as the PRF blend, but contain varying amounts of iso- and n-paraffins. Species time-histories and ignition delay times were measured using laser absorption methods over a temperature range of 1350-1550 K and pressures near 2 atm. Measured species time-histories and ignition delay times of the PRF blend and the two FACE fuels agreed reasonably well. However, when compared to recent gasoline surrogate mechanisms, the simulations did not capture some of the kinetic trends found in the species profiles. To our knowledge, this work provides some of the first shock tube species time-history data for gasoline fuels and PRF surrogates and should enable further improvements in detailed kinetic mechanisms of gasoline fuels.

  8. Biotin- and glycoprotein-coated microspheres: potential surrogates for studying filtration of cryptosporidium parvum in porous media. (United States)

    Pang, Liping; Nowostawska, Urszula; Weaver, Louise; Hoffman, Gabrielle; Karmacharya, Anjuman; Skinner, Alexandra; Karki, Naveena


    Cryptosporidium parvum is a waterborne pathogen, yet no suitable surrogate has been established for quantifying its filtration removal in porous media. Carboxyl polystyrene microspheres with size, density, and shape similar to C. parvum were coated with biotin (free and containing amine, NH(2)) and glycoprotein. These biomolecules have isoelectric points similar to C. parvum (pH ≈ 2), and glycoprotein is a major type of surface protein that oocysts possess. Zeta potential (ζ) and filtration removal of particles in sand of two different grain sizes were examined. Compared to unmodified microspheres, modified microspheres achieved a superior match to the oocysts in ζ, concentration, mass recovery, and collision coefficient. They showed the same log reduction in concentration as oocysts, whereas results from unmodified microspheres deviated by 1 order of magnitude. Of the three types of modified microspheres, glycoprotein-coated microspheres best resembled oocyst concentration, despite having ζ similar to NH(2)-biotin-coated microspheres, suggesting that surface protein also played an important role in particle attachment on solid surfaces. With further validation in environmental conditions, the surrogates developed here could be a cost-effective new tool for assessing oocyst filtration in porous media, for example, to evaluate the performance of sand filters in water and wastewater treatment, water recycling through riverbank filtration, and aquifer recharge.

  9. Total lymphocyte count is a reliable surrogate marker for CD4 cell counts after the first year of antiretroviral therapy: data from an Indonesian cohort study. (United States)

    de Jong, Marrigje A; Wisaksana, Rudi; Meijerink, Hinta; Indrati, Agnes; van de Ven, Andre J A M; Alisjahbana, Bachti; van Crevel, Reinout


    Many studies have evaluated the total lymphocyte count (TLC) as a cheap surrogate marker for CD4 cells in HIV-infected patients not receiving antiretroviral therapy (ART). We assessed whether TLC can replace CD4 cell counts in evaluating the immunological response to ART. In a cohort of patients in Indonesia TLC, if measured after at least 1-year ART, correctly identified patients with <200 CD4 cells, and reliably excluded immunological failure, obviating the need for CD4 cell measurement in 43% of patients. © 2012 Blackwell Publishing Ltd.

  10. Developments in Surrogating Methods

    Directory of Open Access Journals (Sweden)

    Hans van Dormolen


    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.

  11. Divergent rules for pollen and nectar foraging bumblebees--a laboratory study with artificial flowers offering diluted nectar substitute and pollen surrogate. (United States)

    Konzmann, Sabine; Lunau, Klaus


    Almost all bees collect nectar and pollen from flowers. Female bees collect pollen to provision their nest cells, whereas they use nectar for individual energy supply and nest cell provisioning. Bees fine-tune nectar foraging to the amount and to the concentration of nectar, but the individual bees' response to variability of amount and concentration of pollen reward has not yet been studied thoroughly in laboratory settings. We developed an experimental set-up in which bumblebees simultaneously collected sugar solution and pollen from artificial flowers; natural pollen was mixed with cellulose powder or glass powder as a pollen surrogate. Here we show that bumblebee (Bombus terrestris) workers do not specialise in nectar or pollen collection, but regularly collect both rewards on the same day. When offered a fixed pollen reward and varied amounts and concentrations of sugar solution, the bumblebees fine-tuned sugar solution foraging dependent on both the volume and concentration, with strong preferences for the highest concentration and the greatest volume. In the reciprocal tests, when offered a fixed sugar reward and varied amounts and concentrations of pollen mixed with a nutrient-free pollen surrogate, the bumblebees follow more an all-or-none rule for pollen, accepting all amounts and concentrations except pure surrogate. It is discussed how the bumblebees' ability to sense sugar, and their apparent inability to sense the pollen protein content, shaped their foraging behaviour. It is argued that the rarity of nectar mimicry and the frequency of pollen mimicry in natural flowers might be interpreted in the context of divergent abilities of nectar and pollen recognition in bees.

  12. Divergent rules for pollen and nectar foraging bumblebees--a laboratory study with artificial flowers offering diluted nectar substitute and pollen surrogate.

    Directory of Open Access Journals (Sweden)

    Sabine Konzmann

    Full Text Available Almost all bees collect nectar and pollen from flowers. Female bees collect pollen to provision their nest cells, whereas they use nectar for individual energy supply and nest cell provisioning. Bees fine-tune nectar foraging to the amount and to the concentration of nectar, but the individual bees' response to variability of amount and concentration of pollen reward has not yet been studied thoroughly in laboratory settings. We developed an experimental set-up in which bumblebees simultaneously collected sugar solution and pollen from artificial flowers; natural pollen was mixed with cellulose powder or glass powder as a pollen surrogate. Here we show that bumblebee (Bombus terrestris workers do not specialise in nectar or pollen collection, but regularly collect both rewards on the same day. When offered a fixed pollen reward and varied amounts and concentrations of sugar solution, the bumblebees fine-tuned sugar solution foraging dependent on both the volume and concentration, with strong preferences for the highest concentration and the greatest volume. In the reciprocal tests, when offered a fixed sugar reward and varied amounts and concentrations of pollen mixed with a nutrient-free pollen surrogate, the bumblebees follow more an all-or-none rule for pollen, accepting all amounts and concentrations except pure surrogate. It is discussed how the bumblebees' ability to sense sugar, and their apparent inability to sense the pollen protein content, shaped their foraging behaviour. It is argued that the rarity of nectar mimicry and the frequency of pollen mimicry in natural flowers might be interpreted in the context of divergent abilities of nectar and pollen recognition in bees.

  13. Recent progress in gasoline surrogate fuels

    KAUST Repository

    Sarathy, Mani


    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. Trial end points and natural history in patients with G11778A Leber hereditary optic neuropathy : preparation for gene therapy clinical trial. (United States)

    Lam, Byron L; Feuer, William J; Schiffman, Joyce C; Porciatti, Vittorio; Vandenbroucke, Ruth; Rosa, Potyra R; Gregori, Giovanni; Guy, John


    IMPORTANCE Establishing the natural history of G11778A Leber hereditary optic neuropathy (LHON) is important to determine the optimal end points to assess the safety and efficacy of a planned gene therapy trial. OBJECTIVE To use the results of the present natural history study of patients with G11778A LHON to plan a gene therapy clinical trial that will use allotopic expression by delivering a normal nuclear-encoded ND4 gene into the nuclei of retinal ganglion cells via an adeno-associated virus vector injected into the vitreous. DESIGN, SETTING, AND PARTICIPANTS A prospective observational study initiated in 2008 was conducted in primary and referral institutional practice settings. Participants included 44 individuals with G11778A LHON, recruited between September 2008 and March 2012, who were evaluated every 6 months and returned for 1 or more follow-up visits (6-36 months) as of August 2012. EXPOSURES Complete neuro-ophthalmic examination and main measures. MAIN OUTCOMES AND MEASURES Visual acuity, automated visual field testing, pattern electroretinogram, and spectral-domain optical coherence tomography. RESULTS Clinical measures were stable during the follow-up period, and visual acuity was as good as or better than the other visual factors used for monitoring patients. Based on a criterion of 15 or more letters from the Early Treatment Diabetic Retinopathy Study chart, 13 eyes of 8 patients (18%) improved, but 24 months after the onset of symptoms, any further improvements were to no better than 20/100. Acuity recovery occurred in some patients despite continued marked retinal nerve fiber layer thinning indistinguishable from that in patients who did not recover visual acuity. CONCLUSIONS AND RELEVANCE Spontaneous improvement of visual acuity in patients with G11778A LHON is not common and is partial and limited when it occurs, so improvements in vision with adeno-associated virus-mediated gene therapy of a synthetic wild-type ND4 subunit gene should be

  15. Four points function fitted and first derivative procedure for determining the end points in potentiometric titration curves: statistical analysis and method comparison. (United States)

    Kholeif, S A


    A new method that belongs to the differential category for determining the end points from potentiometric titration curves is presented. It uses a preprocess to find first derivative values by fitting four data points in and around the region of inflection to a non-linear function, and then locate the end point, usually as a maximum or minimum, using an inverse parabolic interpolation procedure that has an analytical solution. The behavior and accuracy of the sigmoid and cumulative non-linear functions used are investigated against three factors. A statistical evaluation of the new method using linear least-squares method validation and multifactor data analysis are covered. The new method is generally applied to symmetrical and unsymmetrical potentiometric titration curves, and the end point is calculated using numerical procedures only. It outperforms the "parent" regular differential method in almost all factors levels and gives accurate results comparable to the true or estimated true end points. Calculated end points from selected experimental titration curves compatible with the equivalence point category of methods, such as Gran or Fortuin, are also compared with the new method.

  16. Locating the QCD critical end point through peaked baryon number susceptibilities along the freeze-out line (United States)

    Li, Zhibin; Chen, Yidian; Li, Danning; Huang, Mei


    We investigate the baryon number susceptibilities up to fourth order along different freeze-out lines in a holographic QCD model with a critical end point (CEP), and we propose that the peaked baryon number susceptibilities along the freeze-out line can be used as a clean signature to locate the CEP in the QCD phase diagram. On the temperature and baryon chemical potential plane, the cumulant ratio of the baryon number susceptibilities (up to fourth order) forms a ridge along the phase boundary, and develops a sword-shaped “mountain” standing upright around the CEP in a narrow and oblate region. The measurement of baryon number susceptibilities from heavy-ion collision experiments is along the freeze-out line. If the freeze-out line crosses the foot of the CEP mountain, then one can observe the peaked baryon number susceptibilities along the freeze-out line, and the kurtosis of the baryon number distributions has the highest magnitude. The data from the first phase of the beam energy scan program at the Relativistic Heavy Ion Collider indicates that there should be a peak of the kurtosis of the baryon number distribution at a collision energy of around 5 GeV, which suggests that the freeze-out line crosses the foot of the CEP mountain and the summit of the CEP should be located nearby, around a collision energy of 3–7 GeV. Supported by NSFC (11275213, and 11261130311) (CRC 110 by DFG and NSFC), CAS key project KJCX2-EW-N01, and Youth Innovation Promotion Association of CAS

  17. Surrogate methods in geophysics (United States)

    Christiansen, Bo


    When testing complicated null-hypotheses where closed analytic expressions are not available we often rely on Monte Carlo methods to produce artificial surrogate data. However, many geophysical time-series have internal structures ranging from the correlations of simple first order auto-regression processes to more complex structures such as pseudo-periodic behavior. Forcing wrong assumptions - in the extreme case, independence - on the artificial data may lead to serious errors such as overestimation of the number of degrees of freedom and therefore also overestimation of p-values and unwarranted acceptance of null-hypotheses. Ideally, the artificial data should therefore fulfill the considered null-hypothesis but in all other aspects be statistically similar to the original data. Such aspects may include temporal correlations, power-spectra, distributions, pseudo-periodicity, and temporal asymmetry. Artificial surrogate data are also used for other purposes such as testing new algorithms on data with a specified structure. The aim of the present paper is to review the different methods to generate artificial data. We include methods based on randomizing the phases of the Fourier spectrum, pseudo-periodic surrogates based on drawing analogs in reconstructed (embedded) phase-space, ARMA processes, methods based on wavelets, and two new approaches based on Empirical Mode Decomposition and Singular Spectrum analysis. The different methods are applied to univariate time-series of different levels of complexity such as the El Nino-Southern Oscillation, the Quasi-biennial oscillation, and the Vostok ice core. The methods' abilities to faithfully reproduce the salient features of the original time-series are compared. We also investigate the possibilities of extending the methods to multivariate fields.

  18. Experimental Design for a Macrofoam Swab Study Relating the Recovery Efficiency and False Negative Rate to Low Concentrations of Two Bacillus anthracis Surrogates on Four Surface Materials

    Energy Technology Data Exchange (ETDEWEB)

    Piepel, Gregory F.; Hutchison, Janine R.


    This report describes the experimental design for a laboratory study to quantify the recovery efficiencies and false negative rates of a validated, macrofoam swab sampling method for low concentrations of Bacillus anthracis Sterne (BAS) and Bacillus atrophaeus (BG) spores on four surface materials (stainless steel, glass, vinyl tile, plastic light cover panel). Two analytical methods (plating/counting and polymerase chain reaction) will be used. Only one previous study has investigated false negative as a function of affecting test factors. The surrogates BAS and BG have not been tested together in the same study previously. Hence, this study will provide for completing gaps in the available information on the performance of macrofoam swab sampling at low concentrations.

  19. Experimental Design for a Macrofoam-Swab Study Relating the Recovery Efficiency and False Negative Rate to Low Concentrations of Two Bacillus anthracis Surrogates on Four Surface Materials

    Energy Technology Data Exchange (ETDEWEB)

    Piepel, Gregory F. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hutchison, Janine R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)


    This report describes the experimental design for a laboratory study to quantify the recovery efficiencies and false negative rates of a validated, macrofoam-swab sampling method for low concentrations of Bacillus anthracis Sterne (BAS) and Bacillus atrophaeus (BG) spores on four surface materials (stainless steel, glass, vinyl tile, plastic light cover panel). Two analytical methods (culture and polymerase chain reaction) will be used. Only one previous study has investigated how the false negative rate depends on test factors. The surrogates BAS and BG have not been tested together in the same study previously. Hence, this study will provide for completing gaps in the available information on the performance of macrofoam-swab sampling at low concentrations.

  20. 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. (United States)

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


    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.

  1. The national Fire and Fire Surrogate study: Effects of fuel reduction methods on forest vegetation structure and fuels (United States)

    Schwilk, D.W.; Keeley, J.E.; Knapp, E.E.; Mciver, J.; Bailey, J. D.; Fettig, C.J.; Fiedler, C.E.; Harrod, R.J.; Moghaddas, J.J.; Outcalt, K.W.; Skinner, C.N.; Stephens, S.L.; Waldrop, T.A.; Yaussy, D.A.; Youngblood, A.


    Changes in vegetation and fuels were evaluated from measurements taken before and after fuel reduction treatments (prescribed fire, mechanical treatments, and the combination of the two) at 12 Fire and Fire Surrogate (FFS) sites located in forests with a surface fire regime across the conterminous United States. To test the relative effectiveness of fuel reduction treatments and their effect on ecological parameters we used an informationtheoretic approach on a suite of 12 variables representing the overstory (basal area and live tree, sapling, and snag density), the understory (seedling density, shrub cover, and native and alien herbaceous species richness), and the most relevant fuel parameters for wildfire damage (height to live crown, total fuel bed mass, forest floor mass, and woody fuel mass). In the short term (one year after treatment), mechanical treatments were more effective at reducing overstory tree density and basal area and at increasing quadratic mean tree diameter. Prescribed fire treatments were more effective at creating snags, killing seedlings, elevating height to live crown, and reducing surface woody fuels. Overall, the response to fuel reduction treatments of the ecological variables presented in this paper was generally maximized by the combined mechanical plus burning treatment. If the management goal is to quickly produce stands with fewer and larger diameter trees, less surface fuel mass, and greater herbaceous species richness, the combined treatment gave the most desirable results. However, because mechanical plus burning treatments also favored alien species invasion at some sites, monitoring and control need to be part of the prescription when using this treatment. ?? 2009 by the Ecological Society of America.

  2. What Sexual Behaviors Relate to Decreased Sexual Desire in Women? A Review and Proposal for End Points in Treatment Trials for Hypoactive Sexual Desire Disorder

    Directory of Open Access Journals (Sweden)

    Robert Pyke, MD, PhD


    Pyke R and Clayton A. What Sexual Behaviors Relate to Decreased Sexual Desire in Women? A Review and Proposal for End Points in Treatment Trials for Hypoactive Sexual Desire Disorder. Sex Med 2017;5:e73–e83.

  3. Multitype Events and the Analysis of Heart Failure Readmissions: Illustration of a New Modeling Approach and Comparison With Familiar Composite End Points. (United States)

    Brown, Paul M; Ezekowitz, Justin A


    Heart failure-related hospital readmissions and mortality are often outcomes in clinical trials. Patients may experience multiple hospital readmissions over time with mortality acting as a dependent terminal event. Univariate composite end points are used for the analysis of readmissions. We may amend these approaches to include emergency department visits as a further outcome. An alternative multivariate modeling approach that categorizes hospital readmissions and emergency department visits as separate event types is proposed. We seek to compare the modeling approach which handles event types as separate, correlated end points against composites that amalgamate them to create a unified end point. Using a heart failure data set for illustration, a model with random effects for event types is estimated. The time-to-first event, unmatched win-ratio, and days-alive-and-out-of-hospital composites are derived for comparison. The model provides supplementary statistics such as the correlation among event types and yields considerably more power than the competing composite end points. The effect on individual outcomes is lost when they are intermingled to form a univariate composite. Simultaneously modeling different outcomes provides an alternative or supplementary analysis that may yield greater statistical power and additional insights. Improvements in software have made the multitype events model easier to implement and thus a useful, more efficient option when analyzing heart failure hospital readmissions and emergency department visits. © 2017 American Heart Association, Inc.

  4. Surrogate Modeling for Geometry Optimization

    DEFF Research Database (Denmark)

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


    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....

  5. The Effects of Prescribed Burning and Thinning on Herpetofauna and Small Mammals in the Upper Piedmont of South Carolina: Preliminary Results of the National Fire and Fire Surrogate Study (United States)

    Eran S. Kilpatrick; Dean B. Kubacz; David C. Guynn; J. Drew Lanham; Thomas A. Waldrop


    Due to heavy fuel loads resulting from years of fire suppression, upland pine and mixed pine hardwood forests in the Upper Piedmont of South Carolina are at risk of severe wildfire. The National Fire and Fire Surrogate Study (NFFS) was conducted on the Clemson Experimental Forest to study the effects of prescribed burning and thinning on a multitude of factors,...

  6. Transcranial laser therapy in acute stroke treatment: results of neurothera effectiveness and safety trial 3, a phase III clinical end point device trial. (United States)

    Hacke, Werner; Schellinger, Peter D; Albers, Gregory W; Bornstein, Natan M; Dahlof, Bjorn L; Fulton, Rachael; Kasner, Scott E; Shuaib, Ashfaq; Richieri, Steven P; Dilly, Stephen G; Zivin, Justin; Lees, Kennedy R


    On the basis of phase II trials, we considered that transcranial laser therapy could have neuroprotective effects in patients with acute ischemic stroke. We studied transcranial laser therapy in a double-blind, sham-controlled randomized clinical trial intended to enroll 1000 patients with acute ischemic stroke treated ≤24 hours after stroke onset and who did not undergo thrombolytic therapy. The primary efficacy measure was the 90-day functional outcome as assessed by the modified Rankin Scale, with hierarchical Bayesian analysis incorporating relevant previous data. Interim analyses were planned after 300 and 600 patients included. The study was terminated on recommendation by the Data Monitoring Committee after a futility analysis of 566 completed patients found no difference in the primary end point (transcranial laser therapy 140/282 [49.6%] versus sham 140/284 [49.3%] for good functional outcome; modified Rankin Scale, 0-2). The results remained stable after inclusion of all 630 randomized patients (adjusted odds ratio, 1.024; 95% confidence interval, 0.705-1.488). Once the results of the interim futility analysis became available, all study support was immediately withdrawn by the capital firms behind PhotoThera, and the company was dissolved. Proper termination of the trial was difficult but was finally achieved through special efforts by former employees of PhotoThera, the CRO Parexel and members of the steering and the safety committees. We conclude that transcranial laser therapy does not have a measurable neuroprotective effect in patients with acute ischemic stroke when applied within 24 hours after stroke onset. Unique identifier: NCT01120301. © 2014 American Heart Association, Inc.

  7. Surrogate decision makers' responses to physicians' predictions of medical futility. (United States)

    Zier, Lucas S; Burack, Jeffrey H; Micco, Guy; Chipman, Anne K; Frank, James A; White, Douglas B


    Although physicians sometimes use the futility rationale to limit the use of life-sustaining treatments, little is known about how surrogate decision makers view this rationale. We sought to determine the attitudes of surrogates of patients who are critically ill toward whether physicians can predict futility and whether these attitudes predict surrogates' willingness to discontinue life support when faced with predictions of futility. This multicenter, mixed qualitative and quantitative study took place at three hospitals in California from 2006 to 2007. We conducted semistructured interviews with surrogate decision makers for 50 patients who were critically ill and incapacitated that addressed their beliefs about medical futility and inductively developed an organizing framework to describe these beliefs. We used a hypothetical scenario with a modified time-trade-off design to examine the relationship between a patient's prognosis and a surrogate's willingness to withdraw life support. We used a mixed-effects regression model to examine the association between surrogates' attitudes about futility and their willingness to limit life support in the face of a very poor prognosis. Validation methods included the use and integration of multiple data sources, multidisciplinary analysis, and member checking. Sixty-four percent of surrogates (n = 32; 95% confidence interval [CI], 49 to 77%) expressed doubt about the accuracy of physicians' futility predictions, 32% of surrogates (n = 16; 95% CI, 20 to 47%) elected to continue life support with a decision makers. The nature of the doubt may have implications for responding to conflicts about futility in clinical practice.

  8. Effect of dronedarone on clinical end points in patients with atrial fibrillation and coronary heart disease: insights from the ATHENA trial. (United States)

    Pisters, Ron; Hohnloser, Stefan H; Connolly, Stuart J; Torp-Pedersen, Christian; Naditch-Brûlé, Lisa; Page, Richard L; Crijns, Harry J G M


    This study aimed to assess safety and cardiovascular outcomes of dronedarone in patients with paroxysmal or persistent atrial fibrillation (AF) with coronary heart disease (CHD). Coronary heart disease is prevalent among AF patients and limits antiarrhythmic drug use because of their potentially life-threatening ventricular proarrhythmic effects. This post hoc analysis evaluated 1405 patients with paroxysmal or persistent AF and CHD from the ATHENA trial. Follow-up lasted 2.5 years, during which patients received either dronedarone (400 mg twice daily) or a double-blind matching placebo. Primary outcome was time to first cardiovascular hospitalization or death due to any cause. Secondary end points included first hospitalization due to cardiovascular events. The primary outcome occurred in 350 of 737 (47%) placebo patients vs. 252 of 668 (38%) dronedarone patients [hazard ratio (HR) = 0.73; 95% confidence interval (CI) = 0.62-0.86; P = 0.0002] without a significant increase in number of adverse events. In addition, 42 of 668 patients receiving dronedarone suffered from a first acute coronary syndrome compared with 67 of 737 patients from the placebo group (HR = 0.67; 95% CI = 0.46-0.99; P = 0.04). In this post hoc analysis, dronedarone on top of standard care in AF patients with CHD reduced cardiovascular hospitalization or death similar to that in the overall ATHENA population, and reduced a first acute coronary syndrome. Importantly, the safety profile in this subpopulation was also similar to that of the overall ATHENA population, with no excess in proarrhythmias. The mechanism of the cardiovascular protective effects is unclear and warrants further investigation.

  9. Characteristics of Clinical Studies Used for US Food and Drug Administration Approval of High-Risk Medical Device Supplements. (United States)

    Zheng, Sarah Y; Dhruva, Sanket S; Redberg, Rita F


    High-risk medical devices often undergo modifications, which are approved by the US Food and Drug Administration (FDA) through various kinds of premarket approval (PMA) supplements. There have been multiple high-profile recalls of devices approved as PMA supplements. To characterize the quality of the clinical studies and data (strength of evidence) used to support FDA approval of panel-track supplements (a type of PMA supplement pathway that is used for significant changes in a device or indication for use and always requires clinical data). Descriptive study of clinical studies supporting panel-track supplements approved by the FDA between April 19, 2006, and October 9, 2015. Panel-track supplement approval. Methodological quality of studies including randomization, blinding, type of controls, clinical vs surrogate primary end points, use of post hoc analyses, and reporting of age and sex. Eighty-three clinical studies supported the approval of 78 panel-track supplements, with 71 panel-track supplements (91%) supported by a single study. Of the 83 studies, 37 (45%) were randomized clinical trials and 25 (30%) were blinded. The median number of patients per study was 185 (interquartile range, 75-305), and the median follow-up duration was 180 days (interquartile range, 84-270 days). There were a total of 150 primary end points (mean [SD], 1.8 [1.2] per study), and 57 primary end points (38%) were compared with controls. Of primary end points with controls, 6 (11%) were retrospective controls and 51 (89%) were active controls. One hundred twenty-one primary end points (81%) were surrogate end points. Thirty-three studies (40%) did not report age and 25 (30%) did not report sex for all enrolled patients. The FDA required postapproval studies for 29 of 78 (37%) panel-track supplements. Among clinical studies used to support FDA approval of high-risk medical device modifications, fewer than half were randomized, blinded, or controlled, and most primary outcomes were

  10. Detection of Lupine (Lupinus spp. L. as a food allergen using three methods: end-point PCR, Real-Time PCR and Elisa

    Directory of Open Access Journals (Sweden)

    Ondrej Revák


    Full Text Available The aim of this work was to compare three methods for the detection and quantification of lupine as an allergen in food. The methods that were used in this work were the direct method: ELISA and the indirect methods: end-point PCR and real-time PCR. We examined the detection limit (the sensitivity with which we can detect the presence of the allergen in a sample and the reliability for performing an analysis. We used 17 samples of plant species from a processing plant for dehydrated soups production and lupine samples from lupine processing companies. Its practical use is wide and it is used mainly in the bakery industry, in the manufacture of confectionery, pasta, sauces, as a substitute for soy and also in the production of gluten-free food, because it does not contain gluten. Lupine, however, is also included in the list of 14 allergenic substances, which in accordance with the EU legislation must be listed on food labels. The high risk group, which suffers from primary sensitization or cross-reaction with peanuts, are allergic patients. In the EU, people who are allergic to peanuts range from 0.7 to 1.5%. In experiment 1, we detected the presence of lupine using primers for the detection of α- and δ-conglutine in the samples, using the end-point PCR method and the detection limit of this reaction was at the level of 100 ppm. For the vizualization of the DNA fragments, we used a 2% agarose gel and UV visualizer. In experiment 2 we detected lupine using the TaqMan real-time PCR reaction and primers for the detection of α and δ-conglutine at the level of 10 ppm of lupine in sample. The CP values of lupine using primers for the detection of α-conglutine was 24.85 ± 0.12 and the reliability equation was R2 = 0.9767. The CP lupine values using primers for the detection of δ-conglutine was 22.52 ± 0.17 and the reliability equation was R2 = 0.9925. In experiment 3, we used a sandwich ELISA method for the detection of lupine and the

  11. Traffic density as a surrogate measure of environmental exposures in studies of air pollution health effects: Long-term mortality in a cohort of US veterans (United States)

    Lipfert, F. W.; Wyzga, R. E.; Baty, J. D.; Miller, J. P.

    Vehicular traffic is an ubiquitous source of air pollution in developed nations, yet relatively few epidemiology studies have considered its long-term health effects. This paper uses an areal measure of traffic density as a surrogate index of exposure to vehicular traffic. We present associations between county-level traffic density (annual vehicle-km traveled km -2), ambient air quality, and mortality in a cohort of about 70,000 male US veterans (the Washington University-EPRI Veterans Cohort) who were enrolled in 1976 and followed through 2001. Traffic density is seen to be a significant and robust predictor of survival in this cohort, more so than ambient air quality, with the possible exception of ozone. Stronger effects of traffic density are seen in the counties that have ambient air quality monitoring data, which also tend to have higher levels of traffic density. These proportional-hazard modeling results indicate only modest changes in traffic-related mortality risks over time, from 1976-2001, despite the decline in regulated tailpipe emissions per vehicle since the mid-1970s. This suggests that other environmental effects may be involved, such as particles from brake, tire, and road wear, traffic noise, psychological stress, and spatial gradients in socioeconomic status.

  12. Development of a versatile tool for the simultaneous differential detection of Pseudomonas savastanoi pathovars by End Point and Real-Time PCR

    Directory of Open Access Journals (Sweden)

    Santilli Elena


    Full Text Available Abstract Background Pseudomonas savastanoi pv. savastanoi is the causal agent of olive knot disease. The strains isolated from oleander and ash belong to the pathovars nerii and fraxini, respectively. When artificially inoculated, pv. savastanoi causes disease also on ash, and pv. nerii attacks also olive and ash. Surprisingly nothing is known yet about their distribution in nature on these hosts and if spontaneous cross-infections occur. On the other hand sanitary certification programs for olive plants, also including P. savastanoi, were launched in many countries. The aim of this work was to develop several PCR-based tools for the rapid, simultaneous, differential and quantitative detection of these P. savastanoi pathovars, in multiplex and in planta. Results Specific PCR primers and probes for the pathovars savastanoi, nerii and fraxini of P. savastanoi were designed to be used in End Point and Real-Time PCR, both with SYBR® Green or TaqMan® chemistries. The specificity of all these assays was 100%, as assessed by testing forty-four P. savastanoi strains, belonging to the three pathovars and having different geographical origins. For comparison strains from the pathovars phaseolicola and glycinea of P. savastanoi and bacterial epiphytes from P. savastanoi host plants were also assayed, and all of them tested always negative. The analytical detection limits were about 5 - 0.5 pg of pure genomic DNA and about 102 genome equivalents per reaction. Similar analytical thresholds were achieved in Multiplex Real-Time PCR experiments, even on artificially inoculated olive plants. Conclusions Here for the first time a complex of PCR-based assays were developed for the simultaneous discrimination and detection of P. savastanoi pv. savastanoi, pv. nerii and pv. fraxini. These tests were shown to be highly reliable, pathovar-specific, sensitive, rapid and able to quantify these pathogens, both in multiplex reactions and in vivo. Compared with the other

  13. End point prick test: could this new test be used to predict the outcome of oral food challenge in children with cow's milk allergy?

    Directory of Open Access Journals (Sweden)

    Bellini Federica


    Full Text Available Abstract Background Cow's milk allergy (CMA is the most frequent food allergy in childhood; the trend of CMA is often characterized by a progressive improvement to achieve tolerance in the first 4 to 5 years of life. It has been observed that specific IgE (sIgE towards cow's milk proteins decrease when the age increases. Although food allergy can be easily diagnosed, it is difficult to predict the outcome of the oral food challenge (OFC, that remains the gold standard in the diagnosis of food allergy, by allergometric tests. Methods We considered 44 children with CMA diagnosed through OFC who returned to our Allergy and Immunology Pediatric Department between January to December 2010 to evaluate the persistence of allergy or the achievement of tolerance. On the basis of the history, we performed both allergometric skin tests and OFC in children that were still following a milk-free diet, whereas only allergometric skin tests those that had already undergone spontaneous introduction of milk protein at home without presenting symptoms. Objective The aim of this study was to investigate the relationship between the persistence of CMA or the acquisition of tolerance and the results of the end point prick test (EPT. Results and Discussion The OFC with cow's milk was performed on 30 children, 4 children were excluded because of a history of severe reactions to cow's milk, and 10 because they had spontaneously already taken milk food derivates at home without problems. 16/30 (53% children showed clinical reactions and the challenge was stopped, 14/30 (47% did not have any reaction. Comparing the mean wheal diameter of every EPT's dilution between the group of allergic children and the tolerant ones, we obtained a significant difference (p We have also calculated sensitivity (SE, specificity (SP, the positive predictive value (PPV and the negative predictive value (NPV for each EPT dilution. Conclusions EPT is a safe and cheap test, easy to be executed

  14. Are lipid profiles true surrogate biomarkers of coronary heart disease in periodontitis patients?: A case-control study in a south Indian population. (United States)

    Gita, Bagavad; Sajja, Chandrasekaran; Padmanabhan, Preethi


    There is abundant literature delving into whether periodontal infection contributes to atherosclerosis. However, whether periodontitis is a definite risk factor for atherosclerosis still remains empirical, with no systematic reviews or longitudinal studies to confirm this hypothesis. The prevalence of periodontitis and coronary artery disease also varies among racial and ethnic groups based on various factors such as diet, lifestyle, and genetic predisposition. This study was designed in a south Indian population with the aim of assessing and correlating the lipid levels (a surrogate biomarker for coronary heart disease) in patients with periodontitis and health. (1) To assess the levels of total cholesterol, low density lipoproteins (LDL), high density lipoproteins (HDL), and triglycerides in periodontal disease, and health in a south Indian population. (2) To assess associations between elevated lipid profiles and periodontal disease. This case control study included 60 individuals. Blood sampling for lipid levels and periodontal examination were performed for each study group. Appropriate statistical tools like Chi-square (P0.05) after eliminating confounding factors. Odds Ratio=(Total cholesterol (1.005), HDL (0.971), LDL (1.006), VLDL (0.997), CHO-HDL (1.358), TGL (1.007), LDL-HDL (1.180)). The odds ratio stated that there is no significant relation between the lipid levels and periodontal condition. The above findings confirm that there is still no concrete evidence which determines if periodontitis is an independent risk factor for atherosclerotic cardiovascular disease. Future periodontal interventional studies and assessment of genetic markers can ascertain the validity of this hypothesis. There is no association among periodontal disease and the levels of total cholesterol, LDL, HDL, and triglycerides.

  15. Scope and outcomes of surrogate decision making among hospitalized older adults. (United States)

    Torke, Alexia M; Sachs, Greg A; Helft, Paul R; Montz, Kianna; Hui, Siu L; Slaven, James E; Callahan, Christopher M


    Hospitalized older adults often lack decisional capacity, but outside of the intensive care unit and end-of-life care settings, little is known about the frequency of decision making by family members or other surrogates or its implications for hospital care. To describe the scope of surrogate decision making, the hospital course, and outcomes for older adults. Prospective, observational study conducted in medicine and medical intensive care unit services of 2 hospitals in 1 Midwestern city in 1083 hospitalized older adults identified by their physicians as requiring major medical decisions. Clinical characteristics, hospital outcomes, nature of major medical decisions, and surrogate involvement. According to physician reports, at 48 hours of hospitalization, 47.4% (95% CI, 44.4%-50.4%) of older adults required at least some surrogate involvement, including 23.0% (20.6%-25.6%) with all decisions made by a surrogate. Among patients who required a surrogate for at least 1 decision within 48 hours, 57.2% required decisions about life-sustaining care (mostly addressing code status), 48.6% about procedures and operations, and 46.9% about discharge planning. Patients who needed a surrogate experienced a more complex hospital course with greater use of ventilators (2.5% of patients who made decisions and 13.2% of patients who required any surrogate decisions; P care facility (21.2% with patient decisions and 40.9% with surrogate decisions; P hospital mortality (0.0% patients and 5.9% surrogates; P care representative document in the medical record. Surrogate decision making occurs for nearly half of hospitalized older adults and includes both complete decision making by the surrogate and joint decision making by the patient and surrogate. Surrogates commonly face a broad range of decisions in the intensive care unit and the hospital ward setting. Hospital functions should be redesigned to account for the large and growing role of surrogates, supporting them as they make

  16. Effects of Different End-Point Cooking Temperatures on the Efficiency of Encapsulated Phosphates on Lipid Oxidation Inhibition in Ground Meat. (United States)

    Kılıç, B; Şimşek, A; Claus, J R; Atılgan, E; Aktaş, N


    Effects of 0.5% encapsulated (e) phosphates (sodium tripolyphosphate, STP; sodium hexametaphosphate, HMP; sodium pyrophosphate, SPP) on lipid oxidation during storage (0, 1, and 7 d) of ground meat (chicken, beef) after being cooked to 3 end-point cooking temperatures (EPCT; 71, 74, and 77 °C) were evaluated. The use of STP or eSTP resulted in lower (P led to a significant increase in CL (P meat industry and the efficiency of encapsulated phosphates on lipid oxidation inhibition can be enhanced by lowering EPCT. © 2015 Institute of Food Technologists®

  17. Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo

    DEFF Research Database (Denmark)

    Bentley-Lewis, Rhonda; Aguilar, David; Riddle, Matthew C


    BACKGROUND: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagon-like peptide 1 receptor agonist....... The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population at high CV risk. The primary efficacy end point is a composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Data are systematically...

  18. Glycated Hemoglobin, Albuminuria and Surrogate Markers of Macrovascular Disease: The Guangzhou Biobank Cohort Study, Cardiovascular Disease Subcohort. (United States)

    Toulis, Konstantinos A; Jiang, Chao Q; Hemming, Karla; Nirantharakumar, Krishnarajah; Cheng, Kar K; Lam, Tai H; Thomas, G Neil


    To explore the clinical utility of glycated hemoglobin (A1C) levels as an early marker of albuminuria, macrovascular disease and subclinical cardiovascular disease in comparison to fasting and postprandial glucose levels in a well-characterized Chinese population with no history of diabetes. The study population consisted of 1223 individuals who were enrolled in the Guangzhou Biobank Cohort Study, Cardiovascular Disease Subcohort, and who had undergone oral glucose tolerance tests. The associations between each glycemic measure and albuminuria, carotid intima-media thickness (CIMT) and CIMT-based presence of carotid plaques and aortic arch calcification were assessed by chest radiographs. The overall prevalence of albuminuria, carotid plaque and any aortic arch calcification was 20.6%, 22.8% and 25.8%, respectively. All 3 glycemia indices were significantly associated with albuminuria, but only 1 (fasting glucose) was associated with carotid plaques. No significant difference was detected among them in the area under the curve for albuminuria (chi-square test; p=0.84), carotid plaques (p=0.28) or calcifications (p=0.29). In sensitivity analysis, adjusted for age and sex, the above findings remained unchanged. Although there was evidence suggesting differential associations, the performance of the glycemic indices was similar, and their association with macrovascular disease and albuminuria was modest. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

  19. Serum total immunoglobulin E is a surrogate of atopy in adult-onset asthma: a longitudinal study. (United States)

    Carsin, Anne-Elie; Zock, Jan-Paul; Jarvis, Deborah; Basagaña, Xavier; Heinrich, Joachim; Toren, Kjell; Janson, Christer; Anto, Josep Maria; Sunyer, Jordi


    Studies have shown that serum total immunoglobulin E (IgE) levels are higher in asthmatics. However, the role of the serum total IgE level, independently from atopy, in adult asthma is not understood. We studied the associations between serum total IgE, the number of sensitizations and the sum of specific IgEs and new-onset asthma using longitudinal data from the European Community Respiratory Health Survey. Serum total and specific IgE to 4 common inhalant allergens were measured at baseline in 9,175 participants, with a follow-up of 9 years. Individuals with asthma history and/or asthma symptoms were excluded. Atopy was defined as the presence of at least one specific IgE ≥0.35 kU/l. Total and specific IgEs were regressed against new-onset asthma using multivariate logistic regression with a random intercept for the study centre. Two hundred and ninety-seven participants had developed asthma during follow-up (incidence rate 5.7 per 1,000 person-years). A 10% higher level of total IgE was associated with a 12% increased risk of new-onset asthma (p = 0.005). However, after adjustment for the number of positive specific IgEs [odds ratio (OR) for multiple sensitization 1.74, 95% confidence interval (CI) 1.05–2.88] and the sum of allergenspecific IgEs (OR 1.18, 95% CI 1.00–1.40), the association between total IgE and asthma disappeared (OR 1.00, 95% CI 0.91–1.10). Seventeen percent of new-onset asthma cases could be attributed to atopy, and this estimate was not largely modified when the total IgE level was simultaneously taken into account. After taking into account the number and intensity of 4 specific IgEs, the serum total IgE level was not associated with new-onset asthma in adults.

