Gating treatment delivery QA based on a surrogate motion analysis

International Nuclear Information System (INIS)

Chojnowski, J.; Simpson, E.

2011-01-01

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

Magnetic Resonance Imaging Features as Surrogate Markers of X-Linked Hypophosphatemic Rickets Activity.

Science.gov (United States)

Lempicki, Marta; Rothenbuhler, Anya; Merzoug, Valérie; Franchi-Abella, Stéphanie; Chaussain, Catherine; Adamsbaum, Catherine; Linglart, Agnès

2017-01-01

X-linked hypophosphatemic rickets (XLH) is the most common form of inheritable rickets. Rickets treatment is monitored by assessing alkaline phosphatase (ALP) levels, clinical features, and radiographs. Our objectives were to describe the magnetic resonance imaging (MRI) features of XLH and to assess correlations with disease activity. Twenty-seven XLH patients (median age 9.2 years) were included in this prospective single-center observational study. XLH activity was assessed using height, leg bowing, dental abscess history, and serum ALP levels. We looked for correlations between MRI features and markers of disease activity. On MRI, the median maximum width of the physis was 5.6 mm (range 4.8-7.8; normal 1.5 mm in all of the patients. The appearance of the zone of provisional calcification was abnormal on 21 MRI images (78%), Harris lines were present on 24 (89%), and bone marrow signal abnormalities were present on 16 (59%). ALP levels correlated with the maximum physeal widening and with the transverse extent of the widening. MRI of the knee provides precise rickets patterns that are correlated with ALP, an established biochemical marker of the disease, avoiding X-ray exposure and providing surrogate quantitative markers of disease activity. © 2017 S. Karger AG, Basel.

TH-B-204-02: Application of Implanted Markers in Proton Therapy

International Nuclear Information System (INIS)

Park, S.

2016-01-01

Implanted markers as target surrogates have been widely used for treatment verification, as they provide safe and reliable monitoring of the inter- and intra-fractional target motion. The rapid advancement of technology requires a critical review and recommendation for the usage of implanted surrogates in current field. The symposium, also reporting an update of AAPM TG 199 - Implanted Target Surrogates for Radiation Treatment Verification, will be focusing on all clinical aspects of using the implanted target surrogates for treatment verification and related issues. A wide variety of markers available in the market will be first reviewed, including radiopaque markers, MRI compatible makers, non-migrating coils, surgical clips and electromagnetic transponders etc. The pros and cons of each kind will be discussed. The clinical applications of implanted surrogates will be presented based on different anatomical sites. For the lung, we will discuss gated treatments and 2D or 3D real-time fiducial tracking techniques. For the prostate, we will be focusing on 2D-3D, 3D-3D matching and electromagnetic transponder based localization techniques. For the liver, we will review techniques when patients are under gating, shallow or free breathing condition. We will review techniques when treating challenging breast cancer as deformation may occur. Finally, we will summarize potential issues related to the usage of implanted target surrogates with TG 199 recommendations. A review of fiducial migration and fiducial derived target rotation in different disease sites will be provided. The issue of target deformation, especially near the diaphragm, and related suggestions will be also presented and discussed. Learning Objectives: Knowledge of a wide variety of markers Knowledge of their application for different disease sites Understand of issues related to these applications Z. Wang: Research funding support from Brainlab AG Q. Xu: Consultant for Accuray; Q. Xu, I am a consultant

TH-B-204-02: Application of Implanted Markers in Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

Park, S. [McLaren-Flint, Flint, MI (United States)

2016-06-15

Implanted markers as target surrogates have been widely used for treatment verification, as they provide safe and reliable monitoring of the inter- and intra-fractional target motion. The rapid advancement of technology requires a critical review and recommendation for the usage of implanted surrogates in current field. The symposium, also reporting an update of AAPM TG 199 - Implanted Target Surrogates for Radiation Treatment Verification, will be focusing on all clinical aspects of using the implanted target surrogates for treatment verification and related issues. A wide variety of markers available in the market will be first reviewed, including radiopaque markers, MRI compatible makers, non-migrating coils, surgical clips and electromagnetic transponders etc. The pros and cons of each kind will be discussed. The clinical applications of implanted surrogates will be presented based on different anatomical sites. For the lung, we will discuss gated treatments and 2D or 3D real-time fiducial tracking techniques. For the prostate, we will be focusing on 2D-3D, 3D-3D matching and electromagnetic transponder based localization techniques. For the liver, we will review techniques when patients are under gating, shallow or free breathing condition. We will review techniques when treating challenging breast cancer as deformation may occur. Finally, we will summarize potential issues related to the usage of implanted target surrogates with TG 199 recommendations. A review of fiducial migration and fiducial derived target rotation in different disease sites will be provided. The issue of target deformation, especially near the diaphragm, and related suggestions will be also presented and discussed. Learning Objectives: Knowledge of a wide variety of markers Knowledge of their application for different disease sites Understand of issues related to these applications Z. Wang: Research funding support from Brainlab AG Q. Xu: Consultant for Accuray; Q. Xu, I am a consultant

Limited Role for Biliary Stent as Surrogate Fiducial Marker in Pancreatic Cancer: Stent and Intratumoral Fiducials Compared

Energy Technology Data Exchange (ETDEWEB)

Horst, Astrid van der, E-mail: a.vanderhorst@amc.uva.nl [Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Lens, Eelco; Wognum, Silvia; Jong, Rianne de [Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Hooft, Jeanin E. van [Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Tienhoven, Geertjan van; Bel, Arjan [Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands)

2014-07-01

Purpose: Because of low soft-tissue contrast of cone beam computed tomography (CBCT), fiducial markers are often used for radiation therapy patient setup verification. For pancreatic cancer patients, biliary stents have been suggested as surrogate fiducials. Using intratumoral fiducials as standard for tumor position, this study aims to quantify the suitability of biliary stents for measuring interfractional and respiratory-induced position variations of pancreatic tumors. Methods and Materials: Eleven pancreatic cancer patients with intratumoral fiducials and a biliary stent were included in this study. Daily CBCT scans (243 in total) were registered with a reference CT scan, based on bony anatomy, on fiducial markers, and on the biliary stent, respectively. We analyzed the differences in tumor position (ie, markers center-of-mass position) among these 3 registrations. In addition, we measured for 9 patients the magnitude of respiratory-induced motion (MM) of the markers and of the stent on 4-dimensional CT (4DCT) and determined the difference between these 2 magnitudes (ΔMM). Results: The stent indicated tumor position better than bony anatomy in 67% of fractions; the absolute difference between the markers and stent registration was >5 mm in 46% of fractions and >10 mm in 20% of fractions. Large PTV margins (superior-inferior direction, >19 mm) would be needed to account for this interfractional position variability. On 4DCT, we found in superior-inferior direction a mean ΔMM of 0.5 mm (range, –2.6 to 4.2 mm). Conclusions: For respiratory-induced motion, the mean ΔMM is small, but for individual patients the absolute difference can be >4 mm. For interfractional position variations, a stent is, on average, a better surrogate fiducial than bony anatomy, but large PTV margins would still be required. Therefore, intratumoral fiducials are recommended for online setup verification for all pancreatic patients scheduled for radiation therapy, including

Serum plant sterols as surrogate markers of dietary compliance in familial dyslipidemias.

Science.gov (United States)

Mateo-Gallego, Rocío; Baila-Rueda, Lucía; Mouratidou, Theodora; De Castro-Orós, Isabel; Bea, Ana M; Perez-Calahorra, Sofía; Cenarro, Ana; Moreno, Luis A; Civeira, Fernando

2015-06-01

A well-balanced diet is the first-line treatment in hyperlipidemia. The objective was to study the association between serum phytosterols and dietary patterns to use them as surrogate markers of dietary compliance in primary dyslipidemias. 288 patients with primary hyperlipidemias (192 autosomal dominant hypercholesterolemia (ADH) and 96 familial combined hyperlipidemia (FCHL)) were included. Principal factor analysis identified 2 major dietary patterns using a 137-item food frequency questionnaire. "Vegetable & Fruits pattern" was characterized by higher intake of fruits, green beans, nuts, tomatoes, roasted or boiled potatoes, lettuce and chard and lower of processed baked goods, pizza and beer. "Western pattern" was positively characterized by hamburgers, pasta, sunflower oil, rice, chickpeas, whole milk, veal, red beans and negatively with white fish. Serum non-cholesterol sterols were determined by HPLC-MS/MS. Plant sterols to-total cholesterol (TC) levels were lower with a higher adherence to a "Vegetable & Fruits pattern" (P = 0.009), mainly in ADH subjects (R(2) = 0.019). Their concentration was greater with higher compliance to "Western pattern" especially in FCHL (P = 0.014). Higher levels of synthesis markers-to-TC with a greater adherence to "Vegetable & Fruits pattern" were found (P = 0.001) (R(2) = 0.033 and R(2) = 0.109 in ADH and FCHL respectively). In subjects with primary dislipidemia, dietary patterns associate with serum absorption and synthesis markers, but no with lipid concentrations. The influence of diet on non-cholesterol sterols levels is not powerful enough to use them as subrogate markers. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

TH-B-204-03: TG-199: Implanted Markers for Radiation Treatment Verification

International Nuclear Information System (INIS)

Wang, Z.

2016-01-01

Implanted markers as target surrogates have been widely used for treatment verification, as they provide safe and reliable monitoring of the inter- and intra-fractional target motion. The rapid advancement of technology requires a critical review and recommendation for the usage of implanted surrogates in current field. The symposium, also reporting an update of AAPM TG 199 - Implanted Target Surrogates for Radiation Treatment Verification, will be focusing on all clinical aspects of using the implanted target surrogates for treatment verification and related issues. A wide variety of markers available in the market will be first reviewed, including radiopaque markers, MRI compatible makers, non-migrating coils, surgical clips and electromagnetic transponders etc. The pros and cons of each kind will be discussed. The clinical applications of implanted surrogates will be presented based on different anatomical sites. For the lung, we will discuss gated treatments and 2D or 3D real-time fiducial tracking techniques. For the prostate, we will be focusing on 2D-3D, 3D-3D matching and electromagnetic transponder based localization techniques. For the liver, we will review techniques when patients are under gating, shallow or free breathing condition. We will review techniques when treating challenging breast cancer as deformation may occur. Finally, we will summarize potential issues related to the usage of implanted target surrogates with TG 199 recommendations. A review of fiducial migration and fiducial derived target rotation in different disease sites will be provided. The issue of target deformation, especially near the diaphragm, and related suggestions will be also presented and discussed. Learning Objectives: Knowledge of a wide variety of markers Knowledge of their application for different disease sites Understand of issues related to these applications Z. Wang: Research funding support from Brainlab AG Q. Xu: Consultant for Accuray; Q. Xu, I am a consultant

TH-B-204-03: TG-199: Implanted Markers for Radiation Treatment Verification

Energy Technology Data Exchange (ETDEWEB)

Wang, Z. [Duke University Medical Center (United States)

2016-06-15

Implanted markers as target surrogates have been widely used for treatment verification, as they provide safe and reliable monitoring of the inter- and intra-fractional target motion. The rapid advancement of technology requires a critical review and recommendation for the usage of implanted surrogates in current field. The symposium, also reporting an update of AAPM TG 199 - Implanted Target Surrogates for Radiation Treatment Verification, will be focusing on all clinical aspects of using the implanted target surrogates for treatment verification and related issues. A wide variety of markers available in the market will be first reviewed, including radiopaque markers, MRI compatible makers, non-migrating coils, surgical clips and electromagnetic transponders etc. The pros and cons of each kind will be discussed. The clinical applications of implanted surrogates will be presented based on different anatomical sites. For the lung, we will discuss gated treatments and 2D or 3D real-time fiducial tracking techniques. For the prostate, we will be focusing on 2D-3D, 3D-3D matching and electromagnetic transponder based localization techniques. For the liver, we will review techniques when patients are under gating, shallow or free breathing condition. We will review techniques when treating challenging breast cancer as deformation may occur. Finally, we will summarize potential issues related to the usage of implanted target surrogates with TG 199 recommendations. A review of fiducial migration and fiducial derived target rotation in different disease sites will be provided. The issue of target deformation, especially near the diaphragm, and related suggestions will be also presented and discussed. Learning Objectives: Knowledge of a wide variety of markers Knowledge of their application for different disease sites Understand of issues related to these applications Z. Wang: Research funding support from Brainlab AG Q. Xu: Consultant for Accuray; Q. Xu, I am a consultant

Self- and surrogate-reported communication functioning in aphasia.

Science.gov (United States)

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

2013-06-01

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

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

Science.gov (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

2015-01-01

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.

TH-B-204-00: Implanted Markers for Radiation Therapy and TG 199 Update

International Nuclear Information System (INIS)

2016-01-01

Implanted markers as target surrogates have been widely used for treatment verification, as they provide safe and reliable monitoring of the inter- and intra-fractional target motion. The rapid advancement of technology requires a critical review and recommendation for the usage of implanted surrogates in current field. The symposium, also reporting an update of AAPM TG 199 - Implanted Target Surrogates for Radiation Treatment Verification, will be focusing on all clinical aspects of using the implanted target surrogates for treatment verification and related issues. A wide variety of markers available in the market will be first reviewed, including radiopaque markers, MRI compatible makers, non-migrating coils, surgical clips and electromagnetic transponders etc. The pros and cons of each kind will be discussed. The clinical applications of implanted surrogates will be presented based on different anatomical sites. For the lung, we will discuss gated treatments and 2D or 3D real-time fiducial tracking techniques. For the prostate, we will be focusing on 2D-3D, 3D-3D matching and electromagnetic transponder based localization techniques. For the liver, we will review techniques when patients are under gating, shallow or free breathing condition. We will review techniques when treating challenging breast cancer as deformation may occur. Finally, we will summarize potential issues related to the usage of implanted target surrogates with TG 199 recommendations. A review of fiducial migration and fiducial derived target rotation in different disease sites will be provided. The issue of target deformation, especially near the diaphragm, and related suggestions will be also presented and discussed. Learning Objectives: Knowledge of a wide variety of markers Knowledge of their application for different disease sites Understand of issues related to these applications Z. Wang: Research funding support from Brainlab AG Q. Xu: Consultant for Accuray; Q. Xu, I am a consultant

TH-B-204-00: Implanted Markers for Radiation Therapy and TG 199 Update

Energy Technology Data Exchange (ETDEWEB)

NONE

2016-06-15

Implanted markers as target surrogates have been widely used for treatment verification, as they provide safe and reliable monitoring of the inter- and intra-fractional target motion. The rapid advancement of technology requires a critical review and recommendation for the usage of implanted surrogates in current field. The symposium, also reporting an update of AAPM TG 199 - Implanted Target Surrogates for Radiation Treatment Verification, will be focusing on all clinical aspects of using the implanted target surrogates for treatment verification and related issues. A wide variety of markers available in the market will be first reviewed, including radiopaque markers, MRI compatible makers, non-migrating coils, surgical clips and electromagnetic transponders etc. The pros and cons of each kind will be discussed. The clinical applications of implanted surrogates will be presented based on different anatomical sites. For the lung, we will discuss gated treatments and 2D or 3D real-time fiducial tracking techniques. For the prostate, we will be focusing on 2D-3D, 3D-3D matching and electromagnetic transponder based localization techniques. For the liver, we will review techniques when patients are under gating, shallow or free breathing condition. We will review techniques when treating challenging breast cancer as deformation may occur. Finally, we will summarize potential issues related to the usage of implanted target surrogates with TG 199 recommendations. A review of fiducial migration and fiducial derived target rotation in different disease sites will be provided. The issue of target deformation, especially near the diaphragm, and related suggestions will be also presented and discussed. Learning Objectives: Knowledge of a wide variety of markers Knowledge of their application for different disease sites Understand of issues related to these applications Z. Wang: Research funding support from Brainlab AG Q. Xu: Consultant for Accuray; Q. Xu, I am a consultant

Copeptin, a surrogate marker for arginine vasopressin, is associated with cardiovascular and all-cause mortality in patients with type 2 diabetes (ZODIAC-31)

NARCIS (Netherlands)

Riphagen, Ineke J.; Boertien, Wendy E.; Alkhalaf, Alaa; Kleefstra, Nanno; Gansevoort, Ron T.; Groenier, Klaas H.; van Hateren, Kornelis J. J.; Struck, Joachim; Navis, Gerjan; Bilo, Henk J. G.; Bakker, Stephan J. L.

2013-01-01

OBJECTIVE: Copeptin, a surrogate marker for arginine vasopressin, has been associated with cardiovascular (CV) events and mortality in patients with type 2 diabetes complicated by end-stage renal disease or acute myocardial infarction. For stable outpatients, these associations are unknown. Our aim

The role of serum non-cholesterol sterols as surrogate markers of absolute cholesterol synthesis and absorption.

Science.gov (United States)

Miettinen, T A; Gylling, H; Nissinen, M J

2011-10-01

To study the whole-body cholesterol metabolism in man, cholesterol synthesis and absorption need to be measured. Because of the complicated methods of the measurements, new approaches were developed including the analysis of serum non-cholesterol sterols. In current lipidologic papers and even in intervention studies, serum non-cholesterol sterols are frequently used as surrogate markers of cholesterol metabolism without any validation to the absolute metabolic variables. The present review compares serum non-cholesterol sterols with absolute measurements of cholesterol synthesis and absorption in published papers to find out whether the serum markers are valid indicators of cholesterol metabolism in various conditions. During statin treatment, during interventions of dietary fat, and in type 2 diabetes the relative and absolute variables of cholesterol synthesis and absorption were frequently but not constantly correlated with each other. In some occasions, especially in subjects with apolipoprotein E3/4 and E4/4 phenotypes, the relative metabolic markers were even more sensitive than the absolute ones to reflect changes in cholesterol metabolism during dietary interventions. Even in general population at very high absorption the homeostasis of cholesterol metabolism is disturbed damaging the validity of the serum markers. It is worth using several instead of only one precursor and absorption sterol marker for making conclusions of altered synthesis or absorption of cholesterol, and even then the presence of at least some absolute measurement is valuable. During consumption of plant sterol-enriched diets and in situations of interfered cholesterol homeostasis the relative markers do not adequately reflect cholesterol metabolism. Accordingly, the validity of the relative markers of cholesterol metabolism should not be considered as self-evident. Copyright © 2011 Elsevier B.V. All rights reserved.

Mitigating Errors in External Respiratory Surrogate-Based Models of Tumor Position

International Nuclear Information System (INIS)

Malinowski, Kathleen T.; McAvoy, Thomas J.; George, Rohini; Dieterich, Sonja; D'Souza, Warren D.

2012-01-01

Purpose: To investigate the effect of tumor site, measurement precision, tumor–surrogate correlation, training data selection, model design, and interpatient and interfraction variations on the accuracy of external marker-based models of tumor position. Methods and Materials: Cyberknife Synchrony system log files comprising synchronously acquired positions of external markers and the tumor from 167 treatment fractions were analyzed. The accuracy of Synchrony, ordinary-least-squares regression, and partial-least-squares regression models for predicting the tumor position from the external markers was evaluated. The quantity and timing of the data used to build the predictive model were varied. The effects of tumor–surrogate correlation and the precision in both the tumor and the external surrogate position measurements were explored by adding noise to the data. Results: The tumor position prediction errors increased during the duration of a fraction. Increasing the training data quantities did not always lead to more accurate models. Adding uncorrelated noise to the external marker-based inputs degraded the tumor–surrogate correlation models by 16% for partial-least-squares and 57% for ordinary-least-squares. External marker and tumor position measurement errors led to tumor position prediction changes 0.3–3.6 times the magnitude of the measurement errors, varying widely with model algorithm. The tumor position prediction errors were significantly associated with the patient index but not with the fraction index or tumor site. Partial-least-squares was as accurate as Synchrony and more accurate than ordinary-least-squares. Conclusions: The accuracy of surrogate-based inferential models of tumor position was affected by all the investigated factors, except for the tumor site and fraction index.

Mitigating Errors in External Respiratory Surrogate-Based Models of Tumor Position

Energy Technology Data Exchange (ETDEWEB)

Malinowski, Kathleen T. [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Fischell Department of Bioengineering, University of Maryland, College Park, MD (United States); McAvoy, Thomas J. [Fischell Department of Bioengineering, University of Maryland, College Park, MD (United States); Department of Chemical and Biomolecular Engineering and Institute of Systems Research, University of Maryland, College Park, MD (United States); George, Rohini [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Dieterich, Sonja [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); D' Souza, Warren D., E-mail: wdsou001@umaryland.edu [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Fischell Department of Bioengineering, University of Maryland, College Park, MD (United States)

2012-04-01

Purpose: To investigate the effect of tumor site, measurement precision, tumor-surrogate correlation, training data selection, model design, and interpatient and interfraction variations on the accuracy of external marker-based models of tumor position. Methods and Materials: Cyberknife Synchrony system log files comprising synchronously acquired positions of external markers and the tumor from 167 treatment fractions were analyzed. The accuracy of Synchrony, ordinary-least-squares regression, and partial-least-squares regression models for predicting the tumor position from the external markers was evaluated. The quantity and timing of the data used to build the predictive model were varied. The effects of tumor-surrogate correlation and the precision in both the tumor and the external surrogate position measurements were explored by adding noise to the data. Results: The tumor position prediction errors increased during the duration of a fraction. Increasing the training data quantities did not always lead to more accurate models. Adding uncorrelated noise to the external marker-based inputs degraded the tumor-surrogate correlation models by 16% for partial-least-squares and 57% for ordinary-least-squares. External marker and tumor position measurement errors led to tumor position prediction changes 0.3-3.6 times the magnitude of the measurement errors, varying widely with model algorithm. The tumor position prediction errors were significantly associated with the patient index but not with the fraction index or tumor site. Partial-least-squares was as accurate as Synchrony and more accurate than ordinary-least-squares. Conclusions: The accuracy of surrogate-based inferential models of tumor position was affected by all the investigated factors, except for the tumor site and fraction index.

Comparison of respiratory surrogates for gated lung radiotherapy without internal fiducials

International Nuclear Information System (INIS)

Korreman, S.; Mostafavi, H.; Le, Q.T.; Boyer, A.

2006-01-01

An investigation was carried out to compare the ability of two respiratory surrogates to mimic actual lung tumor motion during audio coaching. The investigation employed video clips acquired after patients had had fiducial markers implanted in lung tumors to be used for image-guided stereoscopic radiotherapy. The positions of the markers in the clips were measured within the video frames and used as the standard for tumor volume motion. An external marker was tracked optically during the fluoroscopic acquisitions. An image correlation technique was developed to compute a gating signal from the fluoroscopic images. The correlation gating trace was similar to the optical gating trace in the phase regions of the respiratory cycle used for gating. A cross correlation analysis and comparison of the external optical marker gating with internal fluoroscopic gating was performed. The fluoroscopic image correlation surrogate was found to be superior to the external optical surrogate in the AP-views in four out of six cases. In one of the remaining two cases, the two surrogates performed comparably, while in the last case, the external fiducial trace performed best. It was concluded that fluoroscopic gating based on correlation of native image features in the fluoroscopic images will be adequate for respiratory gating

Comparison of respiratory surrogates for gated lung radiotherapy without internal fiducials

Energy Technology Data Exchange (ETDEWEB)

Korreman, S. [Rigshospitalet, Copenhagen (Denmark). Dept. of Radiation Oncology; Mostafavi, H. [Varian Medical Systems, Mountain View, CA (United States). Gintzon Technology Center; Le, Q.T.; Boyer, A. [Stanford Univ. School of Medicine, CA (United States). Dept. of Radiation Oncology

2006-09-15

An investigation was carried out to compare the ability of two respiratory surrogates to mimic actual lung tumor motion during audio coaching. The investigation employed video clips acquired after patients had had fiducial markers implanted in lung tumors to be used for image-guided stereoscopic radiotherapy. The positions of the markers in the clips were measured within the video frames and used as the standard for tumor volume motion. An external marker was tracked optically during the fluoroscopic acquisitions. An image correlation technique was developed to compute a gating signal from the fluoroscopic images. The correlation gating trace was similar to the optical gating trace in the phase regions of the respiratory cycle used for gating. A cross correlation analysis and comparison of the external optical marker gating with internal fluoroscopic gating was performed. The fluoroscopic image correlation surrogate was found to be superior to the external optical surrogate in the AP-views in four out of six cases. In one of the remaining two cases, the two surrogates performed comparably, while in the last case, the external fiducial trace performed best. It was concluded that fluoroscopic gating based on correlation of native image features in the fluoroscopic images will be adequate for respiratory gating.

Tumor Heterogeneity: Mechanisms and Bases for a Reliable Application of Molecular Marker Design

Science.gov (United States)

Diaz-Cano, Salvador J.

2012-01-01

Tumor heterogeneity is a confusing finding in the assessment of neoplasms, potentially resulting in inaccurate diagnostic, prognostic and predictive tests. This tumor heterogeneity is not always a random and unpredictable phenomenon, whose knowledge helps designing better tests. The biologic reasons for this intratumoral heterogeneity would then be important to understand both the natural history of neoplasms and the selection of test samples for reliable analysis. The main factors contributing to intratumoral heterogeneity inducing gene abnormalities or modifying its expression include: the gradient ischemic level within neoplasms, the action of tumor microenvironment (bidirectional interaction between tumor cells and stroma), mechanisms of intercellular transference of genetic information (exosomes), and differential mechanisms of sequence-independent modifications of genetic material and proteins. The intratumoral heterogeneity is at the origin of tumor progression and it is also the byproduct of the selection process during progression. Any analysis of heterogeneity mechanisms must be integrated within the process of segregation of genetic changes in tumor cells during the clonal expansion and progression of neoplasms. The evaluation of these mechanisms must also consider the redundancy and pleiotropism of molecular pathways, for which appropriate surrogate markers would support the presence or not of heterogeneous genetics and the main mechanisms responsible. This knowledge would constitute a solid scientific background for future therapeutic planning. PMID:22408433

Evaluation of surrogate markers for human immunodeficiency virus infection among blood donors at the blood bank of "Hospital Universitário Regional Norte do Paraná", Londrina, PR, Brazil

Directory of Open Access Journals (Sweden)

Reiche Edna Maria Vissoci

2003-01-01

Full Text Available This study evaluated the usefulness of the anti-HBc, hepatitis C virus antibodies (anti-HCV, human T cell lymphotropic virus I and II antibodies (anti-HTLV I/II, serologic tests for syphilis, and surface antigen of hepatitis B virus (HBsAg as surrogate markers for the risk for HIV infection in 80,284 serum samples from blood donors from the Blood Bank of "Hospital Universitário Regional Norte do Paraná", Londrina, Paraná State, Brazil, analyzed from July 1994 to April 2001. Among 39 blood donors with positive serology for HIV, 12 (30.8% were anti-HBc positive, 10 (25.6% for anti-HCV, 1 (2.6% for anti-HTLV I/I, 1 (2.6% was positive for syphilis, and 1 (2.6% for HBsAg. Among the donors with negative serology for HIV, these markers were detected in 8,407 (10.5%, 441 (0.5%, 189 (0.2%, 464 (0.6%, and 473 (0.6% samples, respectively. The difference was statistically significant (p < 0.001 for anti-HBc and anti-HCV. Although the predictive positive value for these surrogate markers were low for HIV infection, the results confirmed the anti-HBc and anti-HCV as useful surrogate markers for HIV infection thus reinforcing the maintenance of them in the screening for blood donors contributing to the prevention of the small number of cases in which HIV is still transmitted by transfusion.

Muscle sympathetic nerve activity is related to a surrogate marker of endothelial function in healthy individuals.

Directory of Open Access Journals (Sweden)

Yrsa Bergmann Sverrisdóttir

Full Text Available BACKGROUND: Evidence from animal studies indicates the importance of an interaction between the sympathetic nervous system and the endothelium for cardiovascular regulation. However the interaction between these two systems remains largely unexplored in humans. The aim of this study was to investigate whether directly recorded sympathetic vasoconstrictor outflow is related to a surrogate marker of endothelial function in healthy individuals. METHODS AND RESULTS: In 10 healthy normotensive subjects (3 f/7 m, (age 37+/-11 yrs, (BMI 24+/-3 kg/m(2 direct recordings of sympathetic action potentials to the muscle vascular bed (MSNA were performed and endothelial function estimated with the Reactive Hyperaemia- Peripheral Arterial Tonometry (RH-PAT technique. Blood samples were taken and time spent on leisure-time physical activities was estimated. In all subjects the rate between resting flow and the maximum flow, the Reactive Hyperemic index (RH-PAT index, was within the normal range (1.9-3.3 and MSNA was as expected for age and gender (13-44 burst/minute. RH-PAT index was inversely related to MSNA (r = -0.8, p = 0.005. RH-PAT index and MSNA were reciprocally related to time (h/week spent on physical activity (p = 0.005 and p = 0.006 respectively and platelet concentration (PLT (p = 0.02 and p = 0.004 respectively. CONCLUSIONS: Our results show that sympathetic nerve activity is related to a surrogate marker of endothelial function in healthy normotensive individuals, indicating that sympathetic outflow may be modulated by changes in endothelial function. In this study time spent on physical activity is identified as a predictor of sympathetic nerve activity and endothelial function in a group of healthy individuals. The results are of importance in understanding mechanisms underlying sympathetic activation in conditions associated with endothelial dysfunction and emphasise the importance of a daily exercise routine for maintenance of cardiovascular

Tumor Heterogeneity: Mechanisms and Bases for a Reliable Application of Molecular Marker Design

Directory of Open Access Journals (Sweden)

Salvador J. Diaz-Cano

2012-02-01

Full Text Available Tumor heterogeneity is a confusing finding in the assessment of neoplasms, potentially resulting in inaccurate diagnostic, prognostic and predictive tests. This tumor heterogeneity is not always a random and unpredictable phenomenon, whose knowledge helps designing better tests. The biologic reasons for this intratumoral heterogeneity would then be important to understand both the natural history of neoplasms and the selection of test samples for reliable analysis. The main factors contributing to intratumoral heterogeneity inducing gene abnormalities or modifying its expression include: the gradient ischemic level within neoplasms, the action of tumor microenvironment (bidirectional interaction between tumor cells and stroma, mechanisms of intercellular transference of genetic information (exosomes, and differential mechanisms of sequence-independent modifications of genetic material and proteins. The intratumoral heterogeneity is at the origin of tumor progression and it is also the byproduct of the selection process during progression. Any analysis of heterogeneity mechanisms must be integrated within the process of segregation of genetic changes in tumor cells during the clonal expansion and progression of neoplasms. The evaluation of these mechanisms must also consider the redundancy and pleiotropism of molecular pathways, for which appropriate surrogate markers would support the presence or not of heterogeneous genetics and the main mechanisms responsible. This knowledge would constitute a solid scientific background for future therapeutic planning.

An Efficient Constraint Boundary Sampling Method for Sequential RBDO Using Kriging Surrogate Model

Energy Technology Data Exchange (ETDEWEB)

Kim, Jihoon; Jang, Junyong; Kim, Shinyu; Lee, Tae Hee [Hanyang Univ., Seoul (Korea, Republic of); Cho, Sugil; Kim, Hyung Woo; Hong, Sup [Korea Research Institute of Ships and Ocean Engineering, Busan (Korea, Republic of)

2016-06-15

Reliability-based design optimization (RBDO) requires a high computational cost owing to its reliability analysis. A surrogate model is introduced to reduce the computational cost in RBDO. The accuracy of the reliability depends on the accuracy of the surrogate model of constraint boundaries in the surrogated-model-based RBDO. In earlier researches, constraint boundary sampling (CBS) was proposed to approximate accurately the boundaries of constraints by locating sample points on the boundaries of constraints. However, because CBS uses sample points on all constraint boundaries, it creates superfluous sample points. In this paper, efficient constraint boundary sampling (ECBS) is proposed to enhance the efficiency of CBS. ECBS uses the statistical information of a kriging surrogate model to locate sample points on or near the RBDO solution. The efficiency of ECBS is verified by mathematical examples.

Serum hepatitis B core-related antigen is a satisfactory surrogate marker of intrahepatic covalently closed circular DNA in chronic hepatitis B.

Science.gov (United States)

Chen, En-Qiang; Feng, Shu; Wang, Meng-Lan; Liang, Ling-Bo; Zhou, Ling-Yun; Du, Ling-Yao; Yan, Li-Bo; Tao, Chuan-Min; Tang, Hong

2017-03-14

Recently, hepatitis B core-related antigen (HBcrAg) has been suggested as an additional marker of hepatitis B virus (HBV) infection. This study aimed to investigate whether serum quantitative HBcrAg (qHBcrAg) was a satisfactory surrogate marker of intrahepatic covalently closed circular DNA (cccDNA). A total of 139 patients with liver biopsy were enrolled, consisting of 59 patients in immune tolerance (IT) phase, 52 patients in immune clearance (IC) phase, 18 patients in low-replication (LR) phase, and 10 patients in reactivation phase. All patients in IC phase have received entecavir (ETV) therapy, and 32 of them undergone a second liver biopsy at 24 months. Among those patients, qHBcrAg was strongly correlated with intrahepatic cccDNA, which is superior to that of qHBsAg and HBV DNA. And similar findings were also observed in patients in IT, IC, LR and reactivation phases. Among the 32 ETV-treated patients with a second liver biopsy in IC phase, the decline of intrahepatic cccDNA was accompanied by changes in both qHBcrAg and qHBsAg. However, as compared to qHBsAg, the change of qHBcrAg was more strongly associated with intrahepatic cccDNA-decline. In summary, serum qHBcrAg should be a satisfactory surrogate of intrahepatic HBV cccDNA in CHB patients.

Impact of short-term nutritional supplementation on surrogate markers of undernutrition in hemodialysis patients - prospective real-life interventional study.

Science.gov (United States)

Ocepek, Andreja; Bevc, Sebastjan; Ekart, Robert

Hemodialysis (HD) patients are at increased risk for undernutrition, especially protein wasting. We present the results of a prospective study in HD patients after 4 months of intervention with oral nutritional supplements (ONS). After a 3-month wash-out period, 92 HD patients were enrolled in the study. Patients were tested for undernutrition with composite parameters, laboratory tests, bioelectrical impedance analysis (BIA), and hand-grip strength test (HGS). All patients fulfilling criteria for, or at high risk of, undernutrition were given ONS in addition to their regular diet. The impact of short-term ONS on surrogate markers of undernutrition was statistically analyzed. Data for 84 patients, 45 (53.6%) male, average age 63.3 years, were available for analysis after 4 months. Patients were divided into three groups: group A (n = 28), patients with normal nutritional status (NUS) at baseline not necessitating ONS; group B (n = 43), patients entitled to receive ONS; group C (n = 13), patients entitled to receive but refused to take ONS. In group B patients, received on average 4.1 bottles of ONS (902 mL; 1,623.6 kcal; 73.06 g protein) per week. Baseline results showed statistically-significant differences between groups in serum albumin levels and phase angle (PhA) but not in HGS. After 4 months of ONS, we noticed stagnation of observed markers in group B. Interestingly, in group A, significant deterioration of serum albumin and PhA was observed, but HGS improved. There was a trend towards worsening of serum albumin levels and HGS in group C not reaching statistical significance. In undernourished HD patients after ONS we did not find statistically-significant improvement of NUS evaluating surrogate markers. Nevertheless, in undernourished patients not receiving ONS, serum albumin and HGS showed a trend towards worsening, and even in well-nourished patients, nutritional markers (serum albumin and PhA) declined. We speculate that a certain positive

Homocysteine and C-reactive protein as useful surrogate markers for evaluating CKD risk in adults.

Science.gov (United States)

Chuang, Chung-Hsun; Lee, Yi-Yen; Sheu, Bor-Fuh; Hsiao, Cheng-Ting; Loke, Song-Seng; Chen, Jih-Chang; Li, Wen-Cheng

2013-01-01

This study aimed to evaluate the effectiveness of homocysteine and C-reactive protein (CRP) as potential markers for chronic kidney disease (CKD) in adults in Taiwan, and to identify associations between these factors and CKD, stratifying by gender. This cross-sectional study analyzed multi-center data retrospectively. Data were collected from 22,043 adult Taiwanese at Chang-Gung Memorial Hospital from 2005 to 2011. Smoking/drinking history, personal medical/medication history, pregnancy, fasting times as well as laboratory parameters, including homocysteine and CRP were measured and analyzed. Significant differences were observed between four homocysteine and CRP quartiles in eGFR and CKD. For males, only one model showed significant associations between plasma homocysteine and CKD, while in females, all three models showed significant associations with CKD. On the contrary, the gender difference in the case of CRP was opposite. Combined homocysteine and CRP were associated with CKD in males but not in females. Among Taiwanese adults, plasma homocysteine is associated with CKD in females and plasma hsCRP is associated with CKD in males. High hsCRP/high homocysteine is associated with elevated CKD risk in male. Our results suggest that homocysteine and hsCRP may be useful surrogate markers for evaluating CKD risk in adults. © 2013 S. Karger AG, Basel.

Homocysteine and C-Reactive Protein as Useful Surrogate Markers for Evaluating CKD Risk in Adults

Directory of Open Access Journals (Sweden)

Chung-Hsun Chuang

2013-10-01

Full Text Available Background/Aims: This study aimed to evaluate the effectiveness of homocysteine and C-reactive protein (CRP as potential markers for chronic kidney disease (CKD in adults in Taiwan, and to identify associations between these factors and CKD, stratifying by gender. Methods: This cross-sectional study analyzed multi-center data retrospectively. Data were collected from 22,043 adult Taiwanese at Chang-Gung Memorial Hospital from 2005 to 2011. Smoking/drinking history, personal medical/medication history, pregnancy, fasting times as well as laboratory parameters, including homocysteine and CRP were measured and analyzed. Results: Significant differences were observed between four homocysteine and CRP quartiles in eGFR and CKD. For males, only one model showed significant associations between plasma homocysteine and CKD, while in females, all three models showed significant associations with CKD. On the contrary, the gender difference in the case of CRP was opposite. Combined homocysteine and CRP were associated with CKD in males but not in females. Conclusion: Among Taiwanese adults, plasma homocysteine is associated with CKD in females and plasma hsCRP is associated with CKD in males. High hsCRP/high homocysteine is associated with elevated CKD risk in male. Our results suggest that homocysteine and hsCRP may be useful surrogate markers for evaluating CKD risk in adults.

Loss of chromosome 1p/19q in oligodendroglial tumors: refinement of chromosomal critical regions and evaluation of internexin immunostaining as a surrogate marker.

LENUS (Irish Health Repository)

Buckley, Patrick G

2011-03-01

Loss of chromosome 1p\\/19q in oligodendrogliomas represents a powerful predictor of good prognosis. Expression of internexin (INA), a neuronal specific intermediate filament protein, has recently been proposed as a surrogate marker for 1p\\/19q deletion based on the high degree of correlation between both parameters in oligodendrogliomas. The aim of this study was to assess further the diagnostic utility of INA expression in a set of genetically well-characterized oligodendrogliomas. On the basis of a conservative approach for copy number determination, using both comparative genomic hybridization and fluorescent in situ hybridization, INA expression as a surrogate marker for 1p\\/19q loss had both reduced specificity (80%) and sensitivity (79%) compared with respective values of 86% and 96% reported in the previous report. The histologic interpretation and diagnostic value of INA expression in oligodendrogliomas should therefore be assessed with greater caution when compared with 1p\\/19q DNA copy number analysis. In addition, DNA copy number aberrations of chromosomes 10, 16, and 17 were detected exclusively in 1p\\/19q codeleted samples, suggesting that other regions of the genome may contribute to the 1p\\/19q-deleted tumor phenotype inthese samples.

Revisiting photodynamic therapy dosimetry: reductionist & surrogate approaches to facilitate clinical success

Science.gov (United States)

Pogue, Brian W.; Elliott, Jonathan T.; Kanick, Stephen C.; Davis, Scott C.; Samkoe, Kimberley S.; Maytin, Edward V.; Pereira, Stephen P.; Hasan, Tayyaba

2016-04-01

Photodynamic therapy (PDT) can be a highly complex treatment, with many parameters influencing treatment efficacy. The extent to which dosimetry is used to monitor and standardize treatment delivery varies widely, ranging from measurement of a single surrogate marker to comprehensive approaches that aim to measure or estimate as many relevant parameters as possible. Today, most clinical PDT treatments are still administered with little more than application of a prescribed drug dose and timed light delivery, and thus the role of patient-specific dosimetry has not reached widespread clinical adoption. This disconnect is at least partly due to the inherent conflict between the need to measure and understand multiple parameters in vivo in order to optimize treatment, and the need for expedience in the clinic and in the regulatory and commercialization process. Thus, a methodical approach to selecting primary dosimetry metrics is required at each stage of translation of a treatment procedure, moving from complex measurements to understand PDT mechanisms in pre-clinical and early phase I trials, towards the identification and application of essential dose-limiting and/or surrogate measurements in phase II/III trials. If successful, identifying the essential and/or reliable surrogate dosimetry measurements should help facilitate increased adoption of clinical PDT. In this paper, examples of essential dosimetry points and surrogate dosimetry tools that may be implemented in phase II/III trials are discussed. For example, the treatment efficacy as limited by light penetration in interstitial PDT may be predicted by the amount of contrast uptake in CT, and so this could be utilized as a surrogate dosimetry measurement to prescribe light doses based upon pre-treatment contrast. Success of clinical ALA-based skin lesion treatment is predicted almost uniquely by the explicit or implicit measurements of photosensitizer and photobleaching, yet the individualization of treatment

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

Science.gov (United States)

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

2007-03-01

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

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

Science.gov (United States)

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

2015-09-01

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

Surrogate Endpoint Evaluation: Principal Stratification Criteria and the Prentice Definition

Science.gov (United States)

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

2015-01-01

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

Emotional experiences in surrogate mothers: A qualitative study.

Science.gov (United States)

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

2014-07-01

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

Triglycerides/glucose index is a useful surrogate marker of insulin resistance among adolescents.

Science.gov (United States)

Kang, B; Yang, Y; Lee, E Y; Yang, H K; Kim, H-S; Lim, S-Y; Lee, J-H; Lee, S-S; Suh, B-K; Yoon, K-H

2017-05-01

Our aim was to investigate the association between the triglycerides/glucose index (TyG index) and the homeostasis model assessment-estimated insulin resistance (HOMA-IR) in the prediction of insulin resistance (IR) among adolescents. We conducted a cross-sectional study among 221 Korean adolescents (168 males and 53 females aged 9-13 years) from May to June 2014 in Chung-ju city. The TyG index was calculated as ln [triglycerides (mg dl -1 ) × fasting glucose (mg dl -1 )/2]. IR was defined using HOMA-IR >95th percentile for age and sex. In the IR group, weight, body mass index (BMI), waist circumference, body fat, fasting insulin, fasting plasma glucose, triglyceride levels and triglycerides/high-density lipoprotein cholesterol (TG/HDL-C) were significantly higher than that in the non-IR group. The TG index was significantly different between the IR group (n=22) and non-IR group (n=199), at 8.43±0.45 and 8.05±0.41, respectively (Pindex was well correlated with HOMA-IR (r=0.41; Pindex for diagnosis of insulin resistance was 8.18. The TyG index is a simple, cost-effective surrogate marker of insulin resistance among adolescents compared with HOMA-IR.

Evaluation of the geometric accuracy of surrogate-based gated VMAT using intrafraction kilovoltage x-ray images

International Nuclear Information System (INIS)

Li Ruijiang; Mok, Edward; Han, Bin; Koong, Albert; Xing Lei

2012-01-01

Purpose: To evaluate the geometric accuracy of beam targeting in external surrogate-based gated volumetric modulated arc therapy (VMAT) using kilovoltage (kV) x-ray images acquired during dose delivery. Methods: Gated VMAT treatments were delivered using a Varian TrueBeam STx Linac for both physical phantoms and patients. Multiple gold fiducial markers were implanted near the target. The reference position was created for each implanted marker, representing its correct position at the gating threshold. The gating signal was generated from the RPM system. During the treatment, kV images were acquired immediately before MV beam-on at every breathing cycle, using the on-board imaging system. All implanted markers were detected and their 3D positions were estimated using in-house developed software. The positioning error of a marker is defined as the distance of the marker from its reference position for each frame of the images. The overall error of the system is defined as the average over all markers. For the phantom study, both sinusoidal motion (1D and 3D) and real human respiratory motion was simulated for the target and surrogate. In the baseline case, the two motions were synchronized for the first treatment fraction. To assess the effects of surrogate-target correlation on the geometric accuracy, a phase shift of 5% and 10% between the two motions was introduced. For the patient study, intrafraction kV images of five stereotactic body radiotherapy (SBRT) patients were acquired for one or two fractions. Results: For the phantom study, a high geometric accuracy was achieved in the baseline case (average error: 0.8 mm in the superior-inferior or SI direction). However, the treatment delivery is prone to geometric errors if changes in the target-surrogate relation occur during the treatment: the average error was increased to 2.3 and 4.7 mm for the phase shift of 5% and 10%, respectively. Results obtained with real human respiratory curves show a similar trend

Surrogate MRI markers for hyperthermia-induced release of doxorubicin from thermosensitive liposomes in tumors.

Science.gov (United States)

Peller, Michael; Willerding, Linus; Limmer, Simone; Hossann, Martin; Dietrich, Olaf; Ingrisch, Michael; Sroka, Ronald; Lindner, Lars H

2016-09-10

The efficacy of systemically applied, classical anti-cancer drugs is limited by insufficient selectivity to the tumor and the applicable dose is limited by side effects. Efficacy could be further improved by targeting of the drug to the tumor. Using thermosensitive liposomes (TSL) as a drug carrier, targeting is achieved by control of temperature in the target volume. In such an approach, effective local hyperthermia (40-43°C) (HT) of the tumor is considered essential but technically challenging. Thus, visualization of local heating and drug release using TSL is considered an important tool for further improvement. Visualization and feasibility of chemodosimetry by magnetic resonance imaging (MRI) has previously been demonstrated using TSL encapsulating both, contrast agent (CA) and doxorubicin (DOX) simultaneously in the same TSL. Dosimetry has been facilitated using T1-relaxation time change as a surrogate marker for DOX deposition in the tumor. To allow higher loading of the TSL and to simplify clinical development of new TSL formulations a new approach using a mixture of TSL either loaded with DOX or MRI-CA is suggested. This was successfully tested using phosphatidyldiglycerol-based TSL (DPPG2-TSL) in Brown Norway rats with syngeneic soft tissue sarcomas (BN175) implanted at both hind legs. After intravenous application of DOX-TSL and CA-TSL, heating of one tumor above 40°C for 1h using laser light resulted in highly selective DOX uptake. The DOX-concentration in the heated tumor tissue compared to the non-heated tumor showed an almost 10-fold increase. T1 and additional MRI surrogate parameters such as signal phase change were correlated to intratumoral DOX concentration. Visualization of DOX delivery in the sense of a chemodosimetry was demonstrated. Although phase-based MR-thermometry was affected by CA-TSL, phase information was found suitable for DOX concentration assessment. Local differences of DOX concentration in the tumors indicated the need for

Revisiting photodynamic therapy dosimetry: reductionist and surrogate approaches to facilitate clinical success

International Nuclear Information System (INIS)

Pogue, Brian W; Elliott, Jonathan T; Kanick, Stephen C; Davis, Scott C; Samkoe, Kimberley S; Maytin, Edward V; Pereira, Stephen P; Hasan, Tayyaba

2016-01-01

Photodynamic therapy (PDT) can be a highly complex treatment, with many parameters influencing treatment efficacy. The extent to which dosimetry is used to monitor and standardize treatment delivery varies widely, ranging from measurement of a single surrogate marker to comprehensive approaches that aim to measure or estimate as many relevant parameters as possible. Today, most clinical PDT treatments are still administered with little more than application of a prescribed drug dose and timed light delivery, and thus the role of patient-specific dosimetry has not reached widespread clinical adoption. This disconnect is at least partly due to the inherent conflict between the need to measure and understand multiple parameters in vivo in order to optimize treatment, and the need for expedience in the clinic and in the regulatory and commercialization process. Thus, a methodical approach to selecting primary dosimetry metrics is required at each stage of translation of a treatment procedure, moving from complex measurements to understand PDT mechanisms in pre-clinical and early phase I trials, towards the identification and application of essential dose-limiting and/or surrogate measurements in phase II/III trials. If successful, identifying the essential and/or reliable surrogate dosimetry measurements should help facilitate increased adoption of clinical PDT. In this paper, examples of essential dosimetry points and surrogate dosimetry tools that may be implemented in phase II/III trials are discussed. For example, the treatment efficacy as limited by light penetration in interstitial PDT may be predicted by the amount of contrast uptake in CT, and so this could be utilized as a surrogate dosimetry measurement to prescribe light doses based upon pre-treatment contrast. Success of clinical ALA-based skin lesion treatment is predicted almost uniquely by the explicit or implicit measurements of photosensitizer and photobleaching, yet the individualization of treatment

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

International Nuclear Information System (INIS)

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

2012-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-04-01

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

WE-FG-206-12: Enhanced Laws Textures: A Potential MRI Surrogate Marker of Hepatic Fibrosis in a Murine Model

International Nuclear Information System (INIS)

Li, B; Yu, H; Jara, H; Soto, J; Anderson, S

2016-01-01

Purpose: To compare enhanced Laws texture derived from parametric proton density (PD) maps to other MRI-based surrogate markers (T2, PD, ADC) in assessing degrees of liver fibrosis in a murine model of hepatic fibrosis using 11.7T scanner. Methods: This animal study was IACUC approved. Fourteen mice were divided into control (n=1) and experimental (n=13). The latter were fed a DDC-supplemented diet to induce hepatic fibrosis. Liver specimens were imaged using an 11.7T scanner; the parametric PD, T2, and ADC maps were generated from spin-echo pulsed field gradient and multi-echo spin-echo acquisitions. Enhanced Laws texture analysis was applied to the PD maps: first, hepatic blood vessels and liver margins were segmented/removed using an automated dual-clustering algorithm; secondly, an optimal thresholding algorithm was applied to reduce the partial volume artifact; next, mean and stdev were corrected to minimize grayscale variation across images; finally, Laws texture was extracted. Degrees of fibrosis was assessed by an experienced pathologist and digital image analysis (%Area Fibrosis). Scatterplots comparing enhanced Laws texture, T2, PD, and ADC values to degrees of fibrosis were generated and correlation coefficients were calculated. Unenhanced Laws texture was also compared to assess the effectiveness of the proposed enhancements. Results: Hepatic fibrosis and the enhanced Laws texture were strongly correlated with higher %Area Fibrosis associated with higher Laws texture (r=0.89). Only a moderate correlation was detected between %Area Fibrosis and unenhanced Laws texture (r=0.70). Strong correlation also existed between ADC and %Area Fibrosis (r=0.86). Moderate correlations were seen between %Area Fibrosis and PD (r=0.65) and T2 (r=0.66). Conclusions: Higher degrees of hepatic fibrosis are associated with increased Laws texture. The proposed enhancements improve the accuracy of Laws texture. Enhanced Laws texture features are more accurate than PD and T2 in

WE-FG-206-12: Enhanced Laws Textures: A Potential MRI Surrogate Marker of Hepatic Fibrosis in a Murine Model

Energy Technology Data Exchange (ETDEWEB)

Li, B; Yu, H; Jara, H; Soto, J; Anderson, S [Boston University Medical Center, Boston, MA (United States)

2016-06-15

Purpose: To compare enhanced Laws texture derived from parametric proton density (PD) maps to other MRI-based surrogate markers (T2, PD, ADC) in assessing degrees of liver fibrosis in a murine model of hepatic fibrosis using 11.7T scanner. Methods: This animal study was IACUC approved. Fourteen mice were divided into control (n=1) and experimental (n=13). The latter were fed a DDC-supplemented diet to induce hepatic fibrosis. Liver specimens were imaged using an 11.7T scanner; the parametric PD, T2, and ADC maps were generated from spin-echo pulsed field gradient and multi-echo spin-echo acquisitions. Enhanced Laws texture analysis was applied to the PD maps: first, hepatic blood vessels and liver margins were segmented/removed using an automated dual-clustering algorithm; secondly, an optimal thresholding algorithm was applied to reduce the partial volume artifact; next, mean and stdev were corrected to minimize grayscale variation across images; finally, Laws texture was extracted. Degrees of fibrosis was assessed by an experienced pathologist and digital image analysis (%Area Fibrosis). Scatterplots comparing enhanced Laws texture, T2, PD, and ADC values to degrees of fibrosis were generated and correlation coefficients were calculated. Unenhanced Laws texture was also compared to assess the effectiveness of the proposed enhancements. Results: Hepatic fibrosis and the enhanced Laws texture were strongly correlated with higher %Area Fibrosis associated with higher Laws texture (r=0.89). Only a moderate correlation was detected between %Area Fibrosis and unenhanced Laws texture (r=0.70). Strong correlation also existed between ADC and %Area Fibrosis (r=0.86). Moderate correlations were seen between %Area Fibrosis and PD (r=0.65) and T2 (r=0.66). Conclusions: Higher degrees of hepatic fibrosis are associated with increased Laws texture. The proposed enhancements improve the accuracy of Laws texture. Enhanced Laws texture features are more accurate than PD and T2 in

Coastal aquifer management under parameter uncertainty: Ensemble surrogate modeling based simulation-optimization

Science.gov (United States)

Janardhanan, S.; Datta, B.

2011-12-01

saltwater intrusion are considered. The salinity levels resulting at strategic locations due to these pumping are predicted using the ensemble surrogates and are constrained to be within pre-specified levels. Different realizations of the concentration values are obtained from the ensemble predictions corresponding to each candidate solution of pumping. Reliability concept is incorporated as the percent of the total number of surrogate models which satisfy the imposed constraints. The methodology was applied to a realistic coastal aquifer system in Burdekin delta area in Australia. It was found that all optimal solutions corresponding to a reliability level of 0.99 satisfy all the constraints and as reducing reliability level decreases the constraint violation increases. Thus ensemble surrogate model based simulation-optimization was found to be useful in deriving multi-objective optimal pumping strategies for coastal aquifers under parameter uncertainty.

Effect of imputing markers from a low-density chip on the reliability of genomic breeding values in Holstein populations

DEFF Research Database (Denmark)

Dassonneville, R; Brøndum, Rasmus Froberg; Druet, T

2011-01-01

The purpose of this study was to investigate the imputation error and loss of reliability of direct genomic values (DGV) or genomically enhanced breeding values (GEBV) when using genotypes imputed from a 3,000-marker single nucleotide polymorphism (SNP) panel to a 50,000-marker SNP panel. Data...... of missing markers and prediction of breeding values were performed using 2 different reference populations in each country: either a national reference population or a combined EuroGenomics reference population. Validation for accuracy of imputation and genomic prediction was done based on national test...... with a national reference data set gave an absolute loss of 0.05 in mean reliability of GEBV in the French study, whereas a loss of 0.03 was obtained for reliability of DGV in the Nordic study. When genotypes were imputed using the EuroGenomics reference, a loss of 0.02 in mean reliability of GEBV was detected...