  20. How Surrogates Decide: A Secondary Data Analysis of Decision-Making Principles Used by the Surrogates of Hospitalized Older Adults. (United States)

    Devnani, Rohit; Slaven, James E; Bosslet, Gabriel T; Montz, Kianna; Inger, Lev; Burke, Emily S; Torke, Alexia M


    Many hospitalized adults do not have the capacity to make their own health care decisions and thus require a surrogate decision-maker. While the ethical standard suggests that decisions should focus on a patient's preferences, our study explores the principles that surrogates consider most important when making decisions for older hospitalized patients. We sought to determine how frequently surrogate decision-makers prioritized patient preferences in decision-making and what factors may predict their doing so. We performed a secondary data analysis of a study conducted at three local hospitals that surveyed surrogate decision-makers for hospitalized patients 65 years of age and older. Surrogates rated the importance of 16 decision-making principles and selected the one that was most important. We divided the surrogates into two groups: those who prioritized patient preferences and those who prioritized patient well-being. We analyzed the two groups for differences in knowledge of patient preferences, presence of advance directives, and psychological outcomes. A total of 362 surrogates rated an average of six principles as being extremely important in decision-making; 77.8% of surrogates selected a patient well-being principle as the most important, whereas only 21.1% selected a patient preferences principle. Advance directives were more common to the patient preferences group than the patient well-being group (61.3% vs. 44.9%; 95% CI: 1.01-3.18; p = 0.04), whereas having conversations with the patient about their health care preferences was not a significant predictor of surrogate group identity (81.3% vs. 67.4%; 95% CI: 0.39-1.14; p = 0.14). We found no differences between the two groups regarding surrogate anxiety, depression, or decisional conflict. While surrogates considered many factors, they focused more often on patient well-being than on patient preferences, in contravention of our current ethical framework. Surrogates more commonly prioritized

  1. Constraints on grip selection in hemiparetic cerebral palsy: Effects of lesional side, end-point accuracy and context.

    NARCIS (Netherlands)

    Steenbergen, B.; Meulenbroek, R.G.J.; Rosenbaum, D.A.


    This study was concerned with the selection criteria used for grip planning in adolescents with left or right hemiparetic cerebral palsy. In the first experiment participants picked up a pencil and placed the tip in a pre-defined target region. We varied the size of the target to test the hypothesis

  2. Galleria mellonella is low cost and suitable surrogate host for studying virulence of human pathogenic Vibrio cholerae. (United States)

    Bokhari, Habib; Ali, Amjad; Noreen, Zobia; Thomson, Nicholas; Wren, Brendan W


    Vibrio cholerae causes a severe diarrheal disease affecting millions of people worldwide, particularly in low income countries. V. cholerae successfully persist in aquatic environment and its pathogenic strains results in sever enteric disease in humans. This dual life style contributes towards its better survival and persistence inside host gut and in the environment. Alternative animal replacement models are of great value in studying host-pathogen interaction and for quick screening of various pathogenic strains. One such model is Galleria mellonella, a wax moth which has a complex innate immune system and here we investigate its suitability as a model for clinical human isolates of O1 El TOR, Ogawa serotype belonging to two genetically distinct subclades found in Pakistan (PSC-1 and PSC-2). We demonstrate that the PSC-2 strain D59 frequently isolated from inland areas, was more virulent than PSC-1 strain K7 mainly isolated from coastal areas (p=0.0001). In addition, we compared the relative biofilm capability of the representative strains as indicators of their survival and persistence in the environment and K7 showed enhanced biofilm forming capabilities (p=0.004). Finally we present the annotated genomes of the strains D59 and K7, and compared them with the reference strain N16961. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. The design of contact lens based ocular drug delivery systems for single-day use: Part (I) Structural factors, surrogate ophthalmic dyes and passive diffusion studies. (United States)

    Mahomed, Anisa; Tighe, Brian J


    The poor retention and efficacy of instilled drops as a means of delivering drugs to the ophthalmic environment is well-recognised. The potential value of contact lenses as a means of ophthalmic drug delivery, and consequent improvement of pre-corneal retention is one obvious route to the development of a more effective ocular delivery system. Furthermore, the increasing availability and clinical use of daily disposable contact lenses provides the platform for the development of viable single-day use drug delivery devices based on existing materials and lenses. In order to provide a basis for the effective design of such devices, a systematic understanding of the factors affecting the interaction of individual drugs with the lens matrix is required. Because a large number of potential structural variables are involved, it is necessary to achieve some rationalisation of the parameters and physicochemical properties (such as molecular weight, charge, partition coefficients) that influence drug interactions. Ophthalmic dyes and structurally related compounds based on the same core structure were used to investigate these various factors and the way in which they can be used in concert to design effective release systems for structurally different drugs. Initial studies of passive diffusional release form a necessary precursor to the investigation of the features of the ocular environment that over-ride this simple behaviour. Commercially available contact lenses of differing structural classifications were used to study factors affecting the uptake of the surrogate actives and their release under 'passive' conditions. The interaction between active and lens material shows considerable and complex structure dependence, which is not simply related to equilibrium water content. The structure of the polymer matrix itself was found to have the dominant controlling influence on active uptake; hydrophobic interaction with the ophthalmic dye playing a major role. © The

  4. Comparison of computer- and human-derived coronary angiographic end-point measures for controlled therapy trials (United States)

    Mack, W. J.; Selzer, R. H.; Pogoda, J. M.; Lee, P. L.; Shircore, A. M.; Azen, S. P.; Blankenhorn, D. H.


    The Cholesterol Lowering Atherosclerosis Study, a randomized angiographic clinical trial, demonstrated the beneficial effect of niacin/colestipol plus diet therapy on coronary atherosclerosis. Outcome was determined by panel-based estimates (viewed in both still and cine modes) of percent stenosis severity and change in native artery and bypass graft lesions. Computer-based quantitative coronary angiography (QCA) was also used to measure lesion and bypass graft stenosis severity and change in individual frames closely matched in orientation, opacification, and cardiac phase. Both methods jointly evaluated 350 nonoccluded lesions. The correlation between QCA and panel estimates of lesion size was 0.70 (p less than 0.0001) and for change in lesion size was 0.28 (p = 0.002). Agreement between the two methods in classifying lesion changes (i.e., regression, unchanged, or progression) occurred for 60% (210 of 350) of the lesions kappa +/- SEM = 0.20 +/- 0.05, p less than 0.001). The panel identified 442 nonoccluded lesions for which QCA stenosis measurements could not be obtained. Lesions not measurable by QCA included those with stenosis greater than 85% that could not be reliably edge tracked, segments with diffuse or ecstatic disease that had no reliable reference diameter, and segments for which matched frames could not be located. Seventy-nine lesions, the majority between 21% and 40% stenosis, were identified and measured by QCA but were not identified by the panel. This comparison study demonstrates the need to consider available angiographic measurement methods in relation to the goals of their use.

  5. Evidence of low-density and high-density liquid phases and isochore end point for water confined to carbon nanotube. (United States)

    Nomura, Kentaro; Kaneko, Toshihiro; Bai, Jaeil; Francisco, Joseph S; Yasuoka, Kenji; Zeng, Xiao Cheng


    Possible transition between two phases of supercooled liquid water, namely the low- and high-density liquid water, has been only predicted to occur below 230 K from molecular dynamics (MD) simulation. However, such a phase transition cannot be detected in the laboratory because of the so-called "no-man's land" under deeply supercooled condition, where only crystalline ices have been observed. Here, we show MD simulation evidence that, inside an isolated carbon nanotube (CNT) with a diameter of 1.25 nm, both low- and high-density liquid water states can be detected near ambient temperature and above ambient pressure. In the temperature-pressure phase diagram, the low- and high-density liquid water phases are separated by the hexagonal ice nanotube (hINT) phase, and the melting line terminates at the isochore end point near 292 K because of the retracting melting line from 292 to 278 K. Beyond the isochore end point (292 K), low- and high-density liquid becomes indistinguishable. When the pressure is increased from 10 to 600 MPa along the 280-K isotherm, we observe that water inside the 1.25-nm-diameter CNT can undergo low-density liquid to hINT to high-density liquid reentrant first-order transitions.

  6. Revisiting algorithms for generating surrogate time series

    CERN Document Server

    Raeth, C; Papadakis, I E; Brinkmann, W


    The method of surrogates is one of the key concepts of nonlinear data analysis. Here, we demonstrate that commonly used algorithms for generating surrogates often fail to generate truly linear time series. Rather, they create surrogate realizations with Fourier phase correlations leading to non-detections of nonlinearities. We argue that reliable surrogates can only be generated, if one tests separately for static and dynamic nonlinearities.

  7. Physician understanding and application of surrogate decision-making laws in clinical practice. (United States)

    Comer, Amber Rose; Gaffney, Margaret; Stone, Cynthia L; Torke, Alexia


    Although state surrogate laws are the most common way surrogate decision makers are identified, no studies have been conducted to determine physician understanding of these laws or how these laws are utilized during clinical practice. The purpose of this study is to better understand how surrogate decision-making laws function in practice. A cross-sectional survey of 412 physicians working in Indiana hospitals was conducted between November 2014 and January 2015 to determine physicians' knowledge of Indiana's surrogate decision-making law and physicians' approaches to hypothetical cases using the law in clinical practice. Fewer than half of physicians (48%) were able to correctly identify all legally allowable surrogate decision makers. Of those physicians who knew the law, nearly all of them (98%) indicated that they would violate the law during clinical practice by allowing nonlegal surrogates such as grandchildren to make medical decisions. A majority of physicians endorse relying on surrogates who have strong ties to the patient but are not legally allowable in Indiana. It is possible that these decisions reflect sound ethical reasoning even though they are illegal. Due to the narrow construction of some state surrogate decision laws, physicians may be placed in the position where they must either choose to follow medical ethical principles or the law. To alleviate these issues, state surrogate decision laws need to be amended to include a broader list of surrogates, such as extended family and close friends.

  8. Improved efficiency and robustness in qPCR and multiplex end-point PCR by twisted intercalating nucleic acid modified primers.

    Directory of Open Access Journals (Sweden)

    Uffe Vest Schneider

    Full Text Available We introduce quantitative polymerase chain reaction (qPCR primers and multiplex end-point PCR primers modified by the addition of a single ortho-Twisted Intercalating Nucleic Acid (o-TINA molecule at the 5'-end. In qPCR, the 5'-o-TINA modified primers allow for a qPCR efficiency of 100% at significantly stressed reaction conditions, increasing the robustness of qPCR assays compared to unmodified primers. In samples spiked with genomic DNA, 5'-o-TINA modified primers improve the robustness by increased sensitivity and specificity compared to unmodified DNA primers. In unspiked samples, replacement of unmodified DNA primers with 5'-o-TINA modified primers permits an increased qPCR stringency. Compared to unmodified DNA primers, this allows for a qPCR efficiency of 100% at lowered primer concentrations and at increased annealing temperatures with unaltered cross-reactivity for primers with single nucleobase mismatches. In a previously published octaplex end-point PCR targeting diarrheagenic Escherichia coli, application of 5'-o-TINA modified primers allows for a further reduction (>45% or approximately one hour in overall PCR program length, while sustaining the amplification and analytical sensitivity for all targets in crude bacterial lysates. For all crude bacterial lysates, 5'-o-TINA modified primers permit a substantial increase in PCR stringency in terms of lower primer concentrations and higher annealing temperatures for all eight targets. Additionally, crude bacterial lysates spiked with human genomic DNA show lesser formation of non-target amplicons implying increased robustness. Thus, 5'-o-TINA modified primers are advantageous in PCR assays, where one or more primer pairs are required to perform at stressed reaction conditions.

  9. Biodiesel surrogates: achieving performance demands. (United States)

    Sarin, Rakesh; Kumar, Ravindra; Srivastav, Bhawana; Puri, S K; Tuli, D K; Malhotra, R K; Kumar, Anand


    Synthesis of surrogate molecules is particularly useful for generating in sight of structural-activity relationships, understanding processes and improving the performance. In order to improve upon the physico-chemical properties of biodiesel, methyl, ethyl, isopropyl and n-butyl esters of beta-branched fatty acid have been synthesized, initiating from beta-branched alcohols. Beta-branched alcohols upon oxidation gave corresponding acids, which were converted to their esters. The synthesized esters have substantially better oxidative stability, exhibited by Rancimat oxidation induction period of more than 24 h. The cloud point of synthesized esters is surrogate esters have viscosity in the range of 4.2-4.6 cSt at 40 degrees C, meeting the international diesel and biodiesel standards. The cetane number of synthesized esters is 62-69, which is much better than diesel and biodiesel. The blends of the synthesized esters in diesel at 5% and 10% meet Indian standards of diesel.

  10. Efficacy and tolerability balance of oxycodone/naloxone and tapentadol in chronic low back pain with a neuropathic component: a blinded end point analysis of randomly selected routine data from 12-week prospective open-label observations

    Directory of Open Access Journals (Sweden)

    Ueberall MA


    quality of life in 76.6%/68.0%/50.0% vs 63.9%/54.1%/34.6% (P=0.026/0.022/0.017. Overall, OXN vs TAP treatments were well tolerated, and proportions of patients who either maintained a normal bowel function (68.0% vs 72.2%, reported no central nervous system side effects (91.4% vs 89.5%, or completed the 12-week evaluation period without any TEAE-related treatment discontinuations (93.0% vs 92.5% were similar for both index medications (P= ns for each comparison. Conclusion: In daily practice, the BRP of OXN proved to be noninferior to that of TAP in patients with cLBP-NC, but showed a superior efficacy if stricter analgesic response definitions were evaluated. Keywords: oxycodone/naloxone, tapentadol, chronic low back pain, neuropathic component, noninterventional study, German Pain Registry, random data selection, blinded end point analysis, benefit–risk profile

  11. Surrogates-based prototyping

    NARCIS (Netherlands)

    Du Bois, E.; Horvath, I.


    The research is situated in the system development phase of interactive software products. In this detailed design phase, we found a need for fast testable prototyping to achieve qualitative change proposals on the system design. In this paper, we discuss a literature study on current software

  12. Bedload-surrogate monitoring technologies (United States)

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


    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

  13. Optical coherence tomography for bladder cancer - ready as a surrogate for optical biopsy? - results of a prospective mono-centre study

    Directory of Open Access Journals (Sweden)

    Karl A


    OCT. Furthermore all invasive tumors were staged correctly by OCT regarding tumor growth beyond the lamina propria. There were no false negative lesions detected by OCT. Sensitivity of OCT for detecting the presence of a malignant lesion was 100% and sensitivity for detection of tumor growth beyond the lamina propria was 100% as well. Specificity of OCT for presence of malignancy was 65%, due to the fact that a number of lesions were interpreted as false positive by OCT. Conclusion As a minimally invasive technique, OCT proved to have extremely high sensitivity for detection of malignant lesions as well as estimation of whether a tumor has invaded beyond the lamina propria. However, specificity of OCT within the bladder was impaired (65%, possibly due to a learning curve and/or the relatively low spatial resolution and visualization depth of the OCT technology. Further studies and technical development are needed to establish an adequate surrogate for optical biopsy.

  14. Methods of assessing the functional status of patients with left ventricular systolic dysfunction in interventional studies: can brain natriuretic peptide measurement be used as surrogate for the traditional methods?

    DEFF Research Database (Denmark)

    Abdulla, Jawdat; Køber, Lars; Torp-Pedersen, Christian


    AIM: To review whether brain natriuretic peptides (BNP) can be used as a surrogate for the traditional methods of assessing functional status in interventional studies of patients with left ventricular systolic dysfunction (LVSD). METHODS AND RESULTS: The traditional methods for assessing...... functional status including New York Heart Association (NYHA) class, exercise intolerance and quality of life were reviewed in relation to BNP measurements in patients with LVSD. A meta-analysis of four studies evaluating BNP levels versus exercise peak oxygen uptake or 6-minute walking distance showed...

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


    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. PMID:27330248

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

    Energy Technology Data Exchange (ETDEWEB)

    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.


    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.

  17. What Sexual Behaviors Relate to Decreased Sexual Desire in Women? A Review and Proposal for End Points in Treatment Trials for Hypoactive Sexual Desire Disorder. (United States)

    Pyke, Robert; Clayton, Anita


    Counts of satisfying sexual events (SSEs) per month have been criticized as an end point in treatment trials of women with hypoactive sexual desire disorder (HSDD) but grounding improvement in sexual desire by assessing changes in sexual behavior remains of some importance. We conducted a literature review to find validated measurements that are specific sexual behavioral correlates of low sexual desire. We compared expert-proposed criteria for dysfunctional desire, expert-developed sets of scale items, and self-rated scales developed before issuance of, or in accordance with, the Food and Drug Administration's guidance on developing patient-reported outcomes. Behavioral measurements of HSDD were isolated from these sets of criteria or scales. We outline a plan to evaluate such behavioral measurements of HSDD with reference to SSEs. Eleven rating scales, four expert-originated and seven self-rated scales mainly derived from patient input were identified as well validated and relevant to HSDD. Three recent sets of diagnostic criteria for conditions such as HSDD were compared with the scales. Twenty-four different symptoms were found in the scales. Content found relevant to HSDD during development of the rating scales varied highly among measurements, including the self-rated scales developed in conformity with current recommendations for patient-reported outcome measurements. The only item on all sets was desire for sexual activity. Four other items were in approximately at least half the sets: sexual thoughts or fantasies, frequency of sexual activity, receptivity, and initiations. Sexual thoughts or fantasies were in every expert-derived set but in only three of the seven patient-derived sets. Receptivity was in five of the seven expert-derived sets vs two of the seven patient-derived sets. Frequency of sexual activity was in one of the seven expert-derived sets but in five of the patient-derived sets. Initiation was in approximately half the two sets. All other

  18. Evaluating Pediococcus acidilactici and Enterococcus faecium NRRL B-2354 as Thermal Surrogate Microorganisms for Salmonella for In-Plant Validation Studies of Low-Moisture Pet Food Products. (United States)

    Ceylan, Erdogan; Bautista, Derrick A


    Pediococcus acidilactici ATCC 8042 and Enterococcus faecium NRRL B-2354 were investigated as potential surrogates for Salmonella serovars using thermal death time kinetics in products such as dry pet foods. The D-values of P. acidilactici ATCC 8042, E. faecium NRRL B-2354, and a cocktail of seven Salmonella serovars associated with low-moisture products were determined in a preservative-free dry pet food product at moisture levels of 9.1, 17.9, and 27.0% and heated between 76.7 and 87.8°C. The D-values were calculated by least squares linear regression. The D-values of P. acidilactici ATCC 8042 were higher than those for the Salmonella serovar cocktail but lower than those for E. faecium NRRL 2354. At 9.1% moisture, D-values of 6.54, 11.51, and 11.66 min at 76.7°C, 2.66, 3.22, and 4.08 min at 82.2°C, and 1.07, 1.29, and 1.69 min at 87.8°C were calculated for Salmonella serovars, P. acidilactici ATCC 8042, and E. faecium NRRL B-2354, respectively. The data suggest that the thermal inactivation characteristics of P. acidilactici ATCC 8042 can be utilized as a surrogate to predict the response of Salmonella in dry pet food products that are thermally processed at <90°C.

  19. Surrogate data a secure way to share corporate data (United States)

    Tetko, Igor V.; Abagyan, Ruben; Oprea, Tudor I.


    The privacy of chemical structure is of paramount importance for the industrial sector, in particular for the pharmaceutical industry. At the same time, companies handle large amounts of physico-chemical and biological data that could be shared in order to improve our molecular understanding of pharmacokinetic and toxicological properties, which could lead to improved predictivity and shorten the development time for drugs, in particular in the early phases of drug discovery. The current study provides some theoretical limits on the information required to produce reverse engineering of molecules from generated descriptors and demonstrates that the information content of molecules can be as low as less than one bit per atom. Thus theoretically just one descriptor can be used to completely disclose the molecular structure. Instead of sharing descriptors, we propose to share surrogate data. The sharing of surrogate data is nothing else but sharing of reliably predicted molecules. The use of surrogate data can provide the same information as the original set. We consider the practical application of this idea to predict lipophilicity of chemical compounds and we demonstrate that surrogate and real (original) data provides similar prediction ability. Thus, our proposed strategy makes it possible not only to share descriptors, but also complete collections of surrogate molecules without the danger of disclosing the underlying molecular structures.

  20. Discrepancies in end-of-life decisions between elderly patients and their named surrogates. (United States)

    Foo, Aaron S C; Lee, Tze Wee; Soh, Chai Rick


    This study aims to determine the attitudes of Asian elderly patients towards invasive life support measures, the degree of patient-surrogate concordance in end-of-life decision making, the extent to which patients desire autonomy over end-of-life medical decisions, the reasons behind patients' and surrogates' decisions, and the main factors influencing patients' and surrogates' decision-making processes. We hypothesize that there is significant patient-surrogate discordance in end-of-life decision making in our community. The patient and surrogate were presented with a hypothetical scenario in which the patient experienced gradual functional decline in the community before being admitted for life-threatening pneumonia. It was explained that the outcome was likely to be poor even with intensive care and each patient-surrogate pair was subsequently interviewed separately on their opinions of extraordinary life support using a standardised questionnaire. Both parties were blinded to each other's replies. In total, 30 patients and their surrogate decision-makers were interviewed. Twenty-eight (93.3%) patients and 20 (66.7%) surrogates rejected intensive care. Patient-surrogate concurrence was found in 20 pairs (66.7%). Twenty-four (80.0%) patients desired autonomy over their decision. The patients' and surrogates' top reasons for rejecting intensive treatment were treatment-related discomfort, poor prognosis and financial cost. Surrogates' top reasons for selecting intensive treatment were the hope of recovery, the need to complete final tasks and the sanctity of life. The majority of patients desire autonomy over critical care issues. Relying on the surrogates' decisions to initiate treatment may result in treatment against patients' wishes in up to one-third of critically ill elderly patients.

  1. Surrogate Analysis and Index Developer (SAID) tool (United States)

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


    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.

  2. Determination of selected protoporphyrins in parma ham with use of 5,10,15,20-tetra(4-hydroxyphenyl)porphyrin as a surrogate standard in the recovery study. (United States)

    Maere, Hannelore De; Mey, Eveline De; Baca, Martyna; Sajewicz, Mieczysław; Paelinck, Hubert; Fraeye, Ilse; Kowalska, Teresa


    A high-performance liquid chromatographic method for the determination of hemin, protoporphyrin IX (PPIX), and zinc(II)protoporphyrin IX (Zn(II)PPIX) in Parma ham was developed. The detection was done by means of a universal DAD-detector, whereby quantification of the three naturally occurring protoporphyrins was carried out at lambda = 414 nm, i.e., very close to the respective maxima of their Soret bands. The extraction thereof from the meat matrix was done by a mixture of acetone and chloroacetic acid (100 mL + 0.2 g). Usage of 5,10,15,20-tetra(4-hydroxyphenyl)porphyrin (THPP) as a surrogate standard and its detection fixed at lambda = 444 nm, allowed to obtain accurate (ca. 96%) recovery results. Established concentrations of hemin, Zn(II)PPIX, and PPIX in the Parma ham samples were 15.97, 19.96 and 1.52 µg g(-1), respectively.

  3. Airfoil Shape Optimization based on Surrogate Model (United States)

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


    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.

  4. Airfoil Shape Optimization based on Surrogate Model (United States)

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


    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.

  5. Making fire and fire surrogate science available: a summary of regional workshops with clients (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


    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...

  6. Disinfection byproduct regulatory compliance surrogates and bromide-associated risk. (United States)

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


    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 THM3 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.

  7. Introducing ICD-resistant mortality as an end point to evaluate the clinical efficacy of an implantable cardioverter-defibrillator in ischaemic cardiomyopathy. (United States)

    Floré, Vincent; Vandenberk, Bert; Belmans, Ann; Garweg, Christophe; Ector, Joris; Willems, Rik


    A new end point called ICD-resistant mortality was evaluated to assess the clinical efficacy of ICD implantations. In 302 ICD patients with ischaemic cardiomyopathy, we investigated which clinical parameters predicted useful ICD implantations using cumulative incidence competing risk analysis. Implantation was deemed clinically useful when the ICD provided appropriate therapy and the patient survived implantation by 1 year and the first shock by 30 days. ICD-resistant mortality (ICDRM) was defined as death within 30 days after the first shock, within 1 year of implantation or without previous appropriate ICD therapy. After 5 years, ICDRM occurred in 23% of implantations, while 36% were clinically useful. After multivariable analysis, ICDRM was associated with LVEF <35% (HR: 2.63; p = .005), beta-blocker dose <50% (HR: 2.0; p = .01) and anterior or diffuse infarct location (HR: 3.61; p = .001 and HR: 2.89; p = .02). Useful ICD implantations were associated with beta-blocker dose <50% (HR: 1.64; p = .02) and non-anterior infarct location (HR: 3.22 vs anterior and 1.59 vs diffuse; combined p<.001). Five years after implantation, an ICD could be classified as useful in 1 out of 3, while ICDRM occurred in one out of four patients. At 10 years, up to 80% of implantations could be categorized. Lower LVEF was related with significantly higher incidence of ICDRM. Anterior infarcts were associated with more ICDRM and less useful implantations than non-anterior infarcts. Future risk stratification for ICD should focus more on the discrimination between arrhythmic risk, probably preventable by ICDs and ICD-resistant mortality risk.

  8. Surrogate endpoint analysis: an exercise in extrapolation. (United States)

    Baker, Stuart G; Kramer, Barnett S


    Surrogate endpoints offer the hope of smaller or shorter cancer trials. It is, however, important to realize they come at the cost of an unverifiable extrapolation that could lead to misleading conclusions. With cancer prevention, the focus is on hypothesis testing in small surrogate endpoint trials before deciding whether to proceed to a large prevention trial. However, it is not generally appreciated that a small surrogate endpoint trial is highly sensitive to a deviation from the key Prentice criterion needed for the hypothesis-testing extrapolation. With cancer treatment, the focus is on estimation using historical trials with both surrogate and true endpoints to predict treatment effect based on the surrogate endpoint in a new trial. Successively leaving out one historical trial and computing the predicted treatment effect in the left-out trial yields a standard error multiplier that summarizes the increased uncertainty in estimation extrapolation. If this increased uncertainty is acceptable, three additional extrapolation issues (biological mechanism, treatment following observation of the surrogate endpoint, and side effects following observation of the surrogate endpoint) need to be considered. In summary, when using surrogate endpoint analyses, an appreciation of the problems of extrapolation is crucial.

  9. Imaging Seeker Surrogate for IRCM evaluation

    NARCIS (Netherlands)

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


    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

  10. On Using Surrogates with Genetic Programming. (United States)

    Hildebrandt, Torsten; Branke, Jürgen


    One way to accelerate evolutionary algorithms with expensive fitness evaluations is to combine them with surrogate models. Surrogate models are efficiently computable approximations of the fitness function, derived by means of statistical or machine learning techniques from samples of fully evaluated solutions. But these models usually require a numerical representation, and therefore cannot be used with the tree representation of genetic programming (GP). In this paper, we present a new way to use surrogate models with GP. Rather than using the genotype directly as input to the surrogate model, we propose using a phenotypic characterization. This phenotypic characterization can be computed efficiently and allows us to define approximate measures of equivalence and similarity. Using a stochastic, dynamic job shop scenario as an example of simulation-based GP with an expensive fitness evaluation, we show how these ideas can be used to construct surrogate models and improve the convergence speed and solution quality of GP.

  11. A review of selection-based tests of abiotic surrogates for species representation. (United States)

    Beier, Paul; Sutcliffe, Patricia; Hjort, Jan; Faith, Daniel P; Pressey, Robert L; Albuquerque, Fabio


    Because conservation planners typically lack data on where species occur, environmental surrogates--including geophysical settings and climate types--have been used to prioritize sites within a planning area. We reviewed 622 evaluations of the effectiveness of abiotic surrogates in representing species in 19 study areas. Sites selected using abiotic surrogates represented more species than an equal number of randomly selected sites in 43% of tests (55% for plants) and on average improved on random selection of sites by about 8% (21% for plants). Environmental diversity (ED) (42% median improvement on random selection) and biotically informed clusters showed promising results and merit additional testing. We suggest 4 ways to improve performance of abiotic surrogates. First, analysts should consider a broad spectrum of candidate variables to define surrogates, including rarely used variables related to geographic separation, distance from coast, hydrology, and within-site abiotic diversity. Second, abiotic surrogates should be defined at fine thematic resolution. Third, sites (the landscape units prioritized within a planning area) should be small enough to ensure that surrogates reflect species' environments and to produce prioritizations that match the spatial resolution of conservation decisions. Fourth, if species inventories are available for some planning units, planners should define surrogates based on the abiotic variables that most influence species turnover in the planning area. Although species inventories increase the cost of using abiotic surrogates, a modest number of inventories could provide the data needed to select variables and evaluate surrogates. Additional tests of nonclimate abiotic surrogates are needed to evaluate the utility of conserving nature's stage as a strategy for conservation planning in the face of climate change. © 2015 Society for Conservation Biology.

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

    Directory of Open Access Journals (Sweden)

    Scott E. Field


    generating new waveforms with a surrogate. As waveform generation is one of the dominant costs in parameter estimation algorithms and parameter space exploration, surrogate models offer a new and practical way to dramatically accelerate such studies without impacting accuracy. Surrogates built in this paper, as well as others, are available from GWSurrogate, a publicly available python package.

  13. Total staphylococci as performance surrogate for greywater treatment. (United States)

    Shoults, David C; Ashbolt, Nicholas J


    Faecal indicator bacteria (FIB) are commonly used as water quality indicators; implying faecal contamination and therefore the potential presence of pathogenic enteric bacteria, viruses, and protozoa. Hence in wastewater treatment, the most commonly used treatment process measures (surrogates) are total coliforms, faecal coliforms, Escherichia coli (E. coli), and enterococci. However, greywater potentially contains skin pathogens unrelated to faecal load, and E. coli and other FIB may grow within greywater unrelated to pathogens. Overall, FIB occurs at fluctuating and relatively low concentrations compared to other endogenous greywater bacteria affecting their ability as surrogates for pathogen reduction. Therefore, unlike municipal sewage, FIB provides a very limited and unreliable log-reduction surrogate measure for on-site greywater treatment systems. Based on our recent metagenomic study of laundry greywater, skin-associated bacteria such as Staphylococcus, Corynebacterium, and Propionibacterium spp. dominate and may result in more consistent treatment surrogates than traditional FIB. Here, we investigated various Staphylococcus spp. as potential surrogates to reliably assay over 4-log 10 reduction by the final-stage UV disinfection step commonly used for on-site greywater reuse, and compare them to various FIB/phage surrogates. A collimated UV beam was used to determine the efficacy of UV inactivation (255, 265 and 285 nm) against E. coli, Enterococcus faecalis, E. faecium, E. casseliflavus, Staphylococcus aureus, and S. epidermidis. Staphylococcus spp. was estimated by combining the bi-linear dose-response curves for S. aureus and S. epidermidis and was shown to be less resistant to UV irradiation than the other surrogates examined. Hence, a relative inactivation credit is suggested; whereas, the doses required to achieve a 4 and 5-log 10 reduction of Staphylococcus spp. (13.0 and 20.9 mJ cm -2 , respectively) were used to determine the relative

  14. Allospecific CD154 + T-cytotoxic memory cells as potential surrogate for rejection risk in pediatric intestine transplantation. (United States)

    Sindhi, Rakesh; Ashokkumar, Chethan; Higgs, Brandon W; Gilbert, P B; Sun, Qing; Ranganathan, Sarangarajan; Jaffe, Ron; Snyder, Sara; Ningappa, Mylarappa; Soltys, Kyle A; Bond, Geoffrey J; Mazariegos, George V; Abu-Elmagd, Kareem; Zeevi, Adriana


    Clinical end-points dictate large trial enrollments and exclude children with the rare intestine transplant procedure (ITx), who experience higher drug-related morbidity. We evaluate the novel rejection-risk parameter, allo-(antigen)-specific CD154 + TcMs (i) as surrogates for ACR using Prentice's criteria, (ii) for association with immunosuppression targets to determine Fleming's surrogate end-point designation, and (iii) as time-to-event end-point in a simulated comparison of alemtuzumab (NCT#01208337, n = 14) and rabbit anti-human thymocyte globulin (rATG, n = 16) among 30 children with ITx. CD154 + TcM were measured in MLR before, and at 1-60 and 61-200 days after ITx (NCT#01163578). CD154 + TcM correlate significantly with rejection severity (Spearman r = 0.685, p = 2.03E-5) and associate with biopsy-proven ITx rejection with sensitivity/specificity of 94%/84% [corrected] independent of immunosuppressant. Previously stated sensitivity of 90% is incorrect. [corrected]. The rejection-risk threshold of CD154 + TcM resolves rapidly in 200-day follow-up (46 ± 20 vs. 158 ± 59 days, p = 0.009, K-M) with alemtuzumab, which demonstrates lower 90-day ACR incidence (50% vs. 69%, p=NS, Fisher's exact), and is associated with accelerated prednisone minimization to ≤2.5 mg/day, compared with rATG (120 ± 28 vs. 180 ± 30 days, p = 0.027, K-M). As a surrogate end-point, time-to-rejection-risk resolution measured with CD154 + TcM portends 50% reduction in sample sizes in a simulated trial of alemtuzumab vs. rATG. Rejection-risk assessment with CD154 + TcM may enable informed immunosuppression minimization, and preliminary efficacy comparisons in pediatric ITx. © 2011 John Wiley & Sons A/S.

  15. Salmonella surrogate reduction using industrial peanut dry roasting parameters (United States)

    Studies were conducted to evaluate the effectiveness of industrial peanut dry roasting parameters in Salmonella reduction using a Salmonella surrogate, Enterococcus faecium, which is slightly more heat tolerant than Salmonella. Runner-type peanuts were inoculated with E. faecium and roasted in a lab...

  16. Surrogate consent for dementia research: a national survey of older Americans. (United States)

    Kim, S Y H; Kim, H M; Langa, K M; Karlawish, J H T; Knopman, D S; Appelbaum, P S


    Research in novel therapies for Alzheimer disease (AD) relies on persons with AD as research subjects. Because AD impairs decisional capacity, informed consent often must come from surrogates, usually close family members. But policies for surrogate consent for research remain unsettled after decades of debate. We designed a survey module for a random subsample (n = 1,515) of the 2006 wave of the Health and Retirement Study, a biennial survey of a nationally representative sample of Americans aged 51 and older. The participants answered questions regarding one of four randomly assigned surrogate-based research (SBR) scenarios: lumbar puncture study, drug randomized control study, vaccine study, and gene transfer study. Each participant answered three questions: whether our society should allow family surrogate consent, whether one would want to participate in the research, and whether one would allow one's surrogate some or complete leeway to override stated personal preferences. Most respondents stated that our society should allow family surrogate consent for SBR (67.5% to 82.5%, depending on the scenario) and would themselves want to participate in SBR (57.4% to 79.7%). Most would also grant some or complete leeway to their surrogates (54.8% to 66.8%), but this was true mainly of those willing to participate. There was a trend toward lower willingness to participate in SBR among those from ethnic or racial minority groups. Family surrogate consent-based dementia research is broadly supported by older Americans. Willingness to allow leeway to future surrogates needs to be studied further for its ethical significance for surrogate-based research policy.

  17. Economic evaluation of chemotherapy with mitoxantrone plus prednisone for symptomatic hormone-resistant prostate cancer: based on a Canadian randomized trial with palliative end points. (United States)

    Bloomfield, D J; Krahn, M D; Neogi, T; Panzarella, T; Smith, T J; Warde, P; Willan, A R; Ernst, S; Moore, M J; Neville, A; Tannock, I F


    To evaluate the economic consequences of the use of chemotherapy in patients with symptomatic hormone-resistant prostate cancer (HRPC) in the context of a previously published Canadian open-label, phase III, randomized trial with palliative end points. The trial randomized 161 patients to initial treatment with mitoxantrone and prednisone (M + P) or to prednisone alone (P) and showed better palliation with M + P. There was no significant difference in survival. A detailed retrospective chart review was performed of resources used from randomization until death of 114 of 161 patients enrolled at the three largest centers: these included hospital admissions, outpatient visits, investigations, therapies (which included all chemotherapy and radiation), and palliative care. Cancer center and community hospital costs were calculated by using the hotel approximation method and case costing from the Ontario Case Cost Project, respectively. Cost-utility analysis was performed by transforming the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 global quality-of-life item measured every 3 weeks on trial to an estimate of utility, and extending the last known value through to death or last follow-up. The mean total cost until death or last follow-up by intention-to-treat was M + P CDN $27,300; P CDN $29,000. The 95% confidence intervals on the observed cost difference ranged from a saving of $9,200 for M + P (with palliative benefit) to an increased cost of $5,800 for M + P. The major proportion of cost (M + P 53% v P 66%; CDN $14,500 v $19,100) was for inpatient care. Initial M + P was consistently less expensive in whichever time period was used to compare costs. Cost-utility analysis showed M + P to be the preferred strategy with an upper 95% confidence interval for the incremental cost-utility ratio of CDN $19,700 per quality-adjusted life-year (QALY). A treatment that reduces symptoms and improves quality of life has the potential to reduce

  18. Surrogate Decision Makers and Proxy Ownership: Challenges of Privacy Management in Health Care Decision Making (United States)

    Bute, Jennifer J.; Petronio, Sandra; Torke, Alexia M.


    This study explored the communicative experiences of surrogates who served as decision makers for patients who were unable to convey health information and choices about treatment options. Drawing on assumptions from communication privacy management theory (Petronio, 2002), 35 surrogates were interviewed to explore how they navigated the role of guardian of patients’ private health information while the patient was hospitalized. This research determined that surrogates are not only guardians and thereby co-owners of the patients’ private health information, they actually served in a “proxy ownership” role. Surrogates described obstacles to both obtaining and sharing private health information about the patient, suggesting that their rights as legitimate co-owners of the patients’ information were not fully acknowledged by the medical teams. Surrogates also described challenges in performing the proxy ownership role when they were not fully aware of the patient's wishes. Theoretical and practical implications of these challenges are discussed. PMID:25175060

  19. 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

  20. A computational methodology for formulating gasoline surrogate fuels with accurate physical and chemical kinetic properties

    KAUST Repository

    Ahmed, Ahfaz


    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

  1. Disagreements between central clinical events committee and site investigator assessments of myocardial infarction end- points in an international clinical trial: Review of the PURSUIT study

    NARCIS (Netherlands)

    K.W. Mahaffey (Kenneth); R.A. Harrington (Robert Alex); K.M. Akkerhuis (Martijn); N.S. Kleiman (Neal); L.G. Berdan (Lisa); B.S. Crenshaw (Brian); B.E. Tardiff (Barbara); C.B. Granger (Christopher); I. DeJong (Ingrid); M. Bhapkar (Manju); P. Widimsky (Petr); R. Corbalon (Ramón); K.L. Lee (Kerry); J.W. Deckers (Jaap); M.L. Simoons (Maarten); E.J. Topol (Eric); R.M. Califf (Robert)


    textabstractBackground. Limited information has been published regarding how specific processes for event adjudication can affect event rates in trials. We reviewed nonfatal myocardial infarctions (MIs) reported by site investigators in the international Platelet Glycoprotein IIb/IIIa in Unstable

  2. Disagreements between central clinical events committee and site investigator assessments of myocardial infarction end-points in an international clinical trial: review of the PURSUIT study

    NARCIS (Netherlands)

    K.W. Mahaffey (Kenneth); R.A. Harrington (Robert Alex); N.S. Kleiman (Neal); L.G. Berdan (Lisa); B.S. Crenshaw (Brian); B.E. Tardiff (Barbara); C.B. Granger (Christopher); I. DeJong (Ingrid); M. Bhapkar (Manju); P. Widimsky (Petr); R. Corbalon (Ramón); K.L. Lee (Kerry); J.W. Deckers (Jaap); M.L. Simoons (Maarten); E.J. Topol (Eric); R.M. Califf (Robert); K.M. Akkerhuis (Martijn)


    textabstractAbstract: Background Limited information has been published regarding how specific processes for event adjudication can affect event rates in trials. We reviewed nonfatal myocardial infarctions (MIs) reported by site investigators in the international Platelet Glycoprotein IIb/IIIa in

  3. Kinetic Modeling of Toluene Oxidation for Surrogate Fuel Applications

    Energy Technology Data Exchange (ETDEWEB)

    Frassoldati, A; Mehl, M; Fietzek, R; Faravelli, T; Pitz, W J; Ranzi, E


    New environmental issues, like the effect of combustion-generated greenhouse gases, provide motivation to better characterize oxidation of hydrocarbons. Transportation, in particular, significantly contributes to energy consumption and CO{sub 2} emissions. Kinetic studies about the combustion of fuels under conditions typical of internal combustion engines provides important support to improve mechanism formulation and to eventually provide better computational tools that can be used to increase the engine performance. It is foreseeable that at least in the next 30 years the main transportation fuels will be either gasoline or diesel. Unfortunately, these fuels are very complex mixtures of many components. Moreover, their specifications and performance requirements significantly change the composition of these fuels: gasoline and diesel mixtures are different if coming from different refineries or they are different from winter to summer. At the same time a fuel with a well defined and reproducible composition is needed for both experimental and modeling work. In response to these issues, surrogate fuels are proposed. Surrogate fuels are defined as mixtures of a small number of hydrocarbons whose relative concentrations is adjusted in order to approximate the chemical and physical properties of a real fuel. Surrogate fuels are then very useful both for the design of reproducible experimental tests and also for the development of reliable kinetic models. The primary reference fuels (PRF) are a typical and old example of surrogate fuel: n-heptane and iso-octane mixtures are used to reproduce antiknock propensity of complex mixtures contained in a gasoline. PRFs are not able to surrogate gasoline in operating conditions different from standard ones and new surrogates have been recently proposed. Toluene is included in all of them as a species able to represent the behavior of aromatic compounds. On the other side, the toluene oxidation chemistry is not so well

  4. Summarizing the field of surrogate modeling research (United States)

    Schultz, Colin


    As computer simulations of complex physical interactions grow, so do the time and expense required to operate them. Mirroring the development of such full-scale models has been the related field of surrogate modeling or metamodeling. Surrogate models take a variety of forms, but their shared goal is to provide a numerical output similar to that of a fully complex physical model while minimizing the computational time and cost required to calculate the result. With an eye toward introducing those unfamiliar with the practices and pitfalls of surrogate modeling to the topic and with a focus on its applications to water resources research, Razavi et al. prepared a systematic review of the surrogate modeling literature.

  5. Surrogate Models for Direct Dark Matter Detection


    Cerdeno, D. G.; Cheek, A.; Reid, E.; Schulz, H.


    In this work we introduce RAPIDD, a surrogate model that speeds up the computation of the expected spectrum of dark matter particles in direct detection experiments. RAPIDD replaces the exact calculation of the dark matter differential rate (which in general involves up to three nested integrals) with a much faster parametrization in terms of ordinary polynomials of the dark matter mass and couplings, obtained in an initial training phase. In this article, we validate our surrogate model on t...

  6. Metastasis-Free Survival Is a Strong Surrogate of Overall Survival in Localized Prostate Cancer. (United States)

    Xie, Wanling; Regan, Meredith M; Buyse, Marc; Halabi, Susan; Kantoff, Philip W; Sartor, Oliver; Soule, Howard; Clarke, Noel W; Collette, Laurence; Dignam, James J; Fizazi, Karim; Paruleker, Wendy R; Sandler, Howard M; Sydes, Matthew R; Tombal, Bertrand; Williams, Scott G; Sweeney, Christopher J


    Purpose Adjuvant therapy for intermediate-risk and high-risk localized prostate cancer decreases the number of deaths from this disease. Surrogates for overall survival (OS) could expedite the evaluation of new adjuvant therapies. Methods By June 2013, 102 completed or ongoing randomized trials were identified and individual patient data were collected from 28 trials with 28,905 patients. Disease-free survival (DFS) and metastasis-free survival (MFS) were determined for 21,140 patients from 24 trials and 12,712 patients from 19 trials, respectively. We evaluated the surrogacy of DFS and MFS for OS by using a two-stage meta-analytic validation model by determining the correlation of an intermediate clinical end point with OS and the correlation of treatment effects on both the intermediate clinical end point and OS. Results Trials enrolled patients from 1987 to 2011. After a median follow-up of 10 years, 45% of 21,140 men and 45% of 12,712 men experienced a DFS and MFS event, respectively. For DFS and MFS, 61% and 90% of the patients, respectively, were from radiation trials, and 63% and 66%, respectively, had high-risk disease. At the patient level, Kendall's τ correlation with OS was 0.85 and 0.91 for DFS and MFS, respectively. At the trial level, R(2) was 0.86 (95% CI, 0.78 to 0.90) and 0.83 (95% CI, 0.71 to 0.88) from weighted linear regression of 8-year OS rates versus 5-year DFS and MFS rates, respectively. Treatment effects-measured by log hazard ratios-for the surrogates and OS were well correlated ( R(2), 0.73 [95% CI, 0.53 to 0.82] for DFS and 0.92 [95% CI, 0.81 to 0.95] for MFS). Conclusion MFS is a strong surrogate for OS for localized prostate cancer that is associated with a significant risk of death from prostate cancer.

  7. Assessing the potential of surrogate EPS to mimic natural biofilm mechanical properties (United States)

    Thom, Moritz; Schimmels, Stefan


    Biofilms growing on benthic sediments may increase the resistance towards erosion considerably by the sticky nature of extracellular polymeric substances (EPS). The EPS is a biopolymer which is secreted by the microorganisms inhabiting the biofilm matrix and may be regarded as natural glue. However, laboratory studies on the biostabilization effect mediated by biofilms are often hampered by the unavailability of "environmental" flumes in which light intensities, water temperature and nutrient content can be controlled. To allow investigations on biostabilization in "traditional" flume settings the use of surrogate materials is studied. Another advantage of using appropriate surrogates is the potential to reduce the experimental time, as compared to cultivating natural biofilms, the surrogates can readily be designed to mimic biofilms at different growth stages. Furthermore, the use of surrogates which are expected to have more homogeneous mechanical properties could facilitate fundamental studies to improve our knowledge on biostabilization. Even though a number of studies have already utilized EPS surrogates it is not clear how to mix them to correctly mimic natural EPS mechanical properties. In this study the adhesiveness (a measure of stickiness) on the surface of several EPS surrogates (e.g. Xanthan Gum, sodium alginate) is measured. These surrogates which are originally used in the food industry as rheology modifiers are mixed by adding water to a powder at a desired concentration (C). The measured surface adhesion of different surrogates at different concentrations ranged from 0.5 to 6.7 N/m2, which is well in line with values found for laboratory cultured biofilms. We found that the surrogate characteristics differed largely especially in regard to a) the response of the adhesiveness to increased concentrations (powder to water) and b) in their rheological characteristics. A seemingly promising surrogate for the use in biostabilization studies is Xanthan Gum

  8. Nitrate dry deposition measurements with surrogate surfaces (United States)

    Zhu, Xiang

    Nitrate dry deposition is one of the most important topics in the study of the dry deposition of acidic and acidifying substances. This study measured nitrate dry deposition to (1) a water surface sampler (WSS) which was recently developed in the Department of Chemical and Environmental Engineering at Illinois Institute of Technology, (2) a Nylasorb filter on a knife-edge surrogate surface and (3) a greased strip on a knife-edge surrogate surface. Airborne nitric acid (HNO3), nitrous acid (HNO2), and nitrogen dioxide (NO2) concentrations were also measured concurrently with the flux measurements. These measurements were then used to evaluate the utility of using surrogate surfaces, and in particular the WSS, to measure nitrate dry deposition. The nitrogen containing species that may be responsible for nitrate dry deposition to the WSS include nitrogen monoxide (NO), NO2, peroxyacetyl nitrate (PAN), ammonia (NH3) and ammonium (NH4+), HNO2,/ HNO3, and particulate nitrate. Theoretical calculations and experiments showed that HNO3 and particulate nitrate appear to be the major nitrate contributors to the water surface sampler. Nitrate dry deposition to the water surface, Nylasorb filter and the greased strip were measured during the daytime in June and July 1995 and during both the day and night time in September and October 1995. The results showed that during the daytime in June and July the average nitrate dry deposition to the WSS (36.28 mg/m2-day) was much higher than that to the Nylasorb filter (14.04 mg/m2-day). However, during September and October there is no statistically significant difference in nitrate deposition flux between the WSS (average 4.59 mg/m2-day for the nighttime and 10.58 mg/m2-day for the daytime) and the Nylasorb filter (average 4.53 mg/m2-day for the nighttime and 8.87 mg/m2-day). A set of three experiments showed that particulate nitrate fluxes measured with the greased strip were underestimated due to the loss of volatile particulate

  9. Surrogate mobility and orientation affect the early neurobehavioral development of infant rhesus macaques (Macaca mulatta). (United States)

    Dettmer, Amanda M; Ruggiero, Angela M; Novak, Melinda A; Meyer, Jerrold S; Suomi, Stephen J


    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.

  10. Children of surrogate mothers: psychological well-being, family relationships and experiences of surrogacy. (United States)

    Jadva, V; Imrie, S


    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

  11. Consumption of Alcohol Surrogates Among Alcohol-Dependent Women. (United States)

    Razvodovsky, Yury Evgeny


    This is the first in-depth study of alcohol and surrogate drinking patterns, types, reasons, and correlates among alcohol-dependent women in Belarus. The structured interviews were performed in 2013 with 103 alcohol-dependent women admitted to a narcological clinic in Grodno, Belarus. The results suggest that at least 30.3% of alcohol-dependent women regularly consume samogon (moonshine) and 10.8% of women use surrogates, the most popular among which are medications with a high percentage of ethanol and industrial spirits. The belief that samogon exceeds licensed vodka in quality is the main motive for its consumption. The results from the present study confirm that noncommercial alcohol use is common among alcohol-dependent women although its use may be underreported. These findings emphasize that the implementation of a comprehensive alcohol policy must take fully into account the consumption of alcohol from illicit sources.

  12. Experimental Design for a Sponge-Wipe Study to Relate the Recovery Efficiency and False Negative Rate to the Concentration of a Bacillus anthracis Surrogate for Six Surface Materials

    Energy Technology Data Exchange (ETDEWEB)

    Piepel, Gregory F. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Amidan, Brett G. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Krauter, Paula [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Einfeld, Wayne [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)


    Two concerns were raised by the Government Accountability Office following the 2001 building contaminations via letters containing Bacillus anthracis (BA). These included the: 1) lack of validated sampling methods, and 2) need to use statistical sampling to quantify the confidence of no contamination when all samples have negative results. Critical to addressing these concerns is quantifying the probability of correct detection (PCD) (or equivalently the false negative rate FNR = 1 - PCD). The PCD/FNR may depend on the 1) method of contaminant deposition, 2) surface concentration of the contaminant, 3) surface material being sampled, 4) sample collection method, 5) sample storage/transportation conditions, 6) sample processing method, and 7) sample analytical method. A review of the literature found 17 laboratory studies that focused on swab, wipe, or vacuum samples collected from a variety of surface materials contaminated by BA or a surrogate, and used culture methods to determine the surface contaminant concentration. These studies quantified performance of the sampling and analysis methods in terms of recovery efficiency (RE) and not PCD/FNR (which left a major gap in available information). Quantifying the PCD/FNR under a variety of conditions is a key aspect of validating sample and analysis methods, and also for calculating the confidence in characterization or clearance decisions based on a statistical sampling plan. A laboratory study was planned to partially fill the gap in PCD/FNR results. This report documents the experimental design developed by Pacific Northwest National Laboratory and Sandia National Laboratories (SNL) for a sponge-wipe method. The study will investigate the effects on key response variables from six surface materials contaminated with eight surface concentrations of a BA surrogate (Bacillus atrophaeus). The key response variables include measures of the contamination on test coupons of surface materials tested, contamination

  13. Experimental Design for a Sponge-Wipe Study to Relate the Recovery Efficiency and False Negative Rate to the Concentration of a Bacillus anthracis Surrogate for Six Surface Materials

    Energy Technology Data Exchange (ETDEWEB)

    Piepel, Gregory F.; Amidan, Brett G.; Krauter, Paula; Einfeld, Wayne


    Two concerns were raised by the Government Accountability Office following the 2001 building contaminations via letters containing Bacillus anthracis (BA). These included the: 1) lack of validated sampling methods, and 2) need to use statistical sampling to quantify the confidence of no contamination when all samples have negative results. Critical to addressing these concerns is quantifying the false negative rate (FNR). The FNR may depend on the 1) method of contaminant deposition, 2) surface concentration of the contaminant, 3) surface material being sampled, 4) sample collection method, 5) sample storage/transportation conditions, 6) sample processing method, and 7) sample analytical method. A review of the literature found 17 laboratory studies that focused on swab, wipe, or vacuum samples collected from a variety of surface materials contaminated by BA or a surrogate, and used culture methods to determine the surface contaminant concentration. These studies quantified performance of the sampling and analysis methods in terms of recovery efficiency (RE) and not FNR (which left a major gap in available information). Quantifying the FNR under a variety of conditions is a key aspect of validating sample and analysis methods, and also for calculating the confidence in characterization or clearance decisions based on a statistical sampling plan. A laboratory study was planned to partially fill the gap in FNR results. This report documents the experimental design developed by Pacific Northwest National Laboratory and Sandia National Laboratories (SNL) for a sponge-wipe method. The testing was performed by SNL and is now completed. The study investigated the effects on key response variables from six surface materials contaminated with eight surface concentrations of a BA surrogate (Bacillus atrophaeus). The key response variables include measures of the contamination on test coupons of surface materials tested, contamination recovered from coupons by sponge

  14. An improved and explicit surrogate variable analysis procedure by coefficient adjustment. (United States)

    Lee, Seunggeun; Sun, Wei; Wright, Fred A; Zou, Fei


    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.

  15. Prevalence of and Factors Related to Discordance About Prognosis Between Physicians and Surrogate Decision Makers of Critically Ill Patients. (United States)

    White, Douglas B; Ernecoff, Natalie; Buddadhumaruk, Praewpannarai; Hong, Seoyeon; Weissfeld, Lisa; Curtis, J Randall; Luce, John M; Lo, Bernard


    Misperceptions about prognosis by individuals making decisions for incapacitated critically ill patients (surrogates) are common and often attributed to poor comprehension of medical information. To determine the prevalence of and factors related to physician-surrogate discordance about prognosis in intensive care units (ICUs). Mixed-methods study comprising quantitative surveys and qualitative interviews conducted in 4 ICUs at a major US medical center involving surrogate decision makers and physicians caring for patients at high risk of death from January 4, 2005, to July 10, 2009. Discordance about prognosis, defined as a difference between a physician's and a surrogate's prognostic estimates of at least 20%; misunderstandings by surrogates (defined as any difference between a physician's prognostic estimate and a surrogate's best guess of that estimate); differences in belief (any difference between a surrogate's actual estimate and their best guess of the physician's estimate). Two hundred twenty-nine surrogate decision makers (median age, 47 [interquartile range {IQR}, 35-56] years; 68% women) and 99 physicians were involved in the care of 174 critically ill patients (median age, 60 [IQR, 47-74] years; 44% women). Physician-surrogate discordance about prognosis occurred in 122 of 229 instances (53%; 95% CI, 46.8%-59.7%). In 65 instances (28%), discordance was related to both misunderstandings by surrogates and differences in belief about the patient's prognosis; 38 (17%) were related to misunderstandings by surrogates only; 7 (3%) were related to differences in belief only; and data were missing for 12. Seventy-five patients (43%) died. Surrogates' prognostic estimates were much more accurate than chance alone, but physicians' prognostic estimates were statistically significantly more accurate than surrogates' (C statistic, 0.83 vs 0.74; absolute difference, 0.094; 95% CI, 0.024-0.163; P = .008). Among 71 surrogates interviewed who had beliefs about the

  16. Legal regulation of surrogate motherhood in Israel. (United States)

    Frenkel, D A


    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.

  17. Attitudes toward surrogate motherhood in Canada. (United States)

    Krishnan, V


    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.

  18. Surrogates for validation of electron beam irradiation of foods. (United States)

    Rodriguez, Oscar; Castell-Perez, M Elena; Ekpanyaskun, Nont; Moreira, Rosana G; Castillo, Alejandro


    The aim of this study was to identify a potential surrogate to describe the radiation sensitivity of the most common pathogens encountered in fruits. Three pathogens: Escherichia coli O157:H7 933, Listeria monocytogenes ATCC 51414, and Salmonella Poona, and five non-pathogens: E. coli K-12 MG1655, Listeria innocua Seeliger 1983 (NRRL B-33003 and NRRl B-33014), Enterobacter aerogenes, and Salmonella LT2 were inoculated (populations of 10(7)-10(9) CFU/ml) into model food systems (10% w/w gelatin) and exposed to doses up to 1.0 kGy using a 2 MeV Van der Graaf linear accelerator. The non-pathogen E. coli K-12 MG1655 was highly resistant to radiation (D(10)=0.88 kGy) in comparison to the other strains while L. monocytogenes was the more radiation-resistant pathogen (D(10)=1.09 kGy). Thus, E. coli K-12 MG1655 could be a suitable surrogate for e-beam studies with L. monocytogenes as the indicator pathogen. L. innocua strains were more radiation-sensitive (D(10)=0.66, 0.72 kGy) than their pathogenic counterpart. S. Poona and E. coli O157:H7 were even more radiation-sensitive (D(10)=0.38, 0.36 kGy, respectively). S. LT2 was the least radiation-resistant pathogen with D(10)=0.12 kGy. In a later study, the radiation resistance of the pathogens and the surrogate was evaluated when inoculated in a real food (i.e., fresh cantaloupe). The D(10) values obtained in this experiment were higher than those obtained with the model foods. However, the surrogate was still more radiation-resistant and could therefore be used to indicate decontamination of the target pathogens under electron beam irradiation.

  19. The Oxidation of a Gasoline Surrogate in the Negative Temperature Coefficient Region (United States)


    During the oxidation of the surrogate, three major species were quantified that could only be produced from toluene , specifically, benzaldehyde ...were attributable to toluene decomposition, specifi- cally, benzaldehyde , benzene, phenol, and ethyl-benzene. Two new pathways have been suggested to...Surrogate n-Heptane Iso-octane Toluene 1-Pentene Flow reactor This experimental study investigated the preignition reactivity behavior of a gasoline

  20. Development of novel synthetic muscle tissues for sports impact surrogates. (United States)

    Payne, Thomas; Mitchell, Séan; Bibb, Richard; Waters, Mark


    Impact injuries are commonplace in sport and often lead to performance detriment and debilitation. Personal Protective Equipment (PPE) is prescribed as a mandatory requirement in most sports where these impacts are likely to occur, though the methods of governance and evaluation criteria often do not accurately represent sports specific injury scenarios. One of the key shortcomings of such safety test standards is the human surrogate to which the PPE is affixed; this typically embodies unrepresentative geometries, masses, stiffness and levels of constraint when compared to humans. A key aspect of any human surrogate element is the simulant material used. Most previous sports specific surrogates tend to use off-the-shelf silicone blends to represent all the soft tissue structures within the human limb segment or organ; this approach potentially neglects important human response phenomena caused by the different tissue structures. This study presents an investigation into the use of bespoke additive cure Polydimethysiloxane (PDMS) silicone blends to match the reported mechanical properties of human relaxed and contracted skeletal muscle tissues. The silicone simulants have been tested in uniaxial compression through a range of strain rates and fit with a range of constitutive hyperelastic models (Mooney Rivlin, Ogden and Neo Hookean) and a viscoelastic Prony series. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Real-time ed end-point Polymerase Chain Reaction per la quantizzazione del DNA di Citomegalovirus: confronto tra metodi e con il test per l’antigene pp65

    Directory of Open Access Journals (Sweden)

    Tiziano Allice


    Full Text Available Quantitave Polymerase Chain Reaction (PCR for Cytomegalovirus (CMV DNA provides highly sensitive and specific data for detecting CMV as well as monitoring the infection and determining the appropriate antiviral strategy.To determine the clinical application of a recently introduced real-time (RT PCR assay for CMV DNA quantitation in peripheral blood leukocytes (PBLs and defining its correlation with the commercial quantitative end-point (EP PCR method COBAS AMPLICOR CMV Monitor and pp65 antigen test. Sequential PBL samples (n=158 from 32 liver transplanted patients with CMV asymptomatic infection and positive for CMV DNA by EP-PCR were retrospectively analysed with RT-PCR and studied according to pp65 antigen levels. A good correlation was found between RT-PCR and pp65 antigen test (r=0.691 and between the two PCR assays (r=0.761. RT-PCR data were significantly higher in pre-emptive treated patients (those with >20 pp65+positive cells, median value: 3.8 log10 copies/500,000 PBLs than in not-treated ones (2.9 logs.According to pp65 levels of 0, 1-10, 11-20, 21-50, 51-100 and >100 positive cells/200,000 PBLs, median CMV DNA load by RT-PCR was 2.6, 3.0, 3.6, 4.0. 4.2 and 4.8, log10 copies/ 500,000 PBLs, respectively (EP-PCR CMV DNA levels: 2. 8, 2.9, 3.8, 3.7, 3.9 and 4.0 logs. For samples with >20 pp65+cells, that is above the level at which pre-emptive therapy was started, RT-PCR values were significantly higher than in groups with less than 20 pp65+cells, whereas EP-PCR values did not significantly differ and showed a slower progression rate. Dilutions of DNA from CMV AD169 strain were used to probe RT-PCR reproducibility (between and intra-assay variability < 2% and sensitivity (100% detection rate at 10 copies/reaction, 28.5% with EP-PCR. A significant improvement is coming from the introduction of RT-PCR to the study of CMV DNA dynamics in differently CMV infected patients due to a more reliable quantitation of CMV DNA for moderate and high

  2. Surrogate Motherhood I: Responses to Infertility. (United States)

    Schwartz, Lita Linzer


    Surrogate motherhood is a path to parenthood filled with legal "potholes" and psychological "rocks." Mental health specialists, especially marital and family therapists, may well be called upon to provide their professional services to people attempting to negotiate it. Introduces a number of potential hazards, presenting the…

  3. 34 CFR 303.406 - Surrogate parents. (United States)


    ... 34 Education 2 2010-07-01 2010-07-01 false Surrogate parents. 303.406 Section 303.406 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION EARLY INTERVENTION PROGRAM FOR INFANTS AND TODDLERS WITH...

  4. Surrogate markers of atherosclerosis: impact of statins

    NARCIS (Netherlands)

    Kastelein, John J. P.; Wiegman, Albert; de Groot, Eric


    Carotid artery intima-media thickness (IMT) measured by ultrasound has been shown to be correlated with existing cardiovascular disease (CVD) and predictive of CVD in individuals without clinically evident disease. Carotid IMT is now widely used as a surrogate marker for atherosclerotic disease. A

  5. Nitrate Salt Surrogate Blending Scoping Test Plan

    Energy Technology Data Exchange (ETDEWEB)

    Anast, Kurt Roy [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)


    Test blending equipment identified in the “Engineering Options Assessment Report: Nitrate Salt Waste Stream Processing”. Determine if the equipment will provide adequate mixing of zeolite and surrogate salt/Swheat stream; optimize equipment type and operational sequencing; impact of baffles and inserts on mixing performance; and means of validating mixing performance

  6. "It's not just what the doctor tells me:" factors that influence surrogate decision-makers' perceptions of prognosis. (United States)

    Boyd, Elizabeth A; Lo, Bernard; Evans, Leah R; Malvar, Grace; Apatira, Latifat; Luce, John M; White, Douglas B


    Physicians and surrogate decision-makers for seriously ill patients often have different views of patients' prognoses. We sought to understand what sources of knowledge surrogates rely on when estimating a patient's prognosis. Prospective, mixed-methods study using face-to-face, semistructured interviews with surrogate decision-makers. Four intensive care units at the University of California, San Francisco Medical Center in 2006 to 2007. Participants were 179 surrogate decision-makers for 142 incapacitated, critically ill patients at high risk for death. Less than 2% (3 of 179) of surrogates reported that their beliefs about the patients' prognoses hinged exclusively on prognostic information provided to them by physicians. The majority cited other factors in addition to physicians' predictions that also contributed to their beliefs about the patients' prognoses, including perceptions of the patient's individual strength of character and will to live; the patient's unique history of illness and survival; the surrogate's own observations of the patient's physical appearance; the surrogate's belief that their presence at the bedside may improve the prognosis; and the surrogate's optimism, intuition, and faith. For some surrogates, these other sources of knowledge superseded the importance of the physician's prognostication. However, most surrogates endeavored to balance their own knowledge of the patient with physicians' biomedical knowledge. Surrogates use diverse types of knowledge when estimating their loved ones' prognoses, including individualized attributes of the patient, such as their strength of character and life history, of which physicians may be unaware. Attention to these considerations may help clinicians identify and overcome disagreements about prognosis.

  7. Adhesion kinetics of human primary monocytes, dendritic cells, and macrophages: Dynamic cell adhesion measurements with a label-free optical biosensor and their comparison with end-point assays. (United States)

    Orgovan, Norbert; Ungai-Salánki, Rita; Lukácsi, Szilvia; Sándor, Noémi; Bajtay, Zsuzsa; Erdei, Anna; Szabó, Bálint; Horvath, Robert


    obtained with the high-temporal-resolution Epic BT, but could only provide end-point data. In contrast, complex, nonmonotonic cell adhesion kinetics measured by the high-throughput optical biosensor is expected to open a window on the hidden background of the immune cell-extracellular matrix interactions.

  8. A conceptual model of the role of communication in surrogate decision making for hospitalized adults. (United States)

    Torke, Alexia M; Petronio, Sandra; Sachs, Greg A; Helft, Paul R; Purnell, Christianna


    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.

  9. Identifying family members who may struggle in the role of surrogate decision maker. (United States)

    Majesko, Alyssa; Hong, Seo Yeon; Weissfeld, Lisa; White, Douglas B


    Although acting as a surrogate decision maker can be highly distressing for some family members of intensive care unit patients, little is known about whether there are modifiable risk factors for the occurrence of such difficulties. To identify: 1) factors associated with lower levels of confidence among family members to function as surrogates and 2) whether the quality of clinician-family communication is associated with the timing of decisions to forego life support. We conducted a prospective study of 230 surrogate decision makers for incapacitated, mechanically ventilated patients at high risk of death in four intensive care units at University of California San Francisco Medical Center from 2006 to 2007. Surrogates completed a questionnaire addressing their perceived ability to act as a surrogate and the quality of their communication with physicians. We used clustered multivariate logistic regression to identify predictors of low levels of perceived ability to act as a surrogate and a Cox proportional hazard model to determine whether quality of communication was associated with the timing of decisions to withdraw life support. There was substantial variability in family members' confidence to act as surrogate decision makers, with 27% rating their perceived ability as 7 or lower on a 10-point scale. Independent predictors of lower role confidence were the lack of prior experience as a surrogate (odds ratio 2.2, 95% confidence interval [1.04-4.46], p=.04), no prior discussions with the patient about treatment preferences (odds ratio 3.7, 95% confidence interval [1.79-7.76], pfamily communication was associated with a significantly shorter duration of life-sustaining treatment among patients who died (β=0.11, p=.001). Family members without prior experience as a surrogate and those who had not engaged in advanced discussions with the patient about treatment preferences were at higher risk to report less confidence in carrying out the surrogate role. Better

  10. 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.

  11. Sintering Studies of Ga-Doped CeO{sub 2} (Ga-Doped PuO{sub 2} Surrogate) for Mixed Oxide Nuclear Fuel

    Energy Technology Data Exchange (ETDEWEB)

    Haertling, C.; Huling, J.; Park, Y.S.


    Sintering studies of CeO{sub 2} and CeO{sub 2} + 2 wt. % Ga{sub 2}O{sub 3} were completed. Firing temperatures studied were 1250-1650 C with 2 to 4 hour firing soak times in air. Powders fabricated by three methods (as-received, attrition-mill and nitrite-derived) were studied. Attrition-milled CeO{sub 2} improved densities as compared with as-received CeO{sub 2}. Attrition-milled CeO{sub 2} with 2 wt.% Ga{sub 2}O{sub 3} showed decreased densities with increasing temperatures. As-received CeO{sub 2} with 2 wt.% Ga{sub 2}O{sub 3} showed a opposite trend, increasing in density with increased firing temperature. Two pellet preparation methods were studied, a one-step-press method and a two-step-press method. The two-step-press method showed greater densities at lower firing temperatures and times as compared with the one-step-press method, however for CeO{sub 2} + 2 wt.% Ga{sub 2}O{sub 3}, the two methods gave equivalent results at 1650 C, 6 hr. firing conditions.

  12. 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)


    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.

  13. Optical Coherencetomography for Bladder Cancer-Ready as a Surrogate for Optical Biopsy? Results of a Prospective Mono-Centre Study

    Directory of Open Access Journals (Sweden)

    Karl, H. Stepp


    Full Text Available Nowadays, there is no perfect noninvasive diagnostic technique for bladder cancer. Cystoscopy and transurethral resection (TUR are stil gold standard for the diagnosis of muscle invasive bladder cancer. On the other hand, Optical CoherenceTomography (OCT can be alternative in the future. OCT was the first applied for opthalmology. OCT provides layer by layer images from target tissues with high-resolution, optical cross-sectional tomographic imaging. OCT’s concept is similar to ultrasound, differently it use light for detection. OCT’s resolution may vary from 20 microns (μm up to 1 μm that depends on optical system and lightsource. The image penetration depth of OCT can reach to 2-3 mm. Recently, there are many research about OCT for the diagnosis of urogenital tumors in the literature. In this study, A.Karl reported sensitivity and specificty of OCT for detecting the presence of malignant lession as 100% and %65. But, this small study includes only 52 patients who have 166 suspicious lesions. Specifity of OCT was inadequate due to false positive images, in this report. Contrary, there were no false negative lesions and its sensitivity was 100% depend on all invasive tumors detected and staged correctly beyond the lamina propria. False positive results were associated with edema, inflammation and scar. The overall OCT sensitivity, specificity, accuracy, negative and positive predictive values are reported as 75-100%, 65-98%, 92%, 75% and 100% in the literature. We need more large-scale studies about this topic. It will be promissing technique for diagnostics of urogenital malignant lesions. OCT (optical biopsy will progress with tecnical development and it will be alternative method for staging of bladder cancer.

  14. Emergy and end-point impact assessment of agricultural and food production in the United States:a supply chain-linked ecologically-based life cycle assessment


    Park, Yong Shin; Eğilmez, Gökhan; Küçükvar, Murat


    The concept of tracing the ecologically-based life cycle impacts of agricultural and food industries (AFIs)has become a topic of interest worldwide due to their criticalassociation with the climate change,water and land footprint, and food security. In this study, an indepth analysis of ecology resourceconsumption, atmospheric emissions, land and water footprints of 54 agricultural and food industriesinthe U.S. were examined extensively. Initially, the supply-chain linked ecological life cycl...

  15. Effects of the glyphosate active ingredient and a formulation on Lemna gibba L. at different exposure levels and assessment end-points. (United States)

    Sobrero, M C; Rimoldi, F; Ronco, A E


    The use of formulations of the herbicide glyphosate in transgenic crops of the Pampa's plains of Argentina has extensively increased, though there is scarce information of its impact on non-target vascular plants from agro-ecosystem related surface waters. The sensitivity of a local clone of the macrophyte Lemna gibba L. to glyphosate active principle and Roundup Max formulation was studied in standardized laboratory conditions. Phytotoxic effects, considering the aquatic route, at a concentration range of glyphosate between 0.5 and 80 mg L(-1) as active ingredient during 10 days of exposure were assessed on plant population growth, frond growth, shape and number, total chlorophyll content and colony architecture. Exposure to 1 mg L(-1) of glyphosate (an expected environmental concentration) affects all the studied assessment endpoints, except for population growth and chlorophyll content. Equivalent concentrations of this herbicide as the active ingredient or RoundupMax indicate higher phytotocity of the formulation. Exposed plants at concentrations of herbicide between 1 and 7.5 mg L(-1) exhibit after two days a recovery of the multiplication rate. Frond aggregation and longer stipe was detected between 1 and 15 mg L(-1) of glyphosate, determining more open colony architecture. At higher concentrations of the herbicide fronds break-up. Comparisons with literature data indicate a higher sensitivity of the L. gibba local clone with respect to L. minor and algal species, and also a similar response to the herbicide in field experiments with the same species.

  16. A New Method for Rapid Screening of End-Point PCR Products: Application to Single Genome Amplified HIV and SIV Envelope Amplicons.

    Directory of Open Access Journals (Sweden)

    Laurent Houzet

    Full Text Available PCR is the most widely applied technique for large scale screening of bacterial clones, mouse genotypes, virus genomes etc. A drawback of large PCR screening is that amplicon analysis is usually performed using gel electrophoresis, a step that is very labor intensive, tedious and chemical waste generating. Single genome amplification (SGA is used to characterize the diversity and evolutionary dynamics of virus populations within infected hosts. SGA is based on the isolation of single template molecule using limiting dilution followed by nested PCR amplification and requires the analysis of hundreds of reactions per sample, making large scale SGA studies very challenging. Here we present a novel approach entitled Long Amplicon Melt Profiling (LAMP based on the analysis of the melting profile of the PCR reactions using SYBR Green and/or EvaGreen fluorescent dyes. The LAMP method represents an attractive alternative to gel electrophoresis and enables the quick discrimination of positive reactions. We validate LAMP for SIV and HIV env-SGA, in 96- and 384-well plate formats. Because the melt profiling allows the screening of several thousands of PCR reactions in a cost-effective, rapid and robust way, we believe it will greatly facilitate any large scale PCR screening.

  17. Comparative study on the high pressure inactivation behavior of the Shiga toxin-producing Escherichia coli O104:H4 and O157:H7 outbreak strains and a non-pathogenic surrogate. (United States)

    Reineke, Kai; Sevenich, Robert; Hertwig, Christian; Janßen, Traute; Fröhling, Antje; Knorr, Dietrich; Wieler, Lothar H; Schlüter, Oliver


    Enterohemorrhagic Escherichia coli strains cause each year thousands of illnesses, which are sometimes accompanied by the hemolytic uremic syndrome, like in the 2011 outbreak in Germany. For preservation thermal pasteurization is commonly used, which can cause unwanted quality changes. To prevent this high pressure treatment is a potential alternative. Within this study, the 2011 outbreak strain O104:H4, an O157:H7 and a non-pathogenic strain (DSM1116) were tested. The cells were treated in buffer (pH 7 and pH 5) and carrot juice (pH 5.1) in a pressure temperature range of 0.1-500 MPa and 20-70 °C. Flow cytometry was used to investigate the pressure impact on cell structures of the strain DSM1116. Both pathogenic strains had a much higher resistance in buffer and carrot juice than the non-pathogenic surrogate. Further, strains cultivated and treated at a lower pH-value showed higher pressure stability, presumably due to variations in the membrane composition. This was confirmed for the strain DSM1116 by flow cytometry. Cells cultivated and treated at pH 5 had a stronger ability to retain their membrane potential but showed higher rates of membrane permeabilization at pressures <200 MPa compared to cells cultivated and treated at pH 7. These cells had the lowest membrane permeabilization rate at around 125 MPa, possibly denoting that variations in the fatty acid composition and membrane fluidity contribute to this stabilization phenomenon. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Mónica Amador


    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

  19. Low temperature oxidation, co-oxidation and auto-ignition of olefinic and aromatic blending compounds: Experimental study of interactions during the oxidation of a surrogate fuel; Oxydation, co-oxydation et auto-inflammation a basses temperatures d'alcenes et aromatiques types: etude experimentale des interactions au sein d'un carburant-modele

    Energy Technology Data Exchange (ETDEWEB)

    Vanhove, G.


    The low-temperature (600-900 K) and high-pressure (5-25 bar) oxidation and auto-ignition of the three position isomers of hexene, of binary mixtures of 1-hexene, toluene and iso-octane, and of a surrogate fuel composed of these three compounds were studied in motor conditions using a rapid compression machine. Auto-ignition delay times were measured as long as intermediate products concentrations during the delay. The results show that the oxidation chemistry of the hexenes is very dependent on the position of the double bond inside the molecule, and that strong interactions between the oxidation mechanisms of hydrocarbons in mixtures can occur. The data obtained concerning the surrogate fuel give a good insight into the behaviour of a practical gasoline after an homogeneous charge compression. (author)

  20. Surrogate formulations for thermal treatment of low-level mixed waste. Part 1: Radiological surrogates

    Energy Technology Data Exchange (ETDEWEB)

    Stockdale, J.A.D.; Bostick, W.D.; Hoffmann, D.P. [Martin Marietta Energy Systems, Inc., Oak Ridge, TN (United States); Lee, H.T. [Oak Ridge Associated Universities, TN (United States)


    The evaluation and comparison of proposed thermal treatment systems for mixed wastes can be expedited by tests in which the radioactive components of the wastes are replaced by surrogate materials chosen to mimic, as far as is possible, the chemical and physical properties of the radioactive materials of concern. In this work, sponsored by the Mixed Waste Integrated Project of the US Department of Energy, the authors have examined reported experience with such surrogates and suggest a simplified standard list of materials for use in tests of thermal treatment systems. The chief radioactive nuclides of concern in the treatment of mixed wastes are {sup 239}Pu, {sup 238}U, {sup 235}U, {sup 137}Cs, {sup 103}Ru, {sup 99}Tc, and {sup 90}Sr. These nuclides are largely by-products of uranium enrichment, reactor fuel reprocessing, and weapons program activities. Cs, Ru, and Sr all have stable isotopes that can be used as perfect surrogates for the radioactive forms. Technetium exists only in radioactive form, as do plutonium and uranium. If one wishes to preclude radioactive contamination of the thermal treatment system under trial burn, surrogate elements must be chosen for these three. For technetium, the authors suggest the use of natural ruthenium, and for both plutonium and uranium, they recommend cerium. The seven radionuclides listed can therefore be simulated by a surrogate package containing stable isotopes of ruthenium, strontium, cesium, and cerium.

  1. Primary Reference Fuels (PRFs) as Surrogates for Low Sensitivity Gasoline Fuels

    KAUST Repository

    Bhavani Shankar, Vijai Shankar


    Primary Reference Fuels (PRFs) - binary mixtures of n-heptane and iso-octane based on Research Octane Number (RON) - are popular gasoline surrogates for modeling combustion in spark ignition engines. The use of these two component surrogates to represent real gasoline fuels for simulations of HCCI/PCCI engines needs further consideration, as the mode of combustion is very different in these engines (i.e. the combustion process is mainly controlled by the reactivity of the fuel). This study presents an experimental evaluation of PRF surrogates for four real gasoline fuels termed FACE (Fuels for Advanced Combustion Engines) A, C, I, and J in a motored CFR (Cooperative Fuels Research) engine. This approach enables the surrogate mixtures to be evaluated purely from a chemical kinetic perspective. The gasoline fuels considered in this study have very low sensitivities, S (RON-MON), and also exhibit two-stage ignition behavior. The first stage heat release, which is termed Low Temperature Heat Release (LTHR), controls the combustion phasing in this operating mode. As a result, the performance of the PRF surrogates was evaluated by its ability to mimic the low temperature chemical reactivity of the real gasoline fuels. This was achieved by comparing the LTHR from the engine pressure histories. The PRF surrogates were able to consistently reproduce the amount of LTHR, closely match the phasing of LTHR, and the compression ratio for the start of hot ignition of the real gasoline fuels. This suggests that the octane quality of a surrogate fuel is a good indicator of the fuel’s reactivity across low (LTC), negative temperature coefficient (NTC), and high temperature chemical (HTC) reactivity regimes.