The Low Fall as a Surrogate Marker of Frailty Predicts Long-Term Mortality in Older Trauma Patients.

Directory of Open Access Journals (Sweden)

Ting Hway Wong

Full Text Available Frailty is associated with adverse outcomes including disability, mortality and risk of falls. Trauma registries capture a broad range of injuries. However, frail patients who fall comprise a large proportion of the injuries occurring in ageing populations and are likely to have different outcomes compared to non-frail injured patients. The effect of frail fallers on mortality is under-explored but potentially significant. Currently, many trauma registries define low falls as less than three metres, a height that is likely to include non-frailty falls. We hypothesized that the low fall from less than 0.5 metres, including same-level falls, is a surrogate marker of frailty and predicts long-term mortality in older trauma patients.Using data from the Singapore National Trauma Registry, 2011-2013, matched till September 2014 to the death registry, we analysed adults aged over 45 admitted via the emergency department in public hospitals sustaining blunt injuries with an injury severity score (ISS of 9 or more, excluding isolated hip fractures from same-level falls in the over 65. Patients injured by a low fall were compared to patients injured by high fall and other blunt mechanisms. Logistic regression was used to analyze 12-month mortality, controlling for mechanism of injury, ISS, revised trauma score (RTS, co-morbidities, gender, age and age-gender interaction. Different low fall height definitions, adjusting for injury regions, and analyzing the entire adult cohort were used in sensitivity analyses and did not change our findings.Of the 8111 adults in our cohort, patients who suffered low falls were more likely to die of causes unrelated to their injuries (p<0.001, compared to other blunt trauma and higher fall heights. They were at higher risk of 12-month mortality (OR 1.75, 95% CI 1.18-2.58, p = 0.005, independent of ISS, RTS, age, gender, age-gender interaction and co-morbidities. Falls that were higher than 0.5m did not show this pattern

Physical activity intensity and surrogate markers for cardiovascular health in adolescents.

Science.gov (United States)

Radtke, Thomas; Kriemler, Susi; Eser, Prisca; Saner, Hugo; Wilhelm, Matthias

2013-05-01

We examined the impact of physical activity (PA) on surrogate markers of cardiovascular health in adolescents. 52 healthy students (28 females, mean age 14.5 ± 0.7 years) were investigated. Microvascular endothelial function was assessed by peripheral arterial tonometry to determine reactive hyperemic index (RHI). Vagal activity was measured using 24 h analysis of heart rate variability [root mean square of successive normal-to-normal intervals (rMSSD)]. Exercise testing was performed to determine peak oxygen uptake ([Formula: see text]) and maximum power output. PA was assessed by accelerometry. Linear regression models were performed and adjusted for age, sex, skinfolds, and pubertal status. The cohort was dichotomized into two equally sized activity groups (low vs. high) based on the daily time spent in moderate-to-vigorous PA (MVPA, 3,000-5,200 counts(.)min(-1), model 1) and vigorous PA (VPA, >5,200 counts(.)min(-1), model 2). MVPA was an independent predictor for rMSSD (β = 0.448, P = 0.010), and VPA was associated with maximum power output (β = 0.248, P = 0.016). In model 1, the high MVPA group exhibited a higher vagal tone (rMSSD 49.2 ± 13.6 vs. 38.1 ± 11.7 ms, P = 0.006) and a lower systolic blood pressure (107.3 ± 9.9 vs. 112.9 ± 8.1 mmHg, P = 0.046). In model 2, the high VPA group had higher maximum power output values (3.9 ± 0.5 vs. 3.4 ± 0.5 W kg(-1), P = 0.012). In both models, no significant differences were observed for RHI and [Formula: see text]. In conclusion, in healthy adolescents, PA was associated with beneficial intensity-dependent effects on vagal tone, systolic blood pressure, and exercise capacity, but not on microvascular endothelial function.

Reliability of Urinary Dehydration Markers in Elite Youth Boxers.

Science.gov (United States)

Zubac, Damir; Cular, Drazen; Marusic, Uros

2018-03-01

To determine the reliability and diagnostic accuracy of noninvasive urinary dehydration markers in field-based settings on a day-to-day basis in elite adolescent amateur boxers. Sixty-nine urine samples were collected daily from 23 athletes (17.3 ± 1.9 y) during their weight-stable phase and analyzed by field and laboratory measures of hydration status. Urine osmolality (U OSM ), urine specific gravity (U SG ), total protein content (T PC ), and body-mass stability were evaluated to determine fluid balance and hydration status. Overall macronutrient and water intake were determined using dietary records. According to their anthropometric characteristics, athletes were assigned into 2 groups: lightweight (L WB ) and heavyweight (H WB ) boxers. Data presented on U OSM demonstrated a uniform increment by 11.2% ± 12.8% (L WB ) and 19.9% ± 22.7% (H WB ) (P dehydration markers. Poor correlations were found between U SG and T PC metabolites (r = .27, P = .211). Urinary dehydration markers (both U SG and U OSM ) exhibit high variability and seem to be unreliable diagnostic tools to track actual body-weight loss in real-life settings. The ad libitum fluid intake was apparently inadequate to match acute fluid loss during and after intense preparation. The applicability of a single-time-point hydration-status assessment concept may preclude accurate assessment of actual body-weight deficits in youth boxers.

Imaging-based surrogate markers of transcriptome subclasses and signatures in hepatocellular carcinoma. Preliminary results

Energy Technology Data Exchange (ETDEWEB)

Taouli, Bachir [Icahn School of Medicine at Mount Sinai, Department of Radiology, New York, NY (United States); Icahn School of Medicine at Mount Sinai, Translational and Molecular Imaging Institute, New York, NY (United States); Icahn School of Medicine at Mount Sinai, Liver Cancer Program, Tisch Cancer Institute, New York, NY (United States); Hoshida, Yujin; Chen, Xintong; Sun, Xiaochen; Kojima, Kensuke; Toffanin, Sara; Hirschfield, Hadassa [Icahn School of Medicine at Mount Sinai, Liver Cancer Program, Tisch Cancer Institute, New York, NY (United States); Icahn School of Medicine at Mount Sinai, Division of Liver Diseases, Department of Medicine, New York, NY (United States); Kakite, Suguru [Icahn School of Medicine at Mount Sinai, Translational and Molecular Imaging Institute, New York, NY (United States); Tottori University, Division of Radiology, Department of Pathophysiological and Therapeutic Science, Faculty of Medicine, Yonago City (Japan); Tan, Poh Seng [Icahn School of Medicine at Mount Sinai, Liver Cancer Program, Tisch Cancer Institute, New York, NY (United States); Icahn School of Medicine at Mount Sinai, Division of Liver Diseases, Department of Medicine, New York, NY (United States); National University Health System, Division of Gastroenterology and Hepatology, University Medicine Cluster, Singapore (Singapore); Kihira, Shingo [Icahn School of Medicine at Mount Sinai, Department of Radiology, New York, NY (United States); Fiel, M.I. [Icahn School of Medicine at Mount Sinai, Department of Pathology, New York, NY (United States); Wagner, Mathilde [Icahn School of Medicine at Mount Sinai, Translational and Molecular Imaging Institute, New York, NY (United States); Sorbonne Universites, UPMC, Department of Radiology, Hopital Pitie-Salpetriere, Paris (France); Llovet, Josep M. [Icahn School of Medicine at Mount Sinai, Liver Cancer Program, Tisch Cancer Institute, New York, NY (United States); Icahn School of Medicine at Mount Sinai, Division of Liver Diseases, Department of Medicine, New York, NY (United States); Universitat de Barcelona, HCC Translational Research Laboratory, Barcelona-Clinic Liver Cancer Group Institut d' Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Hospital Clinic de Barcelona, Barcelona (Spain); Institucio Catalana de Recerca i Estudis Avancats, Barcelona (Spain)

2017-11-15

In this preliminary study, we examined whether imaging-based phenotypes are associated with reported predictive gene signatures in hepatocellular carcinoma (HCC). Thirty-eight patients (M/F 30/8, mean age 61 years) who underwent pre-operative CT or MR imaging before surgery as well as transcriptome profiling were included in this IRB-approved single-centre retrospective study. Eleven qualitative and four quantitative imaging traits (size, enhancement ratios, wash-out ratio, tumour-to-liver contrast ratios) were assessed by three observers and were correlated with 13 previously reported HCC gene signatures using logistic regression analysis. Thirty-nine HCC tumours (mean size 5.7 ± 3.2 cm) were assessed. Significant positive associations were observed between certain imaging traits and gene signatures of aggressive HCC phenotype (G3-Boyault, Proliferation-Chiang profiles, CK19-Villanueva, S1/S2-Hoshida) with odds ratios ranging from 4.44-12.73 (P <0.045). Infiltrative pattern at imaging was significantly associated with signatures of microvascular invasion and aggressive phenotype. Significant but weak associations were also observed between each enhancement ratio and tumour-to-liver contrast ratios and certain gene expression profiles. This preliminary study demonstrates a correlation between phenotypic imaging traits with gene signatures of aggressive HCC, which warrants further prospective validation to establish imaging-based surrogate markers of molecular phenotypes in HCC. (orig.)

Imaging-based surrogate markers of transcriptome subclasses and signatures in hepatocellular carcinoma. Preliminary results

International Nuclear Information System (INIS)

Taouli, Bachir; Hoshida, Yujin; Chen, Xintong; Sun, Xiaochen; Kojima, Kensuke; Toffanin, Sara; Hirschfield, Hadassa; Kakite, Suguru; Tan, Poh Seng; Kihira, Shingo; Fiel, M.I.; Wagner, Mathilde; Llovet, Josep M.

2017-01-01

In this preliminary study, we examined whether imaging-based phenotypes are associated with reported predictive gene signatures in hepatocellular carcinoma (HCC). Thirty-eight patients (M/F 30/8, mean age 61 years) who underwent pre-operative CT or MR imaging before surgery as well as transcriptome profiling were included in this IRB-approved single-centre retrospective study. Eleven qualitative and four quantitative imaging traits (size, enhancement ratios, wash-out ratio, tumour-to-liver contrast ratios) were assessed by three observers and were correlated with 13 previously reported HCC gene signatures using logistic regression analysis. Thirty-nine HCC tumours (mean size 5.7 ± 3.2 cm) were assessed. Significant positive associations were observed between certain imaging traits and gene signatures of aggressive HCC phenotype (G3-Boyault, Proliferation-Chiang profiles, CK19-Villanueva, S1/S2-Hoshida) with odds ratios ranging from 4.44-12.73 (P <0.045). Infiltrative pattern at imaging was significantly associated with signatures of microvascular invasion and aggressive phenotype. Significant but weak associations were also observed between each enhancement ratio and tumour-to-liver contrast ratios and certain gene expression profiles. This preliminary study demonstrates a correlation between phenotypic imaging traits with gene signatures of aggressive HCC, which warrants further prospective validation to establish imaging-based surrogate markers of molecular phenotypes in HCC. (orig.)

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

Science.gov (United States)

Lassere, Marissa N

2008-06-01

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

Cluster-based upper body marker models for three-dimensional kinematic analysis: Comparison with an anatomical model and reliability analysis.

Science.gov (United States)

Boser, Quinn A; Valevicius, Aïda M; Lavoie, Ewen B; Chapman, Craig S; Pilarski, Patrick M; Hebert, Jacqueline S; Vette, Albert H

2018-04-27

Quantifying angular joint kinematics of the upper body is a useful method for assessing upper limb function. Joint angles are commonly obtained via motion capture, tracking markers placed on anatomical landmarks. This method is associated with limitations including administrative burden, soft tissue artifacts, and intra- and inter-tester variability. An alternative method involves the tracking of rigid marker clusters affixed to body segments, calibrated relative to anatomical landmarks or known joint angles. The accuracy and reliability of applying this cluster method to the upper body has, however, not been comprehensively explored. Our objective was to compare three different upper body cluster models with an anatomical model, with respect to joint angles and reliability. Non-disabled participants performed two standardized functional upper limb tasks with anatomical and cluster markers applied concurrently. Joint angle curves obtained via the marker clusters with three different calibration methods were compared to those from an anatomical model, and between-session reliability was assessed for all models. The cluster models produced joint angle curves which were comparable to and highly correlated with those from the anatomical model, but exhibited notable offsets and differences in sensitivity for some degrees of freedom. Between-session reliability was comparable between all models, and good for most degrees of freedom. Overall, the cluster models produced reliable joint angles that, however, cannot be used interchangeably with anatomical model outputs to calculate kinematic metrics. Cluster models appear to be an adequate, and possibly advantageous alternative to anatomical models when the objective is to assess trends in movement behavior. Copyright © 2018 Elsevier Ltd. All rights reserved.

Neural markers of errors as endophenotypes in neuropsychiatric disorders

Directory of Open Access Journals (Sweden)

Dara S Manoach

2013-07-01

Full Text Available Learning from errors is fundamental to adaptive human behavior. It requires detecting errors, evaluating what went wrong, and adjusting behavior accordingly. These dynamic adjustments are at the heart of behavioral flexibility and accumulating evidence suggests that deficient error processing contributes to maladaptively rigid and repetitive behavior in a range of neuropsychiatric disorders. Neuroimaging and electrophysiological studies reveal highly reliable neural markers of error processing. In this review, we evaluate the evidence that abnormalities in these neural markers can serve as sensitive endophenotypes of neuropsychiatric disorders. We describe the behavioral and neural hallmarks of error processing, their mediation by common genetic polymorphisms, and impairments in schizophrenia, obsessive-compulsive disorder, and autism spectrum disorders. We conclude that neural markers of errors meet several important criteria as endophenotypes including heritability, established neuroanatomical and neurochemical substrates, association with neuropsychiatric disorders, presence in syndromally-unaffected family members, and evidence of genetic mediation. Understanding the mechanisms of error processing deficits in neuropsychiatric disorders may provide novel neural and behavioral targets for treatment and sensitive surrogate markers of treatment response. Treating error processing deficits may improve functional outcome since error signals provide crucial information for flexible adaptation to changing environments. Given the dearth of effective interventions for cognitive deficits in neuropsychiatric disorders, this represents a promising approach.

Neural markers of errors as endophenotypes in neuropsychiatric disorders.

Science.gov (United States)

Manoach, Dara S; Agam, Yigal

2013-01-01

Learning from errors is fundamental to adaptive human behavior. It requires detecting errors, evaluating what went wrong, and adjusting behavior accordingly. These dynamic adjustments are at the heart of behavioral flexibility and accumulating evidence suggests that deficient error processing contributes to maladaptively rigid and repetitive behavior in a range of neuropsychiatric disorders. Neuroimaging and electrophysiological studies reveal highly reliable neural markers of error processing. In this review, we evaluate the evidence that abnormalities in these neural markers can serve as sensitive endophenotypes of neuropsychiatric disorders. We describe the behavioral and neural hallmarks of error processing, their mediation by common genetic polymorphisms, and impairments in schizophrenia, obsessive-compulsive disorder, and autism spectrum disorders. We conclude that neural markers of errors meet several important criteria as endophenotypes including heritability, established neuroanatomical and neurochemical substrates, association with neuropsychiatric disorders, presence in syndromally-unaffected family members, and evidence of genetic mediation. Understanding the mechanisms of error processing deficits in neuropsychiatric disorders may provide novel neural and behavioral targets for treatment and sensitive surrogate markers of treatment response. Treating error processing deficits may improve functional outcome since error signals provide crucial information for flexible adaptation to changing environments. Given the dearth of effective interventions for cognitive deficits in neuropsychiatric disorders, this represents a potentially promising approach.

Affective traits link to reliable neural markers of incentive anticipation.

Science.gov (United States)

Wu, Charlene C; Samanez-Larkin, Gregory R; Katovich, Kiefer; Knutson, Brian

2014-01-01

While theorists have speculated that different affective traits are linked to reliable brain activity during anticipation of gains and losses, few have directly tested this prediction. We examined these associations in a community sample of healthy human adults (n=52) as they played a Monetary Incentive Delay task while undergoing functional magnetic resonance imaging (FMRI). Factor analysis of personality measures revealed that subjects independently varied in trait Positive Arousal and trait Negative Arousal. In a subsample (n=14) retested over 2.5years later, left nucleus accumbens (NAcc) activity during anticipation of large gains (+$5.00) and right anterior insula activity during anticipation of large losses (-$5.00) showed significant test-retest reliability (intraclass correlations>0.50, p'santicipation of large gains, while trait Negative Arousal correlated with individual differences in right anterior insula activity during anticipation of large losses. Associations of affective traits with neural activity were not attributable to the influence of other potential confounds (including sex, age, wealth, and motion). Together, these results demonstrate selective links between distinct affective traits and reliably-elicited activity in neural circuits associated with anticipation of gain versus loss. The findings thus reveal neural markers for affective dimensions of healthy personality, and potentially for related psychiatric symptoms. © 2013. Published by Elsevier Inc. All rights reserved.

A Study of Carotid Intimomedial Thickness as a Primary Marker of Atherosclerosis in Patients with Rheumatoid Arthritis.

Directory of Open Access Journals (Sweden)

Shivani Patel

2016-01-01

RA is a chronic disease associatedd with chronic subclinical inflammation. In view of the consequentr high risk of atherosclerosis seen in these patients CIMT may serve as an early surrogate marker of atherosclerosis. We can identify these high risk subgroups of patients with a simple, reliable, inexpensive, and non-invasive bedside carotid Doppler sonogram even in resource poor countries such as India. In our view physicians should be vigilant to identify and screen regularly for atherosclerosis with CIMT in RA patients, so that prompt early management can prevent the cardiovascular complications.

A Radiation-Induced Hippocampal Vascular Injury Surrogate Marker Predicts Late Neurocognitive Dysfunction

Energy Technology Data Exchange (ETDEWEB)

Farjam, Reza [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Pramanik, Priyanka; Aryal, Madhava P. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Srinivasan, Ashok [Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Chapman, Christopher H. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Tsien, Christina I. [Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri (United States); Lawrence, Theodore S. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Cao, Yue, E-mail: yuecao@umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan (United States)

2015-11-15

Purpose: We aimed to develop a hippocampal vascular injury surrogate marker for early prediction of late neurocognitive dysfunction in patients receiving brain radiation therapy (RT). Methods and Materials: Twenty-seven patients (17 males and 10 females, 31-80 years of age) were enrolled in an institutional review board-approved prospective longitudinal study. Patients received diagnoses of low-grade glioma or benign tumor and were treated by (3D) conformal or intensity-modulated RT with a median dose of 54 Gy (50.4-59.4 Gy in 1.8-Gy fractions). Six dynamic-contrast enhanced MRI scans were performed from pre-RT to 18-month post-RT, and quantified for vascular parameters related to blood-brain barrier permeability, K{sup trans}, and the fraction of blood plasma volume, V{sub p}. The temporal changes in the means of hippocampal transfer constant K{sup trans} and V{sub p} after starting RT were modeled by integrating the dose effects with age, sex, hippocampal laterality, and presence of tumor or edema near a hippocampus. Finally, the early vascular dose response in hippocampi was correlated with neurocognitive dysfunction at 6 and 18 months post-RT. Results: The mean K{sup trans} Increased significantly from pre-RT to 1-month post-RT (P<.0004), which significantly depended on sex (P<.0007) and age (P<.00004), with the dose response more pronounced in older females. Also, the vascular dose response in the left hippocampus of females correlated significantly with changes in memory function at 6 (r=−0.95, P<.0006) and 18-months (r=−0.88, P<.02) post-RT. Conclusions: The early hippocampal vascular dose response could be a predictor of late neurocognitive dysfunction. A personalized hippocampus sparing strategy may be considered in the future.

A Radiation-Induced Hippocampal Vascular Injury Surrogate Marker Predicts Late Neurocognitive Dysfunction

International Nuclear Information System (INIS)

Farjam, Reza; Pramanik, Priyanka; Aryal, Madhava P.; Srinivasan, Ashok; Chapman, Christopher H.; Tsien, Christina I.; Lawrence, Theodore S.; Cao, Yue

2015-01-01

Purpose: We aimed to develop a hippocampal vascular injury surrogate marker for early prediction of late neurocognitive dysfunction in patients receiving brain radiation therapy (RT). Methods and Materials: Twenty-seven patients (17 males and 10 females, 31-80 years of age) were enrolled in an institutional review board-approved prospective longitudinal study. Patients received diagnoses of low-grade glioma or benign tumor and were treated by (3D) conformal or intensity-modulated RT with a median dose of 54 Gy (50.4-59.4 Gy in 1.8-Gy fractions). Six dynamic-contrast enhanced MRI scans were performed from pre-RT to 18-month post-RT, and quantified for vascular parameters related to blood-brain barrier permeability, K"t"r"a"n"s, and the fraction of blood plasma volume, V_p. The temporal changes in the means of hippocampal transfer constant K"t"r"a"n"s and V_p after starting RT were modeled by integrating the dose effects with age, sex, hippocampal laterality, and presence of tumor or edema near a hippocampus. Finally, the early vascular dose response in hippocampi was correlated with neurocognitive dysfunction at 6 and 18 months post-RT. Results: The mean K"t"r"a"n"s Increased significantly from pre-RT to 1-month post-RT (P<.0004), which significantly depended on sex (P<.0007) and age (P<.00004), with the dose response more pronounced in older females. Also, the vascular dose response in the left hippocampus of females correlated significantly with changes in memory function at 6 (r=−0.95, P<.0006) and 18-months (r=−0.88, P<.02) post-RT. Conclusions: The early hippocampal vascular dose response could be a predictor of late neurocognitive dysfunction. A personalized hippocampus sparing strategy may be considered in the future.

Thrombocytopenia as a surrogate marker of hepatosplenic schistosomiasis in endemic areas for Schistosomiasis mansoni

Directory of Open Access Journals (Sweden)

Sandra Costa Drummond

2014-04-01

Full Text Available Introduction This study aimed to evaluate whether a low platelet count is a good surrogate marker of hepatosplenic schistosomiasis (HSS in a rural area of Brazil. A small district in southeastern Brazil, with a population of 1,543 individuals and a 23% prevalence of schistosomiasis, was selected for this investigation. Methods In July 2012, 384 volunteers were subjected to clinical, ultrasonography (US, and laboratory examinations, including stool sample analysis. The HSS patients were classified into four groups: Group 1 consisted of patients with a spleen >13cm and liver fibrosis; Group 2 consisted of patients with a palpable spleen and spleen>13cm measured by US; Group 3 consisted of patients with a spleen >13cm measured by US; and Group 4 consisted of patients with a palpable spleen. Results Eight patients were in Group 1 (2.1%, twenty-one were in Group 2 (5.5%, eight were in Group 3 (2.1%, and eighteen were in Group 4 (4.7%. A significant difference in the mean platelet counts was observed between the patients with and without HSS (p<0.01. Based on the receiver operating characteristic (ROC curve (platelet count <143,000/mm3, the sensitivity was greater than 92% in all groups, and the specificity varied from 44.4% to 75%. Conclusions We concluded that in endemic areas, thrombocytopenia demonstrates good sensitivity for detecting HSS and may be used as a screening tool to identify patients with HSS.

Quantitative trait loci markers derived from whole genome sequence data increases the reliability of genomic prediction

DEFF Research Database (Denmark)

Brøndum, Rasmus Froberg; Su, Guosheng; Janss, Luc

2015-01-01

This study investigated the effect on the reliability of genomic prediction when a small number of significant variants from single marker analysis based on whole genome sequence data were added to the regular 54k single nucleotide polymorphism (SNP) array data. The extra markers were selected...... with the aim of augmenting the custom low-density Illumina BovineLD SNP chip (San Diego, CA) used in the Nordic countries. The single-marker analysis was done breed-wise on all 16 index traits included in the breeding goals for Nordic Holstein, Danish Jersey, and Nordic Red cattle plus the total merit index...... itself. Depending on the trait’s economic weight, 15, 10, or 5 quantitative trait loci (QTL) were selected per trait per breed and 3 to 5 markers were selected to tag each QTL. After removing duplicate markers (same marker selected for more than one trait or breed) and filtering for high pairwise linkage...

Analysis of Carina Position as Surrogate Marker for Delivering Phase-Gated Radiotherapy

International Nuclear Information System (INIS)

Weide, Lineke van der; Soernsen de Koste, John R. van; Lagerwaard, Frank J.; Vincent, Andrew; Triest, Baukelien van; Slotman, Ben J.; Senan, Suresh

2008-01-01

Purpose: Respiratory gating can mitigate the effect of tumor mobility in radiotherapy (RT) for lung cancer. Because the tumor is generally not visualized, external surrogates of tumor position are used to trigger respiration-gated RT. We evaluated the suitability of the carina position as a surrogate in respiration-gated RT. Methods and Materials: A total of 30 four-dimensional (4D) computed tomography (CT) scans from 14 patients with lung cancer were retrospectively analyzed. Both uncoached (free breathing) and audio-coached 4D-CT scans were acquired from 9 patients, and 12 uncoached 4D-CT scans were acquired from 5 other patients during a 2-4-week period of stereotactic RT. The repeat scans were co-registered. The carina position was identified on the coronal cut planes in all 4D-CT phases. The correlation between the carina position and the total lung volume for each phase was determined, and the reproducibility of the carina position was studied in the 5 patients with repeat uncoached 4D-CT scans. Results: The mean extent of carina motion in 21 uncoached scans was 5.3 ± 1.6 mm in the craniocaudal (CC), 2.3 ± 1.4 mm in the anteroposterior, and 1.5 ± 0.7 mm in the mediolateral direction. Audio coaching resulted in a twofold increase in carina mobility in all directions. The CC carina position correlated with changes in the total lung volume (R = 0.89 ± 0.14), but the correlation was better for the audio-coached than for the uncoached 4D-CT scans (R = 0.93 ± 0.08 vs. R = 0.85 ± 0.17; paired t test, p = 0.034). Preliminary data from the 5 patients indicated that the CC carina motion correlated better with tumor motion than did the motion of the diaphragm. Conclusions: The CC position of the carina correlated well with the total lung volume, indicating that the carina is a good surrogate for verifying the total lung volume during respiration-gated RT

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

Directory of Open Access Journals (Sweden)

Camille Mellin

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

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

Science.gov (United States)

2012-01-01

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

Surrogate markers of visceral fat and response to anti-depressive treatment in patients with major depressive disorder

DEFF Research Database (Denmark)

Tønning, Morten; Petersen, Dorthe; Steglich-Petersen, Marie

2017-01-01

Background: Body mass index (BMI) and body weight have been shown to be associated to treatment outcome in patients with major depressive disorder, but this relationship is not clear. Visceral fat might be an underlying mechanism explaining this relationship. Aims: The aim of this study was to pr......Background: Body mass index (BMI) and body weight have been shown to be associated to treatment outcome in patients with major depressive disorder, but this relationship is not clear. Visceral fat might be an underlying mechanism explaining this relationship. Aims: The aim of this study...... was to prospectively investigate whether visceral fat, as measured by hip-to-waist ratio and waist circumference, affects treatment outcome in patients with major depressive disorder in patients attending a hospital psychiatric care unit in Denmark. Methods: The study was conducted as an observational prospective......) interviews and HAM-D6 self-rating questionnaires. Results: No differences were found in outcome between groups of patients with high vs low visceral fat in this population. Conclusions: The lack of association was evident for all surrogate markers of visceral fat, and suggests that visceral fat has no impact...

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

Directory of Open Access Journals (Sweden)

Lassere Marissa N

2012-03-01

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

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

DEFF Research Database (Denmark)

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

2007-01-01

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

Computer-analyzed facial expression as a surrogate marker for autism spectrum social core symptoms.

Directory of Open Access Journals (Sweden)

Keiho Owada

Full Text Available To develop novel interventions for autism spectrum disorder (ASD core symptoms, valid, reliable, and sensitive longitudinal outcome measures are required for detecting symptom change over time. Here, we tested whether a computerized analysis of quantitative facial expression measures could act as a marker for core ASD social symptoms. Facial expression intensity values during a semi-structured socially interactive situation extracted from the Autism Diagnostic Observation Schedule (ADOS were quantified by dedicated software in 18 high-functioning adult males with ASD. Controls were 17 age-, gender-, parental socioeconomic background-, and intellectual level-matched typically developing (TD individuals. Statistical analyses determined whether values representing the strength and variability of each facial expression element differed significantly between the ASD and TD groups and whether they correlated with ADOS reciprocal social interaction scores. Compared with the TD controls, facial expressions in the ASD group appeared more "Neutral" (d = 1.02, P = 0.005, PFDR 0.05 with lower variability in Happy expression (d = 1.10, P = 0.003, PFDR < 0.05. Moreover, the stronger Neutral facial expressions in the ASD participants were positively correlated with poorer ADOS reciprocal social interaction scores (ρ = 0.48, P = 0.042. These findings indicate that our method for quantitatively measuring reduced facial expressivity during social interactions can be a promising marker for core ASD social symptoms.

Computer-analyzed facial expression as a surrogate marker for autism spectrum social core symptoms.

Science.gov (United States)

Owada, Keiho; Kojima, Masaki; Yassin, Walid; Kuroda, Miho; Kawakubo, Yuki; Kuwabara, Hitoshi; Kano, Yukiko; Yamasue, Hidenori

2018-01-01

To develop novel interventions for autism spectrum disorder (ASD) core symptoms, valid, reliable, and sensitive longitudinal outcome measures are required for detecting symptom change over time. Here, we tested whether a computerized analysis of quantitative facial expression measures could act as a marker for core ASD social symptoms. Facial expression intensity values during a semi-structured socially interactive situation extracted from the Autism Diagnostic Observation Schedule (ADOS) were quantified by dedicated software in 18 high-functioning adult males with ASD. Controls were 17 age-, gender-, parental socioeconomic background-, and intellectual level-matched typically developing (TD) individuals. Statistical analyses determined whether values representing the strength and variability of each facial expression element differed significantly between the ASD and TD groups and whether they correlated with ADOS reciprocal social interaction scores. Compared with the TD controls, facial expressions in the ASD group appeared more "Neutral" (d = 1.02, P = 0.005, PFDR Neutral expression (d = 1.08, P = 0.003, PFDR 0.05) with lower variability in Happy expression (d = 1.10, P = 0.003, PFDR Neutral facial expressions in the ASD participants were positively correlated with poorer ADOS reciprocal social interaction scores (ρ = 0.48, P = 0.042). These findings indicate that our method for quantitatively measuring reduced facial expressivity during social interactions can be a promising marker for core ASD social symptoms.

Surrogate Model for Recirculation Phase LBLOCA and DET Application

International Nuclear Information System (INIS)

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

2014-01-01

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

Birds as biodiversity surrogates

DEFF Research Database (Denmark)

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

2012-01-01

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

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

DEFF Research Database (Denmark)

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

2007-01-01

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

Higher taxa as surrogates of species richness of spiders in insect-resistant transgenic rice

Institute of Scientific and Technical Information of China (English)

Sheng Lin; Min-Sheng You; Liette Vasseur; Guang Yang; Feng-Jing Liu; Feng Guo

2012-01-01

Biodiversity assessments can often be time- and resource-consuming.Several alternative approaches have been proposed to reduce sampling efforts,including indicator taxa and surrogates.In this study,we examine the reliability of higher taxon surrogates to predict species richness in two experimental rice fields of Fujian Province,southeastern China during 2005 and 2009.Spider samples in transgenic and nontransgenic plots were collected using a suction sampler.Both the genus and family surrogates had significant and positive linear relationships with species richness in the transgenic and nontransgenic rice fields.The rice varieties did not significantly influence the linear relationships.Our findings suggest that higher-taxon surrogacy could be a useful alternative to complete species inventory for risk assessments of transgenic rice.

Anatomical landmarks and skin markers are not reliable for accurate labeling of thoracic vertebrae on MRI

International Nuclear Information System (INIS)

Shabshin, Nogah; Schweitzer, Mark E.; Carrino, John A.

2010-01-01

Background: Numbering of the thoracic spine on MRI can be tedious if C2 and L5-S1 are not included and may lead to errors in lesion level. Purpose: To determine whether anatomic landmarks or external markers are reliable as an aid for accurate numbering of thoracic vertebrae on MRI. Material and Methods: Sixty-seven thoracic spine MR studies of 67 patients (30 males, 37 females, age range 18-83 years) were studied, composed of 52 consecutive MR studies and an additional 15 MRI in which vitamin E markers were placed over the skin. In the 52 thoracic MR examinations potential numbering aids such as the level of the sternal apex, pulmonary artery, aortic arch, and osseous or disc abnormalities were numbered on both cervical localizer (standard of reference) and thoracic sagittal images. The additional 15 examinations in which vitamin E markers were placed over the skin were evaluated for consistency in the level of the markers on different sequences in the same exam. Results: The sternal apex level ranged from T2 to T5 [T3 in 28/51 patients (55%), T2 in 10/51 (20%)]. The aortic arch level ranged from T2 to T4 [T4 in 18/48 (38%) and T3 in 17 (35%)]. Pulmonary artery level ranged from T4 to T6-7 disc [T5 in 20/52 patients (38%) and T6 in 14/52 (27%)]. In 3 of 12 patients who had abnormalities in a vertebral body or disc as definite point reference, the non-localizer image mislabelled the level. In 11/15 (73%) patients with vitamin E markers that were placed over the upper thoracic spine, the results showed consistency in the level of the markers in relation to the reference points or consistent inter-marker gap between the sequences. Conclusion: There are only two reliable ways to accurately define the levels if no landmarking feature is available on the magnet. The first is by including C2 in the thoracic sequence of a diagnostic quality, and the second is by using an abnormality in the discs or vertebral bodies as a point of reference

Anatomical landmarks and skin markers are not reliable for accurate labeling of thoracic vertebrae on MRI

Energy Technology Data Exchange (ETDEWEB)

Shabshin, Nogah (Dept. of Diagnostic Imaging, Chaim Sheba Medical Center, Tel-HaShomer (Israel)), e-mail: shabshin@gmail.com; Schweitzer, Mark E. (Dept. of Diagnostic Imaging, Ottawa Hospital and Univ. of Ottawa, Ottawa (Canada)); Carrino, John A. (Dept. of Radiology, Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States))

2010-11-15

Background: Numbering of the thoracic spine on MRI can be tedious if C2 and L5-S1 are not included and may lead to errors in lesion level. Purpose: To determine whether anatomic landmarks or external markers are reliable as an aid for accurate numbering of thoracic vertebrae on MRI. Material and Methods: Sixty-seven thoracic spine MR studies of 67 patients (30 males, 37 females, age range 18-83 years) were studied, composed of 52 consecutive MR studies and an additional 15 MRI in which vitamin E markers were placed over the skin. In the 52 thoracic MR examinations potential numbering aids such as the level of the sternal apex, pulmonary artery, aortic arch, and osseous or disc abnormalities were numbered on both cervical localizer (standard of reference) and thoracic sagittal images. The additional 15 examinations in which vitamin E markers were placed over the skin were evaluated for consistency in the level of the markers on different sequences in the same exam. Results: The sternal apex level ranged from T2 to T5 [T3 in 28/51 patients (55%), T2 in 10/51 (20%)]. The aortic arch level ranged from T2 to T4 [T4 in 18/48 (38%) and T3 in 17 (35%)]. Pulmonary artery level ranged from T4 to T6-7 disc [T5 in 20/52 patients (38%) and T6 in 14/52 (27%)]. In 3 of 12 patients who had abnormalities in a vertebral body or disc as definite point reference, the non-localizer image mislabelled the level. In 11/15 (73%) patients with vitamin E markers that were placed over the upper thoracic spine, the results showed consistency in the level of the markers in relation to the reference points or consistent inter-marker gap between the sequences. Conclusion: There are only two reliable ways to accurately define the levels if no landmarking feature is available on the magnet. The first is by including C2 in the thoracic sequence of a diagnostic quality, and the second is by using an abnormality in the discs or vertebral bodies as a point of reference

Alanine aminotransferase/aspartate aminotransferase ratio is the best surrogate marker for insulin resistance in non-obese Japanese adults

Directory of Open Access Journals (Sweden)

Kawamoto Ryuichi

2012-10-01

Full Text Available Abstract Background The aim of the present study was to examine how liver markers are associated with insulin resistance in Japanese community-dwelling adults. Methods This cross-sectional study included 587 men aged 58 ± 14 (mean ± standard deviation; range, 20–89 years and 755 women aged 60 ± 12 (range, 21–88 years. The study sample consisted of 998 (74.4% non-obese [body mass index (BMI 2] and 344 (25.6% overweight (BMI ≥25 kg/m2 subjects. Insulin resistance was defined by homeostasis model assessment of insulin resistance (HOMA-IR of at least 2.5, and HOMA-IR and potential confounders were compared between the groups. Areas under the curve (AUC of the receiver operating characteristic curves (ROC were used to compare the power of these serum markers. Results In non-obese subjects, the best marker of insulin resistance was alanine aminotransferase (ALT/aspartate aminotransferase (AST ratio of 0.70 (95% confidence interval (CI, 0.63-0.77. In overweight subjects, AUC values for the ALT/AST ratio and ALT were 0.66 (0.59-0.72 and 0.66 (0.59-0.72, respectively. Multiple linear regression analyses for HOMA-IR showed that ALT/AST ratios were independently and significantly associated with HOMA-IR as well as other confounding factors in both non-obese and overweight subjects. The optimal cut-off point to identifying insulin resistance for these markers yielded the following values: ALT/AST ratio of ≥0.82 in non-obese subjects and ≥1.02 in overweight subjects. In non-obese subjects, the positive likelihood ratio was greatest for ALT/AST ratio. Conclusions In non-obese Japanese adults, ALT/AST ratio may be the best reliable marker of insulin resistance.

Improved Reliability-Based Optimization with Support Vector Machines and Its Application in Aircraft Wing Design

Directory of Open Access Journals (Sweden)

Yu Wang

2015-01-01

Full Text Available A new reliability-based design optimization (RBDO method based on support vector machines (SVM and the Most Probable Point (MPP is proposed in this work. SVM is used to create a surrogate model of the limit-state function at the MPP with the gradient information in the reliability analysis. This guarantees that the surrogate model not only passes through the MPP but also is tangent to the limit-state function at the MPP. Then, importance sampling (IS is used to calculate the probability of failure based on the surrogate model. This treatment significantly improves the accuracy of reliability analysis. For RBDO, the Sequential Optimization and Reliability Assessment (SORA is employed as well, which decouples deterministic optimization from the reliability analysis. The improved SVM-based reliability analysis is used to amend the error from linear approximation for limit-state function in SORA. A mathematical example and a simplified aircraft wing design demonstrate that the improved SVM-based reliability analysis is more accurate than FORM and needs less training points than the Monte Carlo simulation and that the proposed optimization strategy is efficient.

The value of surrogate markers to monitor cholesterol absorption, synthesis and bioconversion to bile acids under lipid lowering therapies.

Science.gov (United States)

Stellaard, Frans; von Bergmann, Klaus; Sudhop, Thomas; Lütjohann, Dieter

2017-05-01

Regulation of cholesterol (Chol) homeostasis is controlled by three main fluxes, i.e. intestinal absorption, de novo synthesis (ChS) and catabolism, predominantly as bile acid synthesis (BAS). High serum total Chol and LDL-Chol concentrations in particular are considered risk factors and markers for the development of atherosclerosis. Pharmaceutical treatments to lower serum Chol have focused on reducing absorption or ChS and increasing BAS. Monitoring of these three parameters is complex involving isotope techniques, cholesterol balance experiments and advanced mass spectrometry based analysis methods. Surrogate markers were explored that require only one single fasting blood sample collection. These markers were validated in specific, mostly physiological conditions and during statin treatment to inhibit ChS. They were also applied under cholesterol absorption restriction, but were not validated in this condition. We retrospectively evaluated the use of serum campesterol (Camp), sitosterol (Sit) and cholestanol (Cholol) as markers for cholesterol absorption, lathosterol (Lath) as marker for ChS and 7α-hydroxycholesterol (7α-OH-Ch) and 27-hydroxycholesterol (27-OH-Ch) as markers for BAS under conditions of Chol absorption restriction. Additionally, their values were corrected for Chol concentration (R_sterol or oxysterols). Thirty-seven healthy male omnivore subjects were studied under treatments with placebo (PLAC), ezetimibe (EZE) to inhibit cholesterol absorption, simvastatin (SIMVA) to reduce cholesterol synthesis and a combination of both (EZE+SIMVA). Results were compared to those obtained in 18 pure vegetarian subjects (vegans) whose dietary Chol intake is extremely low. Relative or fractional Chol absorption (FrChA) was measured with the continuous feeding stable isotope procedure, ChS and BAS with the cholesterol balance method. The daily Chol intake (DICh) was inventoried and the daily Chol absorption (DACh) calculated. Monitoring cholesterol

Surrogate waveform models

Science.gov (United States)

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

2015-04-01

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

Licensing Surrogate Decision-Makers.

Science.gov (United States)

Rosoff, Philip M

2017-06-01

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

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

Science.gov (United States)

Berend, Zsuzsa

2010-06-01

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

Visceral adiposity index may be a surrogate marker for the assessment of the effects of obesity on arterial stiffness.

Directory of Open Access Journals (Sweden)

Fan Yang

Full Text Available The relationship between obesity and cardiovascular disease (CVD remains unclear. This study aims to describe the relationship between arterial stiffness and obesity in order to investigate the effects of obesity on CVD.We collected data from 5,158 individuals over 40 years of age from a cross-sectional study in Nanjing, China. Anthropometric, demographic, hemodynamic measurements and arterial stiffness measured through brachial-ankle pulse wave velocity (baPWV were obtained. Subjects were grouped by body mass index (BMI, waist circumference (WC and visceral adiposity index (VAI, a sex-specific index based on BMI, WC, triglyceride (TG and high-density lipoprotein cholesterol (HDL-C.The multivariate regression analysis revealed a negative but weak effect of BMI (β = -0.047, P0.05, it was still obtained between baPWV and VAI quartile (P0.05. However, baPWV significantly increased across groups with higher VAI categories even in the same metabolic category (P<0.01.This study supports the concept of heterogeneity of metabolic status among individuals within the same obesity range. Obese individuals are at an increased risk of arterial stiffness regardless of their metabolic conditions. VAI may be a surrogate marker for the assessment of obesity and the effects of obesity on arterial stiffness.

Surrogacy: the experiences of surrogate mothers.

Science.gov (United States)

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

2003-10-01

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

Detection of vascular risk markers in children and adolescents with type 1 diabetes.

Science.gov (United States)

Kırmızıbekmez, Heves; Güven, Ayla; Yıldız, Metin; Dursun, Fatma; Cebeci, Nurcan; Hancili, Suna

2014-01-01

Type 1 diabetes is a chronic disease that causes persistent vascular injury. This study investigates the benefits of surrogate markers in early detection of vascular injury in children and adolescents with type 1 diabetes. Eighty-four patients (35 male, 49 female) with type 1 diabetes for 5 or more years were included. Serum lipid profile, plasminogen activator inhibitor-1 (PAI-1), lipoprotein (a) (Lpa) and homocystein, were investigated. Patients were divided into two groups according to the duration of diabetes. Patients with and without microvascular complications were also compared. Microvascular complications were present in 14 out of 48 patients in group-1 (29.1%; duration of diabetes: 5-10 years) and in 7 out of 36 patients in group-2 (19.4%; duration of diabetes: >10 years). Serum homocystein, Lpa, PAI-1 and serum lipids were not correlated with the duration of diabetes. Significantly increased triglyceride (TG) and HbA1C levels were associated with the presence of microvascular complications. Providing good glycemic control is very important for preventing vascular injury in children and adolescents with type 1 diabetes. It seems that traditional vascular surrogate markers like LDL/HDL ratio, triglycerides and HbA1C level correspond more to microvascular complications than newly defined surrogate markers that are not commonly available.

Markers for nutrition studies: review of criteria for the evaluation of markers.

Science.gov (United States)

de Vries, Jan; Antoine, Jean-Michel; Burzykowski, Tomasz; Chiodini, Alessandro; Gibney, Mike; Kuhnle, Gunter; Méheust, Agnès; Pijls, Loek; Rowland, Ian

2013-10-01

Markers are important tools to assess the nutrition status and effects of nutrition interventions. There is currently insufficient consensus in nutrition sciences on how to evaluate markers, despite the need for properly evaluating them. To identify the criteria for the evaluation of markers related to nutrition, health and disease and to propose generic criteria for evaluation. The report on "Evaluation of Biomarker and Surrogate Endpoints in Chronic Disease" from the Institute of Medicine was the starting point for the literature search. Additionally, specific search strategies were developed for Pubmed. In nutrition, no set of criteria or systematic approach to evaluate markers is currently available. There is a reliance on the medical area where statistical methods have been developed to quantify the evaluation of markers. Even here, a systematic approach is lacking-markers are still evaluated on a case-by-case basis. The review of publications from the literature search resulted in a database with definitions, criteria for validity and the rationale behind the criteria. It was recognized that, in nutrition, a number of methodological aspects differ from medical research. The following criteria were identified as essential elements in the evaluation of markers: (1) the marker has a causal biological link with the endpoint, (2) there is a significant association between marker and endpoint in the target population, (3) marker changes consistently with the endpoint, e.g., in response to an intervention, and (4) change in the marker explains a substantial proportion of the change in the endpoint in response to the intervention.

Stability of percutaneously implanted markers for lung stereotactic radiotherapy

DEFF Research Database (Denmark)

Persson, Gitte Bjørnsen Fredberg; Josipovic, Mirjana; Von Der Recke, Peter

2013-01-01

The purpose of this study was to evaluate the stability of complex markers implanted into lung tumors throughout a course of stereotactic body radiotherapy (SBRT). Fifteen patients referred for lung SBRT were prospectively included. Radio-opaque markers were implanted percutaneously, guided...... mm in one or more registrations throughout the SBRT course. This is the first study to evaluate stability of complex markers implanted percutaneously into lung tumors for image guidance in SBRT. We conclude that the observed stability of marker position within the tumor indicates that complex markers...... can be used as surrogates for tumor position during a short course of SBRT as long as the uncertainties related to their position within the tumor are incorporated into the planning target volume....

Ulex Europaeus Agglutinin-1 Is a Reliable Taste Bud Marker for In Situ Hybridization Analyses.

Science.gov (United States)

Yoshimoto, Joto; Okada, Shinji; Kishi, Mikiya; Misaka, Takumi

2016-03-01

Taste signals are received by taste buds. To better understand the taste reception system, expression patterns of taste-related molecules are determined by in situ hybridization (ISH) analyses at the histological level. Nevertheless, even though ISH is essential for determining mRNA expression, few taste bud markers can be applied together with ISH. Ulex europaeus agglutinin-1 (UEA-1) appears to be a reliable murine taste bud marker based on immunohistochemistry (IHC) analyses. However, there is no evidence as to whether UEA-1 can be used for ISH. Thus, the present study evaluated UEA-1 using various histochemical methods, especially ISH. When lectin staining was performed after ISH procedures, UEA-1 clearly labeled taste cellular membranes and distinctly indicated boundaries between taste buds and the surrounding epithelial cells. Additionally, UEA-1 was determined as a taste bud marker not only when used in single-colored ISH but also when employed with double-labeled ISH or during simultaneous detection using IHC and ISH methods. These results suggest that UEA-1 is a useful marker when conducting analyses based on ISH methods. To clarify UEA-1 staining details, multi-fluorescent IHC (together with UEA-1 staining) was examined, resulting in more than 99% of cells being labeled by UEA-1 and overlapping with KCNQ1-expressing cells. © 2016 The Histochemical Society.

Technological advances in suspended‐sediment surrogate monitoring

Science.gov (United States)

Gray, John R.; Gartner, Jeffrey W.

2009-01-01

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 generally immune to effects of biological fouling. Cost of a single‐frequency device is about double that of a turbidimeter. Multifrequency arrays also provide the potential to resolve concentrations by clay silt versus sand size fractions. Multifrequency hydroacoustics shows the most promise for revolutionizing collection of

Emulating facial biomechanics using multivariate partial least squares surrogate models.

Science.gov (United States)

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

2014-11-01

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

Mucorales-specific T cells emerge in the course of invasive mucormycosis and may be used as a surrogate diagnostic marker in high-risk patients.

Science.gov (United States)

Potenza, Leonardo; Vallerini, Daniela; Barozzi, Patrizia; Riva, Giovanni; Forghieri, Fabio; Zanetti, Eleonora; Quadrelli, Chiara; Candoni, Anna; Maertens, Johan; Rossi, Giulio; Morselli, Monica; Codeluppi, Mauro; Paolini, Ambra; Maccaferri, Monica; Del Giovane, Cinzia; D'Amico, Roberto; Rumpianesi, Fabio; Pecorari, Monica; Cavalleri, Francesca; Marasca, Roberto; Narni, Franco; Luppi, Mario

2011-11-17

Mucorales-specific T cells were investigated in 28 hematologic patients during the course of their treatment. Three developed proven invasive mucormycosis (IM), 17 had infections of known origin but other than IM, and 8 never had fever during the period of observation. Mucorales-specific T cells could be detected only in patients with IM, both at diagnosis and throughout the entire course of the IM, but neither before nor for long after resolution of the infection. Such T cells predominantly produced IL-4, IFN-γ, IL-10, and to a lesser extent IL-17 and belonged to either CD4(+) or CD8(+) subsets. The specific T cells that produced IFN-γ were able to directly induce damage to Mucorales hyphae. None of the 25 patients without IM had Mucorales-specific T cells. Specific T cells contribute to human immune responses against fungi of the order Mucorales and could be evaluated as a surrogate diagnostic marker of IM.

WE-AB-303-11: Verification of a Deformable 4DCT Motion Model for Lung Tumor Tracking Using Different Driving Surrogates

Energy Technology Data Exchange (ETDEWEB)

Woelfelschneider, J [University Hospital Erlangen, Erlangen, DE (Germany); Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, DE (Germany); Seregni, M; Fassi, A; Baroni, G; Riboldi, M [Politecnico di Milano, Milano (Italy); Bert, C [University Hospital Erlangen, Erlangen, DE (Germany); Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, DE (Germany); GSI - Helmholtz Centre for Heavy Ion Research, Darmstadt, DE (Germany)

2015-06-15

Purpose: Tumor tracking is an advanced technique to treat intra-fractionally moving tumors. The aim of this study is to validate a surrogate-driven model based on four-dimensional computed tomography (4DCT) that is able to predict CT volumes corresponding to arbitrary respiratory states. Further, the comparison of three different driving surrogates is evaluated. Methods: This study is based on multiple 4DCTs of two patients treated for bronchial carcinoma and metastasis. Analyses for 18 additional patients are currently ongoing. The motion model was estimated from the planning 4DCT through deformable image registration. To predict a certain phase of a follow-up 4DCT, the model considers for inter-fractional variations (baseline correction) and intra-fractional respiratory parameters (amplitude and phase) derived from surrogates. In this evaluation, three different approaches were used to extract the motion surrogate: for each 4DCT phase, the 3D thoraco-abdominal surface motion, the body volume and the anterior-posterior motion of a virtual single external marker defined on the sternum were investigated. The estimated volumes resulting from the model were compared to the ground-truth clinical 4DCTs using absolute HU differences in the lung volume and landmarks localized using the Scale Invariant Feature Transform (SIFT). Results: The results show absolute HU differences between estimated and ground-truth images with median values limited to 55 HU and inter-quartile ranges (IQR) lower than 100 HU. Median 3D distances between about 1500 matching landmarks are below 2 mm for 3D surface motion and body volume methods. The single marker surrogates Result in increased median distances up to 0.6 mm. Analyses for the extended database incl. 20 patients are currently in progress. Conclusion: The results depend mainly on the image quality of the initial 4DCTs and the deformable image registration. All investigated surrogates can be used to estimate follow-up 4DCT phases

A method of surface marker location optimization for tumor motion estimation in lung stereotactic body radiation therapy

International Nuclear Information System (INIS)

Lu, Bo; Park, Justin C.; Fan, Qiyong; Kahler, Darren; Liu, Chihray; Chen, Yunmei

2015-01-01

Purpose: Accurately localizing lung tumor localization is essential for high-precision radiation therapy techniques such as stereotactic body radiation therapy (SBRT). Since direct monitoring of tumor motion is not always achievable due to the limitation of imaging modalities for treatment guidance, placement of fiducial markers on the patient’s body surface to act as a surrogate for tumor position prediction is a practical alternative for tracking lung tumor motion during SBRT treatments. In this work, the authors propose an innovative and robust model to solve the multimarker position optimization problem. The model is able to overcome the major drawbacks of the sparse optimization approach (SOA) model. Methods: The principle-component-analysis (PCA) method was employed as the framework to build the authors’ statistical prediction model. The method can be divided into two stages. The first stage is to build the surrogate tumor matrix and calculate its eigenvalues and associated eigenvectors. The second stage is to determine the “best represented” columns of the eigenvector matrix obtained from stage one and subsequently acquire the optimal marker positions as well as numbers. Using 4-dimensional CT (4DCT) and breath hold CT imaging data, the PCA method was compared to the SOA method with respect to calculation time, average prediction accuracy, prediction stability, noise resistance, marker position consistency, and marker distribution. Results: The PCA and SOA methods which were both tested were on all 11 patients for a total of 130 cases including 4DCT and breath-hold CT scenarios. The maximum calculation time for the PCA method was less than 1 s with 64 752 surface points, whereas the average calculation time for the SOA method was over 12 min with 400 surface points. Overall, the tumor center position prediction errors were comparable between the two methods, and all were less than 1.5 mm. However, for the extreme scenarios (breath hold), the

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

Science.gov (United States)

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

2014-01-01

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

Toward a Psychology of Surrogate Decision Making.

Science.gov (United States)

Tunney, Richard J; Ziegler, Fenja V

2015-11-01

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

Using the rate of bacterial clearance determined by real-time polymerase chain reaction as a timely surrogate marker to evaluate the appropriateness of antibiotic usage in critical patients with Acinetobacter baumannii bacteremia.

Science.gov (United States)

Chuang, Yu-Chung; Chang, Shan-Chwen; Wang, Wei-Kung

2012-08-01

Bacteremia caused by Acinetobacter baumannii is becoming more frequent among critically ill patients, and has been associated with high mortality and prolonged hospital stay. Multidrug resistance and delay in blood culture have been shown to be significant barriers to appropriate antibiotic treatment. Quantitative polymerase chain reaction assays were recently used to monitor bacterial loads; we hypothesized that the rate of bacterial clearance determined by quantitative polymerase chain reaction can be used as a timely surrogate marker to evaluate the appropriateness of antibiotic usage. Prospective observational study. University hospital and research laboratory. Patients with culture-proven A. baumannii bacteremia in the intensive care units were prospectively enrolled from April 2008 to February 2009. Plasmid Oxa-51/pCRII-TOPO, which contained a 431-bp fragment of the A. baumannii-specific Oxa-51 gene in a pCRII-TOPO vector, was used as the standard. Sequential bacterial DNA loads in the blood were measured by a quantitative polymerase chain reaction assay. We enrolled 51 patients with A. baumannii bacteremia, and examined 318 sequential whole blood samples. The initial mean bacterial load was 2.15 log copies/mL, and the rate of bacterial clearance was 0.088 log copies/mL/day. Multivariate linear regression using the generalized estimation equation approach revealed that the use of immunosuppressants was an independent predictor for slower bacterial clearance (coefficient, 1.116; pcritical patients. These findings highlight the importance of appropriate antibiotic usage and development of effective antibiotics against A. baumannii in an era of emerging antibiotic resistance. The rate of bacterial clearance could serve as a timely surrogate marker for evaluating the appropriateness of antibiotics.