  2. Ovulation Statuses of Surrogate Gilts Are Associated with the Efficiency of Excellent Pig Cloning.

    Directory of Open Access Journals (Sweden)

    Yanjun Huan

    Full Text Available Somatic cell nuclear transfer (SCNT is an assisted reproductive technique that can produce multiple copies of excellent livestock. However, low cloning efficiency limits the application of SCNT. In this study, we systematically investigated the major influencing factors related to the overall cloning efficiency in pigs. Here, 13620 cloned embryos derived from excellent pigs were transferred into 79 surrogate gilts, and 119 live cloned piglets were eventually generated. During cloning, group of cloned embryos derived from excellent Landrace or Large white pigs presented no significant differences of cleavage and blastocyst rates, blastocyst cell numbers, surrogate pregnancy and delivery rates, average numbers of piglets born and alive and cloning efficiencies, and group of 101-150, 151-200 or 201-250 cloned embryos transferred per surrogate also displayed a similar developmental efficiency. When estrus stage of surrogate gilts was compared, group of embryo transfer on Day 2 of estrus showed significantly higher pregnancy rate, delivery rate, average number of piglets born, average alive piglet number or cloning efficiency than group on Day 1, Day 3, Day 4 or Day 5, respectively (P<0.05. And, in comparison with the preovulation and postovulation groups, group of surrogate gilts during periovulation displayed a significantly higher overall cloning efficiency (P<0.05. Further investigation of surrogate estrus stage and ovulation status displayed that ovulation status was the real factor underlying estrus stage to determine the overall cloning efficiency. And more, follicle puncture for preovulation, not transfer position shallowed for preovulation or deepened for postovulation, significantly improved the average number of piglets alive and cloning efficiency (P<0.05. In conclusion, our results demonstrated that ovulation status of surrogate gilts was the fundamental factor determining the overall cloning efficiency of excellent pigs, and follicle

  3. Compaction behavior of surrogate degraded emplaced WIPP waste.

    Energy Technology Data Exchange (ETDEWEB)

    Broome, Scott Thomas [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bronowski, David R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Kuthakun, Souvanny James [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Herrick, Courtney Grant [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Pfeifle, Thomas W. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)


    The present study results are focused on laboratory testing of surrogate waste materials. The surrogate wastes correspond to a conservative estimate of degraded Waste Isolation Pilot Plant (WIPP) containers and TRU waste materials at the end of the 10,000 year regulatory period. Testing consists of hydrostatic, triaxial, and uniaxial strain 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 (CPR). Axial, lateral, and volumetric strain and axial, lateral, and pore 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 moduli of the samples measured using this technique were consistent with those measured using more conventional methods. The second technique involved performing triaxial tests under lateral strain control. By limiting the lateral strain to zero by controlling the applied confining pressure while loading the specimen axially in compression, one can maintain a right-circular cylindrical geometry even under large deformations. This technique is preferred over standard triaxial testing methods which result in inhomogeneous deformation or (3z(Bbarreling(3y. (BManifestations of the inhomogeneous deformation included non-uniform stress states, as well as unrealistic Poissons ratios (> 0.5) or those that vary significantly along the length of the specimen. Zero lateral strain controlled tests yield a more uniform stress state, and admissible and uniform values of Poissons ratio.

  4. Accounting for treatment by center interaction in sample size determinations and the use of surrogate outcomes in the pessary for the prevention of preterm birth trial: a simulation study. (United States)

    Willan, Andrew R


    The Pessary for the Prevention of Preterm Birth Study (PS3) is an international, multicenter, randomized clinical trial designed to examine the effectiveness of the Arabin pessary in preventing preterm birth in pregnant women with a short cervix. During the design of the study two methodological issues regarding power and sample size were raised. Since treatment in the Standard Arm will vary between centers, it is anticipated that so too will the probability of preterm birth in that arm. This will likely result in a treatment by center interaction, and the issue of how this will affect the sample size requirements was raised. The sample size requirements to examine the effect of the pessary on the baby's clinical outcome was prohibitively high, so the second issue is how best to examine the effect on clinical outcome. The approaches taken to address these issues are presented. Simulation and sensitivity analysis were used to address the sample size issue. The probability of preterm birth in the Standard Arm was assumed to vary between centers following a Beta distribution with a mean of 0.3 and a coefficient of variation of 0.3. To address the second issue a Bayesian decision model is proposed that combines the information regarding the between-treatment difference in the probability of preterm birth from PS3 with the data from the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study that relate preterm birth and perinatal mortality/morbidity. The approach provides a between-treatment comparison with respect to the probability of a bad clinical outcome. The performance of the approach was assessed using simulation and sensitivity analysis. Accounting for a possible treatment by center interaction increased the sample size from 540 to 700 patients per arm for the base case. The sample size requirements increase with the coefficient of variation and decrease with the number of centers. Under the same assumptions used for determining the sample size

  5. Assurance of neuroattenuation of a live vaccine against West Nile virus: a comprehensive study of neuropathogenesis after infection with chimeric WN/DEN4Δ30 vaccine in comparison to two parental viruses and a surrogate flavivirus reference vaccine. (United States)

    Maximova, Olga A; Speicher, James M; Skinner, Jeff R; Murphy, Brian R; St Claire, Marisa C; Ragland, Danny R; Herbert, Richard L; Pare, Dan R; Moore, Rashida M; Pletnev, Alexander G


    The upsurge of West Nile virus (WNV) human infections in 2012 suggests that the US can expect periodic WNV outbreaks in the future. Availability of safe and effective vaccines against WNV in endemic areas, particularly for aging populations that are at high risk of West Nile neuroinvasive disease (WNND), could be beneficial. WN/DEN4Δ30 is a live, attenuated chimeric vaccine against WNV produced by replacement of the genes encoding the pre-membrane and envelope protein genes of the vaccine virus against dengue virus type 4 (DEN4Δ30) with corresponding sequences derived from a wild type WNV. Following intrathalamic inoculation of nonhuman primates (NHPs), a comprehensive neuropathogenesis study was performed and neurovirulence of WN/DEN4Δ30 vaccine candidate was compared to that of two parental viruses (i.e., WNV and DEN4Δ30), as well as to that of an attenuated flavivirus surrogate reference (i.e., yellow fever YF 17D). Clinical and virological data, as well as results of a semi-quantitative histopathological analysis, demonstrated that WN/DEN4Δ30 vaccine is highly attenuated for the central nervous system (CNS) of NHPs in comparison to a wild type WNV. Importantly, based on the virus replicative ability in the CNS of NHPs and the degree of induced histopathological changes, the level of neuroattenuation of WN/DEN4Δ30 vaccine was similar to that of YF 17D, and therefore within an acceptable range. In addition, we show that the DEN4Δ30 vaccine tested in this study also has a low neurovirulence profile. In summary, our results demonstrate a high level of neuroattenuation of two vaccine candidates, WN/DEN4Δ30 and DEN4Δ30. We also show here a remarkable sensitivity of our WNV-NY99 NHP model, as well as striking resemblance of the observed neuropathology to that seen in human WNND. These results support the use of this NHP model for translational studies of WNV neuropathogenesis and/or testing the effectiveness of vaccines and therapeutic approaches. Published

  6. Surrogate decision making in the internet age. (United States)

    Berg, Jessica


    The computer revolution has had an enormous effect on all aspects of the practice of medicine, yet little thought has been given to the role of social media in identifying treatment choices for incompetent patients. We are currently living in the "Internet age" and many people have integrated social media into all aspects of their lives. As use becomes more prevalent, and as users age, social media are more likely to be viewed as a source of information regarding medical care preferences. This article explores the ethical and legal issues raised by the use of social media in surrogate decision making.

  7. Providing support to surrogate decision-makers for people living with dementia: Healthcare professional, organisational and community responsibilities. (United States)

    Shanley, Christopher; Fetherstonhaugh, Deirdre; McAuliffe, Linda; Bauer, Michael; Beattie, Elizabeth


    The prevalence of dementia will continue to increase with the ageing of the population. Many people living with dementia will reach a stage where surrogate decision-makers-mostly family carers-will need to make a range of decisions on their behalf. The aim of this study was to learn from surrogate decision-makers how they can be most effectively supported in this role. The study employed a qualitative design using semi-structured face-to-face or telephone interviews with a purposive sample of 34 surrogate decision-makers of people living with dementia. Transcripts of participant interviews were reviewed using a thematic approach to analysis. Four main themes were identified from this analysis: needing greater community awareness of dementia and its impact; intervening early in cognitive decline; relying on health professionals for ongoing support; and seeking and using support from wherever is relevant for each person. Based on this analysis and a review of the literature, we propose a wholistic set of recommendations for the support of surrogate decision-makers. Healthcare professionals need to help family carers understand the likely trajectory of dementia, including the significance of surrogate decision-making. They can support the person living with dementia and their surrogates to undertake advance care planning and they can act as empathic guides during this process. Health and community care organisations need to provide a "key worker" model wherever possible so that the person living with dementia and their surrogate decision-maker do not have to seek support from multiple staff members or organisations. Carer support programmes can routinely include information and resources about surrogate decision-making. Community and government organisations can help people prepare for the possibility of becoming surrogate decision-makers by promoting a greater public awareness and understanding of both dementia and advance care planning. © 2017 John Wiley & Sons Ltd.

  8. Pull out strength calculator for pedicle screws using a surrogate ensemble approach. (United States)

    Varghese, Vicky; Ramu, Palaniappan; Krishnan, Venkatesh; Saravana Kumar, Gurunathan


    Pedicle screw instrumentation is widely used in the treatment of spinal disorders and deformities. Currently, the surgeon decides the holding power of instrumentation based on the perioperative feeling which is subjective in nature. The objective of the paper is to develop a surrogate model which will predict the pullout strength of pedicle screw based on density, insertion angle, insertion depth and reinsertion. A Taguchi's orthogonal array was used to design an experiment to find the factors effecting pullout strength of pedicle screw. The pullout studies were carried using polyaxial pedicle screw on rigid polyurethane foam block according to American society for testing of materials (ASTM F543). Analysis of variance (ANOVA) and Tukey's honestly significant difference multiple comparison tests were done to find factor effect. Based on the experimental results, surrogate models based on Krigging, polynomial response surface and radial basis function were developed for predicting the pullout strength for different combination of factors. An ensemble of these surrogates based on weighted average surrogate model was also evaluated for prediction. Density, insertion depth, insertion angle and reinsertion have a significant effect (p experimental values and surrogate models. This can be used in pre-surgical planning and decision support system for spine surgeon. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Failed surrogate conceptions: social and ethical aspects of preconception disruptions during commercial surrogacy in India. (United States)

    Mitra, Sayani; Schicktanz, Silke


    During a commercial surrogacy arrangement, the event of embryo transfer can be seen as the formal starting point of the arrangement. However, it is common for surrogates to undergo a failed attempt at pregnancy conception or missed conception after an embryo transfer. This paper attempts to argue that such failed attempts can be understood as a loss. It aims to reconstruct the experiences of loss and grief of the surrogates and the intended parents as a consequence of their collective failure to conceive a surrogate pregnancy. Drawing on a qualitative study conducted over a period of eight months between 2014 and 2015 at two fertility clinics in Delhi and two in Kolkata, India, this paper examines the experiences of the surrogates and the intended parents when faced with missed conceptions or failed conceptions during a surrogacy arrangement. We argue that while the surrogate grieves the non-arrival of a 'good news' as an uncertain loss, the intended parents experience yet another, failure in addition to the losses they might have incurred during their previous fertility treatments. The body of the surrogate becomes a site of 'a lost opportunity'. The surrogate embodies a loss in her quest to achieve social mobility and the intended parents experience a disembodied pregnancy loss. This very emotional experience stands in stark contrast to the conceptualisation of such failed attempts as non-events within the discourse of the surrogacy industry. The experience of loss of the intended parents is recognised but their grief is given no space. We argue that such ambiguity around the nature of losses resulting out of a missed or failed conception during surrogacy is an outcome of lack of interpersonal relationship between the surrogate and the intended parents. Since commercial surrogacy is a relational process, the only way in which the experiences of losses and failures of the actors at the preconception stage can be better addressed is through developing close

  10. Analytical approximations for temperature dependent thermophysical properties of supercritical diesel fuel surrogates used in combustion modeling (United States)

    Kumar, Abhinav; Saini, Vishnu; Dondapati, Raja Sekhar; Usurumarti, Preeti Rao


    Supercritical fluid technology is introduced to combat the critical challenges related with emissions, incomplete and clean diesel fuel combustion. The chemical kinetics of diesel fuel is a strong function of temperature. As surrogate fuels have a potential to represent a real diesel fuel, thermophysical properties of such fuels have been studied in this present work as a function of temperature. Further, two diesel surrogate fuels which have been identified as the components of actual diesel fuel for jet engines are studied and thermophysical properties of these two surrogates are evaluated as a function of temperature at critical pressure. In addition, the accuracy and reliability of the developed correlations is estimated using two statistical parameters such as Absolute Average of Relative Error (AARE) and Sum of Average Residues (SAR). Results show an excellent agreement between the standard data and the correlated property values.

  11. Virucidal Effectiveness Testing Using Feline Calicivirus as Surrogate for Norovirus (United States)

    These documents describe the effectiveness test using Feline Calicivirus as Surrogate for Norovirus, including initial and confirmatory testing and testing with pre-saturated or impregnated towelettes.

  12. Surrogate functionality of celluloses as tablet excipients. (United States)

    Díaz Ramírez, Carmen Cristina; Robles, Leopoldo Villafuerte


    The variety of excipients from different sources and prices to which we have access gives rise to the necessity to evaluate their functional characteristics. The aim of this work is to determine some physical and technological characteristics of celluloses from different sources, India and United States, to ascertain their functionality as tablet excipients. The used surrogate functionality properties are particle morphology and particle size distribution, compactibility, ejection pressure, and the disintegration properties of pure excipients and their compressed tablets. The innovators Avicel and Croscarmellose show advantages over the generic celluloses Alfacel and Carmacel. Avicel PH 101 and 102 show an average of 26% greater compactibility than both types of Alfacel, whereas the compactibility of Croscarmellose is greater than that of Carmacel in about 50%. Avicel tablets compacted at a compaction pressure of 47 MPa exhibit shorter disintegration times (3.7 minutes) than Alfacel tablets (28 minutes), whereas Carmacel show better disintegrant properties than Croscarmellose. This occurs regardless of the similar particle morphology, size, and size distribution. As expected, all celluloses show low ejection pressures. The surrogate functionality properties of the generic celluloses are still considered as satisfactory to be used as tablet excipients, although they are inferior in some aspects to innovator celluloses. Alfacel and Carmacel have the potential to be used as filler, binder, and disintegrant, in the design of tablets. Moreover, one should bear in mind that the differences reported here may be altered because of a possible inter-batch variability and variations in the moisture content.

  13. Imaging seeker surrogate for IRCM evaluation (United States)

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


    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 has several advantages over the use of an operational seeker, which is in service or in development: 1) the system is flexible, allowing both hardware and software modifications to be made in order to test the effectiveness of specific IRCM techniques; 2) the seeker design is open - every last parameter is available to the science team, allowing detailed, end-to-end validation of software models and simulations; 3) the availability of an unclassified seeker facilitates open discussions on CM issues between the participants in the NATO-group. Testing of high intensity countermeasures (for example based on lasers) needs a system with realistic seeker optics, with proper representation of optical scatter in seeker optics, which differs from scatter in commercial infrared camera optics. A technical description of the ISS is given: an overview of the optical design and the detector, the principle of the tracking software and the possibilities to implement alternative tracking algorithms in order to represent different threat CCM techniques. The ISS is built for use both in the laboratory and in the field. Finally, some experimental results will be presented.

  14. Detailed chemical kinetic oxidation mechanism for a biodiesel surrogate

    Energy Technology Data Exchange (ETDEWEB)

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


    A detailed chemical kinetic mechanism has been developed and used to study the oxidation of methyl decanoate, a surrogate for biodiesel fuels. This model has been built by following the rules established by Curran et al. for the oxidation of n-heptane and it includes all the reactions known to be pertinent to both low and high temperatures. Computed results have been compared with methyl decanoate experiments in an engine and oxidation of rapeseed oil methyl esters in a jet stirred reactor. An important feature of this mechanism is its ability to reproduce the early formation of carbon dioxide that is unique to biofuels and due to the presence of the ester group in the reactant. The model also predicts ignition delay times and OH profiles very close to observed values in shock tube experiments fueled by n-decane. These model capabilities indicate that large n-alkanes can be good surrogates for large methyl esters and biodiesel fuels to predict overall reactivity, but some kinetic details, including early CO{sub 2} production from biodiesel fuels, can be predicted only by a detailed kinetic mechanism for a true methyl ester fuel. The present methyl decanoate mechanism provides a realistic kinetic tool for simulation of biodiesel fuels.

  15. Detailed chemical kinetic oxidation mechanism for a biodiesel surrogate

    Energy Technology Data Exchange (ETDEWEB)

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


    A detailed chemical kinetic mechanism has been developed and used to study the oxidation of methyl decanoate, a surrogate for biodiesel fuels. This model has been built by following the rules established by Curran et al. for the oxidation of n-heptane and it includes all the reactions known to be pertinent to both low and high temperatures. Computed results have been compared with methyl decanoate experiments in an engine and oxidation of rapeseed oil methyl esters in a jet stirred reactor. An important feature of this mechanism is its ability to reproduce the early formation of carbon dioxide that is unique to biofuels and due to the presence of the ester group in the reactant. The model also predicts ignition delay times and OH profiles very close to observed values in shock tube experiments fueled by n-decane. These model capabilities indicate that large n-alkanes can be good surrogates for large methyl esters and biodiesel fuels to predict overall reactivity, but some kinetic details, including early CO2 production from biodiesel fuels, can be predicted only by a detailed kinetic mechanism for a true methyl ester fuel. The present methyl decanoate mechanism provides a realistic kinetic tool for simulation of biodiesel fuels.

  16. Norovirus surrogate survival on spinach during preharvest growth. (United States)

    Hirneisen, Kirsten A; Kniel, Kalmia E


    Produce can become contaminated with human viral pathogens in the field through soil, feces, or water used for irrigation; through application of manure, biosolids, pesticides, and fertilizers; and through dust, insects, and animals. The objective of this study was to assess the survival and stability of human noroviruses and norovirus surrogates (Murine norovirus [MNV] and Tulane virus [TV]) on foliar surfaces of spinach plants in preharvest growth conditions. Spinach plants were housed in a biocontrol chamber at optimal conditions for up to 7 days and infectivity was determined by plaque assay. Virus inoculation location had the largest impact on virus survival as viruses present on adaxial leaf surfaces had lower decimal reduction time (D values) than viruses present on abaxial leaf surfaces. Under certain conditions, spinach type impacted virus survival, with greater D values observed from survival on semi-savoy spinach leaves. Additional UVA and UVB exposure to mimic sunlight affected virus survival on adaxial surfaces for both semi-savoy and smooth spinach plants for both viruses. Human GII norovirus inoculated onto semi-savoy spinach had an average D value that was not statistically significant from MNV and TV, suggesting that these surrogates may have similar survival on spinach leaves compared with human noroviruses. An understanding of the behavior of enteric viruses on spinach leaves can be used to enhance growers' guidelines and for risk assessment with certain growing conditions.

  17. FAmily CEntered (FACE) advance care planning: Study design and methods for a patient-centered communication and decision-making intervention for patients with HIV/AIDS and their surrogate decision-makers. (United States)

    Kimmel, Allison L; Wang, Jichuan; Scott, Rachel K; Briggs, Linda; Lyon, Maureen E


    Although the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has become a chronic illness, disease-specific advance care planning has not yet been evaluated for the palliative care needs of adults with HIV/AIDS. This prospective, longitudinal, randomized, two-arm controlled clinical trial aims to test the efficacy of FAmily CEntered advance care planning among adults living with AIDS and/or HIV with co-morbidities on congruence in treatment preferences, healthcare utilization, and quality of life. The FAmily CEntered intervention arm is two face-to-face sessions with a trained, certified facilitator: Session 1) Disease-Specific Advance Care Planning Respecting Choices Interview; Session 2) Completion of advance directive. The Healthy Living Control arm is: Session 1) Developmental/Relationship History; Session 2) Nutrition. Follow-up data will be collected at 3, 6, 12, and 18 months post-intervention. A total of 288 patient/surrogate dyads will be enrolled from five hospital-based, out-patient clinics in Washington, District of Columbia. Participants will be HIV positive and ≥ 21 years of age; surrogates will be ≥ 18 years of age. Exclusion criteria are homicidality, suicidality, psychosis, and impaired cognitive functioning. We hypothesize that this intervention will enhance patient-centered communication with a surrogate decision-maker about end of life treatment preferences over time, enhance patient quality of life and decrease health care utilization. We further hypothesize that this intervention will decrease health disparities for Blacks in completion of advance directives. If proposed aims are achieved, the benefits of palliative care, particularly increased treatment preferences about end-of-life care and enhanced quality of life, will be extended to people living with AIDS. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Psychometric evaluation of the surrogate decision making self-efficacy scale. (United States)

    Lopez, Ruth Palan; Guarino, A J


    Currently, no instrument exists to assess self-efficacy for surrogate decision making. This study assessed the psychometric properties of the Surrogate Decision Making Self-Efficacy Scale (SDM-SES). Interview data from surrogate decision makers (SDMs) were used to generate the items. Items were assessed for face validity by expert gerontological nurses. Responses from a sample of 155 SDMs for nursing home residents with dementia were analyzed to assess the psychometric properties of the scale scores. Internal consistency was calculated using Cronbach's alpha coefficient, and construct validity was evaluated using confirmatory factor analysis. The Cronbach's alpha coefficient suggested high internal consistency, and results of the confirmatory factor analysis supported the construct validity of the instrument. The SDM-SES may be useful as an assessment instrument, as well as an outcome measure for interventions aimed at increasing the capacity of SDMs. Future validations are suggested to optimize its utility. Copyright 2013, SLACK Incorporated.

  19. Enhanced CRISPR/Cas9-mediated biallelic genome targeting with dual surrogate reporter-integrated donors. (United States)

    Wu, Yun; Xu, Kun; Ren, Chonghua; Li, Xinyi; Lv, Huijiao; Han, Furong; Wei, Zehui; Wang, Xin; Zhang, Zhiying


    The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system has recently emerged as a simple, yet powerful genome engineering tool, which has been widely used for genome modification in various organisms and cell types. However, screening biallelic genome-modified cells is often time-consuming and technically challenging. In this study, we incorporated two different surrogate reporter cassettes into paired donor plasmids, which were used as both the surrogate reporters and the knock-in donors. By applying our dual surrogate reporter-integrated donor system, we demonstrate high frequency of CRISPR/Cas9-mediated biallelic genome integration in both human HEK293T and porcine PK15 cells (34.09% and 18.18%, respectively). Our work provides a powerful genetic tool for assisting the selection and enrichment of cells with targeted biallelic genome modification. © 2017 Federation of European Biochemical Societies.

  20. Neutron-induced cross sections of actinides via the surrogate-reaction method

    Directory of Open Access Journals (Sweden)

    Ducasse Q.


    Full Text Available The surrogate-reaction method is an indirect way of determining cross sections for reactions that proceed through a compound nucleus. This technique may enable neutron-induced cross sections to be extracted for short-lived nuclei that otherwise cannot be measured. However, the validity of the surrogate method has to be investigated. In particular, the absence of a compound nucleus formation and the Jπ dependence of the decay probabilities may question the method. In this work we study the reactions 238U(d,p239U, 238U(3He,t238Np, 238U(3He,4He237U as surrogates for neutron-induced reactions on 238U, 237Np and 236U, respectively, for which good quality data exist. The experimental set-up enabled the measurement of fission and gamma-decay probabilities. The first results are hereby presented.

  1. Surrogate fuel formulation for light naphtha combustion in advanced combustion engines

    KAUST Repository

    Ahmed, Ahfaz


    Crude oil once recovered is further separated in to several distinct fractions to produce a range of energy and chemical products. One of the less processed fractions is light naphtha (LN), hence they are more economical to produce than their gasoline and diesel counterparts. Recent efforts have demonstrated usage of LN as transportation fuel for internal combustion engines with slight modifications. In this study, a multicomponent surrogate fuel has been developed for light naphtha fuel using a multi-variable nonlinear constrained optimization scheme. The surrogate, consisting of palette species n-pentane, 2-methylhexane, 2-methylbutane, n-heptane and toluene, was validated against the LN using ignition quality tester following ASTM D6890 methodology. Comparison of LN and the surrogate fuel demonstrated satisfactory agreement.

  2. Designing a Surrogate Fuel for Gas-to-Liquid Derived Diesel

    DEFF Research Database (Denmark)

    Choudhury, H. A.; Intikhab, S.; Kalakul, Sawitree


    in a trade-off in performance when used in a diesel engine. To boost GTL diesel physicochemical properties and thereby enable its use in conventional diesel engines, GTL diesel needs improvement. This can be achieved by mixing suitable additives to the GTL diesel and through the development of surrogate...... their physicochemical properties. These surrogates are further verified using rigorous mathematical tools as well as through advanced experimental techniques. An optimal surrogate MI-5 is identified, which closely mimics GTL diesel-conventional diesel blends in terms of its physicochemical properties. An engine study......Synthetic diesel fuel produced from natural gas via gas-to-liquid (GTL) technology is referred to as ultraclean fuel but is still challenged for full certification as diesel fuel. GTL diesel lacks certain hydrocarbons and chemical constituents, which although are benign to the environment, result...

  3. Development, validation and transfer of a near infrared method to determine in-line the end point of a fluidised drying process for commercial production batches of an approved oral solid dose pharmaceutical product. (United States)

    Peinado, Antonio; Hammond, Jonathan; Scott, Andrew


    Pharmaceutical companies are progressively adopting and introducing the principles of Quality by Design with the main purpose of assurance and built-in quality throughout the whole manufacturing process. Within this framework, a Partial Least Square (PLS) model, based on Near Infrared (NIR) spectra and humidity determinations, was built in order to determine in-line the drying end point of a fluidized bed process. The in-process method was successfully validated following the principles described within The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use - ICH Q2 (r1) - Validation of Analytical Procedures: Text and Methodology. However, in some aspects, the cited guidelines were not appropriate to in-process methods developed and validated exclusively with in-line samples and implemented in dynamic systems, such as drying processes. In this work, a customized interpretation of guidelines has been adopted which provided the framework of evidence to support a validated application. The application has been submitted to the United States Food and Drug Administration (FDA) and The European Medicines Agency (EMA) during applications for grant of licences. Representatives from these Regulatory Authorities have specifically reviewed this novel application during on-site inspections, and have subsequently approved both the product and this application. Currently, the NIR method is implemented as a primary in-line method to control the drying end point in real-time (to below a control limit of not greater than 1.2% w/w) for commercial production batches of an approved, solid, oral-dose medicine. The implementation of this in-process method allows real-time control with benefits including a reduction in operation time and labour; sample handling and waste generation; and a reduced risk to product quality in further unit operations due to improved consistency of intermediate output at this stage. To date

  4. Simultaneous tumor and surrogate motion tracking with dynamic MRI for radiation therapy planning (United States)

    Park, Seyoun; Farah, Rana; Shea, Steven M.; Tryggestad, Erik; Hales, Russell; Lee, Junghoon


    Respiration-induced tumor motion is a major obstacle for achieving high-precision radiotherapy of cancers in the thoracic and abdominal regions. Surrogate-based estimation and tracking methods are commonly used in radiotherapy, but with limited understanding of quantified correlation to tumor motion. In this study, we propose a method to simultaneously track the lung tumor and external surrogates to evaluate their spatial correlation in a quantitative way using dynamic MRI, which allows real-time acquisition without ionizing radiation exposure. To capture the lung and whole tumor, four MRI-compatible fiducials are placed on the patient’s chest and upper abdomen. Two different types of acquisitions are performed in the sagittal orientation including multi-slice 2D cine MRIs to reconstruct 4D-MRI and two-slice 2D cine MRIs to simultaneously track the tumor and fiducials. A phase-binned 4D-MRI is first reconstructed from multi-slice MR images using body area as a respiratory surrogate and groupwise registration. The 4D-MRI provides 3D template volumes for different breathing phases. 3D tumor position is calculated by 3D–2D template matching in which 3D tumor templates in the 4D-MRI reconstruction and the 2D cine MRIs from the two-slice tracking dataset are registered. 3D trajectories of the external surrogates are derived via matching a 3D geometrical model of the fiducials to their segmentations on the 2D cine MRIs. We tested our method on ten lung cancer patients. Using a correlation analysis, the 3D tumor trajectory demonstrates a noticeable phase mismatch and significant cycle-to-cycle motion variation, while the external surrogate was not sensitive enough to capture such variations. Additionally, there was significant phase mismatch between surrogate signals obtained from the fiducials at different locations.

  5. Integrating surrogate models into subsurface simulation framework allows computation of complex reactive transport scenarios (United States)

    De Lucia, Marco; Kempka, Thomas; Jatnieks, Janis; Kühn, Michael


    Reactive transport simulations - where geochemical reactions are coupled with hydrodynamic transport of reactants - are extremely time consuming and suffer from significant numerical issues. Given the high uncertainties inherently associated with the geochemical models, which also constitute the major computational bottleneck, such requirements may seem inappropriate and probably constitute the main limitation for their wide application. A promising way to ease and speed-up such coupled simulations is achievable employing statistical surrogates instead of "full-physics" geochemical models [1]. Data-driven surrogates are reduced models obtained on a set of pre-calculated "full physics" simulations, capturing their principal features while being extremely fast to compute. Model reduction of course comes at price of a precision loss; however, this appears justified in presence of large uncertainties regarding the parametrization of geochemical processes. This contribution illustrates the integration of surrogates into the flexible simulation framework currently being developed by the authors' research group [2]. The high level language of choice for obtaining and dealing with surrogate models is R, which profits from state-of-the-art methods for statistical analysis of large simulations ensembles. A stand-alone advective mass transport module was furthermore developed in order to add such capability to any multiphase finite volume hydrodynamic simulator within the simulation framework. We present 2D and 3D case studies benchmarking the performance of surrogates and "full physics" chemistry in scenarios pertaining the assessment of geological subsurface utilization. [1] Jatnieks, J., De Lucia, M., Dransch, D., Sips, M.: "Data-driven surrogate model approach for improving the performance of reactive transport simulations.", Energy Procedia 97, 2016, p. 447-453. [2] Kempka, T., Nakaten, B., De Lucia, M., Nakaten, N., Otto, C., Pohl, M., Chabab [Tillner], E., Kühn, M

  6. How taxonomic diversity, community structure, and sample size determine the reliability of higher taxon surrogates. (United States)

    Neeson, Thomas M; Van Rijn, Itai; Mandelik, Yael


    Ecologists and paleontologists often rely on higher taxon surrogates instead of complete inventories of biological diversity. Despite their intrinsic appeal, the performance of these surrogates has been markedly inconsistent across empirical studies, to the extent that there is no consensus on appropriate taxonomic resolution (i.e., whether genus- or family-level categories are more appropriate) or their overall usefulness. A framework linking the reliability of higher taxon surrogates to biogeographic setting would allow for the interpretation of previously published work and provide some needed guidance regarding the actual application of these surrogates in biodiversity assessments, conservation planning, and the interpretation of the fossil record. We developed a mathematical model to show how taxonomic diversity, community structure, and sampling effort together affect three measures of higher taxon performance: the correlation between species and higher taxon richness, the relative shapes and asymptotes of species and higher taxon accumulation curves, and the efficiency of higher taxa in a complementarity-based reserve-selection algorithm. In our model, higher taxon surrogates performed well in communities in which a few common species were most abundant, and less well in communities with many equally abundant species. Furthermore, higher taxon surrogates performed well when there was a small mean and variance in the number of species per higher taxa. We also show that empirically measured species-higher-taxon correlations can be partly spurious (i.e., a mathematical artifact), except when the species accumulation curve has reached an asymptote. This particular result is of considerable practical interest given the widespread use of rapid survey methods in biodiversity assessment and the application of higher taxon methods to taxa in which species accumulation curves rarely reach an asymptote, e.g., insects.

  7. Effectiveness of external respiratory surrogates for in vivo liver motion estimation

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Kai-Hsiang; Ho, Ming-Chih; Yeh, Chi-Chuan; Chen, Yu-Chien; Lian, Feng-Li; Lin, Win-Li; Yen, Jia-Yush; Chen, Yung-Yaw [Department of Electrical Engineering, National Taiwan University, Taipei 10617, Taiwan (China); Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 10041, Taiwan (China); Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, Taiwan (China); Department of Electrical Engineering, National Taiwan University, Taipei 10617, Taiwan (China); Institute of Biomedical Engineering, National Taiwan University, Taipei 10041, Taiwan (China); Department of Mechanical Engineering, National Taiwan University, Taipei 10617, Taiwan (China); Department of Electrical Engineering and Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, Taiwan (China)


    Purpose: Due to low frame rate of MRI and high radiation damage from fluoroscopy and CT, liver motion estimation using external respiratory surrogate signals seems to be a better approach to track liver motion in real-time for liver tumor treatments in radiotherapy and thermotherapy. This work proposes a liver motion estimation method based on external respiratory surrogate signals. Animal experiments are also conducted to investigate related issues, such as the sensor arrangement, multisensor fusion, and the effective time period. Methods: Liver motion and abdominal motion are both induced by respiration and are proved to be highly correlated. Contrary to the difficult direct measurement of the liver motion, the abdominal motion can be easily accessed. Based on this idea, our study is split into the model-fitting stage and the motion estimation stage. In the first stage, the correlation between the surrogates and the liver motion is studied and established via linear regression method. In the second stage, the liver motion is estimated by the surrogate signals with the correlation model. Animal experiments on cases of single surrogate signal, multisurrogate signals, and long-term surrogate signals are conducted and discussed to verify the practical use of this approach. Results: The results show that the best single sensor location is at the middle of the upper abdomen, while multisurrogate models are generally better than the single ones. The estimation error is reduced from 0.6 mm for the single surrogate models to 0.4 mm for the multisurrogate models. The long-term validity of the estimation models is quite satisfactory within the period of 10 min with the estimation error less than 1.4 mm. Conclusions: External respiratory surrogate signals from the abdomen motion produces good performance for liver motion estimation in real-time. Multisurrogate signals enhance estimation accuracy, and the estimation model can maintain its accuracy for at least 10 min. This

  8. On Design Mining: Coevolution and Surrogate Models. (United States)

    Preen, Richard J; Bull, Larry


    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.

  9. Comparison of surrogate models with different methods in ...

    Indian Academy of Sciences (India)

    Surrogate modelling is an effective tool for reducing computational burden of simulation optimization. In this article, polynomial regression (PR), radial basis function artificial neural network (RBFANN), and kriging methods were compared for building surrogate models of a multiphase flow simulation model in a simplified ...

  10. A Training Manual for Surrogate Parents: Rules and Responsibilities. (United States)

    Arkansas State Dept. of Education, Little Rock. Special Education Section.

    The manual is designed for training surrogate parents in identification, evaluation, placement, and programing for the handicapped child in Arkansas. General guidelines for the surrogate parent are listed, including meeting the child before requesting to see any school records, presuming that the agency has the child's best interest at heart, and…

  11. Human surrogate neck response to +Gz vertical impact

    NARCIS (Netherlands)

    Rooij, L. van; Uittenbogaard, J.


    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.

  12. Surrogate Modeling for Geometry Optimization in Material Design

    DEFF Research Database (Denmark)

    Rojas Larrazabal, Marielba de la Caridad; Abraham, Yonas B.; Holzwarth, Natalie A.W.


    We propose a new approach based on surrogate modeling for geometry optimization in material design. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)......We propose a new approach based on surrogate modeling for geometry optimization in material design. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)...

  13. INTEC SBW Solid Sludge Surrogate Recipe and Validation

    Energy Technology Data Exchange (ETDEWEB)

    Maio, Vince; Janikowski, Stuart; Johnson, Jim; Maio, Vince; Pao, Jenn-Hai


    A nonhazardous INTEC tank farm sludge surrogate that incorporated metathesis reactions to generate solids from solutions of known elements present in the radioactive INTEC tank farm sodium-bearing waste sludges was formulated. Elemental analyses, physical property analyses, and filtration testing were performed on waste surrogate and tank farm waste samples, and the results were compared. For testing physical systems associated with moving the tank farm solids, the surrogate described in this report is the best currently available choice. No other available surrogate exhibits the noted similarities in behavior to the sludges. The chemical morphology, particle size distribution, and settling and flow characteristics of the surrogate were similar to those exhibited by the waste sludges. Nonetheless, there is a difference in chemical makeup of the surrogate and the tank farm waste. If a chemical treatment process were to be evaluated for final treatment and disposition of the waste sludges, the surrogate synthesis process would likely require modification to yield a surrogate with a closer matching chemical composition.

  14. 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.


    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

  15. Surrogate Motherhood and Abortion for Fetal Abnormality. (United States)

    Walker, Ruth; van Zyl, Liezl


    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.

  16. Tracking contamination through ground beef production and identifying points of recontamination using a novel green fluorescent protein (GFP) expressing, E. coli O103, non-pathogenic surrogate (United States)

    Introduction: Commonly, ground beef processors conduct studies to model contaminant flow through their production systems using surrogate organisms. Typical surrogate organisms may not behave as Escherichia coli O157:H7 during grinding and are not easy to detect at very low levels. Purpose: Develop...

  17. Surrogate Plant Data Base : Volume 1. Introduction, Appendix A : The Development of Surrogate Plant Data ; Appendix B : Application of the Surrogate . (United States)


    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 ...

  18. Examining the Effects of Age on Health Outcomes of Chronic Obstructive Pulmonary Disease: Results From the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease Study and Evaluation of Chronic Obstructive Pulmonary Disease Longitudinally to Identify Predictive Surrogate Endpoints Cohorts. (United States)

    Parulekar, Amit D; Martinez, Carlos; Tsai, Chu-Lin; Locantore, Nicholas; Atik, Mustafa; Yohannes, Abebaw M; Kao, Christina C; Al-Azzawi, Hassan; Mohsin, Ali; Wise, Robert A; Foreman, Marilyn G; Demeo, Dawn L; Regan, Elizabeth A; Make, Barry J; Boriek, Aladin M; Wiener, Laura E; Hanania, Nicola A


    The prevalence of chronic obstructive pulmonary disease (COPD) and its associated comorbidities increase with age. However, little is understood about differences in the disease in patients over 65 years of age compared with younger patients. To determine disease characteristics of COPD and its impact in older patients compared with younger patients. We examined baseline characteristics of patients with COPD (global obstructive lung disease stage II-IV) in 2 large cohorts: Genetic Epidemiology of COPD Study (COPDGene) and Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). We compared demographics, indices of disease severity, prevalence of comorbidities, exacerbation frequency, and quality of life scores in patients ≥65 years of age vs patients <65 years of age. We also tested for associations of age with disease characteristics and health outcomes. In the COPDGene cohort, older patients (n = 1663) had more severe disease as measured by forced expiratory volume in 1 second (1.22 vs 1.52 L, P < .001), use of long-term oxygen therapy (35% vs 22%, P < .001), 6-minute walk distance (355 vs 375 m, P < .001), and radiographic evidence of emphysema (14% vs 8%, P < .001) and air trapping (47% vs 36%, P < .001) and were more likely to have comorbidities compared with younger patients (n = 2027). Similarly, in the ECLIPSE cohort, older patients (n = 1030) had lower forced expiratory volume in 1 second (1.22 vs 1.34 L, P < .001), greater use of long-term oxygen therapy (7% vs 5%, P = .02), shorter 6- minute walk distance (360 vs 389 m, P < .001), and more radiographic evidence of emphysema (17% vs 14%, P = .009) than younger patients (n = 1131). In adjusted analyses of both cohorts, older age was associated with decreased frequency of exacerbations [odds ratio = 0.52, 95% confidence interval (CI) = 0.43-0.64 in COPDGene, odds ratio = 0.79, 95% CI = 0.64-0.99 in ECLIPSE] and a better quality of

  19. Decision conflict and regret among surrogate decision makers in the medical intensive care unit. (United States)

    Miller, Jesse J; Morris, Peter; Files, D Clark; Gower, Emily; Young, Michael


    Family members of critically ill patients in the intensive care unit face significant morbidity. It may be the decision-making process that plays a significant role in the psychological morbidity associated with being a surrogate in the ICU. We hypothesize that family members facing end-of-life decisions will have more decisional conflict and decisional regret than those facing non-end-of-life decisions. We enrolled a sample of adult patients and their surrogates in a tertiary care, academic medical intensive care unit. We queried the surrogates regarding decisions they had made on behalf of the patient and assessed decision conflict. We then contacted the family member again to assess decision regret. Forty (95%) of 42 surrogates were able to identify at least 1 decision they had made on behalf of the patient. End-of-life decisions (defined as do not resuscitate [DNR]/do not intubate [DNI] or continuation of life support) accounted for 19 of 40 decisions (47.5%). Overall, the average Decision Conflict Scale (DCS) score was 21.9 of 100 (range 0-100, with 0 being little decisional conflict and 100 being great decisional conflict). The average DCS score for families facing end-of-life decisions was 25.5 compared with 18.7 for all other decisions. Those facing end-of-life decisions scored higher on the uncertainty subscale (subset of DCS questions that indicates level of certainty regarding decision) with a mean score of 43.4 compared with all other decisions with a mean score of 27.0. Overall, very few surrogates experienced decisional regret with an average DRS score of 13.4 of 100. Nearly all surrogates enrolled were faced with decision-making responsibilities on behalf of his or her critically ill family member. In our small pilot study, we found more decisional conflict in those surrogates facing end-of-life decisions, specifically on the subset of questions dealing with uncertainty. Surrogates report low levels of decisional regret. Copyright © 2015 Elsevier

  20. Process optimization of a non-circular drawing sequence based on multi-surrogate assisted meta-heuristic algorithms

    Energy Technology Data Exchange (ETDEWEB)

    Pholdee, Nantiwat; Bureerat, Su Jin [Khon Kaen University, Khon Kaen (Thailand); Baek, Hyun Moo [DTaQ, Changwon (Korea, Republic of); Im, Yong Taek [KAIST, Daejeon (Korea, Republic of)


    Process optimization of a Non-circular drawing (NCD) sequence of a pearlitic steel wire was performed to improve the mechanical properties of a drawn wire based on surrogate assisted meta-heuristic algorithms. The objective function was introduced to minimize inhomogeneity of effective strain distribution at the cross-section of the drawn wire, which could deteriorate delamination characteristics of the drawn wires. The design variables introduced were die geometry and reduction of area of the NCD sequence. Several surrogate models and their combinations with the weighted sum technique were utilized. In the process optimization of the NCD sequence, the surrogate models were used to predict effective strain distributions at the cross-section of the drawn wire. Optimization using Differential evolution (DE) algorithm was performed, while the objective function was calculated from the predicted effective strains. The accuracy of all surrogate models was investigated, while optimum results were compared with the previous study available in the literature. It was found that hybrid surrogate models can improve prediction accuracy compared to a single surrogate model. The best result was obtained from the combination of Kriging (KG) and Support vector regression (SVR) models, while the second best was obtained from the combination of four surrogate models: Polynomial response surface (PRS), Radial basic function (RBF), KG, and SVR. The optimum results found in this study showed better effective strain homogeneity at the cross-section of the drawn wire with the same total reduction of area of the previous work available in the literature for fewer number of passes. The multi-surrogate models with the weighted sum technique were found to be powerful in improving the delamination characteristics of the drawn wire and reducing the production cost.

  1. Short-term vitamin D3 supplementation lowers plasma renin activity in patients with stable chronic heart failure: an open-label, blinded end point, randomized prospective trial (VitD-CHF trial). (United States)

    Schroten, Nicolas F; Ruifrok, Willem P T; Kleijn, Lennaert; Dokter, Martin M; Silljé, Herman H; Lambers Heerspink, Hiddo J; Bakker, Stephan J L; Kema, Ido P; van Gilst, Wiek H; van Veldhuisen, Dirk J; Hillege, Hans L; de Boer, Rudolf A


    Many chronic heart failure (CHF) patients have low vitamin D (VitD) and high plasma renin activity (PRA), which are both associated with poor prognosis. Vitamin D may inhibit renin transcription and lower PRA. We investigated whether vitamin D3 (VitD3) supplementation lowers PRA in CHF patients. We conducted a single-center, open-label, blinded end point trial in 101 stable CHF patients with reduced left ventricular ejection fraction. Patients were randomized to 6 weeks of 2,000 IU oral VitD3 daily or control. At baseline, mean age was 64 ± 10 years, 93% male, left ventricular ejection fraction 35% ± 8%, and 56% had VitD deficiency. The geometric mean (95% CI) of 25-hydroxyvitamin D3 increased from 48 nmol/L (43-54) at baseline to 80 nmol/L (75-87) after 6 weeks in the VitD3 treatment group and decreased from 47 nmol/L (42-53) to 44 nmol/L (39-49) in the control group (P CHF patients had VitD deficiency and high PRA levels. Six weeks of supplementation with 2,000 IU VitD3 increased 25-hydroxyvitamin D3 levels and decreased PRA and plasma renin concentration. Copyright © 2013 Mosby, Inc. All rights reserved.

  2. Analysis of safety impacts of access management alternatives using the surrogate safety assessment model : final report. (United States)


    The purpose of this study was to evaluate if the Surrogate Safety Assessment Model (SSAM) could be used to assess the safety of a highway segment or an intersection in terms of the number and type of conflicts and to compare the safety effects of mul...

  3. Atmospheric cold plasma iactivation of norovirus surrogates and native microbiota on blueberries (United States)

    Cold plasma (CP) is an emerging, novel, nonthermal technology that can be used for surface decontamination of foods. This study investigated CP technology for the nonthermal inactivation of the human norovirus surrogates, Tulane virus (TV) and Murine Norovirus (MNV), as well as for background microb...

  4. Use of knee height as a surrogate measure of height in older South ...

    African Journals Online (AJOL)

    The study aimed to determine whether knee height would be a more appropriate surrogate measurement than armspan in determining height and body mass index (BMI) in a group of South African older people ( 60 years). A random sample of adults (older than 18 years) who attended selected clinics or who lived in ...

  5. Evaluation and Development of Chemical Kinetic Mechanism Reduction Scheme for Biodiesel and Diesel Fuel Surrogates

    DEFF Research Database (Denmark)

    Poon, Hiew Mun; Ng, Hoon Kiat; Gan, Suyin


    The aim of this study is to evaluate the existing chemical kinetic mechanism reduction techniques. From here, an appropriate reduction scheme was developed to create compact yet comprehensive surrogate models for both diesel and biodiesel fuels for diesel engine applications. The reduction techni...

  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


    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...... system with a small degree of mechanical freeplay, the benchmarked surrogate models perform very well....

  7. Refined ambient PM2.5 exposure surrogates and the risk of myocardial infarction (United States)

    Using a case-crossover study design and conditional logistic regression, we compared the relative odds of transmural (full-wall) myocardial infarction (MI) calculated using exposure surrogates that account for human activity patterns and the indoor transport of ambient PM2....

  8. Robust best linear estimation for regression analysis using surrogate and instrumental variables. (United States)

    Wang, C Y


    We investigate methods for regression analysis when covariates are measured with errors. In a subset of the whole cohort, a surrogate variable is available for the true unobserved exposure variable. The surrogate variable satisfies the classical measurement error model, but it may not have repeated measurements. In addition to the surrogate variables that are available among the subjects in the calibration sample, we assume that there is an instrumental variable (IV) that is available for all study subjects. An IV is correlated with the unobserved true exposure variable and hence can be useful in the estimation of the regression coefficients. We propose a robust best linear estimator that uses all the available data, which is the most efficient among a class of consistent estimators. The proposed estimator is shown to be consistent and asymptotically normal under very weak distributional assumptions. For Poisson or linear regression, the proposed estimator is consistent even if the measurement error from the surrogate or IV is heteroscedastic. Finite-sample performance of the proposed estimator is examined and compared with other estimators via intensive simulation studies. The proposed method and other methods are applied to a bladder cancer case-control study.

  9. A Surrogate model of gravitational waveforms from numerical relativity simulations of precessing binary black hole mergers (United States)

    Blackman, Jonathan; Field, Scott E.; Scheel, Mark A.; Galley, Chad R.; Hemberger, Daniel A.; Schmidt, Patricia; Smith, Rory


    We present the first surrogate model for gravitational waveforms from the coalescence of precessing binary black holes. We call this surrogate model NRSur4d2s. Our methodology significantly extends recently introduced reduced-order and surrogate modeling techniques, and is capable of directly modeling numerical relativity waveforms without introducing phenomenological assumptions or approximations to general relativity. Motivated by GW150914, LIGO's first detection of gravitational waves from merging black holes, the model is built from a set of 276 numerical relativity (NR) simulations with mass ratios q ≤2 , dimensionless spin magnitudes up to 0.8, and the restriction that the initial spin of the smaller black hole lies along the axis of orbital angular momentum. It produces waveforms which begin ˜30 gravitational wave cycles before merger and continue through ringdown, and which contain the effects of precession as well as all ℓ∈{2 ,3 } spin-weighted spherical-harmonic modes. We perform cross-validation studies to compare the model to NR waveforms not used to build the model and find a better agreement within the parameter range of the model than other, state-of-the-art precessing waveform models, with typical mismatches of 10-3. We also construct a frequency domain surrogate model (called NRSur4d2s_FDROM) which can be evaluated in 50 ms and is suitable for performing parameter estimation studies on gravitational wave detections similar to GW150914.

  10. Oxidation of Alkane Rich Gasoline Fuels and their Surrogates in a Motored Engine

    KAUST Repository

    Shankar, Vijai S B


    The validation of surrogates formulated using a computational framework by Ahmed et al.[1]for two purely paraffinic gasoline fuels labelled FACE A and FACE C was undertaken in this study. The ability of these surrogate mixtures to be used in modelling LTC engines was accessed by comparison of their low temperature oxidation chemistry with that of the respective parent fuel as well as a PRF based on RON. This was done by testing the surrogate mixtures in a modified Cooperative Fuels Research (CFR) engine running in Controlled Autoignition Mode (CAI) mode. The engine was run at a constant speed of 600 rpm at an equivalence ratio of 0.5 with the intake temperature at 150 °C and a pressure of 98 kPa. The low temperature reactivity of the fuels were studied by varying the compression ratio of the engine from the point were very only small low temperature heat release was observed to a point beyond which auto-ignition of the fuel/air mixture occurred. The apparent heat release rates of different fuels was calculated from the pressure histories using first law analysis and the CA 50 times of the low temperature heat release (LTHR) were compared. The surrogates reproduced the cool flame behavior of the parent fuels better than the PRF across all compression ratios.

  11. "Did I make the right decision?": The difficult and unpredictable journey of being a surrogate decision maker for a person living with dementia. (United States)

    Fetherstonhaugh, Deirdre; McAuliffe, Linda; Shanley, Christopher; Bauer, Michael; Beattie, Elizabeth


    Many people living with dementia eventually lose the capacity to make their own decisions and will rely on another person - a surrogate decision maker - to make decisions on their behalf. It is important - especially with the increasing prevalence of dementia - that the role of surrogate decision maker is understood and supported. This qualitative study explored the experiences of 34 surrogate decision makers of persons living with dementia in Australia. Face-to-face and telephone interviews were conducted over six months in 2014. Five themes were identified: becoming the only - or main - surrogate decision maker; growing into the role of surrogate decision maker; dealing with the stress of making decisions; having to challenge healthcare professionals; and getting support - or not - from family members. An overarching construct tying the themes together is the description of the participants' experience as being on a difficult and unpredictable journey. Healthcare professionals can provide support by acting as empathic guides on this journey.

  12. Surrogate Reactions Research at JAEA/Tokyo Tech (United States)

    Chiba, S.; Nishio, K.; Makii, H.; Aritomo, Y.; Nishinaka, I.; Ishii, T.; Tsukada, K.; Asai, M.; Furutaka, K.; Hashimoto, S.; Koura, H.; Ogata, K.; Ohtsuki, T.; Nagayama, T.


    The research activities at JAEA and Tokyo Tech. in the development of a surrogate method based on multi-nucleon transfer reactions induced by (mainly) heavy-ion projectiles are presented. This project consists of 3 parts: the development of an apparatus to measure (1) fission cross sections and (2) neutron capture cross sections, and (3) the development of the underlying theoretical framework. Equipment has already been developed and preliminary experiments carried out to validate the methods and to provide new data. At the same time, theories to describe the surrogate reaction processes were constructed and conditions for the surrogate ratio method to derive the correct neutron-induced cross sections were investigated.

  13. Fast calculating surrogate models for leg and head impact in vehicle-pedestrian collision simulations. (United States)

    Wimmer, Peter; Benedikt, Martin; Huber, Philipp; Ferenczi, Izabella


    In previous research, a tool chain to simulate vehicle-pedestrian accidents from ordinary driving state to in-crash has been developed. This tool chain allows for injury criteria-based, vehicle-specific (geometry, stiffness, active safety systems, etc.) assessments. Due to the complex nature of the included finite element analysis (FEA) models, calculation times are very high. This is a major drawback for using FEA models in large-scale effectiveness assessment studies. Therefore, fast calculating surrogate models to approximate the relevant injury criteria as a function of pedestrian vehicle collision constellations have to be developed. The development of surrogate models for head and leg injury criteria to overcome the problem of long calculation times while preserving high detail level of results for effectiveness analysis is shown in this article. These surrogate models are then used in the tool chain as time-efficient replacements for the FEA model to approximate the injury criteria values. The method consists of the following steps: Selection of suitable training data sets out of a large number of given collision constellations, detailed FEA calculations with the training data sets as input, and training of the surrogate models with the FEA model's input and output values. A separate surrogate model was created for each injury criterion, consisting of a response surface that maps the input parameters (i.e., leg impactor position and velocity) to the output value. In addition, a performance test comparing surrogate model predictions of additional collision constellations to the results of respective FEA calculations was carried out. The developed method allows for prediction of injury criteria based on impact constellation for a given vehicle. Because the surrogate models are specific to a certain vehicle, training has to be redone for a new vehicle. Still, there is a large benefit regarding calculation time when doing large-scale studies. The method can be

  14. Polynomial Chaos Surrogates for Bayesian Inference

    KAUST Repository

    Le Maitre, Olivier


    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.


    Directory of Open Access Journals (Sweden)

    Mr. Muntaha


    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.

  16. Ovulation Statuses of Surrogate Gilts Are Associated with the Efficiency of Excellent Pig Cloning. (United States)

    Huan, Yanjun; Hu, Kui; Xie, Bingteng; Shi, Yongqian; Wang, Feng; Zhou, Yang; Liu, Shichao; Huang, Bo; Zhu, Jiang; Liu, Zhongfeng; He, Yilong; Li, Jingyu; Kong, Qingran; Liu, Zhonghua


    Somatic cell nuclear transfer (SCNT) is an assisted reproductive technique that can produce multiple copies of excellent livestock. However, low cloning efficiency limits the application of SCNT. In this study, we systematically investigated the major influencing factors related to the overall cloning efficiency in pigs. Here, 13620 cloned embryos derived from excellent pigs were transferred into 79 surrogate gilts, and 119 live cloned piglets were eventually generated. During cloning, group of cloned embryos derived from excellent Landrace or Large white pigs presented no significant differences of cleavage and blastocyst rates, blastocyst cell numbers, surrogate pregnancy and delivery rates, average numbers of piglets born and alive and cloning efficiencies, and group of 101-150, 151-200 or 201-250 cloned embryos transferred per surrogate also displayed a similar developmental efficiency. When estrus stage of surrogate gilts was compared, group of embryo transfer on Day 2 of estrus showed significantly higher pregnancy rate, delivery rate, average number of piglets born, average alive piglet number or cloning efficiency than group on Day 1, Day 3, Day 4 or Day 5, respectively (Pcloning efficiency (Pcloning efficiency. And more, follicle puncture for preovulation, not transfer position shallowed for preovulation or deepened for postovulation, significantly improved the average number of piglets alive and cloning efficiency (Pcloning efficiency of excellent pigs, and follicle puncture, not transfer position change, improved cloning efficiency. This work would have important implications in preserving and breeding excellent livestock and improving the overall cloning efficiency.

  17. Ovulation Statuses of Surrogate Gilts Are Associated with the Efficiency of Excellent Pig Cloning (United States)

    Huan, Yanjun; Hu, Kui; Xie, Bingteng; Shi, Yongqian; Wang, Feng; Zhou, Yang; Liu, Shichao; Huang, Bo; Zhu, Jiang; Liu, Zhongfeng; He, Yilong; Li, Jingyu; Kong, Qingran; Liu, Zhonghua


    Somatic cell nuclear transfer (SCNT) is an assisted reproductive technique that can produce multiple copies of excellent livestock. However, low cloning efficiency limits the application of SCNT. In this study, we systematically investigated the major influencing factors related to the overall cloning efficiency in pigs. Here, 13620 cloned embryos derived from excellent pigs were transferred into 79 surrogate gilts, and 119 live cloned piglets were eventually generated. During cloning, group of cloned embryos derived from excellent Landrace or Large white pigs presented no significant differences of cleavage and blastocyst rates, blastocyst cell numbers, surrogate pregnancy and delivery rates, average numbers of piglets born and alive and cloning efficiencies, and group of 101–150, 151–200 or 201–250 cloned embryos transferred per surrogate also displayed a similar developmental efficiency. When estrus stage of surrogate gilts was compared, group of embryo transfer on Day 2 of estrus showed significantly higher pregnancy rate, delivery rate, average number of piglets born, average alive piglet number or cloning efficiency than group on Day 1, Day 3, Day 4 or Day 5, respectively (Pgilts during periovulation displayed a significantly higher overall cloning efficiency (Pgilts was the fundamental factor determining the overall cloning efficiency of excellent pigs, and follicle puncture, not transfer position change, improved cloning efficiency. This work would have important implications in preserving and breeding excellent livestock and improving the overall cloning efficiency. PMID:26565717

  18. Effect of public deliberation on attitudes toward surrogate consent for dementia research. (United States)

    Kim, S Y H; Kim, H M; Knopman, D S; De Vries, R; Damschroder, L; Appelbaum, P S


    To assess the informed, deliberative views of the older general public toward a policy of allowing surrogate consent for Alzheimer disease (AD) research. A total of 503 persons aged 50+ recruited by random digit dialing were randomly assigned to 1 of 3 groups: deliberation, education, or control. The deliberation group attended an all-day education/peer deliberation session; the education group received written information only. Participants were surveyed at baseline, after deliberation session (or equivalent time), and 1 month after the session, regarding their attitudes toward a policy of allowing surrogate consent for research studies of varying risks and potential benefits (a lumbar puncture study, a drug randomized controlled trial, a vaccine randomized controlled trial, and an early phase gene transfer trial). At baseline, a policy of surrogate consent for AD research was supported by 55%-91%, depending on the scenario. The education group had a transient increase in support for one research scenario after receiving the information materials. In the deliberation group, support for surrogate consent was higher after deliberation for all scenarios (67% to 97%), with much of the increase sustained 1 month after the deliberation session. No changes occurred in the control group. The study's limitations include self-selection of participants due to the demanding nature of attendance at the deliberation sessions. This sample of the older general public generally supported a policy of surrogate consent for AD research at baseline. Their support increased with democratic deliberation involving informed, in-depth exploration of the relevant scientific and ethical issues.

  19. How important is 'accuracy' of surrogate decision-making for research participation?

    Directory of Open Access Journals (Sweden)

    Scott Y H Kim

    Full Text Available There is a longstanding concern about the accuracy of surrogate consent in representing the health care and research preferences of those who lose their ability to decide for themselves. We sought informed, deliberative views of the older general public (≥50 years old regarding their willingness to participate in dementia research and to grant leeway to future surrogates to choose an option contrary to their stated wishes.503 persons aged 50+ recruited by random digit dialing were randomly assigned to one of three groups: deliberation, education, or control. The deliberation group attended an all-day education/peer deliberation session; the education group received written information only. Participants were surveyed at baseline, after the deliberation session (or equivalent time, and one month after the session, regarding their willingness to participate in dementia research and to give leeway to surrogates, regarding studies of varying risk-benefit profiles (a lumbar puncture study, a drug randomized controlled trial, a vaccine randomized controlled trial, and an early phase gene transfer trial. At baseline, 48% (gene transfer scenario to 92% (drug RCT were willing to participate in future dementia research. A majority of respondents (57-71% depending on scenario were willing to give leeway to future surrogate decision-makers. Democratic deliberation increased willingness to participate in all scenarios, to grant leeway in 3 of 4 scenarios (lumbar puncture, vaccine, and gene transfer, and to enroll loved ones in research in all scenarios. On average, respondents were more willing to volunteer themselves for research than to enroll their loved ones.Most people were willing to grant leeway to their surrogates, and this willingness was either sustained or increased after democratic deliberation, suggesting that the attitude toward leeway is a reliable opinion. Eliciting a person's current preferences about future research participation should

  20. Compositional effects on PAH and soot formation in counterflow diffusion flames of gasoline surrogate fuels

    KAUST Repository

    Park, Sungwoo


    Gasoline surrogate fuels are widely used to understand the fundamental combustion properties of complex refinery gasoline fuels. In this study, the compositional effects on polycyclic aromatic hydrocarbons (PAHs) and soot formation were investigated experimentally for gasoline surrogate mixtures comprising n-heptane, iso-octane, and toluene in counterflow diffusion flames. A comprehensive kinetic model for the gasoline surrogate mixtures was developed to accurately predict the fuel oxidation along with the formation of PAHs and soot in flames. This combined model was first tested against ignition delay times and laminar burning velocities data. The proposed model for the formation and growth of PAHs up to coronene (C24H12) was based on previous studies and was tested against existing and present new experimental data. Additionally, in the accompanied soot model, PAHs with sizes larger than (including) pyrene were used for the inception of soot particles, followed by particle coagulations and PAH condensation/chemical reactions on soot surfaces. The major pathways for the formation of PAHs were also identified for the surrogate mixtures. The model accurately captures the synergistic PAH formation characteristics observed experimentally for n-heptane/toluene and iso-octane/toluene binary mixtures. Furthermore, the present experimental and modeling results also elucidated different trends in the formation of larger PAHs and soot between binary n-heptane/iso-octane and ternary n-heptane/iso-octane/toluene mixtures. Propargyl radicals (C3H3) were shown to be important in the formation and growth of PAHs for n-heptane/iso-octane mixtures when the iso-octane concentration increased; however, reactions involving benzyl radicals (C6H5CH2) played a significant role in the formation of PAHs for n-heptane/iso-octane/toluene mixtures. These results indicated that the formation of PAHs and subsequently soot was strongly affected by the composition of gasoline surrogate mixtures.

  1. Evaluation Of FWENC Process For Treatment Of MVST Sludges, Supernates, And Surrogates

    Energy Technology Data Exchange (ETDEWEB)

    Barton, JW


    In 1998, the Foster Wheeler Environmental Corporation (FWENC) was awarded an 11-year contract to treat transuranic waste at the Oak Ridge National Laboratory, including Melton Valley Storage Tank (MVST) waste. Their baseline tank waste process consists of: (1) Separating the supernate from the sludge, (2) Washing the sludge with water and adding this wash water to the supernate, (3) Stabilizing the supernate/wash water or the washed sludge with additives if either are projected to fail Resource Conservation Recovery Act (RCRA) Toxic Characteristics Leaching Protocol (TCLP) criteria, and (4) Stabilizing both the washed sludge and supernate/wash water by vacuum evaporation. An ''Optimum'' treatment procedure consisted of adding a specified quantity of two stabilizers--ThioRed{reg_sign} and ET Soil Polymer{reg_sign}--and an ''Alternate'' treatment simply increased the amount of ThioRed{reg_sign} added. This report presents the results of a study funded by the Tanks Focus Area (TFA) to provide Oak Ridge Operations (ORO) with independent laboratory data on the performance of the baseline process for treating the sludges, including washing the sludge and treating the wash water (although supernates were not included in the wash water tests). Two surrogate and seven actual tank wastes were used in this evaluation. Surrogate work, as well as the initial work with actual tank sludge, was based on an existing sludge sample from Bethel Valley Evaporator Storage Tank (BVEST) W23. One surrogate was required to be based on a surrogate previously developed to mimic the weighted average chemical composition of the MVST-BVEST using a simple mix of reagent grade chemicals and water, called the ''Quick and Dirty'' surrogate (QnD). The composition of this surrogate was adjusted toward the measured composition of W23 samples. The other surrogate was prepared to be more representative of the W23 sludge sample by precipitation

  2. Uncertainty Quantification for Combined Polynomial Chaos Kriging Surrogate Models (United States)

    Weinmeister, Justin; Gao, Xinfeng; Krishna Prasad, Aditi; Roy, Sourajeet


    Surrogate modeling techniques are currently used to perform uncertainty quantification on computational fluid dynamics (CFD) models for their ability to identify the most impactful parameters on CFD simulations and help reduce computational cost in engineering design process. The accuracy of these surrogate models depends on a number of factors, such as the training data created from the CFD simulations, the target functions, the surrogate model framework, and so on. Recently, we have combined polynomial chaos expansions (PCE) and Kriging to produce a more accurate surrogate model, polynomial chaos Kriging (PCK). In this talk, we analyze the error convergence rate for the Kriging, PCE, and PCK model on a convection-diffusion-reaction problem, and validate the statistical measures and performance of the PCK method for its application to practical CFD simulations.

  3. Hepatology may have problems with putative surrogate outcome measures

    DEFF Research Database (Denmark)

    Gluud, Christian; Brok, Jesper; Gong, Yan


    hepatitis C, serum bilirubin concentration following ursodeoxycholic acid or immunosuppressants for patients with primary biliary cirrhosis, and nutritional outcomes following artificial nutrition for liver patients may not be valid surrogates for morbidity or mortality. The challenge is to develop reliable...

  4. A new formulation of physical surrogates of FACE A gasoline fuel based on heating and evaporation characteristics

    KAUST Repository

    Elwardani, Ahmed Elsaid


    The US Department of Energy has formulated various sets of gasoline fuels, called fuels for advanced combustion engines (FACE), which are consistent in composition and properties. The analysis of heating and evaporation of FACE A gasoline fuel (paraffin-rich) is studied by replacing the 66 components with 19 components to represent this fuel. The reduction in the number of components is based on merging components from the same chemical groups and having the same chemical formula, which have very close thermophysical properties; the components with the highest initial compositions are chosen to be the representative components. Modelling of heating and evaporation of FACE A gasoline fuel and various surrogates is carried out based on the effective thermal conductivity/effective diffusivity model (ETC/ED). The model takes into account the effect of finite liquid thermal conductivity, finite liquid mass diffusivity and recirculation inside the droplets due to their non-zero velocities relative to the ambient air. Four surrogates of FACE A found in the literature are used in the analysis. These surrogates include the five component surrogate chosen for its ability to match the ignition delay time of the FACE A gasoline fuel (Surr1), the primary reference fuel surrogate (PRF84) that matches the research octane number (RON) of FACE A, the one that matches hydrogen-to-carbon ratio (H/C), RON, density and distillation curve with FACE A (Surr2), and the one that matches the RON based on mole fraction linear blending (Surr3). It is shown that these surrogates cannot predict adequately the time evolution of surface temperatures and radii of FACE A droplets. New \\'physical\\' surrogates with 8, 7 and 6 components (Surr4, Surr5, and Surr6) are introduced to match the evaporation characteristics of FACE A. It is found that Surr5 (7 components surrogate) can predict droplet lifetime and time evolution of surface temperature of a FACE A droplet with errors of up to 5% and 0

  5. Surrogate assisted multidisciplinary design optimization for an all-electric GEO satellite (United States)

    Shi, Renhe; Liu, Li; Long, Teng; Liu, Jian; Yuan, Bin


    State-of-the-art all-electric geostationary earth orbit (GEO) satellites use electric thrusters to execute all propulsive duties, which significantly differ from the traditional all-chemical ones in orbit-raising, station-keeping, radiation damage protection, and power budget, etc. Design optimization task of an all-electric GEO satellite is therefore a complex multidisciplinary design optimization (MDO) problem involving unique design considerations. However, solving the all-electric GEO satellite MDO problem faces big challenges in disciplinary modeling techniques and efficient optimization strategy. To address these challenges, we presents a surrogate assisted MDO framework consisting of several modules, i.e., MDO problem definition, multidisciplinary modeling, multidisciplinary analysis (MDA), and surrogate assisted optimizer. Based on the proposed framework, the all-electric GEO satellite MDO problem is formulated to minimize the total mass of the satellite system under a number of practical constraints. Then considerable efforts are spent on multidisciplinary modeling involving geosynchronous transfer, GEO station-keeping, power, thermal control, attitude control, and structure disciplines. Since orbit dynamics models and finite element structural model are computationally expensive, an adaptive response surface surrogate based optimizer is incorporated in the proposed framework to solve the satellite MDO problem with moderate computational cost, where a response surface surrogate is gradually refined to represent the computationally expensive MDA process. After optimization, the total mass of the studied GEO satellite is decreased by 185.3 kg (i.e., 7.3% of the total mass). Finally, the optimal design is further discussed to demonstrate the effectiveness of our proposed framework to cope with the all-electric GEO satellite system design optimization problems. This proposed surrogate assisted MDO framework can also provide valuable references for other all

  6. Optimization using surrogate models - by the space mapping technique

    DEFF Research Database (Denmark)

    Søndergaard, Jacob


    Surrogate modelling and optimization techniques are intended for engineering design in the case where an expensive physical model is involved. This thesis provides a literature overview of the field of surrogate modelling and optimization. The space mapping technique is one such method for constr......Surrogate modelling and optimization techniques are intended for engineering design in the case where an expensive physical model is involved. This thesis provides a literature overview of the field of surrogate modelling and optimization. The space mapping technique is one such method...... conditions are satisfied. So hybrid methods, combining the space mapping technique with classical optimization methods, should be used if convergence to high accuracy is wanted. Approximation abilities of the space mapping surrogate are compared with those of a Taylor model of the expensive model. The space...... mapping surrogate has a lower approximation error for long steps. For short steps, however, the Taylor model of the expensive model is best, due to exact interpolation at the model origin. Five algorithms for space mapping optimization are presented and the numerical performance is evaluated. Three...

  7. 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.

  8. Habitats as surrogates of taxonomic and functional fish assemblages in coral reef ecosystems: a critical analysis of factors driving effectiveness.

    Directory of Open Access Journals (Sweden)

    Simon Van Wynsberge

    surrogates is needed for every case study.

  9. Italian gay fathers' experiences of transnational surrogacy and their relationship with the surrogate pre- and post-birth. (United States)

    Carone, Nicola; Baiocco, Roberto; Lingiardi, Vittorio


    This study aims to explore the experience of transnational surrogacy and the relationship with the surrogate pre- and post-birth in Italian gay father families. Couple and individual semi-structured interviews were carried out with 30 Italian gay partnered fathers with at least one child born through gestational surrogacy in California or Canada. No couples had known their surrogates or egg donors previously. The Interpretative Phenomenological Analysis indicated that three interrelated themes could be helpful for understanding the gay fathers' experience of their geographical distance from the surrogate: the perceived loss of control over the pregnancy; the surrogate as a person who facilitates the fathers' feelings of being emotionally connected to their developing child; the surrogate as an 'aunty' who, along with her family, maintains a relationship with the fathers. None of the fathers mentioned the egg donor during the interview. The study inspires reflections in offshore fertility practitioners on how pre- and ongoing surrogacy counselling for prospective gay fathers should be tailored. It further calls for the necessity of offering psychological counselling in gay fathers' resident countries in order to promote informed decisions before starting surrogacy abroad and to elaborate on potential difficulties related to surrogacy after the child's birth. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  10. Public's approach to surrogate consent for dementia research: cautious pragmatism. (United States)

    De Vries, Raymond; Ryan, Kerry A; Stanczyk, Aimee; Appelbaum, Paul S; Damschroder, Laura; Knopman, David S; Kim, Scott Y H


    To describe how members of the older general public deliberate with one another in finding solutions to the dilemma of involving persons with decisional incapacity in dementia research. One hundred sixty persons age 50 years and older who participated in an all-day deliberative democracy session on the ethics of surrogate consent for dementia research. The deliberative democracy day consisted of both extensive, interactive education with experts in clinical research and ethics, as well as small group deliberations. Audiotaped small group deliberations were transcribed and analyzed and the main thematic elements were coded. 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 benefits, 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. 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. Copyright © 2013 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. Detailed chemical kinetic mechanism for the oxidation of biodiesel fuels blend surrogate.

    Energy Technology Data Exchange (ETDEWEB)

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


    Detailed chemical kinetic mechanisms were developed and used to study the oxidation of two large unsaturated esters: methyl-5-decenoate and methyl-9-decenoate. These models were built from a previous methyl decanoate mechanism and were compared with rapeseed oil methyl esters oxidation experiments in a jet stirred reactor. A comparative study of the reactivity of these three oxygenated compounds was performed and the differences in the distribution of the products of the reaction were highlighted showing the influence of the presence and the position of a double bond in the chain. Blend surrogates, containing methyl decanoate, methyl-5-decenoate, methyl-9-decenoate and n-alkanes, were tested against rapeseed oil methyl esters and methyl palmitate/n-decane experiments. These surrogate models are realistic kinetic tools allowing the study of the combustion of biodiesel fuels in diesel and homogeneous charge compression ignition engines.

  12. 'Biracial'-Looking Twins: A New Twin Type?/Twin Research: Twins with Cystic Teratomas; Sleep Quality and Body Mass Index; Previable Membrane Rupture/Print and Online Reports: Twins Born to a Sister Surrogate; NASA Twin Study; African-Cosmopolitan Twin Fashion Inspirations; Triplet Hockey Stars. (United States)

    Segal, Nancy L


    Dizygotic (DZ) co-twins born to mothers and fathers from different racial or ethnic backgrounds often resemble one parent much more than the other. As such, these pairs comprise a unique subset of twins for investigating how others' responses to their different looks may affect their personalities and self-esteem. This article describes some of these twin pairs and some challenges of raising them, and suggests ways they may be used in research. Next, recent twin research on cystic teratomas, relations between sleep quality and body mass index, and previable membrane rupture is described. The final section concerns twins, twin studies, and related events in the media, namely: twins born to a sister surrogate, the NASA twin investigation, inspiring African-Cosmopolitan twins in fashion, and triplet Hockey Stars.

  13. Numerical investigation for erratic behavior of Kriging surrogate model

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Hyun Gil; Yi, Seul Gi [KAIST, Daejeon (Korea, Republic of); Choi, Seong Im [Virginia Polytechnic Institute and State University, Blacksburg (United States)


    Kriging model is one of popular spatial/temporal interpolation models in engineering field since it could reduce the time resources for the expensive analysis. But generation of the Kriging model is hardly a sinecure because internal semi-variogram structure of the Kriging often reveals numerically unstable or erratic behaviors. In present study, the issues in the maximum likelihood estimation which are the vital-parts of the construction of the Kriging model, is investigated. These issues are divided into two aspects; Issue I is for the erratic response of likelihood function itself, and Issue II is for numerically unstable behaviors in the correlation matrix. For both issues, studies for specific circumstances which might raise the issue, and the reason of that are conducted. Some practical ways further are suggested to cope with them. Furthermore, the issue is studied for practical problem; aerodynamic performance coefficients of two-dimensional airfoil predicted by CFD analysis. Result shows that such erratic behavior of Kriging surrogate model can be effectively resolved by proposed solution. In conclusion, it is expected this paper could be helpful to prevent such an erratic and unstable behavior.

  14. Investigation of ethosomes as surrogate carriers for bioactives

    Directory of Open Access Journals (Sweden)

    Devina Verma


    Full Text Available Background: Ethosomal vesicular system delivering a bioactive phytochemical, chrysin, was developed for transdermal delivery to increase its permeability and penetrability. Materials and Methods: Ethosomal system was optimized by keeping lecithin and ethanol concentration as independent variable while size and size distribution were taken as dependent variables. The optimized formulation was then subjected to various in vitro characterization parameters. Results: Ethosomal vesicle with an optimum size and polydispersity index of 134 ± 35 nm and 0.153, respectively, and entrapment efficiency of 80.05 ± 2.6% was considered as optimized and subjected to characterization. The scanning electron microscopy and transmission electron microscopy showed spherical entities with uniform surface whereas in vitro permeation and retention study showed the sustained mode of drug release and better skin retention as compared to hydroethanolic solution of the drug. The confocal laser scanning microscopy study reiterated high penetrability of vesicles into the skin. Histopathological and Fourier transform infrared spectroscopy analysis revealed its mechanism of penetration. Conclusion : The study thus demonstrated the ability of the ethosomal vesicles as surrogate carriers for delivery of bioactive agents through the skin for better amelioration of skin inflammation and other diseases.

  15. Wide Disagreement Between Alternative Assessments of Premorbid Physical Activity: Subjective Patient and Surrogate Reports and Objective Smartphone Data. (United States)

    Gluck, Samuel; Summers, Matthew J; Goddard, Thomas P; Andrawos, Alice; Smith, Natalie C; Lange, Kylie; Iwashyna, Theodore J; Deane, Adam M


    Surrogate-decision maker and patient self-reported estimates of the distances walked prior to acute illness are subjective and may be imprecise. It may be possible to extract objective data from a patient's smartphone, specifically, step and global position system data, to quantify physical activity. The objectives were to 1) assess the agreement between surrogate-decision maker and patient self-reported estimates of distance and time walked prior to resting and daily step-count and 2) determine the feasibility of extracting premorbid physical activity (step and global position system) data from critically ill patients. Prospective cohort study. Quaternary ICU. Fifty consecutively admitted adult patients who owned a smartphone, who were ambulatory at baseline, and who remained in ICU for more than 48 hours participated. There was no agreement between patients and surrogates for all premorbid walking metrics (mean bias 108% [99% lower to 8,700% higher], 83% [97% to 2,100%], and 71% [96% to 1,080%], for distance, time, and steps, respectively). Step and/or global position system data were successfully extracted from 24 of 50 phones (48%; 95% CI, 35-62%). Surrogate-decision makers, but not patient self-reported, estimates of steps taken per day correlated with smartphone data (surrogates: n = 13, ρ = 0.56, p smartphones was feasible in approximately 50% of patients.