Breast Cancer Survival Defined by the ER/PR/HER2 Subtypes and a Surrogate Classification according to Tumor Grade and Immunohistochemical Bio markers

International Nuclear Information System (INIS)

Parise, C. A.; Caggiano, V.

2014-01-01

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.

Use of Surrogate end points in HTA

Directory of Open Access Journals (Sweden)

Mangiapane, Sandra

2009-08-01

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

Sequential optimization and reliability assessment method for metal forming processes

International Nuclear Information System (INIS)

Sahai, Atul; Schramm, Uwe; Buranathiti, Thaweepat; Chen Wei; Cao Jian; Xia, Cedric Z.

2004-01-01

Uncertainty is inevitable in any design process. The uncertainty could be due to the variations in geometry of the part, material properties or due to the lack of knowledge about the phenomena being modeled itself. Deterministic design optimization does not take uncertainty into account and worst case scenario assumptions lead to vastly over conservative design. Probabilistic design, such as reliability-based design and robust design, offers tools for making robust and reliable decisions under the presence of uncertainty in the design process. Probabilistic design optimization often involves double-loop procedure for optimization and iterative probabilistic assessment. This results in high computational demand. The high computational demand can be reduced by replacing computationally intensive simulation models with less costly surrogate models and by employing Sequential Optimization and reliability assessment (SORA) method. The SORA method uses a single-loop strategy with a series of cycles of deterministic optimization and reliability assessment. The deterministic optimization and reliability assessment is decoupled in each cycle. This leads to quick improvement of design from one cycle to other and increase in computational efficiency. This paper demonstrates the effectiveness of Sequential Optimization and Reliability Assessment (SORA) method when applied to designing a sheet metal flanging process. Surrogate models are used as less costly approximations to the computationally expensive Finite Element simulations

Surrogate versus couple therapy in vaginismus.

Science.gov (United States)

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

2007-05-01

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

Nonspinning numerical relativity waveform surrogates: assessing the model

Science.gov (United States)

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

2015-04-01

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

ETHICAL ISSUES IN THE SURROGATE MATERNITY PRACTICE

OpenAIRE

TÜRK, Rukiye; TERZİOĞLU, Fusun

2014-01-01

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

Psychosocial aspects of surrogate motherhood.

Science.gov (United States)

van den Akker, Olga B A

2007-01-01

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

Evaluating the immortal strand hypothesis in cancer stem cells: symmetric/self-renewal as the relevant surrogate marker of tumorigenicity.

Science.gov (United States)

Winquist, Raymond J; Hall, Amy B; Eustace, Brenda K; Furey, Brinley F

2014-09-15

Stem cells subserve repair functions for the lifetime of the organism but, as a consequence of this responsibility, are candidate cells for accumulating numerous genetic and/or epigenetic aberrations leading to malignant transformation. However, given the importance of this guardian role, stem cells likely harbor some process for maintaining their precious genetic code such as non-random segregation of chromatid strands as predicted by the Immortal Strand Hypothesis (ISH). Discerning such non-random chromosomal segregation and asymmetric cell division in normal or cancer stem cells has been complicated by methodological shortcomings but also by differing division kinetics amongst tissues and the likelihood that both asymmetric and symmetric cell divisions, dictated by local extrinsic factors, are operant in these cells. Recent data suggest that cancer stem cells demonstrate a higher incidence of symmetric versus asymmetric cell division with both daughter cells retaining self-renewal characteristics, a profile which may underlie poorly differentiated morphology and marked clonal diversity in tumors. Pathways and targets are beginning to emerge which may provide opportunities for preventing such a predilection in cancer stem cells and that will hopefully translate into new classes of chemotherapeutics in oncology. Thus, although the existence of the ISH remains controversial, the shift of cell division dynamics to symmetric random chromosome segregation/self-renewal, which would negate any likelihood of template strand retention, appears to be a surrogate marker for the presence of highly malignant tumorigenic cell populations. Copyright © 2014 Elsevier Inc. All rights reserved.

Surrogate Analysis and Index Developer (SAID) tool

Science.gov (United States)

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

2015-10-01

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

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

Directory of Open Access Journals (Sweden)

Kangsoo Kim

2017-07-01

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

Ethical Problems Related to Surrogate Motherhood

OpenAIRE

Erdem Aydin

2006-01-01

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

Role of Soluble ST2 as a Marker for Rejection after Heart Transplant

OpenAIRE

Lee, Ga Yeon; Choi, Jin-Oh; Ju, Eun-Seon; Lee, Yoo-Jung; Jeon, Eun-Seok

2016-01-01

Background and Objectives Endomyocardial biopsy is obligatory during the first year after heart transplant (HTx) for the surveillance of acute rejection. Previous attempts using cardiac biomarkers for the detection of rejection failed to show enough evidence to substitute endomyocardial biopsy. Therefore, this study sought the possibility of using soluble ST2 (sST2), a novel cardiovascular marker, as a surrogate marker for acute allograft rejection after HTx. Subjects and Methods A total of 4...

Recent progress in gasoline surrogate fuels

KAUST Repository

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

2017-01-01

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

Recent progress in gasoline surrogate fuels

KAUST Repository

Sarathy, Mani

2017-12-06

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

Overview of selected surrogate technologies for high-temporal resolution suspended-sediment monitoring

Science.gov (United States)

Gray, John R.; Gartner, Jeffrey W.

2010-01-01

Traditional methods for characterizing selected properties of suspended sediments in rivers are being augmented and in some cases replaced by cost-effective surrogate instruments and methods that produce a temporally dense time series of quantifiably accurate data for use primarily in sediment-flux computations. Turbidity is the most common such surrogate technology, and the first to be sanctioned by the U.S. Geological Survey for use in producing data used in concert with water-discharge data to compute sediment concentrations and fluxes for storage in the National Water Information System. Other technologies, including laser-diffraction, digital photo-optic, acoustic-attenuation and backscatter, and pressure-difference techniques are being evaluated for producing reliable sediment concentration and, in some cases, particle-size distribution data. Each technology addresses a niche for sediment monitoring. Their performances range from compelling to disappointing. Some of these technologies have the potential to revolutionize fluvial-sediment data collection, analysis, and availability.

Hypothesis test for synchronization: twin surrogates revisited.

Science.gov (United States)

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

2009-03-01

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

So not mothers: responsibility for surrogate orphans.

Science.gov (United States)

Parks, Jennifer A; Murphy, Timothy F

2018-04-12

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

Surrogate Modeling for Geometry Optimization

DEFF Research Database (Denmark)

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

2009-01-01

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

Neutron-induced cross-sections via the surrogate method

International Nuclear Information System (INIS)

Boutoux, G.

2011-11-01

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

Variable expression of molecular markers in juvenile nasopharyngeal angiofibroma.

Science.gov (United States)

Mishra, A; Pandey, A; Mishra, S C

2017-09-01

Molecular categorisation may explain the wide variation in the clinical characteristics of juvenile nasopharyngeal angiofibroma. Variations in molecular markers in juvenile nasopharyngeal angiofibroma in an Indian population were investigated and compared with global reports. Variable molecular marker expression was demonstrated at the regional and global levels. A wide variation in molecular characteristics is evident. Molecular data have been reported for only 11 countries, indicating a clear geographical bias. Only 58 markers have been studied, and most are yet to be validated. Research into the molecular epidemiology of juvenile nasopharyngeal angiofibroma is still in its infancy. Although the molecular variation is not well understood, data obtained so far have prompted important research questions. Hence, multicentre collaborative molecular studies are needed to establish the aetiopathogenesis and establish molecular surrogates for clinical characteristics.

Bedload-surrogate monitoring technologies

Science.gov (United States)

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

2010-01-01

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

Ethical Problems Related to Surrogate Motherhood

Directory of Open Access Journals (Sweden)

Erdem Aydin

2006-03-01

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

OCT4 and SOX2 are reliable markers in detecting stem cells in odontogenic lesions

Directory of Open Access Journals (Sweden)

Abhishek Banerjee

2016-01-01

Full Text Available Context (Background: Stem cells are a unique subpopulation of cells in the human body with a capacity to initiate differentiation into various cell lines. Tumor stem cells (TSCs are a unique subpopulation of cells that possess the ability to initiate a neoplasm and sustain self-renewal. Epithelial stem cell (ESC markers such as octamer-binding transcription factor 4 (OCT4 and sex-determining region Y (SRY-box 2 (SOX2 are capable of identifying these stem cells expressed during the early stages of tooth development. Aims: To detect the expression of the stem cell markers OCT4 and SOX2 in the normal odontogenic tissues and the odontogenic cysts and tumors. Materials and Methods: Paraffin sections of follicular tissue, radicular cyst, dentigerous cyst, odontogenic keratocyst, ameloblastoma, adenomatoid odontogenic tumor, and ameloblastic carcinoma were obtained from the archives. The sections were subjected to immunohistochemical assay by the use of mouse monoclonal antibodies to OCT4 and SOX2. Statistical Analysis: The results were evaluated by descriptive analysis. Results: The results show the presence of stem cells in the normal and lesional tissues with these stem cell identifying markers. SOX2 was found to be more consistent and reliable in the detection of stem cells. Conclusion: The stem cell expressions are maintained in the tumor transformation of tissue and probably suggest that there is no phenotypic change of stem cells in progression from normal embryonic state to its tumor component. The quantification and localization reveals interesting trends that indicate the probable role of the cells in the pathogenesis of the lesions.

The Reparative Motive in Surrogate Mothers.

Science.gov (United States)

Kanefield, Linda

1999-01-01

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

Imaging Seeker Surrogate for IRCM evaluation

NARCIS (Netherlands)

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

2007-01-01

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

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

Science.gov (United States)

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

2018-02-23

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

34 CFR 303.406 - Surrogate parents.

Science.gov (United States)

2010-07-01

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

34 CFR 300.519 - Surrogate parents.

Science.gov (United States)

2010-07-01

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

Cross-parent reliability in rating ASD markers in infants.

Science.gov (United States)

Ben-Sasson, Ayelet; Amit-Ben-Simhon, Hemda; Meyer, Sonya

2015-06-01

To investigate the congruence and discrepancies between mother and father reports of early autism spectrum disorders (ASD) markers. Mothers (n = 80) and fathers (n = 78) of 12-month-old infants (55% boys) completed the first year inventory (FYI), an ASD norm-referenced screening questionnaire. Mothers also completed the Infant Toddler Social Emotional Assessment (ITSEA). There were significant and moderate intra-class correlations between mother and father reports for most FYI factors. Fathers' median FYI social-communication domain score was almost twice that of mothers. Mann-Whitney tests indicated that fathers rated their child significantly higher than mothers on the four FYI social-communication factors and on the sensory processing factor. Linear weighted kappa analyses indicated poor agreement on gaze-related and reactivity FYI items. FYI social-communication and sensory-regulatory factors showed significant correlations with corresponding ITSEA scores. Social-communication markers pose a greater challenge for consistent report across parents than sensory-regulatory markers.

Interpretations, perspectives and intentions in surrogate motherhood

OpenAIRE

van Zyl, L.; van Niekerk, A.

2000-01-01

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

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

International Nuclear Information System (INIS)

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

2017-01-01

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

The Summating Potential Is a Reliable Marker of Electrode Position in Electrocochleography: Cochlear Implant as a Theragnostic Probe.

Science.gov (United States)

Helmstaedter, Victor; Lenarz, Thomas; Erfurt, Peter; Kral, Andrej; Baumhoff, Peter

2017-12-14

For the increasing number of cochlear implantations in subjects with residual hearing, hearing preservation, and thus the prevention of implantation trauma, is crucial. A method for monitoring the intracochlear position of a cochlear implant (CI) and early indication of imminent cochlear trauma would help to assist the surgeon to achieve this goal. The aim of this study was to evaluate the reliability of the different electric components recorded by an intracochlear electrocochleography (ECochG) as markers for the cochleotopic position of a CI. The measurements were made directly from the CI, combining intrasurgical diagnostics with the therapeutical use of the CI, thus, turning the CI into a "theragnostic probe." Intracochlear ECochGs were measured in 10 Dunkin Hartley guinea pigs of either sex, with normal auditory brainstem response thresholds. All subjects were fully implanted (4 to 5 mm) with a custom six contact CI. The ECochG was recorded simultaneously from all six contacts with monopolar configuration (retroauricular reference electrode). The gross ECochG signal was filtered off-line to separate three of its main components: compound action potential, cochlear microphonic, and summating potential (SP). Additionally, five cochleae were harvested and histologically processed to access the spatial position of the CI contacts. Both ECochG data and histological reconstructions of the electrode position were fitted with the Greenwood function to verify the reliability of the deduced cochleotopic position of the CI. SPs could be used as suitable markers for the frequency position of the recording electrode with an accuracy of ±1/4 octave in the functioning cochlea, verified by histology. Cochlear microphonics showed a dependency on electrode position but were less reliable as positional markers. Compound action potentials were not suitable for CI position information but were sensitive to "cochlear health" (e.g., insertion trauma). SPs directly recorded from

Nogo-A is a reliable oligodendroglial marker in adult human and mouse CNS and in demyelinated lesions

DEFF Research Database (Denmark)

Kuhlmann, Tanja; Remington, Leah; Maruschak, Brigitte

2007-01-01

to be strongly expressed in mature oligodendrocytes in vivo. In the present investigation we analyzed the expression patterns of Nogo-A in adult mouse and human CNS as well as in demyelinating animal models and multiple sclerosis lesions. Nogo-A expression was compared with that of other frequently used...... oligodendroglial markers such as CC1, CNP, and in situ hybridization for proteolipid protein mRNA. Nogo-A strongly and reliably labeled oligodendrocytes in the adult CNS as well as in demyelinating lesions and thus represents a valuable tool for the identification of oligodendrocytes in human and mouse CNS tissue...

Procalcitonin is not sufficiently reliable to be the sole marker of neonatal sepsis of nosocomial origin

Directory of Open Access Journals (Sweden)

Moro Serrano Manuel

2006-05-01

Full Text Available Abstract Background It has recently been suggested that serum procalcitonin (PCT is of value in the diagnosis of neonatal sepsis, with varying results. The aim of this prospective multicenter study was to assess the usefulness of PCT as a marker of neonatal sepsis of nosocomial origin. Methods One hundred infants aged between 4 and 28 days of life admitted to the Neonatology Services of 13 acute-care teaching hospitals in Spain over 1-year with clinical suspicion of neonatal sepsis of nosocomial origin were included in the study. Serum PCT concentrations were determined by a specific immunoluminometric assay. The reliability of PCT for the diagnosis of nosocomial neonatal sepsis at the time of suspicion of infection and at 12–24 h and 36–48 h after the onset of symptoms was calculated by receiver-operating characteristics (ROC curves. The Youden's index (sensitivity + specificity - 1 was used for determination of optimal cutoff values of the diagnostic tests in the different postnatal periods. Sensitivity, specificity, and the likelihood ratio of a positive and negative result with the 95% confidence interval (CI were calculated. Results The diagnosis of nosocomial sepsis was confirmed in 61 neonates. Serum PCT concentrations were significantly higher at initial suspicion and at 12–24 h and 36–48 h after the onset of symptoms in neonates with confirmed sepsis than in neonates with clinically suspected but not confirmed sepsis. Optimal PCT thresholds according to ROC curves were 0.59 ng/mL at the time of suspicion of sepsis (sensitivity 81.4%, specificity 80.6%; 1.34 ng/mL within 12–24 h of birth (sensitivity 73.7%, specificity 80.6%, and 0.69 ng/mL within 36–48 h of birth (sensitivity 86.5%, specificity 72.7%. Conclusion Serum PCT concentrations showed a moderate diagnostic reliability for the detection of nosocomial neonatal sepsis from the time of suspicion of infection. PCT is not sufficiently reliable to be the sole marker of

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

International Nuclear Information System (INIS)

Methy, Nicolas; Bedenne, Laurent; Bonnetain, Franck

2010-01-01

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

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

Science.gov (United States)

Methy, Nicolas; Bedenne, Laurent; Bonnetain, Franck

2010-06-10

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

Surrogate-Based Optimization of Biogeochemical Transport Models

Science.gov (United States)

Prieß, Malte; Slawig, Thomas

2010-09-01

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

Visit-to-visit blood pressure variability as a prognostic marker in patients with cardiovascular and cerebrovascular diseases--relationships and comparisons with vascular markers of atherosclerosis.

Science.gov (United States)

Lau, Kui Kai; Wong, Yuen Kwun; Chan, Yap Hang; Teo, Kay Cheong; Chan, Koon Ho; Wai Li, Leonard Sheung; Cheung, Raymond Tak Fai; Siu, Chung Wah; Ho, Shu Leong; Tse, Hung Fat

2014-07-01

Visit-to-visit blood pressure variability (BPV) is a simple surrogate marker for the development of atherosclerotic diseases, cardiovascular and all-cause mortality. Nevertheless, the relative prognostic value of BPV in comparison with other established vascular assessments remain uncertain. We prospectively followed-up 656 high-risk patients with diabetes or established cardiovascular or cerebrovascular diseases for the occurrence of major adverse cardiovascular events (MACEs). Baseline brachial endothelial function, carotid intima-media thickness (IMT) and plaque burden, ankle-brachial index and arterial stiffness were determined. Visit-to-visit BPV were recorded during a mean 18 ± 9 outpatient clinic visits. After a mean 81 ± 12 month's follow-up, 123 patients (19%) developed MACEs. Patients who developed a MACE had significantly higher systolic BPV, more severe endothelial function, arterial stiffness and systemic atherosclerotic burden compared to patients who did not develop a MACE (all Parea under receiver operating characteristic curve (AUC) 0.69 ± 0.03, PAUC 0.65 ± 0.03, P<0.01). After adjustment of confounding factors, a high BPV remained a significant independent predictor of MACE (hazards ratio 1.67, 95% confidence interval 1.14-2.43, P<0.01). Compared with established surrogate markers of atherosclerosis, visit-to-visit BPV provides similar prognostic information and may represent a new and simple marker for adverse outcomes in patients with vascular diseases. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

[Immunological Markers in Organ Transplantation].

Science.gov (United States)

Beckmann, J H; Heits, N; Braun, F; Becker, T

2017-04-01

The immunological monitoring in organ transplantation is based mainly on the determination of laboratory parameters as surrogate markers of organ dysfunction. Structural damage, caused by alloreactivity, can only be detected by invasive biopsy of the graft, which is why inevitably rejection episodes are diagnosed at a rather progressive stage. New non-invasive specific markers that enable transplant clinicians to identify rejection episodes at an earlier stage, on the molecular level, are needed. The accurate identification of rejection episodes and the establishment of operational tolerance permit early treatment or, respectively, a controlled cessation of immunosuppression. In addition, new prognostic biological markers are expected to allow a pre-transplant risk stratification thus having an impact on organ allocation and immunosuppressive regimen. New high-throughput screening methods allow simultaneous examination of hundreds of characteristics and the generation of specific biological signatures, which might give concrete information about acute rejection, chronic dysfunction as well as operational tolerance. Even though multiple studies and a variety of publications report about important advances on this subject, almost no new biological marker has been implemented in clinical practice as yet. Nevertheless, new technologies, in particular analysis of the genome, transcriptome, proteome and metabolome will make personalised transplantation medicine possible and will further improve the long-term results and graft survival rates. This article gives a survey of the limitations and possibilities of new immunological markers in organ transplantation. Georg Thieme Verlag KG Stuttgart · New York.

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

Science.gov (United States)

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

2016-01-01

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

Molecular Pathology: Predictive, Prognostic, and Diagnostic Markers in Uterine Tumors.

Science.gov (United States)

Ritterhouse, Lauren L; Howitt, Brooke E

2016-09-01

This article focuses on the diagnostic, prognostic, and predictive molecular biomarkers in uterine malignancies, in the context of morphologic diagnoses. The histologic classification of endometrial carcinomas is reviewed first, followed by the description and molecular classification of endometrial epithelial malignancies in the context of histologic classification. Taken together, the molecular and histologic classifications help clinicians to approach troublesome areas encountered in clinical practice and evaluate the utility of molecular alterations in the diagnosis and subclassification of endometrial carcinomas. Putative prognostic markers are reviewed. The use of molecular alterations and surrogate immunohistochemistry as prognostic and predictive markers is also discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Magnetic Resonance Imaging–Guided versus Surrogate-Based Motion Tracking in Liver Radiation Therapy: A Prospective Comparative Study

Energy Technology Data Exchange (ETDEWEB)

Paganelli, Chiara, E-mail: chiara.paganelli@polimi.it [Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano (Italy); Seregni, Matteo; Fattori, Giovanni [Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano (Italy); Summers, Paul [Division of Radiology, Istituto Europeo di Oncologia, Milano (Italy); Bellomi, Massimo [Division of Radiology, Istituto Europeo di Oncologia, Milano (Italy); Department of Health Sciences, Università degli Studi di Milano, Milano (Italy); Baroni, Guido; Riboldi, Marco [Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano (Italy); Bioengineering Unit, CNAO Foundation, Pavia (Italy)

2015-03-15

Purpose: This study applied automatic feature detection on cine–magnetic resonance imaging (MRI) liver images in order to provide a prospective comparison between MRI-guided and surrogate-based tracking methods for motion-compensated liver radiation therapy. Methods and Materials: In a population of 30 subjects (5 volunteers plus 25 patients), 2 oblique sagittal slices were acquired across the liver at high temporal resolution. An algorithm based on scale invariant feature transform (SIFT) was used to extract and track multiple features throughout the image sequence. The position of abdominal markers was also measured directly from the image series, and the internal motion of each feature was quantified through multiparametric analysis. Surrogate-based tumor tracking with a state-of-the-art external/internal correlation model was simulated. The geometrical tracking error was measured, and its correlation with external motion parameters was also investigated. Finally, the potential gain in tracking accuracy relying on MRI guidance was quantified as a function of the maximum allowed tracking error. Results: An average of 45 features was extracted for each subject across the whole liver. The multi-parametric motion analysis reported relevant inter- and intrasubject variability, highlighting the value of patient-specific and spatially-distributed measurements. Surrogate-based tracking errors (relative to the motion amplitude) were were in the range 7% to 23% (1.02-3.57mm) and were significantly influenced by external motion parameters. The gain of MRI guidance compared to surrogate-based motion tracking was larger than 30% in 50% of the subjects when considering a 1.5-mm tracking error tolerance. Conclusions: Automatic feature detection applied to cine-MRI allows detailed liver motion description to be obtained. Such information was used to quantify the performance of surrogate-based tracking methods and to provide a prospective comparison with respect to MRI

Altruistic surrogacy: the necessary objectification of surrogate mothers.

Science.gov (United States)

Tieu, M M

2009-03-01

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

AK-SYS: An adaptation of the AK-MCS method for system reliability

International Nuclear Information System (INIS)

Fauriat, W.; Gayton, N.

2014-01-01

A lot of research work has been proposed over the last two decades to evaluate the probability of failure of a structure involving a very time-consuming mechanical model. Surrogate model approaches based on Kriging, such as the Efficient Global Reliability Analysis (EGRA) or the Active learning and Kriging-based Monte-Carlo Simulation (AK-MCS) methods, are very efficient and each has advantages of its own. EGRA is well suited to evaluating small probabilities, as the surrogate can be used to classify any population. AK-MCS is built in relation to a given population and requires no optimization program for the active learning procedure to be performed. It is therefore easier to implement and more likely to spend computational effort on areas with a significant probability content. When assessing system reliability, analytical approaches and first-order approximation are widely used in the literature. However, in the present paper we rather focus on sampling techniques and, considering the recent adaptation of the EGRA method for systems, a strategy is presented to adapt the AK-MCS method for system reliability. The AK-SYS method, “Active learning and Kriging-based SYStem reliability method”, is presented. Its high efficiency and accuracy are illustrated via various examples

Cross Sections for Neutron-induced Reactions on Actinide Targets Extracted from Surrogate Experiments: A Status Report

International Nuclear Information System (INIS)

Escher, J.E.; Burke, J.T.; Dietrich, F.S.; Lesher, S.R.; Scielzo, N.D.; Thompson, I.J.; Younes, W.

2009-01-01

The Surrogate nuclear reactions method, an indirect approach for determining cross sections for compound-nuclear reactions involving difficult-to-measure targets, is reviewed. Focusing on cross sections for neutron-induced reactions on actinides, we review the successes of past and present applications of the method and assess its uncertainties and limitations. The approximations used in the analyses of most experiments work reasonably well for (n,f) cross sections for neutron energies above 1-2 MeV, but lead to discrepancies for low-energy (n,f) reactions, as well as for (n,γ) applications. Correcting for some of the effects neglected in the approximate analyses leads to improved (n,f) results. We outline steps that will further improve the accuracy and reliability of the Surrogate method and extend its applicability to reactions that cannot be approached with the present implementation of the method.

Cross Sections for Neutron-induced Reactions on Actinide Targets Extracted from Surrogate Experiments: A Status Report

Energy Technology Data Exchange (ETDEWEB)

Escher, J E; Burke, J T; Dietrich, F S; Lesher, S R; Scielzo, N D; Thompson, I J; Younes, W

2009-10-01

The Surrogate nuclear reactions method, an indirect approach for determining cross sections for compound-nuclear reactions involving difficult-to-measure targets, is reviewed. Focusing on cross sections for neutron-induced reactions on actinides, we review the successes of past and present applications of the method and assess its uncertainties and limitations. The approximations used in the analyses of most experiments work reasonably well for (n,f) cross sections for neutron energies above 1-2 MeV, but lead to discrepancies for low-energy (n,f) reactions, as well as for (n,{gamma}) applications. Correcting for some of the effects neglected in the approximate analyses leads to improved (n,f) results. We outline steps that will further improve the accuracy and reliability of the Surrogate method and extend its applicability to reactions that cannot be approached with the present implementation of the method.

A novel surrogate index for hepatic insulin resistance.

LENUS (Irish Health Repository)

Vangipurapu, J

2011-03-01

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

Attitudes toward surrogate motherhood in Canada.

Science.gov (United States)

Krishnan, V

1994-01-01

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

Triglyceride Glucose-Body Mass Index Is a Simple and Clinically Useful Surrogate Marker for Insulin Resistance in Nondiabetic Individuals.