  16. "RéaNet", the Internet utilization among surrogates of critically ill patients with sepsis. (United States)

    Nguyen, Yên-Lan; Porcher, Raphaël; Argaud, Laurent; Piquilloud, Lise; Guitton, Christophe; Tamion, Fabienne; Hraiech, Sami; Mira, Jean-Paul


    Health-related Internet utilization is common but its use by proxies of critically ill patients is unknown. Our objective was to describe the prevalence and the Internet utilization characteristics among surrogates of critically ill septic patients. We conducted a prospective observational study in French ICUs. Three survey instruments were used to describe ICU organization regarding information delivery, patients and surrogates characteristics. 169 surrogates of 146 septic patients hospitalized in 19 ICUs were included. One sixth of ICUs (n = 3, 16%) had their own website. Majority of patients were males (n = 100, 68%), aged 64±1 years old, with a SAPS2 score at 53±17 and required vasopressors (n = 117, 83%), mechanical ventilation (n = 116, 82%). More than one quarter required renal replacement therapy (n = 36, 26%). Majority of surrogates were female, in their fifties. Only one in five knew the word sepsis (n = 27, 16%). Majority of proxies internet users (n = 77; 55%) search on the internet about sepsis. The main motivation was curiosity. Majority of surrogates found the information online reliable, suitable for request and concordant. Prior use of health-related Internet (OR = 20.7 [4.30-100.1]), the presence of a nursing staff during family-physician meetings (OR = 3.33 [1.17-9.53]), a younger patient age (OR = 1.32 [1.01-1.72]) and renal replacement therapy requirement (OR = 2.58 [1.06-6.26]) were associated with health-related Internet use. Neither satisfaction with medical care or information provision, neither presence of anxiety-depression symptoms, were associated with health-related Internet use. Majority of surrogates (N = 76 (52%)) would have like receiving a list of selected websites on sepsis. Majority of proxies of critically ill patients with sepsis use Internet to learn more about sepsis. Internet utilization is independent of satisfaction with global ICU care, perceived quality of information delivery by doctors or the existence of anxiety

  17. Validity of fish, birds and mammals as surrogates for amphibians and reptiles in pesticide toxicity assessment. (United States)

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


    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

  18. Total lymphocyte count as a surrogate marker for CD4 count in resource-limited settings. (United States)

    Obirikorang, Christian; Quaye, Lawrence; Acheampong, Isaac


    CD4 testing is the recognized gold standard used to stage HIV/AIDS, guide treatment decisions for HIV-infected persons and evaluate effectiveness of therapy. The need for a less expensive surrogate marker that can be used in resource-limited setting is however necessary. The study sought to assess the suitability of Total lymphocyte count (TLC) as a surrogate marker for CD4 count in resource-limited localities in Ghana. This observational study was conducted at the Central Regional Hospital, which has one of the established antiretroviral therapy centres in Ghana. A total of one hundred and eighty-four (184) confirmed HIV I seropositive subjects were included in the study. Blood samples were taken from all the subjects for estimation of CD4 and total lymphocyte counts. The study subjects were further categorised into three (3) groups according to the Centers for Disease Control and Prevention (CDC) classification criteria as follows: CD4 counts (1) ≥ 500 cells/mm3 (2) 200-499 cells/mm3 and (3) Lymphocyte count obtained. The sensitivity, specificity, positive and negative predictive values of TLC 1200 cells/ mm3 to predict CD4 count were Lymphocyte count can therefore adequately serve as a surrogate marker for CD4 count in HIV patients who are naïve for antiretroviral therapy in resource-limited areas.

  19. Surrogate pregnancy: a guide for Canadian prenatal health care providers. (United States)

    Reilly, Dan R


    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.

  20. A computer-based education intervention to enhance surrogates' informed consent for genomics research. (United States)

    Shelton, Ann K; Freeman, Bradley D; Fish, Anne F; Bachman, Jean A; Richardson, Lloyd I


    Many research studies conducted today in critical care have a genomics component. Patients' surrogates asked to authorize participation in genomics research for a loved one in the intensive care unit may not be prepared to make informed decisions about a patient's participation in the research. To examine the effectiveness of a new, computer-based education module on surrogates' understanding of the process of informed consent for genomics research. A pilot study was conducted with visitors in the waiting rooms of 2 intensive care units in a Midwestern tertiary care medical center. Visitors were randomly assigned to the experimental (education module plus a sample genomics consent form; n = 65) or the control (sample genomics consent form only; n = 69) group. Participants later completed a test on informed genomics consent. Understanding the process of informed consent was greater (P = .001) in the experimental group than in the control group. Specifically, compared with the control group, the experimental group had a greater understanding of 8 of 13 elements of informed consent: intended benefits of research (P = .02), definition of surrogate consenter (P= .001), withdrawal from the study (P = .001), explanation of risk (P = .002), purpose of the institutional review board (P = .001), definition of substituted judgment (P = .03), compensation for harm (P = .001), and alternative treatments (P = .004). Computer-based education modules may be an important addition to conventional approaches for obtaining informed consent in the intensive care unit. Preparing patients' family members who may consider serving as surrogate consenters is critical to facilitating genomics research in critical care. ©2015 American Association of Critical-Care Nurses.

  1. Conceptualizing surrogate decision making at end of life in the intensive care unit using cognitive task analysis. (United States)

    Dionne-Odom, J Nicholas; Willis, Danny G; Bakitas, Marie; Crandall, Beth; Grace, Pamela J


    Surrogate decision makers (SDMs) face difficult decisions at end of life (EOL) for decisionally incapacitated intensive care unit (ICU) patients. To identify and describe the underlying psychological processes of surrogate decision making for adults at EOL in the ICU. Qualitative case study design using a cognitive task analysis interviewing approach. Participants were recruited from October 2012 to June 2013 from an academic tertiary medical center's ICU located in the rural Northeastern United States. Nineteen SDMs for patients who had died in the ICU completed in-depth semistructured cognitive task analysis interviews. The conceptual framework formulated from data analysis reveals that three underlying, iterative, psychological dimensions (gist impressions, distressing emotions, and moral intuitions) impact an SDM's judgment about the acceptability of either the patient's medical treatments or his or her condition. The framework offers initial insights about the underlying psychological processes of surrogate decision making and may facilitate enhanced decision support for SDMs. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Reliability analysis of pipelines with corrosion defects using surrogate models

    Energy Technology Data Exchange (ETDEWEB)

    Torres, Juliana V.S. [Federal University of Pernambuco (UFPE), Recife, PE (Brazil); Afonso, Silvana M. Bastos [Federal University of Pernambuco (UFPE), Recife, PE (Brazil). Dept. of Civil Engineering; Vaz, Luiz Eloy [Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil). Dept. of Applied Mechanics and Structures


    The most adequate procedure for measuring the structural safety is through the quantification of its failure probability. The determination of this value can be made using the first order reliability method (FORM) that leads to an optimization problem to solve the structural reliability problem. Other alternative is to apply Monte Carlo simulation method. The present work has the aim to present a methodology for safety verification and optimum design of pipelines with defect caused by corrosion. The methods used here to verify the safety of pipelines with corrosion defects use information from the deterministic analysis in its calculations. The choice of the deterministic method directly affects the calculation of failure probability of the structure. To obtain the failure pressure load, the FEM is applied considering both physical and geometric nonlinearities. This is a costly simulation problem even for a single simulation. When, in a reliability analysis procedure using the FEM, many random variables and gradient evaluations are applied, the issued related to computational time becomes very critical, and could be even prohibitively, depending on the case of study. Surrogate models are here used to overcome the above mentioned problem. (author)

  3. Early vessel healing of the Avantgarde cobalt-chromium coronary stent: the ON-GARDE OCT study. (United States)

    Prati, Francesco; Monaco, Sergio; Pawlosky, Tomasz; Mallus, Maria Teresa; Di Giorgio, Alessandro; Imola, Fabrizio; Ficarra, Eleonora; Ramazzotti, Vito; Biondi-Zoccai, Giuseppe; Albertucci, Mario


    Uncoverage and malapposition of stent struts at optical coherence tomography (OCT) have been associated with stent thrombosis. Stent uncoverage by OCT is being used as a surrogate to address the propensity of a stent to develop thrombosis. We aimed to appraise early vessel healing in patients with ST-elevation myocardial infarction (STEMI) treated with the novel Avantgarde stent. Patients with STEMI and multivessel disease were enrolled. The stent deployed on the infarct-related artery was imaged by frequency domain-OCT during deferred intervention (4-7 days apart). The primary end-point was the percentage of uncovered struts. Secondary end-points were the percentage of malapposed struts and struts covered with thrombus. Twenty patients (20 lesions) were enrolled, with 18 (18 stents) achieving a complete OCT pull-back and thus entering the final analysis (1497 cross-sections, 11 446 struts). Uncovered struts were 3.9%, whilst 8.0% of struts were malapposed and 2.6% were covered by thrombus. At per-stent analysis, all stents but two had a homogeneous distribution of strut coverage (i.e. % of uncovered struts ≥10). This study, originally exploiting OCT data early after stenting in STEMI patients, shows that the Avantgarde stent is associated with favourable vessel healing features.

  4. Deliberative assessment of surrogate consent in dementia research. (United States)

    Kim, Scott Y H; Uhlmann, Rebecca A; Appelbaum, Paul S; Knopman, David S; Kim, H Myra; Damschroder, Laura; Beattie, Elizabeth; Struble, Laura; De Vries, Raymond


    Research involving incapacitated persons with dementia entails complex scientific, legal, and ethical issues, making traditional surveys of layperson views on the ethics of such research challenging. We therefore assessed the impact of democratic deliberation (DD), involving balanced, detailed education and peer deliberation, on the views of those responsible for persons with dementia. One hundred and seventy-eight community-recruited caregivers or primary decision-makers for persons with dementia were randomly assigned to either an all-day DD session group or a control group. Educational materials used for the DD session were vetted for balance and accuracy by an interdisciplinary advisory panel. We assessed the acceptability of family-surrogate consent for dementia research ("surrogate-based research") from a societal policy perspective as well as from the more personal perspectives of deciding for a loved one or for oneself (surrogate and self-perspectives), assessed at baseline, immediately post-DD session, and 1 month after DD date, for four research scenarios of varying risk-benefit profiles. At baseline, a majority in both the DD and control groups supported a policy of family consent for dementia research in all research scenarios. The support for a policy of family consent for surrogate-based research increased in the DD group, but not in the control group. The change in the DD group was maintained 1 month later. In the DD group, there were transient changes in attitudes from surrogate or self-perspectives. In the control group, there were no changes from baseline in attitude toward surrogate consent from any perspective. Intensive, balanced, and accurate education, along with peer deliberation provided by democratic deliberation, led to a sustained increase in support for a societal policy of family consent in dementia research among those responsible for dementia patients. Copyright 2010 The Alzheimer

  5. Space Mapping Optimization of Microwave Circuits Exploiting Surrogate Models

    DEFF Research Database (Denmark)

    Bakr, M. H.; Bandler, J. W.; Madsen, Kaj


    is a convex combination of a mapped coarse model and a linearized fine model. It exploits, in a novel way, a linear frequency-sensitive mapping. During the optimization iterates, the coarse and fine models are simulated at different sets of frequencies. This approach is shown to be especially powerful......A powerful new space-mapping (SM) optimization algorithm is presented in this paper. It draws upon recent developments in both surrogate model-based optimization and modeling of microwave devices, SM optimization is formulated as a general optimization problem of a surrogate model. This model...

  6. Replacing FEA for sheet metal forming by surrogate modeling

    Directory of Open Access Journals (Sweden)

    Simon Wessing


    Full Text Available This paper presents an innovative approach for employing surrogate modeling in computer-aided design of sheet metal work pieces. The surrogate models replace expensive finite element analysis and thus shorten development time in the early design stages considerably. We experimentally compare neural networks and Kriging models for the task of predicting the sheet metal thickness after cold forming of B-pillars in automotive engineering. We also discuss some aspects of handling large data-sets and exploiting certain structures in the data.

  7. Sparse Polynomial Chaos Surrogate for ACME Land Model via Iterative Bayesian Compressive Sensing (United States)

    Sargsyan, K.; Ricciuto, D. M.; Safta, C.; Debusschere, B.; Najm, H. N.; Thornton, P. E.


    For computationally expensive climate models, Monte-Carlo approaches of exploring the input parameter space are often prohibitive due to slow convergence with respect to ensemble size. To alleviate this, we build inexpensive surrogates using uncertainty quantification (UQ) methods employing Polynomial Chaos (PC) expansions that approximate the input-output relationships using as few model evaluations as possible. However, when many uncertain input parameters are present, such UQ studies suffer from the curse of dimensionality. In particular, for 50-100 input parameters non-adaptive PC representations have infeasible numbers of basis terms. To this end, we develop and employ Weighted Iterative Bayesian Compressive Sensing to learn the most important input parameter relationships for efficient, sparse PC surrogate construction with posterior uncertainty quantified due to insufficient data. Besides drastic dimensionality reduction, the uncertain surrogate can efficiently replace the model in computationally intensive studies such as forward uncertainty propagation and variance-based sensitivity analysis, as well as design optimization and parameter estimation using observational data. We applied the surrogate construction and variance-based uncertainty decomposition to Accelerated Climate Model for Energy (ACME) Land Model for several output QoIs at nearly 100 FLUXNET sites covering multiple plant functional types and climates, varying 65 input parameters over broad ranges of possible values. This work is supported by the U.S. Department of Energy, Office of Science, Biological and Environmental Research, Accelerated Climate Modeling for Energy (ACME) project. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

  8. Predicting trace organic compound attenuation by ozone oxidation: Development of indicator and surrogate models. (United States)

    Park, Minkyu; Anumol, Tarun; Daniels, Kevin D; Wu, Shimin; Ziska, Austin D; Snyder, Shane A


    Ozone oxidation has been demonstrated to be an effective treatment process for the attenuation of trace organic compounds (TOrCs); however, predicting TOrC attenuation by ozone processes is challenging in wastewaters. Since ozone is rapidly consumed, determining the exposure times of ozone and hydroxyl radical proves to be difficult. As direct potable reuse schemes continue to gain traction, there is an increasing need for the development of real-time monitoring strategies for TOrC abatement in ozone oxidation processes. Hence, this study is primarily aimed at developing indicator and surrogate models for the prediction of TOrC attenuation by ozone oxidation. To this end, the second-order kinetic equations with a second-phase Rct value (ratio of hydroxyl radical exposure to molecular ozone exposure) were used to calculate comparative kinetics of TOrC attenuation and the reduction of indicator and spectroscopic surrogate parameters, including UV absorbance at 254 nm (UVA254) and total fluorescence (TF). The developed indicator model using meprobamate as an indicator compound and the surrogate models with UVA254 and TF exhibited good predictive power for the attenuation of 13 kinetically distinct TOrCs in five filtered and unfiltered wastewater effluents (R2 values > 0.8). This study is intended to help provide a guideline for the implementation of indicator/surrogate models for real-time monitoring of TOrC abatement with ozone processes and integrate them into a regulatory framework in water reuse. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Flame chemistry of alkane-rich gasoline fuels and a surrogate using photoionization mass spectrometry: I. Primary reference fuel

    KAUST Repository

    Selim, H.


    Improving the gasoline engines performance requires thorough understanding of their fundamental chemistry of combustion. Since the actual gasoline fuels are difficult to examine, due to the lack of knowledge about their exact composition as well as their numerous fuel components, the approach of using simpler gasoline fuels with limited number of components or using surrogate fuels has become more common. In this study, the combustion chemistry of laminar premixed flame of different gasoline fuels/surrogate has been examined. In this particular paper, the primary reference fuel, PRF84, has been examined at equivalence ratio of 1 and pressure of 20 Torr. The gas analysis was conducted using vacuum ultraviolet photoionization mass spectrometry.

  10. The value of enduring environmental surrogates as predictors of estuarine benthic macroinvertebrate assemblages (United States)

    Wildsmith, Michelle D.; Valesini, Fiona J.; Robinson, Samuel F.


    This study tested the extent to which spatial differences in the benthic macroinvertebrate assemblages of a temperate microtidal estuary were 'explained' by the enduring (biophysical) vs non-enduring (water and sediment quality) environmental attributes of a diverse range of habitats, and thus the potential of those environmental surrogates to support faunal prediction. Species composition differed significantly among habitats in each season, with the greatest differences occurring in winter and spring and the least in summer. The pattern of habitat differences, as defined by their enduring environmental characteristics, was significantly and well matched with that in the fauna in each season. In contrast, significant matches between the non-enduring environmental and faunal data were only detected in winter and/or spring, and to a lesser extent. Field validation of the faunal prediction capacity of the biophysical surrogate framework at various 'test' sites throughout the estuary showed good agreement between the actual vs predicted key species. These findings demonstrate that enduring environmental criteria, which can be readily measured from mapped data, provide a better and more cost-effective surrogate for explaining spatial differences in the invertebrate fauna of this system than non-enduring criteria, and are thus a promising basis for faunal prediction. The approaches developed in this study are also readily adapted to any estuary worldwide.

  11. An information-theoretic approach for the evaluation of surrogate endpoints based on causal inference. (United States)

    Alonso, Ariel; Van der Elst, Wim; Molenberghs, Geert; Buyse, Marc; Burzykowski, Tomasz


    In this work a new metric of surrogacy, the so-called individual causal association (ICA), is introduced using information-theoretic concepts and a causal inference model for a binary surrogate and true endpoint. The ICA has a simple and appealing interpretation in terms of uncertainty reduction and, in some scenarios, it seems to provide a more coherent assessment of the validity of a surrogate than existing measures. The identifiability issues are tackled using a two-step procedure. In the first step, the region of the parametric space of the distribution of the potential outcomes, compatible with the data at hand, is geometrically characterized. Further, in a second step, a Monte Carlo approach is proposed to study the behavior of the ICA on the previous region. The method is illustrated using data from the Collaborative Initial Glaucoma Treatment Study. A newly developed and user-friendly R package Surrogate is provided to carry out the evaluation exercise. © 2016, The International Biometric Society.

  12. Cyclist deceleration rate as surrogate safety measure in Montreal using smartphone GPS data. (United States)

    Strauss, Jillian; Zangenehpour, Sohail; Miranda-Moreno, Luis F; Saunier, Nicolas


    Urban areas in North American cities with positive trends in bicycle usage also witness a high number of cyclist injuries every year. Previous cyclist safety studies based on the traditional approach, which relies on historical crash data, are known to have some limitations such as the fact that crashes need to happen (a reactive approach). This paper explores the use of GPS deceleration events as a surrogate-proactive measure and investigates the relationship between reported cyclist road injuries and deceleration events. The surrogate safety measure is defined based on deceleration values representing hard breaking situations. This work uses a large sample of GPS cyclist trip data from a smartphone application to extract deceleration rates at intersections and along segments and to explore its relationship with the number of observed injuries and validate deceleration rate (DR) as a surrogate safety measure. Using Spearman's rank correlation coefficient, we compared the ranking of sites based on the expected number of injuries and based on DR. The ranks of expected injuries and dangerous decelerations were found to have a correlation of 0.60 at signalized intersections, 0.53 at non-signalized intersections and 0.57 at segments. Despite the promising results of this study, more granular data and validation work needs to be done to improve the reliability of the measures. The technological limitations and future work are discussed at the end of the paper. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Bacillus thuringiensis as a surrogate for Bacillus anthracis in aerosol research. (United States)

    Tufts, Jenia A M; Calfee, M Worth; Lee, Sang Don; Ryan, Shawn P


    Characterization of candidate surrogate spores prior to experimental use is critical to confirm that the surrogate characteristics are as closely similar as possible to those of the pathogenic agent of interest. This review compares the physical properties inherent to spores of Bacillus anthracis (Ba) and Bacillus thuringiensis (Bt) that impact their movement in air and interaction with surfaces, including size, shape, density, surface morphology, structure and hydrophobicity. Also evaluated is the impact of irradiation on the physical properties of both Bacillus species. Many physical features of Bt and Ba have been found to be similar and, while Bt is considered typically non-pathogenic, it is in the B. cereus group, as is Ba. When cultured and sporulated under similar conditions, both microorganisms share a similar cylindrical pellet shape, an aerodynamic diameter of approximately 1 μm (in the respirable size range), have an exosporium with a hairy nap, and have higher relative hydrophobicities than other Bacillus species. While spore size, morphology, and other physical properties can vary among strains of the same species, the variations can be due to growth/sporulation conditions and may, therefore, be controlled. Growth and sporulation conditions are likely among the most important factors that influence the representativeness of one species, or preparation, to another. All Bt spores may, therefore, not be representative of all Ba spores. Irradiated spores do not appear to be a good surrogate to predict the behavior of non-irradiated spores due to structural damage caused by the irradiation. While the use of Bt as a surrogate for Ba in aerosol testing appears to be well supported, this review does not attempt to narrow selection between Bt strains. Comparative studies should be performed to test the hypothesis that viable Ba and Bt spores will behave similarly when suspended in the air (as an aerosol) and to compare the known microscale characteristics

  14. Greedy Sampling and Incremental Surrogate Model-Based Tailoring of Aeroservoelastic Model Database for Flexible Aircraft (United States)

    Wang, Yi; Pant, Kapil; Brenner, Martin J.; Ouellette, Jeffrey A.


    This paper presents a data analysis and modeling framework to tailor and develop linear parameter-varying (LPV) aeroservoelastic (ASE) model database for flexible aircrafts in broad 2D flight parameter space. The Kriging surrogate model is constructed using ASE models at a fraction of grid points within the original model database, and then the ASE model at any flight condition can be obtained simply through surrogate model interpolation. The greedy sampling algorithm is developed to select the next sample point that carries the worst relative error between the surrogate model prediction and the benchmark model in the frequency domain among all input-output channels. The process is iterated to incrementally improve surrogate model accuracy till a pre-determined tolerance or iteration budget is met. The methodology is applied to the ASE model database of a flexible aircraft currently being tested at NASA/AFRC for flutter suppression and gust load alleviation. Our studies indicate that the proposed method can reduce the number of models in the original database by 67%. Even so the ASE models obtained through Kriging interpolation match the model in the original database constructed directly from the physics-based tool with the worst relative error far below 1%. The interpolated ASE model exhibits continuously-varying gains along a set of prescribed flight conditions. More importantly, the selected grid points are distributed non-uniformly in the parameter space, a) capturing the distinctly different dynamic behavior and its dependence on flight parameters, and b) reiterating the need and utility for adaptive space sampling techniques for ASE model database compaction. The present framework is directly extendible to high-dimensional flight parameter space, and can be used to guide the ASE model development, model order reduction, robust control synthesis and novel vehicle design of flexible aircraft.

  15. Optimal design of hydraulic excavator working device based on multiple surrogate models

    Directory of Open Access Journals (Sweden)

    Qingying Qiu


    Full Text Available The optimal design of hydraulic excavator working device is often characterized by computationally expensive analysis methods such as finite element analysis. Significant difficulties also exist when using a sensitivity-based decomposition approach to such practical engineering problems because explicit mathematical formulas between the objective function and design variables are impossible to formulate. An effective alternative is known as the surrogate model. The purpose of this article is to provide a comparative study on multiple surrogate models, including the response surface methodology, Kriging, radial basis function, and support vector machine, and select the one that best fits the optimization of the working device. In this article, a new modeling strategy based on the combination of the dimension variables between hinge joints and the forces loaded on hinge joints of the working device is proposed. In addition, the extent to which the accuracy of the surrogate models depends on different design variables is presented. The bionic intelligent optimization algorithm is then used to obtain the optimal results, which demonstrate that the maximum stresses calculated by the predicted method and finite element analysis are quite similar, but the efficiency of the former is much higher than that of the latter.

  16. Concentration and retention of Toxoplasma gondii surrogates from seawater by red abalone (Haliotis rufescens) (United States)

    Schott, Kristen C; Krusor, Colin; Tinker, M. Tim; Moore, James G.; Conrad, Patricia A.; Shapiro, Karen


    Small marine snails and abalone have been identified as high- and low-risk prey items, respectively, for exposure of threatened southern sea otters to Toxoplasma gondii, a zoonotic parasite that can cause fatal encephalitis in animals and humans. While recent work has characterized snails as paratenic hosts for T. gondii, the ability of abalone to vector the parasite has not been evaluated. To further elucidate why abalone predation may be protective against T. gondii exposure, this study aimed to determine whether: (1) abalone are physiologically capable of acquiring T. gondii; and (2) abalone and snails differ in their ability to concentrate and retain the parasite. Abalone were exposed to T. gondii surrogate microspheres for 24 h, and fecal samples were examined for 2 weeks following exposure. Concentration of surrogates was 2–3 orders of magnitude greater in abalone feces than in the spiked seawater, and excretion of surrogates continued for 14 days post-exposure. These results indicate that, physiologically, abalone and snails can equally vector T. gondii as paratenic hosts. Reduced risk of T. gondii infection in abalone-specializing otters may therefore result from abalone's high nutritional value, which implies otters must consume fewer animals to meet their caloric needs.

  17. Ignition of alkane-rich FACE gasoline fuels and their surrogate mixtures

    KAUST Repository

    Sarathy, Mani


    Petroleum derived gasoline is the most used transportation fuel for light-duty vehicles. In order to better understand gasoline combustion, this study investigated the ignition propensity of two alkane-rich FACE (Fuels for Advanced Combustion Engines) gasoline test fuels and their corresponding PRF (primary reference fuel) blend in fundamental combustion experiments. Shock tube ignition delay times were measured in two separate facilities at pressures of 10, 20, and 40 bar, temperatures from 715 to 1500 K, and two equivalence ratios. Rapid compression machine ignition delay times were measured for fuel/air mixtures at pressures of 20 and 40 bar, temperatures from 632 to 745 K, and two equivalence ratios. Detailed hydrocarbon analysis was also performed on the FACE gasoline fuels, and the results were used to formulate multi-component gasoline surrogate mixtures. Detailed chemical kinetic modeling results are presented herein to provide insights into the relevance of utilizing PRF and multi-component surrogate mixtures to reproduce the ignition behavior of the alkane-rich FACE gasoline fuels. The two FACE gasoline fuels and their corresponding PRF mixture displayed similar ignition behavior at intermediate and high temperatures, but differences were observed at low temperatures. These trends were mimicked by corresponding surrogate mixture models, except for the amount of heat release in the first stage of a two-stage ignition events, when observed. © 2014 The Combustion Institute.

  18. Developing a New Surrogate Safety Indicator Based on Motion Equations

    Directory of Open Access Journals (Sweden)

    Hamid Behbahani


    Full Text Available Collision avoidance system (CAS, with the help of surrogate safety measures is a beneficial tool for reducing driver errors and preventing rear-end collisions. One of the most well-known surrogate safety measures to detect rear-end conflicts is Time-to-collision (TTC. TTC refers to the time remaining before the rear-end accident if the course and the speed of vehicles are maintained constant. Different surrogate measures have been derived from TTC; however, the most important are Time Exposed Time-to-collision (TET and Time Integrated Time-to-collision (TIT. In this paper a new surrogate safety measure based on TTC notion has been developed. This new indicator merges TET and TIT into one measure and gives a score between 0 and 100%, as the probability of collision. Applying this indicator in CAS as a safety measure will be more useful than TET&TIT, to reduce driver errors and rear-end collisions.

  19. Development of Cranial Bone Surrogate Structures Using Stereolithographic Additive Manufacturing (United States)


    public release; distribution is unlimited. vi Acknowledgments We would like to acknowledge Jacob Schimelman for assistance with the tensile...print anatomical surrogates. However, limitations in printing resolution precludes the reproduction of micronscale features while the random, organic...trabecular bone requires high-resolution manufacturing methods, which makes SLA one of the best suited compared to other AM techniques at present. In our

  20. Bayesian Analysis of Multivariate Probit Models with Surrogate Outcome Data (United States)

    Poon, Wai-Yin; Wang, Hai-Bin


    A new class of parametric models that generalize the multivariate probit model and the errors-in-variables model is developed to model and analyze ordinal data. A general model structure is assumed to accommodate the information that is obtained via surrogate variables. A hybrid Gibbs sampler is developed to estimate the model parameters. To…

  1. 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)


    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."

  2. Surrogate motherhood in illness that does not cause infertility

    African Journals Online (AJOL)

    birth to a child and that the condition is permanent and irreversible'. I refer to this as the 'threshold requirement' for surrogate mother- hood, following the judgment in AB and Another v Minister of. Social Development.[6] Persons qualifying in terms of the threshold requirement include male same-sex couples and single men ...

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

    DEFF Research Database (Denmark)

    Andreassen, Erik; Ferrari, Federico; Sigmund, Ole


    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...... associated with computation of eigenvalues in very large problems....

  4. Adaptation-II of the surrogate methods for linear programming ...

    African Journals Online (AJOL)

    Adaptation-II of the surrogate methods for linear programming problems. SO Oko. Abstract. No Abstract. Global Journal of Mathematical Sciences Vol. 5(1) 2006: 63-71. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT ·

  5. Comparison of surrogate models with different methods in ...

    Indian Academy of Sciences (India)

    and sea water intrusion management problems. Hemker et al. (2008) used kriging method to build the surrogate model of simulation model to reduce optimization computation cost in ground- water management problem. It is difficult to say if one of these ..... on a 3.0 GHz AMD CPU and 2 GB RAM PC platform. 40 input data ...

  6. Desorption of a methamphetamine surrogate from wallboard under remediation conditions (United States)

    Poppendieck, Dustin; Morrison, Glenn; Corsi, Richard


    Thousands of homes in the United States are found to be contaminated with methamphetamine each year. Buildings used to produce illicit methamphetamine are typically remediated by removing soft furnishings and stained materials, cleaning and sometimes encapsulating surfaces using paint. Methamphetamine that has penetrated into paint films, wood and other permanent materials can be slowly released back into the building air over time, exposing future occupants and re-contaminating furnishings. The objective of this study was to determine the efficacy of two wallboard remediation techniques for homes contaminated with methamphetamine: 1) enhancing desorption by elevating temperature and relative humidity while ventilating the interior space, and 2) painting over affected wallboard to seal the methamphetamine in place. The emission of a methamphetamine surrogate, N-isopropylbenzylamine (NIBA), from pre-dosed wallboard chambers over 20 days at 32 °C and two values of relative humidity were studied. Emission rates from wallboard after 15 days at 32 °C ranged from 35 to 1400 μg h-1 m-2. Less than 22% of the NIBA was removed from the chambers over three weeks. Results indicate that elevating temperatures during remediation and latex painting of impacted wallboard will not significantly reduce freebase methamphetamine emissions from wallboard. Raising the relative humidity from 27% to 49% increased the emission rates by a factor of 1.4. A steady-state model of a typical home using the emission rates from this study and typical residential building parameters and conditions shows that adult inhalation reference doses for methamphetamine will be reached when approximately 1 g of methamphetamine is present in the wallboard of a house.

  7. Perinatal outcomes after natural conception versus in vitro fertilization (IVF) in gestational surrogates: a model to evaluate IVF treatment versus maternal effects. (United States)

    Woo, Irene; Hindoyan, Rita; Landay, Melanie; Ho, Jacqueline; Ingles, Sue Ann; McGinnis, Lynda K; Paulson, Richard J; Chung, Karine


    To study the perinatal outcomes between singleton live births achieved with the use of commissioned versus spontaneously conceived embryos carried by the same gestational surrogate. Retrospective cohort study. Academic in vitro fertilization center. Gestational surrogate. None. Pregnancy outcome, gestational age at birth, birth weight, perinatal complications. We identified 124 gestational surrogates who achieved a total of 494 pregnancies. Pregnancy outcomes for surrogate and spontaneous pregnancies were significantly different (P<.001), with surrogate pregnancies more likely to result in twin pregnancies: 33% vs. 1%. Miscarriage and ectopic rates were similar. Of these pregnancies, there were 352 singleton live births: 103 achieved from commissioned embryos and 249 conceived spontaneously. Surrogate births had lower mean gestational age at delivery (38.8 ± 2.1 vs. 39.7 ± 1.4), higher rates of preterm birth (10.7% vs. 3.1%), and higher rates of low birth weight (7.8% vs. 2.4%). Neonates from surrogacy had birth weights that were, on average, 105 g lower. Surrogate births had significantly higher obstetrical complications, including gestational diabetes, hypertension, use of amniocentesis, placenta previa, antibiotic requirement during labor, and cesarean section. Neonates born from commissioned embryos and carried by gestational surrogates have increased adverse perinatal outcomes, including preterm birth, low birth weight, hypertension, maternal gestational diabetes, and placenta previa, compared with singletons conceived spontaneously and carried by the same woman. Our data suggest that assisted reproductive procedures may potentially affect embryo quality and that its negative impact can not be overcome even with a proven healthy uterine environment. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  8. Recent Progress in the Development of Diesel Surrogate Fuels

    Energy Technology Data Exchange (ETDEWEB)

    Pitz, W J; Mueller, C J


    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

  9. Recent Progress in the Development of Diesel Surrogate Fuels

    Energy Technology Data Exchange (ETDEWEB)

    Pitz, W J


    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 do-decane which 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 the cycloalkanes, 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 multidimensional 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 diesel

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

  11. Of fads, fashion, surrogate endpoints and dual RAS blockade. (United States)

    Messerli, Franz H; Staessen, Jan A; Zannad, Faiez


    Dual renin-angiotensin system (RAS) blockade, mostly by combining an angiotensin converting enzyme (ACE) inhibitor with an angiotensin receptor blocker (ARB), is increasingly used in patients with hypertension and diabetes and/or proteinuria and in those with resistant heart failure. However, in the zest of achieving greater nephroprotection and cardioprotection, even patients with uncomplicated essential hypertension are not uncommonly treated with dual RAS blockade. In 2003 the COOPERATE trial, seemed to confirm that dual RAS blockade was beneficial and that proteinuria reduction was synonymous with nephroprotection. This study had to be withdrawn recently attesting to the suspicion that the data looked to good to be true. Moreover, the large prospective ONTARGET data argue against a nephroprotective effect of dual RAS blockade and together with renal findings from ACCOMPLISH, cast doubt on albuminuria/proteinuria being a reliable surrogate endpoint for renal outcome. Although in heart failure, dual RAS blockade had some benefit without reducing mortality, there remains a distinct safety issue with regard to hyperkalemia and elevated creatinine. Neither in ischaemic heart disease nor in left ventricular hypertrophy had dual RAS blockade any benefits when compared with single RAS blockade. Of note, the combination of an ACE inhibitor with an ARB was recently shown to reduce the risk of dementia. All dual RAS blockade may be created equal and the combination of valsartan with aliskiren, a direct renin inhibitor will be evaluated in diabetic patients in the prospective, randomized ALTITUDE study. For the time being, given the adverse effects and lack of consistent survival benefits, the use of dual RAS blockade should be avoided unless ironclad data emerge to the contrary.

  12. Enhancing Convective Heat Transfer over a Surrogate Photovoltaic Panel (United States)

    Fouladi, Fama

    This research is particularly focused on studying heat transfer enhancement of a photovoltaic (PV) panel by putting an obstacle at the panel's windward edge. The heat transfer enhancement is performed by disturbing the airflow over the surface and increasing the heat and momentum transfer. Different objects such as triangular, square, rectangular, and discrete rectangular ribs and partial grids were applied at the leading edge of a surrogate PV panel and flow and the heat transfer of the panel are investigated experimentally. This approach was selected to expand understanding of effect of these different objects on the flow and turbulence structures over a flat surface by analyzing the flow comprehensively. It is observed that, a transverse object at the plate's leading edge would cause some flow blockage in the streamwise direction, but at the same time creates some velocity in the normal and cross stream directions. In addition to that, the obstacle generates some turbulence over the surface which persists for a long downstream distance. Also, among all studied objects, discrete rectangular ribs demonstrate the highest heat transfer rate enhancement (maximum Nu/Nu0 of 1.5). However, ribs with larger gap ratios are observed to be more effective at enhancing the heat transfer augmentation at closer distances to the rib, while at larger downstream distances from the rib, discrete ribs with smaller gap ratios are more effective. Furthermore, this work attempted to recognize the most influential flow parameters on the heat transfer enhancement of the surface. It is seen that the flow structure over a surface downstream of an object (flow separation-reattachment behaviour) has a significant effect on the heat transfer enhancement trend. Also, turbulence intensities are the most dominant parameters in enhancing the heat transfer rate from the surface; however, flow velocity (mostly normal velocity) is also an important factor.

  13. Safety surrogate histograms (SSH): A novel real-time safety assessment of dilemma zone related conflicts at signalized intersections. (United States)

    Ghanipoor Machiani, Sahar; Abbas, Montasir


    Drivers' indecisiveness in dilemma zones (DZ) could result in crash-prone situations at signalized intersections. DZ is to the area ahead of an intersection in which drivers encounter a dilemma regarding whether to stop or proceed through the intersection when the signal turns yellow. An improper decision to stop by the leading driver, combined with the following driver deciding to go, can result in a rear-end collision, unless the following driver recognizes a collision is imminent and adjusts his or her behavior at or shortly after the onset of yellow. Considering the significance of DZ-related crashes, a comprehensive safety measure is needed to characterize the level of safety at signalized intersections. In this study, a novel safety surrogate measure was developed utilizing real-time radar field data. This new measure, called safety surrogate histogram (SSH), captures the degree and frequency of DZ-related conflicts at each intersection approach. SSH includes detailed information regarding the possibility of crashes, because it is calculated based on the vehicles conflicts. An example illustrating the application of the new methodology at two study sites in Virginia is presented and discussed, and a comparison is provided between SSH and other DZ-related safety surrogate measures mentioned in the literature. The results of the study reveal the efficacy of the SSH as complementary to existing surrogate measures. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Elevated pressure improves the extraction and identification of proteins recovered from formalin-fixed, paraffin-embedded tissue surrogates.

    Directory of Open Access Journals (Sweden)

    Carol B Fowler


    Full Text Available Proteomic studies of formalin-fixed paraffin-embedded (FFPE tissues are frustrated by the inability to extract proteins from archival tissue in a form suitable for analysis by 2-D gel electrophoresis or mass spectrometry. This inability arises from the difficulty of reversing formaldehyde-induced protein adducts and cross-links within FFPE tissues. We previously reported the use of elevated hydrostatic pressure as a method for efficient protein recovery from a hen egg-white lysozyme tissue surrogate, a model system developed to study formalin fixation and histochemical processing.In this study, we demonstrate the utility of elevated hydrostatic pressure as a method for efficient protein recovery from FFPE mouse liver tissue and a complex multi-protein FFPE tissue surrogate comprised of hen egg-white lysozyme, bovine carbonic anhydrase, bovine ribonuclease A, bovine serum albumin, and equine myoglobin (55∶15∶15∶10∶5 wt%. Mass spectrometry of the FFPE tissue surrogates retrieved under elevated pressure showed that both the low and high-abundance proteins were identified with sequence coverage comparable to that of the surrogate mixture prior to formaldehyde treatment. In contrast, non-pressure-extracted tissue surrogate samples yielded few positive and many false peptide identifications. Studies with soluble formalin-treated bovine ribonuclease A demonstrated that pressure modestly inhibited the rate of reversal (hydrolysis of formaldehyde-induced protein cross-links. Dynamic light scattering studies suggest that elevated hydrostatic pressure and heat facilitate the recovery of proteins free of formaldehyde adducts and cross-links by promoting protein unfolding and hydration with a concomitant reduction in the average size of the protein aggregates.These studies demonstrate that elevated hydrostatic pressure treatment is a promising approach for improving the recovery of proteins from FFPE tissues in a form suitable for proteomic analysis.

  15. Elevated pressure improves the extraction and identification of proteins recovered from formalin-fixed, paraffin-embedded tissue surrogates. (United States)

    Fowler, Carol B; Chesnick, Ingrid E; Moore, Cedric D; O'Leary, Timothy J; Mason, Jeffrey T


    Proteomic studies of formalin-fixed paraffin-embedded (FFPE) tissues are frustrated by the inability to extract proteins from archival tissue in a form suitable for analysis by 2-D gel electrophoresis or mass spectrometry. This inability arises from the difficulty of reversing formaldehyde-induced protein adducts and cross-links within FFPE tissues. We previously reported the use of elevated hydrostatic pressure as a method for efficient protein recovery from a hen egg-white lysozyme tissue surrogate, a model system developed to study formalin fixation and histochemical processing. In this study, we demonstrate the utility of elevated hydrostatic pressure as a method for efficient protein recovery from FFPE mouse liver tissue and a complex multi-protein FFPE tissue surrogate comprised of hen egg-white lysozyme, bovine carbonic anhydrase, bovine ribonuclease A, bovine serum albumin, and equine myoglobin (55∶15∶15∶10∶5 wt%). Mass spectrometry of the FFPE tissue surrogates retrieved under elevated pressure showed that both the low and high-abundance proteins were identified with sequence coverage comparable to that of the surrogate mixture prior to formaldehyde treatment. In contrast, non-pressure-extracted tissue surrogate samples yielded few positive and many false peptide identifications. Studies with soluble formalin-treated bovine ribonuclease A demonstrated that pressure modestly inhibited the rate of reversal (hydrolysis) of formaldehyde-induced protein cross-links. Dynamic light scattering studies suggest that elevated hydrostatic pressure and heat facilitate the recovery of proteins free of formaldehyde adducts and cross-links by promoting protein unfolding and hydration with a concomitant reduction in the average size of the protein aggregates. These studies demonstrate that elevated hydrostatic pressure treatment is a promising approach for improving the recovery of proteins from FFPE tissues in a form suitable for proteomic analysis.

  16. Investigation of the surrogate-reaction method via the simultaneous measurement of gamma-emission and fission probabilities

    Directory of Open Access Journals (Sweden)

    Jurado B.


    Full Text Available We present the results of two experiments where we have measured for the first time simultaneously the fission and gamma-decay probabilities induced by different surrogate reactions. In particular, we have investigated the 238U(d,p, 238U(3He,t and 238U(3He,4He reactions as surrogates for the neutron-induced n +  238U, n +  237Np and n +  236U reactions, respectively. In the region where gamma emission, neutron emission and fission compete, our results for the fission probabilities agree fairly well with the neutron-induced data, whereas our gamma-decay probabilities are significantly higher than the neutron-induced data. The interpretation of these results is not obvious and is discussed within the framework of the statistical model with preliminary results for calculated spin-parity distributions populated in surrogate reactions. We also present future plans for surrogate-reaction studies in inverse kinematics with radioactive-ion beams at storage rings.

  17. Investigation of the surrogate-reaction method via the simultaneous measurement of gamma-emission and fission probabilities (United States)

    Jurado, B.; Marini, P.; Mathieu, L.; Aiche, M.; Czajkowski, S.; Tsekhanovich, I.; Audouin, L.; Boutoux, G.; Denis-Petit, D.; Guttormsen, M.; Kessedjian, G.; Lebois, M.; Méot, V.; Oberstedt, A.; Oberstedt, S.; Roig, O.; Sérot, O.; Tassan-Got, L.; Wilson, J. N.


    We present the results of two experiments where we have measured for the first time simultaneously the fission and gamma-decay probabilities induced by different surrogate reactions. In particular, we have investigated the 238U(d,p), 238U(3He,t) and 238U(3He,4He) reactions as surrogates for the neutron-induced n + 238U, n + 237Np and n + 236U reactions, respectively. In the region where gamma emission, neutron emission and fission compete, our results for the fission probabilities agree fairly well with the neutron-induced data, whereas our gamma-decay probabilities are significantly higher than the neutron-induced data. The interpretation of these results is not obvious and is discussed within the framework of the statistical model with preliminary results for calculated spin-parity distributions populated in surrogate reactions. We also present future plans for surrogate-reaction studies in inverse kinematics with radioactive-ion beams at storage rings.

  18. In situ densimetric measurements as a surrogate for suspended-sediment concentrations in the Rio Puerco, New Mexico (United States)

    Brown, Jeb E.; Gray, John R.; Hornewer, Nancy J.


    Surrogate measurements of suspended-sediment concentration (SSC) are increasingly used to provide continuous, high-resolution, and demonstrably accurate data at a reasonable cost. Densimetric data, calculated from the difference between two in situ pressure measurements, exploit variations in real-time streamflow densities to infer SSCs. Unlike other suspendedsediment surrogate technologies based on bulk or digital optics, laser, or hydroacoustics, the accuracy of SSC data estimated using the pressure-difference (also referred to as densimetric) surrogate technology theoretically improves with increasing SCCs. Coupled with streamflow data, continuous suspended-sediment discharges can be calculated using SSC data estimated in real-time using the densimetric technology. The densimetric technology was evaluated at the Rio Puerco in New Mexico, a stream where SSC values regularly range from 10,000-200,000 milligrams per liter (mg/L) and have exceeded 500,000 mg/L. The constant-flow dual-orifice bubbler measures pressure using two precision pressure-transducer sensors at vertically aligned fixed locations in a water column. Water density is calculated from the temperature-compensated differential pressure and SSCs are inferred from the density data. A linear regression model comparing density values to field-measured SSC values yielded an R² of 0.74. Although the application of the densimetric surrogate is likely limited to fluvial systems with SSCs larger than about 10,000 mg/L, based on this and previous studies, the densimetric technology fills a void for monitoring streams with high SSCs.

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

    KAUST Repository

    Butnaru, Daniel


    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.

  20. Regression calibration with more surrogates than mismeasured variables

    KAUST Repository

    Kipnis, Victor


    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.

  1. Commercial agencies and surrogate motherhood: a transaction cost approach. (United States)

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


    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.

  2. Investigating the Hydrolysis Reactions of a Chemical Warfare Agent Surrogate. A Systematic Study using 1H, 13C, 17O, 19F, 31P, and 35Cl NMR Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Alam, Todd M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Wilson, Brendan W. [West Virginia Univ., Morgantown, WV (United States)


    During the summer of 2015, I participated in the DHS HS-STEM fellowship at Sandia National Laboratories (SNL, NM) under the supervision of Dr. Todd M. Alam in his Nuclear Magnetic Resonance (NMR) Spectroscopy research group. While with the group, my main project involved pursing various hydrolysis reactions with Diethyl Chlorophosphate (DECP), a surrogate for the agent Sarin (GB). Specifically, I performed different hydrolysis reactions, monitored and tracked the different phosphorous containing species using phosphorous (31P) NMR spectroscopy. With the data collected, I performed kinetics studies mapping the rates of DECP hydrolysis. I also used the NMR of different nuclei such as 1H, 13C, 17O, and 35Cl to help understand the complexity of the reactions that take place. Finally, my last task at SNL was to work with Insensitive Nuclei Enhanced by Polarization Transfer (INEPT) NMR Spectroscopy optimizing conditions for 19F- 31P filtering NMR experiments.

  3. Surrogate Assisted Design Optimization of an Air Turbine

    Directory of Open Access Journals (Sweden)

    Rameez Badhurshah


    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. Love as a regulative ideal in surrogate decision making. (United States)

    Stonestreet, Erica Lucast


    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:

  5. An Artificial Turf-Based Surrogate Surface Collector for the ... (United States)

    This paper describes the development of a new artificial turf surrogate surface (ATSS) sampler for use in the measurement of mercury (Hg) dry deposition. In contrast to many existing surrogate surface designs, the ATSS utilizes a three-dimensional deposition surface that may more closely mimic the physical structure of many natural surfaces than traditional flat surrogate surface designs (water, filter, greased Mylar film). The ATSS has been designed to overcome several complicating factors that can impact the integrity of samples with other direct measurement approaches by providing a passive system which can be deployed for both short and extended periods of time (days to weeks), and is not contaminated by precipitation and/or invalidated by strong winds. Performance characteristics including collocated precision, in-field procedural and laboratory blanks were evaluated. The results of these performance evaluations included a mean collocated precision of 9%, low blanks (0.8 ng), high extraction efficiency (97%–103%), and a quantitative matrix spike recovery (100%). In recent years, a growing number of intensive field campaigns and routine measurement networks have provided valuable information on the rates of total mercury (Hg) wet deposition in North America (Guentzel et al., 1995; Rea et al., 1996; Dvonch et al., 1999; Landis and Keeler, 2002; Dvonch et al., 2005; Hall et al., 2005; Keeler et al., 2005; Keeler et al., 2006; Butler et al., 2008; Prestbo an

  6. Ensemble of Surrogates-based Optimization for Identifying an Optimal Surfactant-enhanced Aquifer Remediation Strategy at Heterogeneous DNAPL-contaminated Sites (United States)

    Lu, W., Sr.; Xin, X.; Luo, J.; Jiang, X.; Zhang, Y.; Zhao, Y.; Chen, M.; Hou, Z.; Ouyang, Q.


    The purpose of this study was to identify an optimal surfactant-enhanced aquifer remediation (SEAR) strategy for aquifers contaminated by dense non-aqueous phase liquid (DNAPL) based on an ensemble of surrogates-based optimization technique. A saturated heterogeneous medium contaminated by nitrobenzene was selected as case study. A new kind of surrogate-based SEAR optimization employing an ensemble surrogate (ES) model together with a genetic algorithm (GA) is presented. Four methods, namely radial basis function artificial neural network (RBFANN), kriging (KRG), support vector regression (SVR), and kernel extreme learning machines (KELM), were used to create four individual surrogate models, which were then compared. The comparison enabled us to select the two most accurate models (KELM and KRG) to establish an ES model of the SEAR simulation model, and the developed ES model as well as these four stand-alone surrogate models was compared. The results showed that the average relative error of the average nitrobenzene removal rates between the ES model and the simulation model for 20 test samples was 0.8%, which is a high approximation accuracy, and which indicates that the ES model provides more accurate predictions than the stand-alone surrogate models. Then, a nonlinear optimization model was formulated for the minimum cost, and the developed ES model was embedded into this optimization model as a constrained condition. Besides, GA was used to solve the optimization model to provide the optimal SEAR strategy. The developed ensemble surrogate-optimization approach was effective in seeking a cost-effective SEAR strategy for heterogeneous DNAPL-contaminated sites. This research is expected to enrich and develop the theoretical and technical implications for the analysis of remediation strategy optimization of DNAPL-contaminated aquifers.

  7. Expanding a fluorescent RNA alphabet: synthesis, photophysics and utility of isothiazole-derived purine nucleoside surrogates. (United States)

    Rovira, Alexander R; Fin, Andrea; Tor, Yitzhak


    A series of emissive ribonucleoside purine mimics, all comprised of an isothiazolo[4,3-d]pyrimidine core, was prepared using a divergent pathway involving a key Thorpe-Ziegler cyclization. In addition to an adenosine and a guanosine mimic, analogues of the noncanonical xanthosine, isoguanosine, and 2-aminoadenosine were also synthesized and found to be emissive. Isothiazolo 2-aminoadenosine, an adenosine surrogate, was found to be particularly emissive and effectively deaminated by adenosine deaminase. Competitive studies with adenosine deaminase with each analogue in combination with native adenosine showed preference for the native substrate while still deaminating the isothiazolo analogues.

  8. Taxonomic and functional surrogates of sessile benthic diversity in Mediterranean marine caves.

    Directory of Open Access Journals (Sweden)

    Vasilis Gerovasileiou

    Full Text Available Hard substrates host globally a rich biodiversity, orders of magnitude higher in species number than that in surrounding soft substrates. Among them, marine caves support unique biodiversity and fragile communities but suffer lack of quantitative data on their structure and function, hindering their conservation status assessment. A first approach to the non-destructive ecological monitoring of marine caves by testing surrogates of structural and functional composition of sessile benthos was attempted in two species-rich Mediterranean marine caves. Photographic sampling was performed in different positions on the cave walls, across the horizontal axis, from the entrance inwards. Eighty-four taxa were identified and assigned to 6 biological traits and 32 modalities related to morphology, behavior and ecological affinities, with sponges being the dominant taxon in species richness and coverage. In quest of possible biological surrogates, we examined the spatial variability of the total community structure and function and separately the sponge community structure and function. The observed patterns of the above metrics were significantly correlated with the distance from the entrance, the small-scale variability and their interaction. A positive correlation was found between all examined pairs of those metrics, supporting that: (i the developed functional approach could be used for the study of marine cave sessile communities, and (ii sponges could be used as a surrogate taxon for the structural and functional study of these communities. The suggested method could be tested in other types of hard substrate habitats and in multiple locations of the Mediterranean waters, facilitating monitoring schemes and conservation actions.

  9. Taxonomic and functional surrogates of sessile benthic diversity in Mediterranean marine caves. (United States)

    Gerovasileiou, Vasilis; Dimitriadis, Charalampos; Arvanitidis, Christos; Voultsiadou, Eleni


    Hard substrates host globally a rich biodiversity, orders of magnitude higher in species number than that in surrounding soft substrates. Among them, marine caves support unique biodiversity and fragile communities but suffer lack of quantitative data on their structure and function, hindering their conservation status assessment. A first approach to the non-destructive ecological monitoring of marine caves by testing surrogates of structural and functional composition of sessile benthos was attempted in two species-rich Mediterranean marine caves. Photographic sampling was performed in different positions on the cave walls, across the horizontal axis, from the entrance inwards. Eighty-four taxa were identified and assigned to 6 biological traits and 32 modalities related to morphology, behavior and ecological affinities, with sponges being the dominant taxon in species richness and coverage. In quest of possible biological surrogates, we examined the spatial variability of the total community structure and function and separately the sponge community structure and function. The observed patterns of the above metrics were significantly correlated with the distance from the entrance, the small-scale variability and their interaction. A positive correlation was found between all examined pairs of those metrics, supporting that: (i) the developed functional approach could be used for the study of marine cave sessile communities, and (ii) sponges could be used as a surrogate taxon for the structural and functional study of these communities. The suggested method could be tested in other types of hard substrate habitats and in multiple locations of the Mediterranean waters, facilitating monitoring schemes and conservation actions.

  10. Might iodomethyl-{alpha}-tyrosine be a surrogate for BPA in BNCT?

    Energy Technology Data Exchange (ETDEWEB)

    Miura, Michiko; Micca, P.L.; Nawrocky, M.M.; Slatkin, D.N.


    A single-photon emission computed tomography [SPECT] imaging agent that is an analogue of a boron carrier for boron neutron-capture therapy [BNCT] of cerebral gliomas would be useful for assessing the kinetics of boron uptake in tumors and in the surrounding brain tissues noninvasively. BNCT is based on the interaction of thermalized neutrons with {sup 10}B nuclei in the targeted tumor. For BNCT of brain tumors, it is crucial that {sup 10}B concentrations in radiosensitive regions of the brain be minimal since malignant cells and vital brain tissues are often inter-mingled at the margins of the tumor. Currently, boronophenylalanine [BPA]-mediated BNCT is undergoing preliminary clinical study for postoperative radiotherapy of glioblastorna multiforme at Brookhaven National Laboratory. Investigators in Japan are developing {sup 18}F-fluoroboronophenylaianine [FBPA] as a positron {sup 18}F (T{sub 1/2} = 110 min), which is usually emission tomography [PET] surrogate for BPA. generated at a cyclotron dedicated to PET, is generally a minimally perturbing substitute for the 2-H on the aromatic ring because of its small size and the strong covalent bond it forms with carbon. However, SPECT has potential advantages over PET: (1) SPECT is clinically more widely available at lower cost; (2) most radioisotopes for the synthesis of SPECT agents can be purchased; (3) SPECT is less difficult to implement. It is thought that the quality of images derived from the two techniques would each be sufficiently informative for BNCT treatment planning purposes, provided that the SPECT and PET agents being considered were both pharmacokinetic surrogates for BPA. This study evaluated the use of {sup 123}I alpha methyltyrosine as a surrogate for BPA in BNCT.

  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) (United States)


    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. Effect of phytosterols/stanols on LDL concentration and other surrogate markers of cardiovascular risk. (United States)

    Bard, J-M; Paillard, F; Lecerf, J-M


    Plant sterols and stanols are well-known to reduce LDL-cholesterol (LDL-C) concentrations. It is generally accepted that supplementation with 2g/day of sterols/stanols leads to a 10% reduction in LDL. However, most of the clinical trials supporting this conclusion were of short-term duration, and the results of longer interventions are scanty. In four studies, interventions lasting>6 months were carried out and the LDL-C-lowering effects were maintained over this longer duration, although some results suggest that a reduced effect may be observed with sterols, while stanols maintain their effect. In any case, the data are too limited to be definitive. In a free-living population as well as in multiparametric interventional studies, however, the LDL-C-lowering effect has been confirmed, although to a lesser extent than in clinical studies. In the absence of data on cardiovascular morbidity and mortality, data for surrogate markers of cardiovascular risk could be considered adequate alternatives. Several studies have been conducted on this basis, but their results failed to demonstrate any favourable effects. The present report summarizes the different results obtained in long-term studies, and in those comparing the effects of sterols and stanols on lipids and other surrogate markers of cardiovascular risk. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  13. Vertical accelerator device to apply loads simulating blast environments in the military to human surrogates. (United States)

    Yoganandan, Narayan; Pintar, Frank A; Schlick, Michael; Humm, John R; Voo, Liming; Merkle, Andrew; Kleinberger, Michael


    The objective of the study was to develop a simple device, Vertical accelerator (Vertac), to apply vertical impact loads to Post Mortem Human Subject (PMHS) or dummy surrogates because injuries sustained in military conflicts are associated with this vector; example, under-body blasts from explosive devices/events. The two-part mechanically controlled device consisted of load-application and load-receiving sections connected by a lever arm. The former section incorporated a falling weight to impact one end of the lever arm inducing a reaction at the other/load-receiving end. The "launch-plate" on this end of the arm applied the vertical impact load/acceleration pulse under different initial conditions to biological/physical surrogates, attached to second section. It is possible to induce different acceleration pulses by using varying energy absorbing materials and controlling drop height and weight. The second section of Vertac had the flexibility to accommodate different body regions for vertical loading experiments. The device is simple and inexpensive. It has the ability to control pulses and flexibility to accommodate different sub-systems/components of human surrogates. It has the capability to incorporate preloads and military personal protective equipment (e.g., combat helmet). It can simulate vehicle roofs. The device allows for intermittent specimen evaluations (x-ray and palpation, without changing specimen alignment). The two free but interconnected sections can be used to advance safety to military personnel. Examples demonstrating feasibilities of the Vertac device to apply vertical impact accelerations using PMHS head-neck preparations with helmet and booted Hybrid III dummy lower leg preparations under in-contact and launch-type impact experiments are presented. Published by Elsevier Ltd.

  14. Comparison of atorvastatin 80 mg/day versus simvastatin 20 to 40 mg/day on frequency of cardiovascular events late (five years) after acute myocardial infarction (from the Incremental Decrease in End Points through Aggressive Lipid Lowering [IDEAL] trial)

    DEFF Research Database (Denmark)

    Pedersen, TR; Cater, Nilo B; Faergeman, Ole


    Previous studies have demonstrated that benefits of intensive statin therapy compared to standard statin therapy begin shortly after an acute event and are continued up to 2 years of follow-up. However, whether efficacy and safety of intensive statin therapy in patients with a recent cardiac even...

  15. Evaluation of countermeasures for red light running by traffic simulator-based surrogate safety measures. (United States)

    Lee, Changju; So, Jaehyun Jason; Ma, Jiaqi


    The conflicts among motorists entering a signalized intersection with the red light indication have become a national safety issue. Because of its sensitivity, efforts have been made to investigate the possible causes and effectiveness of countermeasures using comparison sites and/or before-and-after studies. Nevertheless, these approaches are ineffective when comparison sites cannot be found, or crash data sets are not readily available or not reliable for statistical analysis. Considering the random nature of red light running (RLR) crashes, an inventive approach regardless of data availability is necessary to evaluate the effectiveness of each countermeasure face to face. The aims of this research are to (1) review erstwhile literature related to red light running and traffic safety models; (2) propose a practical methodology for evaluation of RLR countermeasures with a microscopic traffic simulation model and surrogate safety assessment model (SSAM); (3) apply the proposed methodology to actual signalized intersection in Virginia, with the most prevalent scenarios-increasing the yellow signal interval duration, installing an advance warning sign, and an RLR camera; and (4) analyze the relative effectiveness by RLR frequency and the number of conflicts (rear-end and crossing). All scenarios show a reduction in RLR frequency (-7.8, -45.5, and -52.4%, respectively), but only increasing the yellow signal interval duration results in a reduced total number of conflicts (-11.3%; a surrogate safety measure of possible RLR-related crashes). An RLR camera makes the greatest reduction (-60.9%) in crossing conflicts (a surrogate safety measure of possible angle crashes), whereas increasing the yellow signal interval duration results in only a 12.8% reduction of rear-end conflicts (a surrogate safety measure of possible rear-end crash). Although increasing the yellow signal interval duration is advantageous because this reduces the total conflicts (a possibility of total

  16. Solubility of actinides and surrogates in nuclear glasses; Solubilite des actinides et de leurs simulants dans les verres nucleaires. Limites d'incorporation et comprehension des mecanismes

    Energy Technology Data Exchange (ETDEWEB)

    Lopez, Ch


    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{sub 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)

  17. Development of an RF-EMF Exposure Surrogate for Epidemiologic Research. (United States)

    Roser, Katharina; Schoeni, Anna; Bürgi, Alfred; Röösli, Martin


    Exposure assessment is a crucial part in studying potential effects of RF-EMF. Using data from the HERMES study on adolescents, we developed an integrative exposure surrogate combining near-field and far-field RF-EMF exposure in a single brain and whole-body exposure measure. Contributions from far-field sources were modelled by propagation modelling and multivariable regression modelling using personal measurements. Contributions from near-field sources were assessed from both, questionnaires and mobile phone operator records. Mean cumulative brain and whole-body doses were 1559.7 mJ/kg and 339.9 mJ/kg per day, respectively. 98.4% of the brain dose originated from near-field sources, mainly from GSM mobile phone calls (93.1%) and from DECT phone calls (4.8%). Main contributors to the whole-body dose were GSM mobile phone calls (69.0%), use of computer, laptop and tablet connected to WLAN (12.2%) and data traffic on the mobile phone via WLAN (6.5%). The exposure from mobile phone base stations contributed 1.8% to the whole-body dose, while uplink exposure from other people's mobile phones contributed 3.6%. In conclusion, the proposed approach is considered useful to combine near-field and far-field exposure to an integrative exposure surrogate for exposure assessment in epidemiologic studies. However, substantial uncertainties remain about exposure contributions from various near-field and far-field sources.

  18. Uncertainty quantification of squeal instability via surrogate modelling (United States)

    Nobari, Amir; Ouyang, Huajiang; Bannister, Paul


    One of the major issues that car manufacturers are facing is the noise and vibration of brake systems. Of the different sorts of noise and vibration, which a brake system may generate, squeal as an irritating high-frequency noise costs the manufacturers significantly. Despite considerable research that has been conducted on brake squeal, the root cause of squeal is still not fully understood. The most common assumption, however, is mode-coupling. Complex eigenvalue analysis is the most widely used approach to the analysis of brake squeal problems. One of the major drawbacks of this technique, nevertheless, is that the effects of variability and uncertainty are not included in the results. Apparently, uncertainty and variability are two inseparable parts of any brake system. Uncertainty is mainly caused by friction, contact, wear and thermal effects while variability mostly stems from the manufacturing process, material properties and component geometries. Evaluating the effects of uncertainty and variability in the complex eigenvalue analysis improves the predictability of noise propensity and helps produce a more robust design. The biggest hurdle in the uncertainty analysis of brake systems is the computational cost and time. Most uncertainty analysis techniques rely on the results of many deterministic analyses. A full finite element model of a brake system typically consists of millions of degrees-of-freedom and many load cases. Running time of such models is so long that automotive industry is reluctant to do many deterministic analyses. This paper, instead, proposes an efficient method of uncertainty propagation via surrogate modelling. A surrogate model of a brake system is constructed in order to reproduce the outputs of the large-scale finite element model and overcome the issue of computational workloads. The probability distribution of the real part of an unstable mode can then be obtained by using the surrogate model with a massive saving of

  19. Surrogate based approaches to parameter inference in ocean models

    KAUST Repository

    Knio, Omar


    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.

  20. Fast and accurate prediction of numerical relativity waveforms from binary black hole mergers using surrogate models

    CERN Document Server

    Blackman, Jonathan; Galley, Chad R; Szilagyi, Bela; Scheel, Mark A; Tiglio, Manuel; Hemberger, Daniel A


    Simulating a binary black hole coalescence by solving Einstein's equations is computationally expensive, requiring days to months of supercomputing time. In this paper, we construct an accurate and fast-to-evaluate surrogate model for numerical relativity (NR) waveforms from non-spinning binary black hole coalescences with mass ratios from $1$ to $10$ and durations corresponding to about $15$ orbits before merger. Our surrogate, which is built using reduced order modeling techniques, is distinct from traditional modeling efforts. We find that the full multi-mode surrogate model agrees with waveforms generated by NR to within the numerical error of the NR code. In particular, we show that our modeling strategy produces surrogates which can correctly predict NR waveforms that were {\\em not} used for the surrogate's training. For all practical purposes, then, the surrogate waveform model is equivalent to the high-accuracy, large-scale simulation waveform but can be evaluated in a millisecond to a second dependin...

  1. Breast Cancer Survival Defined by the ER/PR/HER2 Subtypes and a Surrogate Classification according to Tumor Grade and Immunohistochemical Biomarkers

    Directory of Open Access Journals (Sweden)

    Carol A. Parise


    Full Text Available Introduction. ER, PR, and HER2 are routinely available in breast cancer specimens. The purpose of this study is to contrast breast cancer-specific survival for the eight ER/PR/HER2 subtypes with survival of an immunohistochemical surrogate for the molecular subtype based on the ER/PR/HER2 subtypes and tumor grade. Methods. We identified 123,780 cases of stages 1–3 primary female invasive breast cancer from California Cancer Registry. The surrogate classification was derived using ER/PR/HER2 and tumor grade. Kaplan-Meier survival analysis and Cox proportional hazards modeling were used to assess differences in survival and risk of mortality for the ER/PR/HER2 subtypes and surrogate classification within each stage. Results. The luminal B/HER2− surrogate classification had a higher risk of mortality than the luminal B/HER2+ for all stages of disease. There was no difference in risk of mortality between the ER+/PR+/HER2− and ER+/PR+/HER2+ in stage 3. With one exception in stage 3, the ER-negative subtypes all had an increased risk of mortality when compared with the ER-positive subtypes. Conclusions. Assessment of survival using ER/PR/HER2 illustrates the heterogeneity of HER2+ subtypes. The surrogate classification provides clear separation in survival and adjusted mortality but underestimates the wide variability within the subtypes that make up the classification.

  2. Surrogate Safety Analysis of Pedestrian-Vehicle Conflict at Intersections Using Unmanned Aerial Vehicle Videos

    Directory of Open Access Journals (Sweden)

    Peng Chen


    Full Text Available Conflict analysis using surrogate safety measures (SSMs has become an efficient approach to investigate safety issues. The state-of-the-art studies largely resort to video images taken from high buildings. However, it suffers from heavy labor work, high cost of maintenance, and even security restrictions. Data collection and processing remains a common challenge to traffic conflict analysis. Unmanned Aerial Systems (UASs or Unmanned Aerial Vehicles (UAVs, known for easy maneuvering, outstanding flexibility, and low costs, are considered to be a novel aerial sensor. By taking full advantage of the bird’s eye view offered by UAV, this study, as a pioneer work, applied UAV videos for surrogate safety analysis of pedestrian-vehicle conflicts at one urban intersection in Beijing, China. Aerial video sequences for a period of one hour were analyzed. The detection and tracking systems for vehicle and pedestrian trajectory data extraction were developed, respectively. Two SSMs, that is, Postencroachment Time (PET and Relative Time to Collision (RTTC, were employed to represent how spatially and temporally close the pedestrian-vehicle conflict is to a collision. The results of analysis showed a high exposure of pedestrians to traffic conflict both inside and outside the crosswalk and relatively risking behavior of right-turn vehicles around the corner. The findings demonstrate that UAV can support intersection safety analysis in an accurate and cost-effective way.

  3. Inactivation of Human Norovirus and Its Surrogates on Alfalfa Seeds by Aqueous Ozone. (United States)

    Wang, Qing; Markland, Sarah; Kniel, Kalmia E


    Alfalfa sprouts have been associated with numerous foodborne outbreaks. Previous studies investigated the effectiveness of aqueous ozone on bacterially contaminated seeds, yet little is known about the response of human norovirus (huNoV). This study assessed aqueous ozone for the disinfection of alfalfa seeds contaminated with huNoV and its surrogates. The inactivation of viruses without a food matrix was also investigated. Alfalfa seeds were inoculated with huNoV genogroup II, Tulane virus (TV), and murine norovirus (MNV); viruses alone or inoculated on seeds were treated in deionized water containing 6.25 ppm of aqueous ozone with agitation at 22°C for 0.5, 1, 5, 15, or 30 min. The data showed that aqueous ozone resulted in reductions of MNV and TV infectivity from 1.66 ± 1.11 to 5.60 ± 1.11 log PFU/g seeds; for all treatment times, significantly higher reductions were observed for MNV (P seeds; the reduction of TV inoculated in water was similar to that of huNoV, whereas MNV had significantly greater reductions in genomic copies (P seeds. The behavior of TV was similar to that of huNoV, which makes it a promising surrogate for these types of scenarios.

  4. An architecture for efficient gravitational wave parameter estimation with multimodal linear surrogate models (United States)

    O'Shaughnessy, Richard; Blackman, Jonathan; Field, Scott E.


    The recent direct observation of gravitational waves has further emphasized the desire for fast, low-cost, and accurate methods to infer the parameters of gravitational wave sources. Due to expense in waveform generation and data handling, the cost of evaluating the likelihood function limits the computational performance of these calculations. Building on recently developed surrogate models and a novel parameter estimation pipeline, we show how to quickly generate the likelihood function as an analytic, closed-form expression. Using a straightforward variant of a production-scale parameter estimation code, we demonstrate our method using surrogate models of effective-one-body and numerical relativity waveforms. Our study is the first time these models have been used for parameter estimation and one of the first ever parameter estimation calculations with multi-modal numerical relativity waveforms, which include all \\ell ≤slant 4 modes. Our grid-free method enables rapid parameter estimation for any waveform with a suitable reduced-order model. The methods described in this paper may also find use in other data analysis studies, such as vetting coincident events or the computation of the coalescing-compact-binary detection statistic.

  5. Spatial network surrogates for disentangling complex system structure from spatial embedding of nodes (United States)

    Wiedermann, Marc; Donges, Jonathan F.; Kurths, Jürgen; Donner, Reik V.


    Networks with nodes embedded in a metric space have gained increasing interest in recent years. The effects of spatial embedding on the networks' structural characteristics, however, are rarely taken into account when studying their macroscopic properties. Here, we propose a hierarchy of null models to generate random surrogates from a given spatially embedded network that can preserve certain global and local statistics associated with the nodes' embedding in a metric space. Comparing the original network's and the resulting surrogates' global characteristics allows one to quantify to what extent these characteristics are already predetermined by the spatial embedding of the nodes and links. We apply our framework to various real-world spatial networks and show that the proposed models capture macroscopic properties of the networks under study much better than standard random network models that do not account for the nodes' spatial embedding. Depending on the actual performance of the proposed null models, the networks are categorized into different classes. Since many real-world complex networks are in fact spatial networks, the proposed approach is relevant for disentangling the underlying complex system structure from spatial embedding of nodes in many fields, ranging from social systems over infrastructure and neurophysiology to climatology.

  6. The evaluation of new multi-material human soft tissue simulants for sports impact surrogates. (United States)

    Payne, Thomas; Mitchell, Séan; Bibb, Richard; Waters, Mark


    Previous sports impact reconstructions have highlighted the inadequacies in current measures to evaluate the effectiveness of personal protective equipment (PPE) and emphasised the need for improved impact surrogates that provide a more biofidelic representation of human impact response. The skin, muscle and subcutaneous adipose tissues were considered to constitute the structures primarily governing the mechanical behaviour of the human body segment. A preceding study by Payne et al. (in press) investigated the formulation and characterisation of muscle tissue simulants. The present study investigates the development of bespoke blends of additive cure polydimethysiloxane (PDMS) silicones to represent both skin and adipose tissues using the same processes previously reported. These simulants were characterised mechanically through a range of strain rates and a range of hyperelastic and viscoelastic constitutive models were evaluated to describe their behaviour. To explore the worth of the silicone simulants, finite element (FE) models were developed using anthropometric parameters representative of the human thigh segment, derived from the Visible Human Project. The multi-material silicone construction was validated experimentally and compared with both organic tissue data from literature and commonly used single material simulants: Dow Corning Silastic 3480 series silicones and ballistics gelatin when subject to a representative sports specific knee impact. Superior biofidelic performance is reported for the PDMS silicone formulations and surrogate predictions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Effect of proton and gamma irradiation on human lung carcinoma cells: Gene expression, cell cycle, cell death, epithelial–mesenchymal transition and cancer-stem cell trait as biological end points

    Energy Technology Data Exchange (ETDEWEB)

    Narang, Himanshi, E-mail: [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Kumar, Amit [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Bhat, Nagesh [Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Pandey, Badri N.; Ghosh, Anu [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085 (India)


    Highlights: • Biological effectiveness of proton and gamma irradiation is compared in A549 cells. • Proton irradiation is two times more cytotoxic than gamma irradiation. • It alters ten times more number of early genes, as observed by microarray study. • It does not enhance cell migration, invasion and adhesion, unlike gamma irradiation. • It was more effective in reducing the percentage of cancer stem cell like cells. - Abstract: Proton beam therapy is a cutting edge modality over conventional gamma radiotherapy because of its physical dose deposition advantage. However, not much is known about its biological effects vis-a-vis gamma irradiation. Here we investigated the effect of proton- and gamma- irradiation on cell cycle, death, epithelial-mesenchymal transition (EMT) and “stemness” in human non-small cell lung carcinoma cells (A549). Proton beam (3 MeV) was two times more cytotoxic than gamma radiation and induced higher and longer cell cycle arrest. At equivalent doses, numbers of genes responsive to proton irradiation were ten times higher than those responsive to gamma irradiation. At equitoxic doses, the proton-irradiated cells had reduced cell adhesion and migration ability as compared to the gamma-irradiated cells. It was also more effective in reducing population of Cancer Stem Cell (CSC) like cells as revealed by aldehyde dehydrogenase activity and surface phenotyping by CD44{sup +}, a CSC marker. These results can have significant implications for proton therapy in the context of suppression of molecular and cellular processes that are fundamental to tumor expansion.

  8. The representation of healthcare end users' perspectives by surrogates in healthcare decisions: a literature review. (United States)

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


    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

  9. Use of Meta-Analysis for the Validation of Surrogate Endpoints and Biomarkers in Cancer Trials


    Buyse, Marc


    This article discusses statistical approaches to the validation of surrogate biomarkers and endpoints. One approach that has been successfully used in oncology consists of estimating associations at two levels: the association between the surrogate and the clinical endpoint, called the individual-level association, and the association between the effects of treatment on the surrogate and the clinical endpoint, called the trial-level association. This approach requires data to be available fro...


    African Journals Online (AJOL)

    instruments, in various sizes of small, medium and large depending on the size of the elephant. The small horns measure approximately 35 - 40 centimeters long while the medium and large are 45 and 50 - 55 centimeters long respectively. The bigger orifice of the mmen tapers to a smaller end where the opening is corked.

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

    LENUS (Irish Health Repository)

    Beddy, Peter


    "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.

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

    KAUST Repository

    Selim, Hatem


    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.

  13. Bayesian calibration of the Community Land Model using surrogates

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  14. 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)


    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.

  15. Response to "comment on 'structural determinants of drug partitioning in surrogates of phosphatidylcholine bilayer strata'". (United States)

    Balaz, Stefan


    We used the solvatochromic correlation to explain the influence of characteristics of studied compounds on the partition coefficients (P) measured using n-hexadecane (C16) and the novel headgroup surrogate (diacetyl phosphatidylcholine, DAcPC), and compared them with those in other systems, including the C16/water (W) system. The comment analyzes why our correlation for the C16/W system has the standard deviation (SD) higher than that published previously. The main reason is that in our, much smaller, data set the measured P values are complemented by the P values predicted by a reliable, unrelated method. We believe that this approach is acceptable for the aforementioned comparison. We did not use just experimental values, as suggested in the comment, because the solvatochromic correlation, although exhibiting 35% reduction in the SD, was accompanied by a sign change of one of the regression coefficients. The recommended use of special solvatochromic solute characteristics for a few compounds and replacement of a predicted PC16/W value by the experimental value resulted in improved correlations. The observed differences between our correlation and those published in the comment and in a previous article do not affect our main conclusions regarding the solvation of solutes in the surrogates (DAcPC and C16) of intrabilayer strata.

  16. Influence of Chitosan Treatment on Surrogate Serum Markers of Cholesterol Metabolism in Obese Subjects. (United States)

    Lütjohann, Dieter; Marinova, Milka; Wolter, Karsten; Willinek, Winfried; Bitterlich, Norman; Coenen, Martin; Coch, Christoph; Stellaard, Frans


    Chitosan treatment results in significantly lower serum low density lipoprotein (LDL) cholesterol concentrations. To assess the working mechanisms of chitosan, we measured serum surrogate markers of cholesterol absorption (campesterol, sitosterol, cholestanol), synthesis (lathosterol, lanosterol, desmosterol), and degradation to bile acids (7α-hydroxy-cholesterol, 27-hydroxy-cholesterol), corrected for cholesterol concentration (R_sterols). Over 12 weeks, 116 obese subjects (Body Mass Index, BMI 31.7, range 28.1-38.9 kg/m²) were studied under chitosan (n = 61) and placebo treatments (n = 55). The participants were briefly educated regarding improvement of nutrition quality and energy expenditure. Daily chitosan intake was 3200 mg. Serum LDL cholesterol concentration decreased significantly more (p = 0.0252) under chitosan (-8.67 ± 18.18 mg/dL, 5.6%) than under placebo treatment (-1.00 ± 24.22 mg/dL, 0.9%). This reduction was not associated with the expected greater decreases in markers of cholesterol absorption under chitosan treatment. Also, increases in markers of cholesterol synthesis and bile acid synthesis under chitosan treatment were not any greater than under placebo treatment. In conclusion, a significant selective reduction of serum LDL cholesterol under chitosan treatment is neither associated with a reduction of serum surrogate markers of cholesterol absorption, nor with increases of markers for cholesterol and bile acid synthesis.

  17. An adaptive fuzzy prediction model for real time tumor tracking in radiotherapy via external surrogates. (United States)

    Esmaili Torshabi, Ahmad; Riboldi, Marco; Imani Fooladi, Abbas Ali; Modarres Mosalla, Seyed Mehdi; Baroni, Guido


    In the radiation treatment of moving targets with external surrogates, information on tumor position in real time can be extracted by using accurate correlation models. A fuzzy environment is proposed here to correlate input surrogate data with tumor motion estimates in real time. In this study, two different data clustering approaches were analyzed due to their substantial effects on the fuzzy modeler performance. Moreover, a comparative investigation was performed on two fuzzy-based and one neuro-fuzzy-based inference systems with respect to state-of-the-art models. Finally, due to the intrinsic interpatient variability in fuzzy models' performance, a model selectivity algorithm was proposed to select an adaptive fuzzy modeler on a case-by-case basis. The performance of multiple and adaptive fuzzy logic models were retrospectively tested in 20 patients treated with CyberKnife real-time tumor tracking. Final results show that activating adequate model selection of our fuzzy-based modeler can significantly reduce tumor tracking errors.

  18. Global design optimization for an axial-flow tandem pump based on surrogate method (United States)

    Li, D. H.; Zhao, Y.; Y Wang, G.


    Tandem pump, compared with multistage pump, goes without guide vanes between impellers. Better cavitation performance and significant reduction of the axial geometry scale is important for high-speed propulsion. This study presents a global design optimization method based on surrogated method for an axial-flow tandem pump to enhance trade-off performances: energy and cavitation performances. At the same time, interactions between impellers and impacts on the performances are analyzed. Fixed angle of blades in impellers and phase angle are performed as design variables. Efficiency and minimum average pressure coefficient (MAPC) on axial sectional surface in front impeller are the objective function, which can represent energy and cavitation performances well. Different surrogate models are constructed, and Global Sensitivity Analysis and Pareto Front method are used. The results show that, 1) Influence from phase angle on performances can be neglected compared with other two design variables, 2) Impact ratio of fixed angle of blades in two impellers on efficiency are the same as their designed loading distributions, which is 4:6, 3) The optimization results can enhance the trade-off performances well: efficiency is improved by 0.6%, and the MAPC is improved by 4.5%.