Science.gov (United States)

Er, Leay-Kiaw; Wu, Semon; Chou, Hsin-Hua; Hsu, Lung-An; Teng, Ming-Sheng; Sun, Yu-Chen; Ko, Yu-Lin

2016-01-01

Insulin resistance (IR) and the consequences of compensatory hyperinsulinemia are pathogenic factors for a set of metabolic abnormalities, which contribute to the development of diabetes mellitus and cardiovascular diseases. We compared traditional lipid levels and ratios and combined them with fasting plasma glucose (FPG) levels or adiposity status for determining their efficiency as independent risk factors for IR. We enrolled 511 Taiwanese individuals for the analysis. The clinical usefulness of various parameters--such as traditional lipid levels and ratios; visceral adiposity indicators, visceral adiposity index (VAI), and lipid accumulation product (LAP); the product of triglyceride (TG) and FPG (the TyG index); TyG with adiposity status (TyG-body mass index [BMI]) and TyG-waist circumference index [WC]); and adipokine levels and ratios--was analyzed to identify IR. For all lipid ratios, the TG/high-density lipoprotein cholesterol (HDL-C) ratio had the highest additional percentage of variation in the homeostasis model assessment of insulin resistance (HOMA-IR; 7.0% in total); for all variables of interest, TyG-BMI and leptin-adiponectin ratio (LAR) were strongly associated with HOMA-IR, with 16.6% and 23.2% of variability, respectively. A logistic regression analysis revealed similar patterns. A receiver operating characteristic (ROC) curve analysis indicated that TG/HDL-C was a more efficient IR discriminator than other lipid variables or ratios. The area under the ROC curve (AUC) for VAI (0.734) and TyG (0.708) was larger than that for TG/HDL-C (0.707). TyG-BMI and LAR had the largest AUC (0.801 and 0.801, respectively). TyG-BMI is a simple, powerful, and clinically useful surrogate marker for early identification of IR.

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

Directory of Open Access Journals (Sweden)

Bonnetain Franck

2010-06-01

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

Impact of deep coalescence on the reliability of species tree inference from different types of DNA markers in mammals.

Directory of Open Access Journals (Sweden)

Alejandro Sánchez-Gracia

Full Text Available An important challenge for phylogenetic studies of closely related species is the existence of deep coalescence and gene tree heterogeneity. However, their effects can vary between species and they are often neglected in phylogenetic analyses. In addition, a practical problem in the reconstruction of shallow phylogenies is to determine the most efficient set of DNA markers for a reliable estimation. To address these questions, we conducted a multilocus simulation study using empirical values of nucleotide diversity and substitution rates obtained from a wide range of mammals and evaluated the performance of both gene tree and species tree approaches to recover the known speciation times and topological relationships. We first show that deep coalescence can be a serious problem, more than usually assumed, for the estimation of speciation times in mammals using traditional gene trees. Furthermore, we tested the performance of different sets of DNA markers in the determination of species trees using a coalescent approach. Although the best estimates of speciation times were obtained, as expected, with the use of an increasing number of nuclear loci, our results show that similar estimations can be obtained with a much lower number of genes and the incorporation of a mitochondrial marker, with its high information content. Thus, the use of the combined information of both nuclear and mitochondrial markers in a species tree framework is the most efficient option to estimate recent speciation times and, consequently, the underlying species tree.

Tumour markers in urology

International Nuclear Information System (INIS)

Schmid, L.; Fornara, P.; Fabricius, P.G.

1988-01-01

The same applies essentially also for the bladder carcinomas: There is no reliable marker for these cancers which would be useful for clinical purposes. TPA has proven to be too non-specific in malignoma-detection and therefore hardly facilitates clinical decision-making in individual cases. The CEA is not sensitive enough to be recommendable for routine application. However, in advanced stages a CEA examination may be useful if applied within the scope of therapeutic efforts made to evaluate efficacy. In cases of carcinomas of the prostate the sour prostate-specific phosphatase (SPP) and, more recently, especially the prostate-specific antigen (PSA) have proven in follow-up and therapy monitoring, whereby the PSA is superior to the SPP. Nevertheless, both these markers should be employed in therapy monitoring because differences in behaviour will be observed when the desired treatment effect is only achieved in one of the two markers producing tumour cell clonuses. Both markers, but especially the PSA, are quite reliably in agreement with the result of the introduced chemo-/hormone therapy, whereby an increase may be a sure indicator of relapse several months previous to clinical symptoms, imaging procedures, so-called routine laboratory results and subjective complaints. However, none of the 2 markers is appropriate for the purposes of screening or early diagnosis of carcinomas of the prostate. (orig.) [de

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

KAUST Repository

Abdul Jameel, Abdul Gani

2018-03-20

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

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

KAUST Repository

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

2018-01-01

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

BMI calculation in older people: The effect of using direct and surrogate measures of height in a community-based setting.

Science.gov (United States)

Butler, Rose; McClinchy, Jane; Morreale-Parker, Claudia; Marsh, Wendy; Rennie, Kirsten L

2017-12-01

There is currently no consensus on which measure of height should be used in older people's body mass index (BMI) calculation. Most estimates of nutritional status include a measurement of body weight and height which should be reliable and accurate, however at present several different methods are used interchangeably. BMI, a key marker in malnutrition assessment, does not reflect age-related changes in height or changes in body composition such as loss of muscle mass or presence of oedema. The aim of this pilot study was to assess how the use of direct and surrogate measures of height impacts on BMI calculation in people aged ≥75 years. A cross-sectional study of 64 free-living older people (75-96 yrs) quantified height by two direct measurements, current height (H C ), and self-report (H R ) and surrogate equations using knee height (H K ) and ulna length (H U ). BMI calculated from current height measurement (BMI C ) was compared with BMI calculated using self-reported height (BMI R ) and height estimated from surrogate equations for knee height (BMI K ) and ulna length (BMI U ). Median difference of BMI C -BMI R was 2.31 kg/m 2 . BMI K gave the closest correlation to BMI C . The percentage of study participants identified at increased risk of under-nutrition (BMI BMI; from 5% (BMI C ), 7.8% (BMI K ), 12.5% (BMI U ), to 14% (BMI R ) respectively. The results of this pilot study in a relatively healthy sample of older people suggest that interchangeable use of current and reported height in people ≥75 years can introduce substantial significant systematic error. This discrepancy could impact nutritional assessment of older people in poor health and lead to misclassification during nutritional screening if other visual and clinical clues are not taken into account. This could result in long-term clinical and cost implications if individuals who need nutrition support are not correctly identified. A consensus is required on which method should be used to

The Different Moral Bases of Patient and Surrogate Decision-Making.

Science.gov (United States)

Brudney, Daniel

2018-01-01

My topic is a problem with our practice of surrogate decision-making in health care, namely, the problem of the surrogate who is not doing her job-the surrogate who cannot be reached or the surrogate who seems to refuse to understand or to be unable to understand the clinical situation. The analysis raises a question about the surrogate who simply disagrees with the medical team. One might think that such a surrogate is doing her job-the team just doesn't like how she is doing it. My analysis raises the question of whether (or perhaps when) she should be overridden. In approaching this problem, I focus not on the range of difficulties in practice but on the underlying moral conceptual issue. My concern will be to show that the moral values that underpin patient decision-making are fundamentally different from those that underpin surrogate decision-making. Identifying the distinctions will set parameters for any successful solution to the "Who should decide?" A patient has a specific kind of moral right to make her own medical decisions. A surrogate has no analogous moral right to decide for someone else. We want the surrogate to make the decision because we believe that she has a relevant epistemological advantage over anyone else on the scene. If and when she has no such advantage or if she refuses or is unable to use it, then there might not be sufficient reason to let her be the decision-maker. © 2018 The Hastings Center.

Evaluation and comparison of predictive individual-level general surrogates.

Science.gov (United States)

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

2018-07-01

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

Statistical characteristics of surrogate data based on geophysical measurements

Directory of Open Access Journals (Sweden)

V. Venema

2006-01-01

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

Multiple Surrogate Modeling for Wire-Wrapped Fuel Assembly Optimization

International Nuclear Information System (INIS)

Raza, Wasim; Kim, Kwang-Yong

2007-01-01

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

Reduced cost mission design using surrogate models

Science.gov (United States)

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

2016-01-01

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

Active Subspaces for Wind Plant Surrogate Modeling

Energy Technology Data Exchange (ETDEWEB)

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

2018-01-12

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

Biological markers of Alzheimer?s disease

Directory of Open Access Journals (Sweden)

Leonardo Cruz de Souza

2014-03-01

Full Text Available The challenges for establishing an early diagnosis of Alzheimer’s disease (AD have created a need for biomarkers that reflect the core pathology of the disease. The cerebrospinal fluid (CSF levels of total Tau (T-tau, phosphorylated Tau (P-Tau and beta-amyloid peptide (Aβ42 reflect, respectively, neurofibrillary tangle and amyloid pathologies and are considered as surrogate markers of AD pathophysiology. The combination of low Aβ42 and high levels of T-tau and P-Tau can accurately identify patients with AD at early stages, even before the development of dementia. The combined analysis of the CSF biomarkers is also helpful for the differential diagnosis between AD and other degenerative dementias. The development of these CSF biomarkers has evolved to a novel diagnostic definition of the disease. The identification of a specific clinical phenotype combined with the in vivo evidence of pathophysiological markers offers the possibility to make a diagnosis of AD before the dementia stage with high specificity.

Adaptive surrogate model based multiobjective optimization for coastal aquifer management

Science.gov (United States)

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

2018-06-01

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

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

Science.gov (United States)

Jovic, Olga S

2011-03-01

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

Surrogate motherhood

OpenAIRE

Arteta-Acosta Cindy

2011-01-01

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

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

International Nuclear Information System (INIS)

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

2002-01-01

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

Term clouds as surrogates for user generated speech

NARCIS (Netherlands)

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

2008-01-01

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

Outcomes for Gestational Carriers Versus Traditional Surrogates in the United States.

Science.gov (United States)

Fuchs, Erika L; Berenson, Abbey B

2018-05-01

Little is known about the obstetric and procedural outcomes of traditional surrogates and gestational carriers. Participants included 222 women living in the United States who completed a brief online survey between November 2015 and February 2016. Differences between gestational carriers (n = 204) and traditional surrogates (n = 18) in demographic characteristics, pregnancy outcomes, and procedural outcomes were examined using chi-squared tests, Fisher's exact tests, and t-tests. Out of 248 eligible respondents, 222 surveys were complete, for a response rate of 89.5%. Overall, obstetric outcomes were similar among gestational carriers and traditional surrogates. Traditional surrogates were more likely than gestational carriers to have a Center for Epidemiologic Studies Depression Scale Revised score of 16 or higher (37.5% vs. 4.0%). Gestational carriers reported higher mean compensation ($27,162.80 vs. $17,070.07) and were more likely to travel over 400 miles (46.0% vs. 0.0%) than traditional surrogates. Procedural differences, but not differences in obstetric outcomes, emerged between gestational carriers and traditional surrogates. To ensure that both traditional surrogates and gestational carriers receive optimal medical care, it may be necessary to extend practice guidelines to ensure that traditional surrogates are offered the same level of care offered to gestational carriers.

Use of hand hygiene agents as a surrogate marker of compliance in Hungarian long-term care facilities: first nationwide survey.

Science.gov (United States)

Szabó, Rita; Morvai, Júlia; Bellissimo-Rodrigues, Fernando; Pittet, Didier

2015-01-01

Hand hygiene practice is an important measure for preventing infections in long-term care facilities (LTCFs). However, low compliance with hand hygiene has been reported in a number of studies. The purpose of this study was to provide an overview of the first reference data collected on alcohol-based handrub (ABHR) and antiseptic soap consumption, as surrogate markers for hand hygiene compliance by healthcare workers (HCWs) in Hungarian LTCFs. The objective was to inform stakeholders on the need of hand hygiene improvement in these settings. Between 5 May and 30 September 2014, we conducted a nationwide, cross-sectional survey using a standardized self-administered questionnaire; all Hungarian LTCFs were eligible. The Statistical Package for Social Sciences (SPSS) version 20.0 was used for data analysis. The questionnaire was completed by 354 LTCFs, representing 24 % of all Hungarian LTCFs. In total, the median consumption of ABHR and antimicrobial soap was 15.5 L (IQR, 0-800 L) and 60 L (IQR, 0-1,680 L) per LTCFs, and 2.2 mL (IQR, 0.4-9.1 mL) and 12.1 mL (IQR, 0.7-32.8 mL) per HCWs in 2013, respectively. The estimated number of hand hygiene actions was 0.6 hygienic handrub/HCW per day (IQR, 0-12.8/HCWs) and 2.4 hygienic handwashing/HCW per day (IQR, 0-21.9/HCWs; P = .001), respectively. This study suggests that non-compliance with hand hygiene is a significant problem in Hungarian LTCFs. Based on our results, there is an urgent need for a nationwide multimodal hand hygiene promotion strategy including education and performance monitoring and feedback in all LTCFs. Furthermore, monitoring of ABHR consumption constitute an additional component of the existing National Nosocomial Surveillance system.

Human surrogate neck response to +Gz vertical impact

NARCIS (Netherlands)

Rooij, L. van; Uittenbogaard, J.

2011-01-01

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

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

Science.gov (United States)

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

2017-08-01

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

Combustion Kinetic Studies of Gasolines and Surrogates

KAUST Repository

Javed, Tamour

2016-11-01

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

Low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio is the best surrogate marker for insulin resistance in non-obese Japanese adults

Directory of Open Access Journals (Sweden)

Takayama Shuzo

2010-12-01

Full Text Available Abstract Background The aim of the present study was to examine how lipid profiles are associated with insulin resistance in Japanese community-dwelling adults. Methods This cross-sectional study included 614 men aged 58 ± 14 (mean ± standard deviation; range, 20-89 years and 779 women aged 60 ± 12 (range, 21-88 years. The study sample were 1,042 (74.8% non-obese (BMI 2 and 351 (25.2% overweight (BMI ≥ 25 kg/m2 subjects. Insulin resistance was defined by homeostasis model assessment of insulin resistance (HOMA-IR of at least 2.5. The areas under the curve (AUC of the receiver operating characteristic curves (ROC were used to compare the power of these serum markers. Results In non-obese subjects, the best marker of insulin resistance was low-density lipoprotein cholesterol (LDL-C/high-density lipoprotein cholesterol (HDL-C ratio of 0.74 (95% confidence interval (CI, 0.66-0.80. The HDL-C, triglyceride (TG/HDL-C ratio, and non-HDL-C also discriminated insulin resistance, as the values for AUC were 0.31 (95% CI, 0.24-0.38, 0.69 (95% CI, 0.62-0.75 and 0.69 (95% CI, 0.62-0.75, respectively. In overweight subjects, the AUC for TG and TG/HDL-C ratio were 0.64 (0.58-0.71 and 0.64 (0.57-0.70, respectively. The optimal cut-off point to identifying insulin resistance for these markers yielded the following values: TG/HDL-C ratio of ≥1.50 and LDL-C/HDL-C ratio of ≥2.14 in non-obese subjects, and ≥2.20, ≥2.25 in overweight subjects. In non-obese subjects, the positive likelihood ratio was greatest for LDL-C/HDL-C ratio. Conclusion In non-obese Japanese adults, LDL-C/HDL-C ratio may be the best reliable marker of insulin resistance.

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

Science.gov (United States)

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

2007-10-01

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

Hepatology may have problems with putative surrogate outcome measures

DEFF Research Database (Denmark)

Gluud, Christian; Brok, Jesper; Gong, Yan

2007-01-01

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

Delta neutrophil index: A reliable marker to differentiate perforated appendicitis from non-perforated appendicitis in the elderly.

Science.gov (United States)

Shin, Dong Hyuk; Cho, Young Suk; Kim, Yoon Sung; Ahn, Hee Cheol; Oh, Young Taeck; Park, Sang O; Won, Moo-Ho; Cho, Jun Hwi; Kim, Young Myeong; Seo, Jeong Yeol; Lee, Young Hwan

2018-01-01

Delta neutrophil index (DNI) is a new inflammatory marker and the present study aimed to evaluate the predictive value of the DNI for the presence of a perforation in elderly with acute appendicitis. This retrospective observational study was conducted on 108 consecutive elderly patients (≥65 years old) with acute appendicitis treated over a 24-month period. Sixty-nine of the 108 patients (median, IQR: 72, 67-77 years) were allocated to the perforated appendicitis group (63.9%) and 39 to the non-perforated appendicitis group (36.1%). WBC, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and DNI were significantly higher in the perforated group. In multiple logistic regression analyses, initial DNI was the only independent marker that can significantly predict the presence of perforation in multiple regression [odds ratio 9.38, 95% confidence interval (2.51-35.00), P=.001]. Receiver operator characteristic curve analysis showed that DNI is a good predictor for the presence of appendiceal perforation at an optimal cut-off for DNI being 1.4% (sensitivity 67.7%, specificity 90.0%, AUC 0.807). Clinicians can reliably differentiate acute perforated appendicitis from non-perforated appendicitis by DNI level of 1.4 or more in elderly patients. © 2017 Wiley Periodicals, Inc.

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

Science.gov (United States)

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

2015-06-01

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

Health information-seeking on behalf of others: characteristics of "surrogate seekers".

Science.gov (United States)

Cutrona, Sarah L; Mazor, Kathleen M; Vieux, Sana N; Luger, Tana M; Volkman, Julie E; Finney Rutten, Lila J

2015-03-01

Understanding the behaviors of surrogate seekers (those who seek health information for others) may guide efforts to improve health information transmission. We used 2011-2012 data from the Health Information National Trends Survey to describe behaviors of online surrogate seekers. Respondents were asked about use of the Internet for surrogate-seeking over the prior 12 months. Data were weighted to calculate population estimates. Two thirds (66.6%) reported surrogate-seeking. Compared to those who sought health information online for only themselves, surrogate seekers were more likely to live in households with others (weighted percent 89.4 vs. 82.5% of self-seekers; p user-generated content: email communication with healthcare providers; visits to social networking sites to read and share about medical topics and participation in online health support groups. On multivariate analysis, those who had looked online for healthcare providers were more likely to be surrogate seekers (OR 1.67, 95% CI 1.08-2.59). In addition to seeking health information, surrogate seekers create and pass along communications that may influence medical care decisions. Research is needed to identify ways to facilitate transmission of accurate health information.

Can the Growth/Differentiation Factor-15 Be a Surrogate Target in Chronic Heart Failure Biomarker-Guided Therapy?

Directory of Open Access Journals (Sweden)

Alexander E. Berezin

2017-03-01

Full Text Available Heart failure (HF biomarker-guided therapy is a promising method, which directs to the improvement of clinical status, attenuation of admission/readmission to the hospital and reduction in mortality rate. Many biological markers, like inflammatory cytokines, are under consideration as a surrogate target for HF treatment, while there are known biomarkers with established predictive value, such as natriuretic peptides. However, discovery of new biomarkers reflecting various underlying mechanisms of HF and appearing to be surrogate targets for biomarker-guided therapy is fairly promising. Nowadays, growth/differentiation factor 15 (GDF-15 is suggested a target biomarker for HF treatment. Although elevated level of GDF-15 is associated with HF development, progression, and prognosis, there is no represented evidence regarding the direct comparison of this biomarker with other clinical risk predictors and biomarkers. Moreover, GDF-15 might serve as a contributor to endothelial progenitor cells (EPC dysfunction by inducing EPC death/autophagy and limiting their response to angiopoetic and reparative effects. The short communication was discussed whether GDF-15 is good molecular target for HF biomarker-guided therapy.

Solubility of actinides and surrogates in nuclear glasses

International Nuclear Information System (INIS)

Lopez, Ch.

2003-01-01

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

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

Science.gov (United States)

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

2017-08-01

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

Surrogate for oropharyngeal cancer HPV status in cancer database studies.

Science.gov (United States)

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

2017-12-01

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

Error modeling for surrogates of dynamical systems using machine learning

Science.gov (United States)

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

2017-12-01

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

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

Science.gov (United States)

Wendler, David; Rid, Annette

2011-03-01

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

Mother-daughter in vitro fertilization triplet surrogate pregnancy.

Science.gov (United States)

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

1988-02-01

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

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

NARCIS (Netherlands)

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

2013-01-01

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

Brief report: benchmarking human pluripotent stem cell markers during differentiation into the three germ layers unveils a striking heterogeneity: all markers are not equal.

Science.gov (United States)

Ramirez, Jean-Marie; Gerbal-Chaloin, Sabine; Milhavet, Ollivier; Qiang, Bai; Becker, Fabienne; Assou, Said; Lemaître, Jean-Marc; Hamamah, Samir; De Vos, John

2011-09-01

Pluripotent stem cells (PSC) are functionally characterized by their capacity to differentiate into all the cell types from the three germ layers. A wide range of markers, the expression of which is associated with pluripotency, has been used as surrogate evidence of PSC pluripotency, but their respective relevance is poorly documented. Here, we compared by polychromatic flow cytometry the kinetics of loss of expression of eight widely used pluripotency markers (SSEA3, SSEA4, TRA-1-60, TRA-1-81, CD24, OCT4, NANOG, and alkaline phosphatase [AP]) at days 0, 5, 7, and 9 after induction of PSC differentiation into cells representative of the three germ layers. Strikingly, each marker showed a different and specific kinetics of disappearance that was similar in all the PSC lines used and for all the induced differentiation pathways. OCT4, SSEA3, and TRA-1-60 were repeatedly the first markers to be downregulated, and their expression was completely lost at day 9. By contrast, AP activity, CD24, and NANOG proteins were still detectable at day 9. In addition, we show that differentiation markers are coexpressed with pluripotency markers before the latter begin to disappear. These results suggest that OCT4, SSEA3, and TRA-1-60 might be better to trace in vitro the emergence of pluripotent cells during reprogramming. Copyright © 2011 AlphaMed Press.

Uncertainty quantification for accident management using ACE surrogates

International Nuclear Information System (INIS)

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

2012-01-01

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

TOXICITY OF PENTACHLOROPHENOL TO ENDANGERED AND SURROGATE FISH SPECIES

Science.gov (United States)

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

One mum too few: maternal status in host surrogate motherhood arrangements.

Science.gov (United States)

Oultram, Stuart

2015-06-01

In a host surrogate motherhood arrangement, the surrogate agrees to be implanted with, and carry to term, an embryo created from the commissioning couple's gametes. When the surrogate child is born, it is the surrogate mother who, according to UK law, holds the legal status of mother. By contrast, the commissioning mother possesses no maternal status and she can only attain it once the surrogate agrees to the completion of the arrangement. One consequence of this is that, in the event that a host arrangement fails, the commissioning mother is left without maternal status. In this paper, I argue that this denial of maternal status misrepresents the commissioning mother's role in the host arrangement and her relationship with the surrogate child. Consequently, I suggest that commissioning mothers participating in host surrogacy arrangements ought to be granted the status of mother in the event that the arrangement fails. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A PCR marker linked to a THCA synthase polymorphism is a reliable tool to discriminate potentially THC-rich plants of Cannabis sativa L.

Science.gov (United States)

Staginnus, Christina; Zörntlein, Siegfried; de Meijer, Etienne

2014-07-01

Neither absolute THC content nor morphology allows the unequivocal discrimination of fiber cultivars and drug strains of Cannabis sativa L. unequivocally. However, the CBD/THC ratio remains constant throughout the plant's life cycle, is independent of environmental factors, and considered to be controlled by a single locus (B) with two codominant alleles (B(T) and B(D)). The homozygous B(T)/B(T) genotype underlies the THC-predominant phenotype, B(D)/B(D) is CBD predominant, and an intermediate phenotype is induced by the heterozygous state (B(T)/B(D)). Using PCR-based markers in two segregating populations, we proved that the THCA synthase gene represents the postulated B locus and that specific sequence polymorphisms are absolutely linked either to the THC-predominant or the THC-intermediate chemotype. The absolute linkage provides an excellent reliability of the marker signal in forensic casework. For validation, the species-specific marker system was applied to a large number of casework samples and fiber hemp cultivars. © 2014 American Academy of Forensic Sciences.

Legal regulation of surrogate motherhood in Israel.

Science.gov (United States)

Frenkel, D A

2001-01-01

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

Liver collagen in cirrhosis correlates with portal hypertension and liver dysfunction

DEFF Research Database (Denmark)

Nielsen, Kåre; Clemmesen, Jens Otto; Vassiliadis, Efstathios

2014-01-01

livers. In 20 of the livers, CPA was measured in more than one tissue sample. CPA showed significant correlations with HVPG and with various surrogate markers of hepatic dysfunction including albumin, bilirubin, INR, MELD score and Child-Pugh score. CPA reliably discriminated HVPG ≥10 mmHg, termed...

Disinfection byproduct regulatory compliance surrogates and bromide-associated risk.

Science.gov (United States)

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

2017-08-01

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

Neonatal metabolic acidosis at birth: In search of a reliable marker.

Science.gov (United States)

Racinet, C; Ouellet, P; Charles, F; Daboval, T

2016-06-01

A newborn may present acidemia on the umbilical artery blood which can result from respiratory acidosis or metabolic acidosis or be of mixed origin. Currently, in the absence of a satisfactory definition, the challenge is to determine the most accurate marker for metabolic acidosis, which can be deleterious for the neonate. We reviewed the methodological and physiological aspects of the perinatal literature to search for the best marker of NMA. Base deficit and pH have been criticized as the standard criteria to predict outcome. The proposed threshold of pathogenicity is not based on convincing studies. The algorithms of various blood gas analyzers differ and do not take into account the specific neonatal acid-base profile. Birth-related neonatal eucapnic pH is described as the most pertinent marker of NMA at birth. The various means of calculating this value and the level below which it seems to play a possible pathogenic role are presented. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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

Science.gov (United States)

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

2015-02-10

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

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

Science.gov (United States)

1988-01-01

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

The Use of Surrogate Data in Demographic Population Viability Analysis: A Case Study of California Sea Lions.

Directory of Open Access Journals (Sweden)

Claudia J Hernández-Camacho

Full Text Available Reliable data necessary to parameterize population models are seldom available for imperiled species. As an alternative, data from populations of the same species or from ecologically similar species have been used to construct models. In this study, we evaluated the use of demographic data collected at one California sea lion colony (Los Islotes to predict the population dynamics of the same species from two other colonies (San Jorge and Granito in the Gulf of California, Mexico, for which demographic data are lacking. To do so, we developed a stochastic demographic age-structured matrix model and conducted a population viability analysis for each colony. For the Los Islotes colony we used site-specific pup, juvenile, and adult survival probabilities, as well as birth rates for older females. For the other colonies, we used site-specific pup and juvenile survival probabilities, but used surrogate data from Los Islotes for adult survival probabilities and birth rates. We assessed these models by comparing simulated retrospective population trajectories to observed population trends based on count data. The projected population trajectories approximated the observed trends when surrogate data were used for one colony but failed to match for a second colony. Our results indicate that species-specific and even region-specific surrogate data may lead to erroneous conservation decisions. These results highlight the importance of using population-specific demographic data in assessing extinction risk. When vital rates are not available and immediate management actions must be taken, in particular for imperiled species, we recommend the use of surrogate data only when the populations appear to have similar population trends.

The Use of Surrogate Data in Demographic Population Viability Analysis: A Case Study of California Sea Lions

Science.gov (United States)

2015-01-01

Reliable data necessary to parameterize population models are seldom available for imperiled species. As an alternative, data from populations of the same species or from ecologically similar species have been used to construct models. In this study, we evaluated the use of demographic data collected at one California sea lion colony (Los Islotes) to predict the population dynamics of the same species from two other colonies (San Jorge and Granito) in the Gulf of California, Mexico, for which demographic data are lacking. To do so, we developed a stochastic demographic age-structured matrix model and conducted a population viability analysis for each colony. For the Los Islotes colony we used site-specific pup, juvenile, and adult survival probabilities, as well as birth rates for older females. For the other colonies, we used site-specific pup and juvenile survival probabilities, but used surrogate data from Los Islotes for adult survival probabilities and birth rates. We assessed these models by comparing simulated retrospective population trajectories to observed population trends based on count data. The projected population trajectories approximated the observed trends when surrogate data were used for one colony but failed to match for a second colony. Our results indicate that species-specific and even region-specific surrogate data may lead to erroneous conservation decisions. These results highlight the importance of using population-specific demographic data in assessing extinction risk. When vital rates are not available and immediate management actions must be taken, in particular for imperiled species, we recommend the use of surrogate data only when the populations appear to have similar population trends. PMID:26413746

Developments in Surrogating Methods

Directory of Open Access Journals (Sweden)

Hans van Dormolen

2005-11-01

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

Surrogate pregnancy: a guide for Canadian prenatal health care providers

OpenAIRE

Reilly, Dan R.

2007-01-01

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

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

OpenAIRE

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

2018-01-01

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

Surrogate utility estimation by long-term partners and unfamiliar dyads.

Science.gov (United States)

Tunney, Richard J; Ziegler, Fenja V

2015-01-01

To what extent are people able to make predictions about other people's preferences and values?We report two experiments that present a novel method assessing some of the basic processes in surrogate decision-making, namely surrogate-utility estimation. In each experiment participants formed dyads who were asked to assign utilities to health related items and commodity items, and to predict their partner's utility judgments for the same items. In experiment one we showed that older adults in long-term relationships were able to accurately predict their partner's wishes. In experiment two we showed that younger adults who were relatively unfamiliar with one another were also able to predict other people's wishes. Crucially we demonstrated that these judgments were accurate even after partialling out each participant's own preferences indicating that in order to make surrogate utility estimations people engage in perspective-taking rather than simple anchoring and adjustment, suggesting that utility estimation is not the cause of inaccuracy in surrogate decision-making. The data and implications are discussed with respect to theories of surrogate decision-making.

Surrogate utility estimation by long-term partners and unfamiliar dyads

Directory of Open Access Journals (Sweden)

Richard J Tunney

2015-03-01

Full Text Available To what extent are people able to make predictions about other people’s preferences and values? We report two experiments that present a novel method assessing some of the basic processes in surrogate decision-making, namely surrogate-utility estimation. In each experiment participants formed dyads who were asked to assign utilities to health related items and commodity items, and to predict their partner’s utility judgments for the same items. In experiment one we showed that older adults in long-term relationships were able to accurately predict their partner’s wishes. In experiment two we showed that younger adults who were relatively unfamiliar with one another were also able to predict other people’s wishes. Crucially we demonstrated that these judgments were accurate even after partialling out each participant’s own preferences indicating that in order to make surrogate utility estimations people engage in perspective-taking rather than simple anchoring and adjustment, suggesting that utility estimation is not the cause of inaccuracy in surrogate decision-making. The data and implications are discussed with respect to theories of surrogate decision-making.

The influence of surrogate blood vessels on the impact response of a physical model of the brain.

Science.gov (United States)

Parnaik, Yednesh; Beillas, Philippe; Demetropoulos, Constantine K; Hardy, Warren N; Yang, King H; King, Albert I

2004-11-01

Cerebral blood vessels are an integral part of the brain and may play a role in the response of the brain to impact. The purpose of this study was to quantify the effects of surrogate vessels on the deformation patterns of a physical model of the brain under various impact conditions. Silicone gel and tubing were used as surrogates for brain tissue and blood vessels, respectively. Two aluminum cylinders representing a coronal section of the brain were constructed. One cylinder was filled with silicone gel only, and the other was filled with silicone gel and silicone tubing arranged in the radial direction in the peripheral region. An array of markers was embedded in the gel in both cylinders to facilitate strain calculation via high-speed video analysis. Both cylinders were simultaneously subjected to a combination of linear and angular acceleration using a two-segment pendulum. Marker motion was tracked, and maximum shear strain (MSS) and maximum principal strain (MPS) were calculated using markers clustered in groups of three. Four test series were conducted. Peak angular acceleration varied from 2,600 to 26,000 rad/s2, and peak angular speed varied from 17 to 29 rad/s. For a given impact condition, the test-to-test variation of these values was less than 5.5%. For all clusters, the peak MSS and peak MPS for both physical models were less than 26% and 32%, respectively. For 90% of the cluster locations, the absolute value of the difference in peak MSS and peak MPS between the physical models was 4% and 6%, respectively. In the physical model with tubing, strain tended to decrease in the periphery (near to the tubing), while it tended to increase toward the center (away from the tubing). Strain amplitudes were found to be sensitive to the peak angular speeds. In general, this study suggests that the vasculature could influence the deformation response of the brain.

Active learning surrogate models for the conception of systems with multiple failure modes

International Nuclear Information System (INIS)

Perrin, G.

2016-01-01

Due to the performance and certification criteria, complex mechanical systems have to taken into account several constraints, which can be associated with a series of performance functions. Different software are generally used to evaluate such functions, whose computational cost can vary a lot. In conception or reliability analysis, we thus are interested in the identification of the boundaries of the domain where all these constraints are satisfied, at the minimal total computational cost. To this end, the present work proposes an iterative method to maximize the knowledge about these limits while trying to minimize the required number of evaluations of each performance function. This method is based first on Gaussian process surrogate models that are defined on nested sub-spaces, and second, on an original selection criterion that takes into account the computational cost associated with each performance function. After presenting the theoretical basis of this approach, this paper compares its efficiency to alternative methods on an example. - Highlights: • An iterative method to identify the limits of a system is proposed. • The method is based on nested Gaussian process surrogate models. • A new selection criterion that is adapted to the system case is presented. • The interest of the method is illustrated on an analytical example.

Development of a Human Cranial Bone Surrogate for Impact Studies

International Nuclear Information System (INIS)

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

2013-01-01

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

Procalcitonin: A Reliable Marker for the Diagnosis of Neonatal Sepsis

Science.gov (United States)

Adib, Minoo; Bakhshiani, Zahra; Navaei, Fakhri; Saheb Fosoul, Fereshteh; Fouladi, Salomeh; Kazemzadeh, Hamidreza

2012-01-01

Objective(s) In the last few years, serum procalcitonin has been proposed as an early marker of infections in neonates, with varying results. In this study, we aimed to investigate the value of procalcitonin, and C- reactive protein in establishing the diagnosis of neonatal sepsis. Materials and Methods Blood samples were collected at admission from 69 neonates with suspected infection (admitted to the Neonatal Intensive Care Units at Alzahra and Dr Beheshti Hospital in and Fatema-Zahra in Najafabad from May 2005 to April 2006). Patients were categorized in different groups according to clinical symptoms of sepsis, bacteriological and laboratory results. Group I consisted of 20 newborns with positive blood cultures and other biological tests which suggested infection. Group II consisted of 49 neonates with negative blood cultures but had two or three of clinical signs of sepsis. The control group included 18 healthy neonates with physiological hyperbilirubinemia and no clinical and biological data of infection, referred to the hospital for bilirubin determination. Procalcitonin and C-reactive protein (CRP) were determined by immunoluminometric assay and nephlometry method respectively. Results Mean levels of procalcitonin and CRP in septic neonates (group I) were significantly higher than the other two groups (P< 0.005). Sensitivity, specificity, positive predictive value and negative predictive value were determined for all markers and compared with each other. Conclusion We conclude that procalcitonin is a better marker than CRP in the diagnosis of neonatal sepsis. PMID:23493845

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

OpenAIRE

Lamba, Nishtha

2018-01-01

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

Using Pill Identification Calls to Poison Centers as a Marker of Drug Abuse at Three Texas Military Bases.

Science.gov (United States)

Ng, Patrick C; Maddry, Joseph K; Sessions, Daniel; Borys, Douglas J; Bebarta, Vikhyat S

2017-11-01

Opioid abuse is a growing problem in civilian communities, and it has developed in the military as well. Telephone calls to poison centers requesting pill identification (ID) is a marker of drug abuse. This study identifies the number of pill ID calls made to the poison centers from areas containing and surrounding three Texas military bases during an 8-year period. We performed a retrospective observational study identifying calls to certified poison centers in Texas from 2002 to 2009 that identified hydrocodone tablets and other pain medications. We noted the calls made from ZIP codes containing and surrounding the three largest military bases in Texas. We reviewed 75,537 drug ID calls for any drug from the ZIP codes of interest. Total drug ID calls increased 105% and the number of calls for hydrocodone increased 463%. In our study most of the drug ID calls from military communities in Texas were for hydrocodone. The rate of calls for hydrocodone increased more than the rate of calls for other analgesics from 2002 to 2009. Using drug ID calls as a surrogate of drug abuse, our results suggest that hydrocodone abuse has increased within military communities and that poison center data can be a reliable surrogate for prescription drug abuse near military bases. Future studies are needed to further understand the extent of this problem in military and civilian communities. We can use this information to heighten awareness, influence prescription practices, establish practice guidelines, and develop educational programs to mitigate the increasing rate of prescription analgesic abuse in the United States.

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

Science.gov (United States)

Mitry, Mina

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

Global Optimization Employing Gaussian Process-Based Bayesian Surrogates

Directory of Open Access Journals (Sweden)

Roland Preuss

2018-03-01

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

Surrogate motherhood in illness that does not cause infertility

African Journals Online (AJOL)

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

Surrogate mothering: exploitation or empowerment?

Science.gov (United States)

Purdy, Laura M

1989-01-01

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

Selection of Surrogate Bacteria for Use in Food Safety Challenge Studies: A Review.

Science.gov (United States)

Hu, Mengyi; Gurtler, Joshua B

2017-09-01

Nonpathogenic surrogate bacteria are prevalently used in a variety of food challenge studies in place of foodborne pathogens such as Listeria monocytogenes, Salmonella, Escherichia coli O157:H7, and Clostridium botulinum because of safety and sanitary concerns. Surrogate bacteria should have growth characteristics and/or inactivation kinetics similar to those of target pathogens under given conditions in challenge studies. It is of great importance to carefully select and validate potential surrogate bacteria when verifying microbial inactivation processes. A validated surrogate responds similar to the targeted pathogen when tested for inactivation kinetics, growth parameters, or survivability under given conditions in agreement with appropriate statistical analyses. However, a considerable number of food studies involving putative surrogate bacteria lack convincing validation sources or adequate validation processes. Most of the validation information for surrogates in these studies is anecdotal and has been collected from previous publications but may not be sufficient for given conditions in the study at hand. This review is limited to an overview of select studies and discussion of the general criteria and approaches for selecting potential surrogate bacteria under given conditions. The review also includes a list of documented bacterial pathogen surrogates and their corresponding food products and treatments to provide guidance for future studies.

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

Science.gov (United States)

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

2016-02-18

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

Surrogate decision making and intellectual virtue.

Science.gov (United States)

Bock, Gregory L

2014-01-01

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

Reliability Correction for Functional Connectivity: Theory and Implementation

Science.gov (United States)

Mueller, Sophia; Wang, Danhong; Fox, Michael D.; Pan, Ruiqi; Lu, Jie; Li, Kuncheng; Sun, Wei; Buckner, Randy L.; Liu, Hesheng

2016-01-01

Network properties can be estimated using functional connectivity MRI (fcMRI). However, regional variation of the fMRI signal causes systematic biases in network estimates including correlation attenuation in regions of low measurement reliability. Here we computed the spatial distribution of fcMRI reliability using longitudinal fcMRI datasets and demonstrated how pre-estimated reliability maps can correct for correlation attenuation. As a test case of reliability-based attenuation correction we estimated properties of the default network, where reliability was significantly lower than average in the medial temporal lobe and higher in the posterior medial cortex, heterogeneity that impacts estimation of the network. Accounting for this bias using attenuation correction revealed that the medial temporal lobe’s contribution to the default network is typically underestimated. To render this approach useful to a greater number of datasets, we demonstrate that test-retest reliability maps derived from repeated runs within a single scanning session can be used as a surrogate for multi-session reliability mapping. Using data segments with different scan lengths between 1 and 30 min, we found that test-retest reliability of connectivity estimates increases with scan length while the spatial distribution of reliability is relatively stable even at short scan lengths. Finally, analyses of tertiary data revealed that reliability distribution is influenced by age, neuropsychiatric status and scanner type, suggesting that reliability correction may be especially important when studying between-group differences. Collectively, these results illustrate that reliability-based attenuation correction is an easily implemented strategy that mitigates certain features of fMRI signal nonuniformity. PMID:26493163

Public’s Approach to Surrogate Consent for Dementia Research: Cautious Pragmatism

Science.gov (United States)

De Vries, Raymond; Ryan, Kerry A.; Stanczyk, Aimee; Appelbaum, Paul S.; Damschroder, Laura; Knopman, David S.; Kim, Scott Y. H.

2011-01-01

Objectives To describe how members of the older general public deliberate with one another in finding solutions to the dilemma of involving decisionally incapable persons in dementia research. Design, Setting, and Participants 160 persons aged 50+ who participated in an all-day deliberative democracy (DD) session on the ethics of surrogate consent for dementia research. The DD day consisted of both extensive, interactive education with experts in clinical research and ethics, as well as small group deliberations. Measurements Audiotaped small group deliberations were transcribed and analyzed, and the main thematic elements were coded. Results During deliberation, participants acknowledged the limitations of advanced research directives and discussed ways to improve their use. Although there was consensus about the necessity of surrogate consent, the participants recognized potential pitfalls and looked for ways to safeguard the process. Participants supporting surrogate consent for research emphasized societal and individual benefit, the importance of assent, and trust in surrogates and the oversight system. Other participants felt that the high risk of some research scenarios was not sufficiently offset by benefits to patients or society. Conclusions Members of the older general public are able to make use of in-depth education and peer deliberation to provide reasoned and informed opinions on the ethical use of surrogate consent for dementia research. The public’s approach to surrogate consent is one of cautious pragmatism: an overall trust in science and future surrogates with awareness of the potential pitfalls, suggesting that their trust cannot be taken for granted. PMID:23498383

Recent Progress in the Development of Diesel Surrogate Fuels

Energy Technology Data Exchange (ETDEWEB)

Pitz, W J; Mueller, C J

2009-12-09

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

Fast Prediction and Evaluation of Gravitational Waveforms Using Surrogate Models

Science.gov (United States)

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

2014-07-01

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

Plasma chitotriosidase and CCL18: Early biochemical surrogate markers in type B Niemann-Pick disease

NARCIS (Netherlands)

Brinkman, J.; Wijburg, F. A.; Hollak, C. E.; Groener, J. E.; Verhoek, M.; Scheij, S.; Aten, J.; Boot, R. G.; Aerts, J. M.

2005-01-01

Type B Niemann-Pick disease (NPD) is a nonneuronopathic lysosomal storage disorder which is characterized by accumulation of sphingomyelin-laden macrophages. The availability of plasma markers for storage cells may be of great value in facilitating therapeutic decisions. Given the similarity of the

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

Science.gov (United States)

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

2013-01-01

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

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

Science.gov (United States)

2013-03-01

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

Plutonium and surrogate fission products in a composite ceramic waste form

International Nuclear Information System (INIS)

Esh, D. W.; Frank, S. M.; Goff, K. M.; Johnson, S. G.; Moschetti, T. L.; O'Holleran, T.

1999-01-01

Argonne National Laboratory is developing a ceramic waste form to immobilize salt containing fission products and transuranic elements. Preliminary results have been presented for ceramic waste forms containing surrogate fission products such as cesium and the lanthanides. In this work results from scanning electron microscopy/energy dispersive spectroscopy and x-ray diffraction are presented in greater detail for ceramic waste forms containing surrogate fission products. Additionally, results for waste forms containing plutonium and surrogate fission products are presented. Most of the surrogate fission products appear to be silicates or aluminosilicates whereas the plutonium is usually found in an oxide form. There is also evidence for the presence of plutonium within the sodalite phase although the chemical speciation of the plutonium is not known

Black-hole kicks from numerical-relativity surrogate models

Science.gov (United States)

Gerosa, Davide; Hébert, François; Stein, Leo C.

2018-05-01

Binary black holes radiate linear momentum in gravitational waves as they merge. Recoils imparted to the black-hole remnant can reach thousands of km /s , thus ejecting black holes from their host galaxies. We exploit recent advances in gravitational waveform modeling to quickly and reliably extract recoils imparted to generic, precessing, black-hole binaries. Our procedure uses a numerical-relativity surrogate model to obtain the gravitational waveform given a set of binary parameters; then, from this waveform we directly integrate the gravitational-wave linear momentum flux. This entirely bypasses the need for fitting formulas which are typically used to model black-hole recoils in astrophysical contexts. We provide a thorough exploration of the black-hole kick phenomenology in the parameter space, summarizing and extending previous numerical results on the topic. Our extraction procedure is made publicly available as a module for the Python programming language named surrkick. Kick evaluations take ˜0.1 s on a standard off-the-shelf machine, thus making our code ideal to be ported to large-scale astrophysical studies.

Emotional experiences in surrogate mothers: A qualitative study

OpenAIRE

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

2014-01-01

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

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

KAUST Repository

Bhavani Shankar, Vijai Shankar

2016-04-05

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.

Effectiveness of external respiratory surrogates for in vivo liver motion estimation

International Nuclear Information System (INIS)

Chang, Kai-Hsiang; Ho, Ming-Chih; Yeh, Chi-Chuan; Chen, Yu-Chien; Lian, Feng-Li; Lin, Win-Li; Yen, Jia-Yush; Chen, Yung-Yaw

2012-01-01

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

Real-time characterization of partially observed epidemics using surrogate models.

Energy Technology Data Exchange (ETDEWEB)

Safta, Cosmin; Ray, Jaideep; Lefantzi, Sophia; Crary, David (Applied Research Associates, Arlington, VA); Sargsyan, Khachik; Cheng, Karen (Applied Research Associates, Arlington, VA)

2011-09-01

We present a statistical method, predicated on the use of surrogate models, for the 'real-time' characterization of partially observed epidemics. Observations consist of counts of symptomatic patients, diagnosed with the disease, that may be available in the early epoch of an ongoing outbreak. Characterization, in this context, refers to estimation of epidemiological parameters that can be used to provide short-term forecasts of the ongoing epidemic, as well as to provide gross information on the dynamics of the etiologic agent in the affected population e.g., the time-dependent infection rate. The characterization problem is formulated as a Bayesian inverse problem, and epidemiological parameters are estimated as distributions using a Markov chain Monte Carlo (MCMC) method, thus quantifying the uncertainty in the estimates. In some cases, the inverse problem can be computationally expensive, primarily due to the epidemic simulator used inside the inversion algorithm. We present a method, based on replacing the epidemiological model with computationally inexpensive surrogates, that can reduce the computational time to minutes, without a significant loss of accuracy. The surrogates are created by projecting the output of an epidemiological model on a set of polynomial chaos bases; thereafter, computations involving the surrogate model reduce to evaluations of a polynomial. We find that the epidemic characterizations obtained with the surrogate models is very close to that obtained with the original model. We also find that the number of projections required to construct a surrogate model is O(10)-O(10{sup 2}) less than the number of samples required by the MCMC to construct a stationary posterior distribution; thus, depending upon the epidemiological models in question, it may be possible to omit the offline creation and caching of surrogate models, prior to their use in an inverse problem. The technique is demonstrated on synthetic data as well as

Summary of Remediated Nitrate Salt Surrogate Formulation and Testing

Energy Technology Data Exchange (ETDEWEB)

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

2016-05-05

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

Children of surrogate mothers: psychological well-being, family relationships and experiences of surrogacy.

Science.gov (United States)

Jadva, V; Imrie, S

2014-01-01

What impact does surrogacy have on the surrogates' own children? The children of surrogate mothers do not experience any negative consequences as a result of their mother's decision to be a surrogate, irrespective of whether or not the surrogate uses her own egg. Participants were recruited as part of a study of the long-term effects of surrogacy for surrogates and their family members. Data were collected from 36 children of surrogates at a single time point. Participants whose mother had been a surrogate 5-15 years prior to interview and who were aged over 12 years were eligible to take part. Thirty-six participants (14 male and 22 female) aged 12-25 years were interviewed (response rate = 52%). Questionnaires assessing psychological health and family functioning were administered. Forty-four per cent (15) of participants' mothers had undergone gestational surrogacy, 39% (14) had used their own egg (genetic surrogacy) and 19% (7) had completed both types of surrogacy. Most surrogates' children (86%, 31) had a positive view of their mother's surrogacy. Forty-seven per cent (17) of children were in contact with the surrogacy child and all reported good relationships with him/her. Forty per cent (14) of children referred to the child as a sibling or half-sibling and this did not differ between genetic and gestational surrogacy. Most children (89%, 32), reported a positive view of family life, with all enjoying spending time with their mother. Mean scores on the questionnaire assessments of psychological health and self-esteem were within the normal range and did not differ by surrogacy type. The sample size for this study was relatively small and not all children chose to take part, therefore their views cannot be known. Nevertheless, this is the first study to assess the experiences of surrogacy from the perspective of the surrogates' own children. There may be some bias from the inclusion of siblings from the same family. Findings of this study show that family

Fast Prediction and Evaluation of Gravitational Waveforms Using Surrogate Models

Directory of Open Access Journals (Sweden)

Scott E. Field

2014-07-01

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

[Biomedical Perspective of the Surrogate Motherhood].

Science.gov (United States)

Jouve de la Barreda, Nicolás

2017-01-01

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

Engagement in Advance Care Planning and Surrogates' Knowledge of Patients' Treatment Goals.

Science.gov (United States)

Fried, Terri R; Zenoni, Maria; Iannone, Lynne; O'Leary, John; Fenton, Brenda T

2017-08-01

A key objective of advance care planning (ACP) is improving surrogates' knowledge of patients' treatment goals. Little is known about whether ACP outside of a trial accomplishes this. The objective was to examine patient and surrogate reports of ACP engagement and associations with surrogate knowledge of goals. Cohort study SETTING: Primary care in a Veterans Affairs Medical Center. 350 community-dwelling veterans age ≥55 years and the individual they would choose to make medical decisions on their behalf, interviewed separately. Treatment goals were assessed by veterans' ratings of 3 health states: severe physical disability, cognitive disability, and pain, as an acceptable or unacceptable result of treatment for severe illness. Surrogates had knowledge if they correctly predicted all 3 responses. Veterans and surrogates were asked about living will and health care proxy completion and communication about life-sustaining treatment and quality versus quantity of life (QOL). Over 40% of dyads agreed that the veteran had not completed a living will or health care proxy and that there was no QOL communication. For each activity, sizeable proportions (18-34%) disagreed about participation. In dyads who agreed QOL communication had occurred, 30% of surrogates had knowledge, compared to 21% in dyads who agreed communication had not occurred and 15% in dyads who disagreed (P = .01). This relationship persisted in multivariable analysis. Agreement about other ACP activities was not associated with knowledge. Disagreement about ACP participation was common. Agreement about communication regarding QOL was modestly associated with surrogate knowledge of treatment goals. Eliciting surrogates' perspectives is critical to ACP. Even dyads who agree about participation may need additional support for successful engagement. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Surrogate formulations for thermal treatment of low-level mixed waste

International Nuclear Information System (INIS)

Stockdale, J.A.D.; Bostick, W.D.; Hoffmann, D.P.; Lee, H.T.

1994-01-01

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 239 Pu, 238 U, 235 U, 137 Cs, 103 Ru, 99 Tc, and 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

Patient Preferences and Surrogate Decision Making in Neuroscience Intensive Care Units

Science.gov (United States)

Cai, Xuemei; Robinson, Jennifer; Muehlschlegel, Susanne; White, Douglas B.; Holloway, Robert G.; Sheth, Kevin N.; Fraenkel, Liana; Hwang, David Y.

2016-01-01

In the neuroscience intensive care unit (NICU), most patients lack the capacity to make their own preferences known. This fact leads to situations where surrogate decision makers must fill the role of the patient in terms of making preference-based treatment decisions, oftentimes in challenging situations where prognosis is uncertain. The neurointensivist has a large responsibility and role to play in this shared decision making process. This review covers how NICU patient preferences are determined through existing advance care documentation or surrogate decision makers and how the optimum roles of the physician and surrogate decision maker are addressed. We outline the process of reaching a shared decision between family and care team and describe a practice for conducting optimum family meetings based on studies of ICU families in crisis. We review challenges in the decision making process between surrogate decision makers and medical teams in neurocritical care settings, as well as methods to ameliorate conflicts. Ultimately, the goal of shared decision making is to increase knowledge amongst surrogates and care providers, decrease decisional conflict, promote realistic expectations and preference-centered treatment strategies, and lift the emotional burden on families of neurocritical care patients. PMID:25990137

The effect of framing on surrogate optimism bias: A simulation study.

Science.gov (United States)

Patel, Dev; Cohen, Elan D; Barnato, Amber E

2016-04-01

To explore the effect of emotion priming and physician communication behaviors on optimism bias. We conducted a 5 × 2 between-subject randomized factorial experiment using a Web-based interactive video designed to simulate a family meeting for a critically ill spouse/parent. Eligibility included age at least 35 years and self-identifying as the surrogate for a spouse/parent. The primary outcome was the surrogate's election of code status. We defined optimism bias as the surrogate's estimate of prognosis with cardiopulmonary resuscitation (CPR) > their recollection of the physician's estimate. Of 373 respondents, 256 (69%) logged in and were randomized and 220 (86%) had nonmissing data for prognosis. Sixty-seven (30%) of 220 overall and 56 of (32%) 173 with an accurate recollection of the physician's estimate had optimism bias. Optimism bias correlated with choosing CPR (P optimism bias. Framing the decision as the patient's vs the surrogate's (25% vs 36%, P = .066) and describing the alternative to CPR as "allow natural death" instead of "do not resuscitate" (25% vs 37%, P = .035) decreased optimism bias. Framing of CPR choice during code status conversations may influence surrogates' optimism bias. Copyright © 2015 Elsevier Inc. All rights reserved.

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

KAUST Repository

Bhavani Shankar, Vijai Shankar; Sajid, Muhammad Bilal; Al-Qurashi, Khalid; Atef, Nour; Al Khesho, Issam; Ahmed, Ahfaz; Chung, Suk-Ho; Roberts, William L.; Morganti, Kai; Sarathy, Mani

2016-01-01

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.

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

Science.gov (United States)

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

2009-12-01

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

Structural reliability analysis under evidence theory using the active learning kriging model

Science.gov (United States)

Yang, Xufeng; Liu, Yongshou; Ma, Panke

2017-11-01

Structural reliability analysis under evidence theory is investigated. It is rigorously proved that a surrogate model providing only correct sign prediction of the performance function can meet the accuracy requirement of evidence-theory-based reliability analysis. Accordingly, a method based on the active learning kriging model which only correctly predicts the sign of the performance function is proposed. Interval Monte Carlo simulation and a modified optimization method based on Karush-Kuhn-Tucker conditions are introduced to make the method more efficient in estimating the bounds of failure probability based on the kriging model. Four examples are investigated to demonstrate the efficiency and accuracy of the proposed method.

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

Data.gov (United States)

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

Development of correlations for combustion modelling with supercritical surrogate jet fuels

Directory of Open Access Journals (Sweden)

Raja Sekhar Dondapati

2017-12-01

Full Text Available Supercritical fluid technology finds its application in almost all engineering aspects in one or other way. Technology of clean jet fuel combustion is also seeing supercritical fluids as one of their contender in order to mitigate the challenges related to global warming and health issues occurred due to unwanted emissions which are found to be the by-products in conventional jet engine combustion. As jet fuel is a blend of hundred of hydrocarbons, thus estimation of chemical kinetics and emission characteristics while simulation become much complex. Advancement in supercritical jet fuel combustion technology demands reliable property statistics of jet fuel as a function temperature and pressure. Therefore, in the present work one jet fuel surrogate (n-dodecane which has been recognized as the constituent of real jet fuel is studied and thermophysical properties of each is evaluated in the supercritical regime. Correlation has been developed for two transport properties namely density and viscosity at the critical pressure and over a wide range of temperatures (TC + 100 K. Further, to endorse the reliability of the developed correlation, two arithmetical parameters have been evaluated which illustrates an outstanding agreement between the data obtained from online NIST Web-Book and the developed correlation.