  19. Heavy metals determination in dry surrogate depositions, characterization of an urban and a natural site

    Energy Technology Data Exchange (ETDEWEB)

    Barilli, L.; Olivieri, P. [ENEA, Centro Ricerche Ezio Clementel, Bologna (Italy). Dipt. Ambiente; Morselli, L.; Cecchini, M. [Bologna Univ., Bologna (Italy). Dipt. di Chmica Industriale e dei Materiali; Amorolo, R.; Di Carlo, V.; Francacaviglia, R.; Gataleta, L. [Istituto Sperimentale per la Nutrizione delle Piante, Rome (Italy)


    The present work describes a methodological approach for the assessment of the amount of several toxic heavy metals (Cd, Cr, Cu, Ni, Pb, Zn) associated with atmospheric particulate matter in surrogate dry deposition. The aim of the study is the evaluation of heavy metal fluxes at ground level in surrogate dry deposition and the comparison between their estimated in two different stations over the period February-December 1997. A description is given of the complete procedure from sampling to data elaboration and results are reported with special attention to the comparative aspects of the two stations. [Italian] Nella presente nota viene descritto un approccio metodologico per la valutazione delle quantita' di alcuni metalli pesanti tossici (Cd, Cr, Cu, Ni, Pb, Zn) associati al particolato atmosferico, nella deposizione secca surrogata a livello del suolo allo scopo di valutare i flussi di metalli pesanti nella deposizione indicata e il confronto tra le due stazioni dal febbraio al dicembre 1997. Viene riportata la descrizione dell'intera procedura, dal campionamento all'elaborazione dei dati, e vengono riportati i risultati.

  20. Statistical surrogate model based sampling criterion for stochastic global optimization of problems with constraints

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Su Gil; Jang, Jun Yong; Kim, Ji Hoon; Lee, Tae Hee [Hanyang University, Seoul (Korea, Republic of); Lee, Min Uk [Romax Technology Ltd., Seoul (Korea, Republic of); Choi, Jong Su; Hong, Sup [Korea Research Institute of Ships and Ocean Engineering, Daejeon (Korea, Republic of)


    Sequential surrogate model-based global optimization algorithms, such as super-EGO, have been developed to increase the efficiency of commonly used global optimization technique as well as to ensure the accuracy of optimization. However, earlier studies have drawbacks because there are three phases in the optimization loop and empirical parameters. We propose a united sampling criterion to simplify the algorithm and to achieve the global optimum of problems with constraints without any empirical parameters. It is able to select the points located in a feasible region with high model uncertainty as well as the points along the boundary of constraint at the lowest objective value. The mean squared error determines which criterion is more dominant among the infill sampling criterion and boundary sampling criterion. Also, the method guarantees the accuracy of the surrogate model because the sample points are not located within extremely small regions like super-EGO. The performance of the proposed method, such as the solvability of a problem, convergence properties, and efficiency, are validated through nonlinear numerical examples with disconnected feasible regions.

  1. Influence of Chitosan Treatment on Surrogate Serum Markers of Cholesterol Metabolism in Obese Subjects

    Directory of Open Access Journals (Sweden)

    Dieter Lütjohann


    Full Text Available Chitosan treatment results in significantly lower serum low density lipoprotein (LDL cholesterol concentrations. To assess the working mechanisms of chitosan, we measured serum surrogate markers of cholesterol absorption (campesterol, sitosterol, cholestanol, synthesis (lathosterol, lanosterol, desmosterol, and degradation to bile acids (7α-hydroxy-cholesterol, 27-hydroxy-cholesterol, corrected for cholesterol concentration (R_sterols. Over 12 weeks, 116 obese subjects (Body Mass Index, BMI 31.7, range 28.1–38.9 kg/m2 were studied under chitosan (n = 61 and placebo treatments (n = 55. The participants were briefly educated regarding improvement of nutrition quality and energy expenditure. Daily chitosan intake was 3200 mg. Serum LDL cholesterol concentration decreased significantly more (p = 0.0252 under chitosan (−8.67 ± 18.18 mg/dL, 5.6% than under placebo treatment (−1.00 ± 24.22 mg/dL, 0.9%. This reduction was not associated with the expected greater decreases in markers of cholesterol absorption under chitosan treatment. Also, increases in markers of cholesterol synthesis and bile acid synthesis under chitosan treatment were not any greater than under placebo treatment. In conclusion, a significant selective reduction of serum LDL cholesterol under chitosan treatment is neither associated with a reduction of serum surrogate markers of cholesterol absorption, nor with increases of markers for cholesterol and bile acid synthesis.

  2. Leukocyte DNA as surrogate for the evaluation of imprinted Loci methylation in mammary tissue DNA.

    Directory of Open Access Journals (Sweden)

    Ludovic Barault

    Full Text Available There is growing interest in identifying surrogate tissues to identify epimutations in cancer patients since primary target tissues are often difficult to obtain. Methylation patterns at imprinted loci are established during gametogenesis and post fertilization and their alterations have been associated with elevated risk of cancer. Methylation at several imprinted differentially methylated regions (GRB10 ICR, H19 ICR, KvDMR, SNRPN/SNURF ICR, IGF2 DMR0, and IGF2 DMR2 were analyzed in DNA from leukocytes and mammary tissue (normal, benign diseases, or malignant tumors from 87 women with and without breast cancer (average age of cancer patients: 53; range: 31-77. Correlations between genomic variants and DNA methylation at the studied loci could not be assessed, making it impossible to exclude such effects. Methylation levels observed in leukocyte and mammary tissue DNA were close to the 50% expected for monoallellic methylation. While no correlation was observed between leukocyte and mammary tissue DNA methylation for most of the analyzed imprinted genes, Spearman's correlations were statistically significant for IGF2 DMR0 and IGF2 DMR2, although absolute methylation levels differed. Leukocyte DNA methylation levels of selected imprinted genes may therefore serve as surrogate markers of DNA methylation in cancer tissue.

  3. A surrogate modelling framework for the optimal deployment of check dams in erosion-prone areas (United States)

    Pal, Debasish; Tang, Honglei; Galelli, Stefano; Ran, Qihua


    Despite the great progresses made in the last decades, the control of soil erosion still remains a key challenge for land-use planning. The nonlinear interactions between hydrologic and morphologic processes and increase in extreme rainfall events predicted with climatic change create new areas of concern and make the problem unresolved. Spatially distributed models are a useful tool for modelling such processes and assessing the effect of large-scale engineering measures, but their computational requests prevent the resolution of problems requiring several model evaluations—sensitivity analysis or optimization, for instance. In this study, we tackle this problem by developing a surrogate modelling framework for the optimal deployment of check dams. The framework combines a spatially distributed model (WaTEM/SEDEM), a multi-objective evolutionary algorithm and artificial neural networks as surrogate model. We test the framework on Shejiagou catchment—a 14 km2 area located in the Loess Plateau, China—where we optimize check dam locations by maximizing the mass of sediments retained in the catchment and minimizing the total number of dams. Preliminary results show that the performance of the existing check dam system could be improved by changing the dam locations.

  4. Near Real-Time Probabilistic Damage Diagnosis Using Surrogate Modeling and High Performance Computing (United States)

    Warner, James E.; Zubair, Mohammad; Ranjan, Desh


    This work investigates novel approaches to probabilistic damage diagnosis that utilize surrogate modeling and high performance computing (HPC) to achieve substantial computational speedup. Motivated by Digital Twin, a structural health management (SHM) paradigm that integrates vehicle-specific characteristics with continual in-situ damage diagnosis and prognosis, the methods studied herein yield near real-time damage assessments that could enable monitoring of a vehicle's health while it is operating (i.e. online SHM). High-fidelity modeling and uncertainty quantification (UQ), both critical to Digital Twin, are incorporated using finite element method simulations and Bayesian inference, respectively. The crux of the proposed Bayesian diagnosis methods, however, is the reformulation of the numerical sampling algorithms (e.g. Markov chain Monte Carlo) used to generate the resulting probabilistic damage estimates. To this end, three distinct methods are demonstrated for rapid sampling that utilize surrogate modeling and exploit various degrees of parallelism for leveraging HPC. The accuracy and computational efficiency of the methods are compared on the problem of strain-based crack identification in thin plates. While each approach has inherent problem-specific strengths and weaknesses, all approaches are shown to provide accurate probabilistic damage diagnoses and several orders of magnitude computational speedup relative to a baseline Bayesian diagnosis implementation.

  5. Status of Health Concerns about Military Use of Depleted Uranium and Surrogate Metals in Armor-Penetrating Munitions (United States)


    occurred as a result of maternal toxicity, but defects such as cleft palate and certain Health Concerns about Military Use of DU and DU Surrogate Metals...exposures might extend as long as the 40-50 years remaining in the individuals’ lives. As these treatment questions were being addressed, a growing...arsenic) lead to large statistical errors in the results, so caution should be exercised in over-interpreting the results of such studies. In the

  6. A randomized controlled trial of eicosapentaenoic acid and/or aspirin for colorectal adenoma prevention during colonoscopic surveillance in the NHS Bowel Cancer Screening Programme (The seAFOod Polyp Prevention Trial): study protocol for a randomized controlled trial. (United States)

    Hull, Mark A; Sandell, Anna C; Montgomery, Alan A; Logan, Richard F A; Clifford, Gayle M; Rees, Colin J; Loadman, Paul M; Whitham, Diane


    The naturally-occurring omega (ω)-3 polyunsaturated fatty acid (PUFA) eicosapentaenoic acid (EPA) reduces colorectal adenoma (polyp) number and size in patients with familial adenomatous polyposis. The safety profile and potential cardiovascular benefits associated with ω-3 PUFAs make EPA a strong candidate for colorectal cancer (CRC) chemoprevention, alone or in combination with aspirin, which itself has recognized anti-CRC activity. Colorectal adenoma number and size are recognized as biomarkers of future CRC risk and are established as surrogate end-points in CRC chemoprevention trials. The seAFOod Polyp Prevention Trial is a randomized, double-blind, placebo-controlled, 2×2 factorial 'efficacy' study, which will determine whether EPA prevents colorectal adenomas, either alone or in combination with aspirin. Participants are 55-73 year-old patients, who have been identified as 'high risk' (detection of ≥5 small adenomas or ≥3 adenomas with at least one being ≥10 mm in diameter) at screening colonoscopy in the English Bowel Cancer Screening Programme (BCSP). Exclusion criteria include the need for more than one repeat endoscopy within the three-month BCSP screening period, malignant change in an adenoma, regular use of aspirin or non-aspirin non-steroidal anti-inflammatory drugs, regular use of fish oil supplements and concomitant warfarin or anti-platelet agent therapy. Patients are randomized to either EPA-free fatty acid 1 g twice daily or identical placebo AND aspirin 300 mg once daily or identical placebo, for approximately 12 months. The primary end-point is the number of participants with one or more adenomas detected at routine one-year BCSP surveillance colonoscopy. Secondary end-points include the number of adenomas (total and 'advanced') per patient, the location (left versus right colon) of colorectal adenomas and the number of participants re-classified as 'intermediate risk' for future surveillance. Exploratory end-points include levels of

  7. Evaluation of renal end points in nephrology trials

    NARCIS (Netherlands)

    Weldegiorgis, Misghina Tekeste


    Chronische nierschade is een volksgezondheidsprobleem en wordt in verband gebracht met een hoog risico op dialyse, niertransplantatie en cardiovasculaire ziekten. Tot op heden zijn weinig interventies bewezen effectief gebleken in het vertragen van de progressie van de daling in de nierfunctie.

  8. Toward meaningful end points of biodiversity in life cycle assessment. (United States)

    Curran, Michael; de Baan, Laura; De Schryver, An M; Van Zelm, Rosalie; Hellweg, Stefanie; Koellner, Thomas; Sonnemann, Guido; Huijbregts, Mark A J


    Halting current rates of biodiversity loss will be a defining challenge of the 21st century. To assess the effectiveness of strategies to achieve this goal, indicators and tools are required that monitor the driving forces of biodiversity loss, the changing state of biodiversity, and evaluate the effectiveness of policy responses. Here, we review the use of indicators and approaches to model biodiversity loss in Life Cycle Assessment (LCA), a methodology used to evaluate the cradle-to-grave environmental impacts of products. We find serious conceptual shortcomings in the way models are constructed, with scale considerations largely absent. Further, there is a disproportionate focus on indicators that reflect changes in compositional aspects of biodiversity, mainly changes in species richness. Functional and structural attributes of biodiversity are largely neglected. Taxonomic and geographic coverage remains problematic, with the majority of models restricted to one or a few taxonomic groups and geographic regions. On a more general level, three of the five drivers of biodiversity loss as identified by the Millennium Ecosystem Assessment are represented in current impact categories (habitat change, climate change and pollution), while two are missing (invasive species and overexploitation). However, methods across all drivers can be greatly improved. We discuss these issues and make recommendations for future research to better reflect biodiversity loss in LCA.

  9. Vertical Flume Testing of WIPP Surrogate Waste Materials (United States)

    Herrick, C. G.; Schuhen, M.; Kicker, D.


    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 ground surface. After emplacement of the waste, the repository will be sealed and decommissioned. The DOE demonstrates compliance with 40 CFR 194 by means of performance assessment (PA) calculations conducted by Sandia National Laboratories. WIPP PA calculations estimate the probability and consequences of radionuclide releases for a 10,000 year regulatory period. Human intrusion scenarios include cases in which a future borehole is drilled through the repository. Drilling mud flowing up the borehole will apply a hydrodynamic shear stress to the borehole wall which could result in erosion of the waste and radionuclides being carried up the borehole. WIPP PA uses the parameter TAUFAIL to represent the shear strength of the degraded waste. The hydrodynamic shear strength can only be measured experimentally by flume testing. Flume testing is typically performed horizontally, mimicking stream or ocean currents. However, in a WIPP intrusion event, the drill bit would penetrate the degraded waste and drilling mud would flow up the borehole in a predominantly vertical direction. In order to simulate this, a flume was designed and built so that the eroding fluid enters an enclosed vertical channel from the bottom and flows up past a specimen of surrogate waste material. The sample is pushed into the current by a piston attached to a step motor. A qualified data acquisition system controls and monitors the fluid's flow rate, temperature, pressure, and conductivity and the step motor's operation. The surrogate materials used correspond to a conservative estimate of degraded TRU waste at the end of the regulatory period. The recipes were previously developed by SNL based on anticipated future states of the waste

  10. Lessons from ECLIPSE

    DEFF Research Database (Denmark)

    Faner, Rosa; Tal-Singer, Ruth; Riley, John H


    The Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study was a large 3-year observational controlled multicentre international study aimed at defining clinically relevant subtypes of chronic obstructive pulmonary disease (COPD) and identifying novel biomar...

  11. Applicability of UV resistant Bacillus pumilus endospores as a human adenovirus surrogate for evaluating the effectiveness of virus inactivation in low-pressure UV treatment systems (United States)

    Recent studies have demonstrated the potential to use Bacillus pumilus endospores as a surrogate of human adenovirus (HAdV) in UV disinfection studies. The use of endospores has been limited by observations of batch-to-batch variation in UV sensitivity. This study reports on a pr...

  12. Metrics for Developing an Endorsed Set of Radiographic Threat Surrogates for JINII/CAARS

    Energy Technology Data Exchange (ETDEWEB)

    Wurtz, R; Walston, S; Dietrich, D; Martz, H


    CAARS (Cargo Advanced Automated Radiography System) is developing x-ray dual energy and x-ray backscatter methods to automatically detect materials that are greater than Z=72 (hafnium). This works well for simple geometry materials, where most of the radiographic path is through one material. However, this is usually not the case. Instead, the radiographic path includes many materials of different lengths. Single energy can be used to compute {mu}y{sub l} which is related to areal density (mass per unit area) while dual energy yields more information. This report describes a set of metrics suitable and sufficient for characterizing the appearance of assemblies as detected by x-ray radiographic imaging systems, such as those being tested by Joint Integrated Non-Intrusive Inspection (JINII) or developed under CAARS. These metrics will be simulated both for threat assemblies and surrogate threat assemblies (such as are found in Roney et al. 2007) using geometrical and compositional information of the assemblies. The imaging systems are intended to distinguish assemblies containing high-Z material from those containing low-Z material, regardless of thickness, density, or compounds and mixtures. The systems in question operate on the principle of comparing images obtained by using two different x-ray end-point energies--so-called 'dual energy' imaging systems. At the direction of the DHS JINII sponsor, this report does not cover metrics that implement scattering, in the form of either forward-scattered radiation or high-Z detection systems operating on the principle of backscatter detection. Such methods and effects will be covered in a later report. The metrics described here are to be used to compare assemblies and not x-ray radiography systems. We intend to use these metrics to determine whether two assemblies do or do not look the same. We are tasked to develop a set of assemblies whose appearance using this class of detection systems is indistinguishable

  13. Conservative strategy-based ensemble surrogate model for optimal groundwater remediation design at DNAPLs-contaminated sites (United States)

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


    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.

  14. Fluorescent microspheres as surrogates in evaluating the efficacy of riverbank filtration for removing Cryptosporidium parvum oocysts and other pathogens (United States)

    Harvey, Ronald W.; Metge, David W.; Sheets, Rodney A.; Jasperse, Jay


    A major benefit of riverbank filtration (RBF) is that it provides a relatively effective means for pathogen removal. There is a need to conduct more injection-and-recovery transport studies at operating RBF sites in order to properly assess the combined effects of the site heterogeneities and ambient physicochemical conditions, which are difficult to replicate in the lab. For field transport studies involving pathogens, there is considerable interest in using fluorescent carboxylated microspheres (FCM) as surrogates, because they are chemically inert, negatively charged, easy to detect, available in a wide variety of sizes, and have been found to be nonhazardous in tracer applications. Although there have been a number of in-situ studies comparing the subsurface transport behaviors of FCM to those of bacteria and viruses, much less is known about their suitability for investigations of protozoa. Oocysts of the intestinal protozoan pathogen Cryptosporidium spp are of particular concern for many RBF operations because of their ubiquity and persistence in rivers and high resistance to chlorine disinfection. Although microspheres often have proven to be less-than-ideal analogs for capturing the abiotic transport behavior of viruses and bacteria, there is encouraging recent evidence regarding use of FCM as surrogates for C. parvum oocysts. This chapter discusses the potential of fluorescent microspheres as safe and easy-to-detect surrogates for evaluating the efficacy of RBF operations for removing pathogens, particularly Cryptosporidium, from source waters at different points along the flow path.

  15. Storytelling in the Early Bereavement Period to Reduce Emotional Distress Among Surrogates Involved in a Decision to Limit Life Support in the ICU: A Pilot Feasibility Trial. (United States)

    Barnato, Amber E; Schenker, Yael; Tiver, Greer; Dew, Mary Amanda; Arnold, Robert M; Nunez, Eduardo R; Reynolds, Charles F


    Surrogate decision makers involved in decisions to limit life support for an incapacitated patient in the ICU have high rates of adverse emotional health outcomes distinct from normal processes of grief and bereavement. Narrative self-disclosure (storytelling) reduces emotional distress after other traumatic experiences. We sought to assess the feasibility, acceptability, and tolerability of storytelling among bereaved surrogates involved in a decision to limit life support in the ICU. Pilot single-blind trial. Five ICUs across three hospitals within a single health system between June 2013 and November 2014. Bereaved surrogates of ICU patients. Storytelling and control conditions involved printed bereavement materials and follow-up assessments. Storytelling involved a single 1- to 2-hour home or telephone visit by a trained interventionist who elicited the surrogate's story. The primary outcomes were feasibility (rates of enrollment, intervention receipt, 3- and 6-mo follow-up), acceptability (closed and open-ended end-of-study feedback at 6 mo), and tolerability (acute mental health services referral). Of 53 eligible surrogates, 32 (60%) consented to treatment allocation. Surrogates' mean age was 55.5 (SD, 11.8), and they were making decisions for their parent (47%), spouse (28%), sibling (13%), child (3%), or other relation (8%). We allocated 14 to control and 18 to storytelling, 17 of 18 (94%) received storytelling, 14 of 14 (100%) and 13 of 14 (94%) control subjects and 16 of 18 (89%) and 17 of 18 (94%) storytelling subjects completed their 3- and 6-month telephone assessments. At 6 months, nine of 13 control participants (69%) and 16 of 17 storytelling subjects (94%) reported feeling "better" or "much better," and none felt "much worse." One control subject (8%) and one storytelling subject (6%) said that the study was burdensome, and one control subject (8%) wished they had not participated. No subjects required acute mental health services referral. A

  16. Design optimization of stent and its dilatation balloon using kriging surrogate model. (United States)

    Li, Hongxia; Liu, Tao; Wang, Minjie; Zhao, Danyang; Qiao, Aike; Wang, Xue; Gu, Junfeng; Li, Zheng; Zhu, Bao


    Although stents have great success of treating cardiovascular disease, it actually undermined by the in-stent restenosis and their long-term fatigue failure. The geometry of stent affects its service performance and ultimately affects its fatigue life. Besides, improper length of balloon leads to transient mechanical injury to the vessel wall and in-stent restenosis. Conventional optimization method of stent and its dilatation balloon by comparing several designs and choosing the best one as the optimal design cannot find the global optimal design in the design space. In this study, an adaptive optimization method based on Kriging surrogate model was proposed to optimize the structure of stent and the length of stent dilatation balloon so as to prolong stent service life and improve the performance of stent. A finite element simulation based optimization method combing with Kriging surrogate model is proposed to optimize geometries of stent and length of stent dilatation balloon step by step. Kriging surrogate model coupled with design of experiment method is employed to construct the approximate functional relationship between optimization objectives and design variables. Modified rectangular grid is used to select initial training samples in the design space. Expected improvement function is used to balance the local and global searches to find the global optimal result. Finite element method is adopted to simulate the free expansion of balloon-expandable stent and the expansion of stent in stenotic artery. The well-known Goodman diagram was used for the fatigue life prediction of stent, while dogboning effect was used for stent expansion performance measurement. As the real design cases, diamond-shaped stent and sv-shaped stent were studied to demonstrate how the proposed method can be harnessed to design and refine stent fatigue life and expansion performance computationally. The fatigue life and expansion performance of both the diamond-shaped stent and sv

  17. Fulfilling the promise of personalized medicine? Systematic review and field synopsis of pharmacogenetic studies.

    Directory of Open Access Journals (Sweden)

    Michael V Holmes

    Full Text Available BACKGROUND: Studies of the genetic basis of drug response could help clarify mechanisms of drug action/metabolism, and facilitate development of genotype-based predictive tests of efficacy or toxicity (pharmacogenetics. OBJECTIVES: We conducted a systematic review and field synopsis of pharmacogenetic studies to quantify the scope and quality of available evidence in this field in order to inform future research. DATA SOURCES: Original research articles were identified in Medline, reference lists from 24 meta-analyses/systematic reviews/review articles and U.S. Food and Drug Administration website of approved pharmacogenetic tests. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTION CRITERIA: We included any study in which either intended or adverse response to drug therapy was examined in relation to genetic variation in the germline or cancer cells in humans. STUDY APPRAISAL AND SYNTHESIS METHODS: Study characteristics and data reported in abstracts were recorded. We further analysed full text from a random 10% subset of articles spanning the different subclasses of study. RESULTS: From 102,264 Medline hits and 1,641 articles from other sources, we identified 1,668 primary research articles (1987 to 2007, inclusive. A high proportion of remaining articles were reviews/commentaries (ratio of reviews to primary research approximately 25 ratio 1. The majority of studies (81.8% were set in Europe and North America focussing on cancer, cardiovascular disease and neurology/psychiatry. There was predominantly a candidate gene approach using common alleles, which despite small sample sizes (median 93 [IQR 40-222] with no trend to an increase over time, generated a high proportion (74.5% of nominally significant (por=4 studies, only 31 meta-analyses were identified. The majority (69.4% of end-points were continuous and likely surrogate rather than hard (binary clinical end-points. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: The high

  18. Approaches toward Identification of Surrogates To Validate Antimicrobial Washes as Preventive Controls for Fresh-Cut Leafy Greens. (United States)

    Shazer, A; Stewart, D; Deng, K; Tortorello, M


    In fresh-cut produce production, antimicrobials may be used during washing to control the risk of cross-contamination by microbial hazards. Surrogate microorganisms have long been used to validate processes, but none have been identified for validating the efficacy of antimicrobial washing of fresh-cut produce. The objective of this study was to develop procedures by which surrogates may be identified for use in validating the control of cross-contamination for fresh-cut lettuce operations. Four microbial characteristics, which may be important factors in cross-contamination events, were quantitatively evaluated in potential surrogate microorganisms for comparison to a reasonably foreseeable hazard, Escherichia coli O157:H7: sensitivity to chlorine in solution, sensitivity to chlorine on lettuce leaf surfaces, shedding from contaminated lettuce leaves into the water during washing, and cross-contamination from inoculated to uninoculated lettuce leaves during chorine washing. A procedure of practical quantitative experiments for comparing the characteristics reduced the original pool of 80 potential strains, which consisted of lactic acid bacteria, probiotics, and isolates obtained from lettuce enrichment cultures, to five strains: Lactobacillus plantarum, Pediococcus pentosaceus, probiotic 22C, and two lettuce enrichment isolates. These strains may be evaluated in additional studies involving comparisons to other reasonably foreseeable hazards and including other potential process variables that should be understood and controlled to prevent cross-contamination in fresh-cut lettuce operations.

  19. Quantitative prediction of respiratory tidal volume based on the external torso volume change: a potential volumetric surrogate

    Energy Technology Data Exchange (ETDEWEB)

    Li Guang; Arora, Naveen C; Xie Huchen; Ning, Holly; Citrin, Deborah; Kaushal, Aradhana; Zach, Leor; Camphausen, Kevin; Miller, Robert W [Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Lu Wei; Low, Daniel [Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO 63110 (United States)], E-mail:


    An external respiratory surrogate that not only highly correlates with but also quantitatively predicts internal tidal volume should be useful in guiding four-dimensional computed tomography (4DCT), as well as 4D radiation therapy (4DRT). A volumetric surrogate should have advantages over external fiducial point(s) for monitoring respiration-induced motion of the torso, which deforms in synchronization with a patient-specific breathing pattern. This study establishes a linear relationship between the external torso volume change (TVC) and lung air volume change (AVC) by validating a proposed volume conservation hypothesis (TVC = AVC) throughout the respiratory cycle using 4DCT and spirometry. Fourteen patients' torso 4DCT images and corresponding spirometric tidal volumes were acquired to examine this hypothesis. The 4DCT images were acquired using dual surrogates in cine mode and amplitude-based binning in 12 respiratory stages, minimizing residual motion artifacts. Torso and lung volumes were calculated using threshold-based segmentation algorithms and volume changes were calculated relative to the full-exhalation stage. The TVC and AVC, as functions of respiratory stages, were compared, showing a high correlation (r = 0.992 {+-} 0.005, p < 0.0001) as well as a linear relationship (slope = 1.027 {+-} 0.061, R{sup 2} = 0.980) without phase shift. The AVC was also compared to the spirometric tidal volumes, showing a similar linearity (slope = 1.030 {+-} 0.092, R{sup 2} = 0.947). In contrast, the thoracic and abdominal heights measured from 4DCT showed relatively low correlation (0.28 {+-} 0.44 and 0.82 {+-} 0.30, respectively) and location-dependent phase shifts. This novel approach establishes the foundation for developing an external volumetric respiratory surrogate.

  20. Is transcutaneous electrical stimulation a realistic surrogate for genuine surgical stimulation during spinal anesthesia for cesarean delivery? (United States)

    Zaidi, Asif S H; Russell, Ian F


    Several studies have investigated differential block during spinal anesthesia using transcutaneous electrical stimulation (TES) applied to patient's skin. These TES stimuli are claimed to be a surrogate for surgical stimulation, but TES has never been shown to be a realistic surrogate for a surgical stimulus during regional anesthesia. We investigated whether patients could appreciate nonpainful TES at the same time as they were undergoing painless cesarean delivery surgery. We applied a nonpainful TES (10 mA, 50 Hz, 1-s duration) to the skin, at 5 different dermatomal levels, in 20 women undergoing elective cesarean delivery during spinal anesthesia. During surgery, all the women were totally pain free but we noted that the level of block to TES was variable: in 30% of women, TES could be felt at the T10 dermatome or more caudally. The first appreciation of touch was consistently at T6 or above. The fact that a nonpainful TES stimulus could be appreciated within the dermatomes directly involved in transmitting surgical stimuli, at a time when the patients were totally pain free, suggests that TES at the tested levels is of little value as a surrogate surgical stimulus.

  1. Cutthroat trout virus as a surrogate in vitro infection model for testing inhibitors of hepatitis E virus replication (United States)

    Debing, Yannick; Winton, James; Neyts, Johan; Dallmeier, Kai


    Hepatitis E virus (HEV) is one of the most important causes of acute hepatitis worldwide. Although most infections are self-limiting, mortality is particularly high in pregnant women. Chronic infections can occur in transplant and other immune-compromised patients. Successful treatment of chronic hepatitis E has been reported with ribavirin and pegylated interferon-alpha, however severe side effects were observed. We employed the cutthroat trout virus (CTV), a non-pathogenic fish virus with remarkable similarities to HEV, as a potential surrogate for HEV and established an antiviral assay against this virus using the Chinook salmon embryo (CHSE-214) cell line. Ribavirin and the respective trout interferon were found to efficiently inhibit CTV replication. Other known broad-spectrum inhibitors of RNA virus replication such as the nucleoside analog 2′-C-methylcytidine resulted only in a moderate antiviral activity. In its natural fish host, CTV levels largely fluctuate during the reproductive cycle with the virus detected mainly during spawning. We wondered whether this aspect of CTV infection may serve as a surrogate model for the peculiar pathogenesis of HEV in pregnant women. To that end the effect of three sex steroids on in vitro CTV replication was evaluated. Whereas progesterone resulted in marked inhibition of virus replication, testosterone and 17β-estradiol stimulated viral growth. Our data thus indicate that CTV may serve as a surrogate model for HEV, both for antiviral experiments and studies on the replication biology of the Hepeviridae.

  2. Development of a surrogate model for analysis of ex-vessel steam explosion in Nordic type BWRs

    Energy Technology Data Exchange (ETDEWEB)

    Grishchenko, Dmitry, E-mail:; Basso, Simone, E-mail:; Kudinov, Pavel, E-mail:


    Highlights: • Severe accident. • Steam explosion. • Surrogate model. • Sensitivity study. • Artificial neural networks. - Abstract: Severe accident mitigation strategy adopted in Nordic type Boiling Water Reactors (BWRs) employs ex-vessel core melt cooling in a deep pool of water below reactor vessel. Energetic fuel–coolant interaction (steam explosion) can occur during molten core release into water. Dynamic loads can threaten containment integrity increasing the risk of fission products release to the environment. Comprehensive uncertainty analysis is necessary in order to assess the risks. Computational costs of the existing fuel–coolant interaction (FCI) codes is often prohibitive for addressing the uncertainties, including the effect of stochastic triggering time. This paper discusses development of a computationally efficient surrogate model (SM) for prediction of statistical characteristics of steam explosion impulses in Nordic BWRs. The TEXAS-V code was used as the Full Model (FM) for the calculation of explosion impulses. The surrogate model was developed using artificial neural networks (ANNs) and the database of FM solutions. Statistical analysis was employed in order to treat chaotic response of steam explosion impulse to variations in the triggering time. Details of the FM and SM implementation and their verification are discussed in the paper.

  3. The effectiveness of surrogate taxa to conserve freshwater biodiversity (United States)

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


    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 (conservation priorities based on a single freshwater aquatic group would not protect all species in the other aquatic groups.

  4. High-Temperature Oxidation of Plutonium Surrogate Metals and Alloys

    Energy Technology Data Exchange (ETDEWEB)

    Sparks, Joshua C. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Krantz, Kelsie E. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Christian, Jonathan H. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Washington, II, Aaron L. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)


    The Plutonium Management and Disposition Agreement (PMDA) is a nuclear non-proliferation agreement designed to remove 34 tons of weapons-grade plutonium from Russia and the United States. While several removal options have been proposed since the agreement was first signed in 2000, processing the weapons-grade plutonium to mixed-oxide (MOX) fuel has remained the leading candidate for achieving the goals of the PMDA. However, the MOX program has received its share of criticisms, which causes its future to be uncertain. One alternative pathway for plutonium disposition would involve oxidizing the metal followed by impurity down blending and burial in the Waste Isolation Pilot Plant (WIPP) in Carlsbad, New Mexico. This pathway was investigated by use of a hybrid microwave and a muffle furnace with Fe and Al as surrogate materials. Oxidation occurred similarly in the microwave and muffle furnace; however, the microwave process time was significantly faster.

  5. Reaction of the captive infant baboon to a surrogate mother | Stoltz ...

    African Journals Online (AJOL)

    Baboon infants were captured with their mothers in the Loskopdam area. The infants were separated from their mothers and raised in a laboratory. Each infant was placed with a surrogate mother. The infants accepted their surrogate mothers immediately. The very young infants spent most of their time with the mother where ...

  6. 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...

  7. Production of cloned NIBS (Nippon Institute for Biological Science) and α-1, 3-galactosyltransferase knockout MGH miniature pigs by somatic cell nuclear transfer using the NIBS breed as surrogates. (United States)

    Shimatsu, Yoshiki; Yamada, Kazuhiko; Horii, Wataru; Hirakata, Atsushi; Sakamoto, Yuji; Waki, Shiori; Sano, Junichi; Saitoh, Toshiki; Sahara, Hisashi; Shimizu, Akira; Yazawa, Hajime; Sachs, David H; Nunoya, Tetsuo


    Nuclear transfer (NT) technologies offer a means for producing the genetically modified pigs necessary to develop swine models for mechanistic studies of disease processes as well as to serve as organ donors for xenotransplantation. Most previous studies have used commercial pigs as surrogates. In this study, we established a cloning technique for miniature pigs by somatic cell nuclear transfer (SCNT) using Nippon Institute for Biological Science (NIBS) miniature pigs as surrogates. Moreover, utilizing this technique, we have successfully produced an α-1, 3-galactosyltransferase knockout (GalT-KO) miniature swine. Fibroblasts procured from a NIBS miniature pig fetus were injected into 1312 enucleated oocytes. The cloned embryos were transferred to 11 surrogates of which five successfully delivered 13 cloned offspring; the production efficiency was 1.0% (13/1312). In a second experiment, lung fibroblasts obtained from neonatal GalT-KO MGH miniature swine were used as donor cells and 1953 cloned embryos were transferred to 12 surrogates. Six cloned offspring were born from five surrogates, a production efficiency of 0.3% (6/1953). These results demonstrate successful establishment of a miniature pig cloning technique by SCNT using NIBS miniature pigs as surrogates. To our knowledge, this is the first demonstration of successful production of GalT-KO miniature swine using miniature swine surrogates. This technique could help to ensure a stable supply of the cloned pigs through the use of miniature pig surrogates and could expand production in countries with limited space or in facilities with special regulations such as specific pathogen-free or good laboratory practice. © 2013 John Wiley & Sons A/S.

  8. Production of cloned NIBS (Nippon Institute for Biological Science) and α-1, 3-galactosyltransferase knockout MGH miniature pigs by somatic cell nuclear transfer using the NIBS breed as surrogates (United States)

    Shimatsu, Yoshiki; Yamada, Kazuhiko; Horii, Wataru; Hirakata, Atsushi; Sakamoto, Yuji; Waki, Shiori; Sano, Junichi; Saitoh, Toshiki; Sahara, Hisashi; Shimizu, Akira; Yazawa, Hajime; Sachs, David H.; Nunoya, Tetsuo


    Background Nuclear transfer (NT) technologies offer a means for producing the genetically modified pigs necessary to develop swine models for mechanistic studies of disease processes as well as to serve as organ donors for xenotransplantation. Most previous studies have used commercial pigs as surrogates. Method and Results In this study, we established a cloning technique for miniature pigs by somatic cell nuclear transfer (SCNT) using Nippon Institute for Biological Science (NIBS) miniature pigs as surrogates. Moreover, utilizing this technique, we have successfully produced an α-1, 3-galactosyltransferase knockout (GalT-KO) miniature swine. Fibroblasts procured from a NIBS miniature pig fetus were injected into 1312 enucleated oocytes. The cloned embryos were transferred to 11 surrogates of which five successfully delivered 13 cloned offspring; the production efficiency was 1.0% (13/1312). In a second experiment, lung fibroblasts obtained from neonatal GalT-KO MGH miniature swine were used as donor cells and 1953 cloned embryos were transferred to 12 surrogates. Six cloned offspring were born from five surrogates, a production efficiency of 0.3% (6/1953). Conclusions These results demonstrate successful establishment of a miniature pig cloning technique by SCNT using NIBS miniature pigs as surrogates. To our knowledge, this is the first demonstration of successful production of GalT-KO miniature swine using miniature swine surrogates. This technique could help to ensure a stable supply of the cloned pigs through the use of miniature pig surrogates and could expand production in countries with limited space or in facilities with special regulations such as specific pathogen-free or good laboratory practice. PMID:23581451

  9. Surrogate-assisted feature extraction for high-throughput phenotyping. (United States)

    Yu, Sheng; Chakrabortty, Abhishek; Liao, Katherine P; Cai, Tianrun; Ananthakrishnan, Ashwin N; Gainer, Vivian S; Churchill, Susanne E; Szolovits, Peter; Murphy, Shawn N; Kohane, Isaac S; Cai, Tianxi


    Phenotyping algorithms are capable of accurately identifying patients with specific phenotypes from within electronic medical records systems. However, developing phenotyping algorithms in a scalable way remains a challenge due to the extensive human resources required. This paper introduces a high-throughput unsupervised feature selection method, which improves the robustness and scalability of electronic medical record phenotyping without compromising its accuracy. The proposed Surrogate-Assisted Feature Extraction (SAFE) method selects candidate features from a pool of comprehensive medical concepts found in publicly available knowledge sources. The target phenotype's International Classification of Diseases, Ninth Revision and natural language processing counts, acting as noisy surrogates to the gold-standard labels, are used to create silver-standard labels. Candidate features highly predictive of the silver-standard labels are selected as the final features. Algorithms were trained to identify patients with coronary artery disease, rheumatoid arthritis, Crohn's disease, and ulcerative colitis using various numbers of labels to compare the performance of features selected by SAFE, a previously published automated feature extraction for phenotyping procedure, and domain experts. The out-of-sample area under the receiver operating characteristic curve and F -score from SAFE algorithms were remarkably higher than those from the other two, especially at small label sizes. SAFE advances high-throughput phenotyping methods by automatically selecting a succinct set of informative features for algorithm training, which in turn reduces overfitting and the needed number of gold-standard labels. SAFE also potentially identifies important features missed by automated feature extraction for phenotyping or experts.

  10. Technological advances in suspended-sediment surrogate monitoring (United States)

    Gray, John R.; Gartner, Jeffrey W.


    Surrogate technologies to continuously monitor suspended sediment show promise toward supplanting traditional data collection methods requiring routine collection and analysis of water samples. Commercially available instruments operating on bulk optic (turbidity), laser optic, pressure difference, and acoustic backscatter principles are evaluated based on cost, reliability, robustness, accuracy, sample volume, susceptibility to biological fouling, and suitable range of mass concentration and particle size distribution. In situ turbidimeters are widely used. They provide reliable data where the point measurements can be reliably correlated to the river's mean cross section concentration value, effects of biological fouling can be minimized, and concentrations remain below the sensor's upper measurement limit. In situ laser diffraction instruments have similar limitations and can cost 6 times the approximate $5000 purchase price of a turbidimeter. However, laser diffraction instruments provide volumetric-concentration data in 32 size classes. Pressure differential instruments measure mass density in a water column, thus integrating substantially more streamflow than a point measurement. They are designed for monitoring medium-to-large concentrations, are generally unaffected by biological fouling, and cost about the same as a turbidimeter. However, their performance has been marginal in field applications. Acoustic Doppler profilers use acoustic backscatter to measure suspended sediment concentrations in orders of magnitude more streamflow than do instruments that rely on point measurements. The technology is relatively robust and