The reliability, accuracy and minimal detectable difference of a multi-segment kinematic model of the foot-shoe complex.

Science.gov (United States)

Bishop, Chris; Paul, Gunther; Thewlis, Dominic

2013-04-01

Kinematic models are commonly used to quantify foot and ankle kinematics, yet no marker sets or models have been proven reliable or accurate when wearing shoes. Further, the minimal detectable difference of a developed model is often not reported. We present a kinematic model that is reliable, accurate and sensitive to describe the kinematics of the foot-shoe complex and lower leg during walking gait. In order to achieve this, a new marker set was established, consisting of 25 markers applied on the shoe and skin surface, which informed a four segment kinematic model of the foot-shoe complex and lower leg. Three independent experiments were conducted to determine the reliability, accuracy and minimal detectable difference of the marker set and model. Inter-rater reliability of marker placement on the shoe was proven to be good to excellent (ICC=0.75-0.98) indicating that markers could be applied reliably between raters. Intra-rater reliability was better for the experienced rater (ICC=0.68-0.99) than the inexperienced rater (ICC=0.38-0.97). The accuracy of marker placement along each axis was <6.7 mm for all markers studied. Minimal detectable difference (MDD90) thresholds were defined for each joint; tibiocalcaneal joint--MDD90=2.17-9.36°, tarsometatarsal joint--MDD90=1.03-9.29° and the metatarsophalangeal joint--MDD90=1.75-9.12°. These thresholds proposed are specific for the description of shod motion, and can be used in future research designed at comparing between different footwear. Copyright © 2012 Elsevier B.V. All rights reserved.

Surrogatvalidierung durch Korrelation und Surrogate Threshold Effect – Ergebnisse von Simulationsstudien

Directory of Open Access Journals (Sweden)

Gillhaus, Johanna

2017-01-01

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

Long-Term Stability Testing Results Using Surrogates And Sorbents For Savannah River Site Organic And Aqueous Wastestreams - 10016

International Nuclear Information System (INIS)

Burns, H.

2009-01-01

The U.S. Department of Energy (DOE) has tasked MSE Technology Applications, Inc. (MSE) with evaluating the long-term stability of various commercially available sorbent materials to solidify two organic surrogate wastestreams (both volatile and nonvolatile), a volatile organic surrogate with a residual aqueous phase, an aqueous surrogate, and an aqueous surrogate with a residual organic phase. The Savannah River Site (SRS) Legacy and F-Canyon plutonium/uranium extraction (PUREX) process waste surrogates constituted the volatile organic surrogates, and various oils constituted the nonvolatile organic surrogates. The aqueous surrogates included a rainwater surrogate and an aqueous organic surrogate. MSE also evaluated the PUREX surrogate with a residual aqueous component with and without aqueous type sorbent materials. Solidification of the various surrogate wastestreams listed above was performed from 2004 to 2006 at the MSE Test Facility located in Butte, Montana. This paper summarizes the comparison of the initial liquid release test (LRT) values with LRT results obtained during subsequent sampling events in an attempt to understand and define the long-term stability characteristics for the solidified wastestreams.

An improved and explicit surrogate variable analysis procedure by coefficient adjustment.

Science.gov (United States)

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

2017-06-01

Unobserved environmental, demographic, and technical factors can negatively affect the estimation and testing of the effects of primary variables. Surrogate variable analysis, proposed to tackle this problem, has been widely used in genomic studies. To estimate hidden factors that are correlated with the primary variables, surrogate variable analysis performs principal component analysis either on a subset of features or on all features, but weighting each differently. However, existing approaches may fail to identify hidden factors that are strongly correlated with the primary variables, and the extra step of feature selection and weight calculation makes the theoretical investigation of surrogate variable analysis challenging. In this paper, we propose an improved surrogate variable analysis using all measured features that has a natural connection with restricted least squares, which allows us to study its theoretical properties. Simulation studies and real data analysis show that the method is competitive to state-of-the-art methods.

A fast surrogate model tailor-made for real time control

DEFF Research Database (Denmark)

Borup, Morten; Thrysøe, Cecilie; Arnbjerg-Nielsen, Karsten

A surrogate model of a detailed hydraulic urban drainage model is created for supplying inflow forecasts to an MPC model for 31 separate locations. The original model is subdivided into 66 relationships extracted from the original model. The surrogate model is 9000 times faster than the original...... model, with just a minor deviation from the original model results....

Pulse wave amplitude drops during sleep are reliable surrogate markers of changes in cortical activity

OpenAIRE

Delessert, A.

2011-01-01

Rapport de synthèseLe syndrome d'apnées obstructives du sommeil (SAOS) est une pathologie respiratoire fréquente. Sa prévalence est estimée entre 2 et 5% de la population adulte générale. Ses conséquences sont importantes. Notamment, une somnolence diurne, des troubles de la concentration, des troubles de la mémoire et une augmentation du risque d'accident de la route et du travail. Il représente également un facteur de risque cardiovasculaire indépendant.Ce syndrome est caractérisé par la su...

Act relating to surrogate parenthood contracts, 10 February 1988.

Science.gov (United States)

1988-01-01

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

Surrogate alcohol containing methanol, social deprivation and public health in Novosibirsk, Russia.

Science.gov (United States)

Neufeld, Maria; Lachenmeier, Dirk; Hausler, Thomas; Rehm, Jürgen

2016-11-01

Surrogate alcohol, i.e. alcohol not intended or not officially intended for human consumption, continues to play an important role in alcohol consumption in Russia, especially for people with alcohol dependence. Among the different types of surrogate alcohol, there are windshield washer antifreeze liquids; these products are the cheapest kinds of non-beverage alcohol available and thus likely to be used by the most deprived and marginalised groups such as homeless people with alcohol dependence. Although it is well known, that non-beverage alcohol is used for consumption by various groups in Russia, and although there are laws to prohibit the use of methanol as part of windshield washer antifreeze liquids for the very reason that such products could be used as surrogate alcohol, we detected products in retail sale which were a mix of water and methanol only. Methanol poses serious health threats including blindness and death, and there had been repeated methanol deaths from surrogate alcohol in Russia over the last years. If law-enforcement does not change for surrogate products, we can expect more methanol-resulting deaths in the most deprived and marginalized groups of people with alcohol dependence in Russia. In addition, ingredients with questionable safety profiles such as formic acid should also be prohibited in non-beverage alcohol products that are likely to be consumed as surrogate alcohol. Copyright © 2016. Published by Elsevier B.V.

Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers

Science.gov (United States)

Ray, Sandipan; Renu, Durairaj; Srivastava, Rajneesh; Gollapalli, Kishore; Taur, Santosh; Jhaveri, Tulip; Dhali, Snigdha; Chennareddy, Srinivasarao; Potla, Ankit; Dikshit, Jyoti Bajpai; Srikanth, Rapole; Gogtay, Nithya; Thatte, Urmila; Patankar, Swati; Srivastava, Sanjeeva

2012-01-01

This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates

Proteomic investigation of falciparum and vivax malaria for identification of surrogate protein markers.

Directory of Open Access Journals (Sweden)

Sandipan Ray

Full Text Available This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM (n = 20, vivax malaria (VM (n = 17 and healthy controls (HC (n = 20 were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC. Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05 serum proteins were identified in FM and VM respectively, and almost half (46.2% of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates

Surrogate Assisted Design Optimization of an Air Turbine

Directory of Open Access Journals (Sweden)

Rameez Badhurshah

2014-01-01

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

Calbindin-D28k is a more reliable marker of human Purkinje cells than standard Nissl stains: a stereological experiment.

Science.gov (United States)

Whitney, Elizabeth R; Kemper, Thomas L; Rosene, Douglas L; Bauman, Margaret L; Blatt, Gene J

2008-02-15

In a study of human Purkinje cell (PC) number, a striking mismatch between the number of PCs observed with the Nissl stain and the number of PCs immunopositive for calbindin-D28k (CB) was identified in 2 of the 10 brains examined. In the remaining eight brains this mismatch was not observed. Further, in these eight brains, analysis of CB immunostained sections counterstained with the Nissl stain revealed that more than 99% Nissl stained PCs were also immunopositive for CB. In contrast, in the two discordant brains, only 10-20% of CB immunopositive PCs were also identified with the Nissl stain. Although this finding was unexpected, a historical survey of the literature revealed that Spielmeyer [Spielmeyer W. Histopathologie des nervensystems. Julius Springer: Berlin; 1922. p. 56-79] described human cases with PCs that lacked the expected Nissl staining intensity, an important historical finding and critical issue when studying postmortem human brains. The reason for this failure in Nissl staining is not entirely clear, but it may result from premortem circumstances since it is not accounted for by postmortem delay or processing variables. Regardless of the exact cause, these observations suggest that Nissl staining may not be a reliable marker for PCs and that CB is an excellent alternative marker.

Surrogate pregnancy: a guide for Canadian prenatal health care providers

Science.gov (United States)

Reilly, Dan R.

2007-01-01

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

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

Science.gov (United States)

Reilly, Dan R

2007-02-13

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

Global end-diastolic volume an emerging preload marker vis-a-vis other markers - Have we reached our goal?

Directory of Open Access Journals (Sweden)

P M Kapoor

2016-01-01

Full Text Available A reliable estimation of cardiac preload is helpful in the management of severe circulatory dysfunction. The estimation of cardiac preload has evolved from nuclear angiography, pulmonary artery catheterization to echocardiography, and transpulmonary thermodilution (TPTD. Global end-diastolic volume (GEDV is the combined end-diastolic volumes of all the four cardiac chambers. GEDV has been demonstrated to be a reliable preload marker in comparison with traditionally used pulmonary artery catheter-derived pressure preload parameters. Recently, a new TPTD system called EV1000™ has been developed and introduced into the expanding field of advanced hemodynamic monitoring. GEDV has emerged as a better preload marker than its previous conventional counterparts. The advantage of it being measured by minimum invasive methods such as PiCCO™ and newly developed EV1000™ system makes it a promising bedside advanced hemodynamic parameter.

Observation of Burial and Migration of Instrumented Surrogate Munitions Deployed in the Swash Zone

Science.gov (United States)

Cristaudo, D.; Puleo, J. A.; Bruder, B. L.

2017-12-01

Munitions (also known as unexploded ordnance; UXO) in the nearshore environment due to past military activities, may be found on the beach, constituting a risk for beach users. Munitions may be transported from offshore to shallower water and/or migrate along the coast. In addition, munitions may bury in place or be exhumed due to hydrodynamic forcing. Observations on munitions mobility have generally been collected offshore, while observations in the swash zone are scarce. The swash zone is the region of the beach alternately covered by wave runup where hydrodynamic processes may be intense. Studies of munitions mobility require the use of realistic surrogates to quantify mobility/burial and hydrodynamic forcing conditions. Four surrogates (BLU-61 Cluster Bomb, 81 mm Mortar, M151-70 Hydra Rocket and M107 155 mm High Explosive Howitzer) were developed and tested during large-scale laboratory and field studies. Surrogates house sensors that measure different components of motion. Errors between real munitions and surrogate parameters (mass, center of gravity and axial moment of inertia) are all within an absolute error of 20%. Internal munitions sensors consist of inertial motion units (for acceleration and angular velocity in and around the three directions and orientation), pressure transducers (for water depth above surrogate), shock recorders (for high frequency acceleration to detect wave impact on the surrogate), and an in-house designed array of optical sensors (for burial/exposure and rolling). An in situ array of sensors to measure hydrodynamics, bed morphology and sediment concentrations, was deployed in the swash zone, aligned with the surrogate deployment. Data collected during the studies will be shown highlighting surrogate sensor capabilities. Sensors response will be compared with GPS measurements and imagery from cameras overlooking the study sites of surrogate position as a function of time. Examples of burial/exposure and migration of surrogates

The social context for surrogates' motivations and satisfaction.

Science.gov (United States)

Berend, Zsuzsa

2014-10-01

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

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.

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

Methylene blue as a lignin surrogate in manganese peroxidase reaction systems.

Science.gov (United States)

Goby, Jeffrey D; Penner, Michael H; Lajoie, Curtis A; Kelly, Christine J

2017-11-15

Manganese peroxidase (MnP) is associated with lignin degradation and is thus relevant to lignocellulosic-utilization technologies. Technological applications require reaction mixture optimization. A surrogate substrate can facilitate this if its susceptibility to degradation is easily monitored and mirrors that of lignin. The dye methylene blue (MB) was evaluated in these respects as a surrogate substrate by testing its reactivity in reaction mixtures containing relevant redox mediators (dicarboxylic acids, fatty acids). Relative rates of MB degradation were compared to available literature reports of lignin degradation under similar conditions, and suggest that MB can be a useful lignin surrogate in MnP systems. Copyright © 2017 Elsevier Inc. All rights reserved.

Adolescents with Classical Polycystic Ovary Syndrome Have Alterations in the Surrogate Markers of Cardiovascular Disease but Not in the Endothelial Function. The Possible Benefits of Metformin.

Science.gov (United States)

Fruzzetti, Franca; Ghiadoni, Lorenzo; Virdis, Agostino; De Negri, Ferdinando; Perini, Daria; Bucci, Fiorella; Giannarelli, Chiara; Gadducci, Angiolo; Taddei, Stefano

2016-10-01

To study whether adolescents with the classical form of polycystic ovary syndrome (PCOS) have alterations in metabolic and vascular structure and function. The effect of metformin was evaluated. Controlled study. University outpatient clinic. Eighteen nonobese adolescents with PCOS were enrolled. Seventeen healthy age-matched adolescents were recruited as control subjects. The metabolic profile and the endothelial structure and function were evaluated. Hormonal and lipid profile, blood pressure (BP) measurement, fasting glucose and insulin levels, C-reactive protein (CRP), homocysteine, tissue-type plasminogen activator, plasminogen activator inhibitor-1 (PAI-1), and plasmin-antiplasmin complexes (PAP) were measured. Flow mediated dilation (FMD), central pulse wave velocity (PWV), radial artery pulse wave, and common carotid intima-media thickness (IMT) were also assessed. Girls with PCOS were also studied 6 months after treatment with metformin (850 mg twice per day). Adolescents with PCOS were insulin resistant and/or hyperinsulinemic and they had higher BP values and levels of CRP and PAI-1 than the control subjects. The levels of tissue-type plasminogen activator and PAP were similar in both groups. FMD, PWV, and IMT were also similar. Metformin significantly (P insulin, BP, CRP, and PAI-1 levels. The PAP levels significantly (P PCOS have alterations in some surrogate markers of cardiovascular risk and they are ameliorated by metformin. No deterioration of vascular structure and function has been detected, probably because of the short duration of exposure to the disease. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

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

International Nuclear Information System (INIS)

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

2017-01-01

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

Families in the making: gestational surrogate mothers in California

OpenAIRE

Bjørn, Henriette Hårseide

2014-01-01

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

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

KAUST Repository

Ahmed, Ahfaz

2015-03-01

Gasoline is the most widely used fuel for light duty automobile transportation, but its molecular complexity makes it intractable to experimentally and computationally study the fundamental combustion properties. Therefore, surrogate fuels with a simpler molecular composition that represent real fuel behavior in one or more aspects are needed to enable repeatable experimental and computational combustion investigations. This study presents a novel computational methodology for formulating surrogates for FACE (fuels for advanced combustion engines) gasolines A and C by combining regression modeling with physical and chemical kinetics simulations. The computational methodology integrates simulation tools executed across different software platforms. Initially, the palette of surrogate species and carbon types for the target fuels were determined from a detailed hydrocarbon analysis (DHA). A regression algorithm implemented in MATLAB was linked to REFPROP for simulation of distillation curves and calculation of physical properties of surrogate compositions. The MATLAB code generates a surrogate composition at each iteration, which is then used to automatically generate CHEMKIN input files that are submitted to homogeneous batch reactor simulations for prediction of research octane number (RON). The regression algorithm determines the optimal surrogate composition to match the fuel properties of FACE A and C gasoline, specifically hydrogen/carbon (H/C) ratio, density, distillation characteristics, carbon types, and RON. The optimal surrogate fuel compositions obtained using the present computational approach was compared to the real fuel properties, as well as with surrogate compositions available in the literature. Experiments were conducted within a Cooperative Fuels Research (CFR) engine operating under controlled autoignition (CAI) mode to compare the formulated surrogates against the real fuels. Carbon monoxide measurements indicated that the proposed surrogates

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

KAUST Repository

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

2016-01-01

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

Application of computational fluid dynamics and surrogate-coupled evolutionary computing to enhance centrifugal-pump performance

Directory of Open Access Journals (Sweden)

Sayed Ahmed Imran Bellary

2016-01-01

Full Text Available To reduce the total design and optimization time, numerical analysis with surrogate-based approaches is being used in turbomachinery optimization. In this work, multiple surrogates are coupled with an evolutionary genetic algorithm to find the Pareto optimal fronts (PoFs of two centrifugal pumps with different specifications in order to enhance their performance. The two pumps were used a centrifugal pump commonly used in industry (Case I and an electrical submersible pump used in the petroleum industry (Case II. The objectives are to enhance head and efficiency of the pumps at specific flow rates. Surrogates such as response surface approximation (RSA, Kriging (KRG, neural networks and weighted-average surrogates (WASs were used to determine the PoFs. To obtain the objective functions’ values and to understand the flow physics, Reynolds-averaged Navier–Stokes equations were solved. It is found that the WAS performs better for both the objectives than any other individual surrogate. The best individual surrogates or the best predicted error sum of squares (PRESS surrogate (BPS obtained from cross-validation (CV error estimations produced better PoFs but was still unable to compete with the WAS. The high CV error-producing surrogate produced the worst PoFs. The performance improvement in this study is due to the change in flow pattern in the passage of the impeller of the pumps.

Coronary Artery Calcium as an Independent Surrogate Marker in the Risk Assessment of Patients With Atrial Fibrillation and an Intermediate Pretest Likelihood for Coronary Artery Disease Admitted to a German Chest Pain Unit.

Science.gov (United States)

Breuckmann, Frank; Olligs, Jan; Hinrichs, Liane; Koopmann, Matthias; Lichtenberg, Michael; Böse, Dirk; Fischer, Dieter; Eckardt, Lars; Waltenberger, Johannes; Garvey, J Lee

2016-03-01

About 10% of patients admitted to a chest pain unit (CPU) exhibit atrial fibrillation (AF). To determine whether calcium scores (CS) are superior over common risk scores for coronary artery disease (CAD) in patients presenting with atypical chest pain, newly diagnosed AF, and intermediate pretest probability for CAD within the CPU. In 73 subjects, CS was related to the following risk scores: Global Registry of Acute Coronary Events (GRACE) score, including a new model of a frequency-normalized approach; Thrombolysis In Myocardial Infarction score; European Society of Cardiology Systematic Coronary Risk Evaluation (SCORE); Framingham risk score; and Prospective Cardiovascular Münster Study score. Revascularization rates during index stay were assessed. Median CS was 77 (interquartile range, 1-270), with higher values in men and the left anterior descending artery. Only the modified GRACE (ρ = 0.27; P = 0.02) and the SCORE (ρ = 0.39; P risk scores and calcium burden, as well as revascularization rates during index stay, were low. By contrast, the determination of CS may be used as an additional surrogate marker in risk stratification in AF patients with intermediate pretest likelihood for CAD admitted to a CPU. © 2016 Wiley Periodicals, Inc.

Detection of HPV and the role of p16INK4A overexpression as a surrogate marker for the presence of functional HPV oncoprotein E7 in colorectal cancer

Directory of Open Access Journals (Sweden)

Lardon Filip

2010-03-01

Full Text Available Abstract Background Based on the well-recognized etiological role of human papillomavirus (HPV in cervical, anogenital and oropharyngeal carcinogenesis, a potential role of HPV in colorectal carcinogenesis has been suggested. For that reason, the aim of the present study was to investigate the presence of HPV DNA in colorectal carcinomas (CRC and to study overexpression of p16INK4A as a marker for the presence of an active HPV oncoprotein E7. These findings were correlated with clinical and pathological prognostic factors of CRC. Methods The presence of HPV was assessed using a multiplex PCR system of 10 non-biotinylated primers. The amplified fragments of HPV positive samples were further analyzed by a highly sensitive, broad spectrum SPF10 PCR and subsequently genotyped using reverse hybridization in a line probe assay. P16INK4A protein expression was investigated in a subset of 90 (30 HPV positive and 60 HPV negative CRC samples by immunohistochemistry. Results HPV DNA was found in 14.2% of the CRC samples with HPV16 as the most prevalent type. No significant differences in clinical and pathological variables were found between HPV positive and negative CRCs, except for age. HPV positive patients were significantly younger (p = 0.05. There was no significant correlation between the presence of HPV and overexpression of p16INK4A (p = 0.325. Conclusions In conclusion, the presence of oncogenic HPV DNA in a small cohort of CRC samples may suggest that HPV may be involved in the carcinogenesis of some CRC. However, contrary to what has been observed in head and neck squamous cell cancer and cancer of the uterine cervix, p16INK4A does not seem to be a surrogate marker for an active HPV infection in CRC. Therefore, further functional analyses are necessary to elucidate the role of HPV in CRC.

Surrogate Motherhood II: Reflections after "Baby M."

Science.gov (United States)

Schwartz, Lita Linzer

1988-01-01

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

Evaluation of countermeasures for red light running by traffic simulator-based surrogate safety measures.

Science.gov (United States)

Lee, Changju; So, Jaehyun Jason; Ma, Jiaqi

2018-01-02

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

Developing Fast and Reliable Flood Models

DEFF Research Database (Denmark)

Thrysøe, Cecilie; Toke, Jens; Borup, Morten

2016-01-01

. A surrogate model is set up for a case study area in Aarhus, Denmark, to replace a MIKE FLOOD model. The drainage surrogates are able to reproduce the MIKE URBAN results for a set of rain inputs. The coupled drainage-surface surrogate model lacks details in the surface description which reduces its overall...... accuracy. The model shows no instability, hence larger time steps can be applied, which reduces the computational time by more than a factor 1400. In conclusion, surrogate models show great potential for usage in urban water modelling....

Mechanical Properties of K Basin Sludge Constituents and Their Surrogates

International Nuclear Information System (INIS)

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

2004-01-01

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

LVAD patients' and surrogates' perspectives on SPIRIT-HF: An advance care planning discussion.

Science.gov (United States)

Metzger, Maureen; Song, Mi-Kyung; Devane-Johnson, Stephanie

2016-01-01

To describe LVAD patients' and surrogates' experiences with, and perspectives on SPIRIT-HF, an advance care planning (ACP) intervention. ACP is important for patients with LVAD, yet little is known about their experiences or those of their surrogates who have participated in ACP discussions. We used qualitative content analysis techniques to conduct a secondary analysis of 28 interviews with patients with LVAD (n = 14) and their surrogates (n = 14) who had participated in an RCT pilot study of SPIRIT-HF. Main themes from the data include: 1) sharing their HF stories was very beneficial; 2) participating in SPIRIT-HF led to greater peace of mind for patients and surrogates; 3) "one size does not fit all" when it comes to timing of ACP discussions. An understanding patient and surrogate perspectives may inform clinicians' approach to ACP discussions. Copyright © 2016 Elsevier Inc. All rights reserved.

Validating (d,p gamma) as a Surrogate for Neutron Capture

Energy Technology Data Exchange (ETDEWEB)

Ratkiewicz, A. [Rutgers University; Cizewski, J. A. [Rutgers University; Pain, S. [Oak Ridge National Laboratory (ORNL); Adekola, A. S. [Rutgers University; Burke, J. T. [Lawrence Livermore National Laboratory (LLNL); Casperson, R.J. [Lawrence Livermore National Laboratory (LLNL); Fotiades, N. [Los Alamos National Laboratory (LANL); McCleskey, M. [Texas A& M University; Burcher, S. [Rutgers University; Shand, C. M. [Rutgers Univ./Univ. of Surrey, UK; Austin, R. A. E. [Saint Mary’s University, Halifa, Canada; Baugher, T. [Rutgers University; Carpenter, M. P. [Argonne National Laboratory (ANL); Devlin, M. [Los Alamos National Laboratory (LANL); Escher, J. E. [Lawrence Livermore National Laboratory (LLNL); Hardy, S. [Rutgers Univ./Univ. of Surrey, UK; Hatarik, R. [Lawrence Livermore National Laboratory (LLNL); Howard, M. [Rutgers University; Hughes, R. [University of Richmond, VA; Jones, K. L. [University of Tennessee, Knoxville (UTK); Kozub, R. L. [Tennessee Technological University (TTU); Lister, C. J. [University of Massachusetts, Lowell; Manning, B. [Rutgers University; O' Donnell, J. M. [Los Alamos National Laboratory (LANL); Peters, W. A. [Oak Ridge Associated Universities (ORAU); Ross, T.J. [University of Richmond, VA; Scielzo, N.D. [Lawrence Livermore National Laboratory (LLNL); Seweryniak, D. [Argonne National Laboratory (ANL); Zhu, S. [Argonne National Laboratory (ANL)

2015-01-01

The r-process is responsible for creating roughly half of the elements heavier than iron. It has recently become understood that the rates at which neutron capture reactions proceed at late times in the rprocess may dramatically affect the final abundance pattern. However, direct measurements of neutron capture reaction rates on exotic nuclei are exceptionally difficult, necessitating the development of indirect approaches such as the surrogate technique. The (d,py) reaction at low energies was identified as a promising surrogate for the (n,y) reaction, as both reactions share many characteristics. We report on a program to validate (d,py) as a surrogate for (n,y) using 95Mo as a target. The experimental campaign includes direct measurements of the y-ray intensities from the decay of excited states populated in the 95Mo(n,y) and 95Mo(d,py) reactions.

Development of an instrumented spinal cord surrogate using optical fibers: A feasibility study.

Science.gov (United States)

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

2017-10-01

In vitro replication of traumatic spinal cord injury is necessary to understand its biomechanics and to improve animal models. During a traumatic spinal cord injury, the spinal cord withstands an impaction at high velocity. In order to fully assess the impaction, the use of spinal canal occlusion sensor is necessary. A physical spinal cord surrogate is also often used to simulate the presence of the spinal cord and its surrounding structures. In this study, an instrumented physical spinal cord surrogate is presented and validated. The sensing is based on light transmission loss observed in embedded bare optical fibers subjected to bending. The instrumented surrogate exhibits similar mechanical properties under static compression compared to fresh porcine spinal cords. The instrumented surrogate has a compression sensing threshold of 40% that matches the smallest compression values leading to neurological injuries. The signal obtained from the sensor allows calculating the compression of the spinal cord surrogate with a maximum of 5% deviation. Excellent repeatability was also observed under repetitive loading. The proposed instrumented spinal cord surrogate is promising with satisfying mechanical properties and good sensing capability. It is the first attempt at proposing a method to assess the internal loads sustained by the spinal cord during a traumatic injury. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

Surrogate screening models for the low physical activity criterion of frailty.

Science.gov (United States)

Eckel, Sandrah P; Bandeen-Roche, Karen; Chaves, Paulo H M; Fried, Linda P; Louis, Thomas A

2011-06-01

Low physical activity, one of five criteria in a validated clinical phenotype of frailty, is assessed by a standardized, semiquantitative questionnaire on up to 20 leisure time activities. Because of the time demanded to collect the interview data, it has been challenging to translate to studies other than the Cardiovascular Health Study (CHS), for which it was developed. Considering subsets of activities, we identified and evaluated streamlined surrogate assessment methods and compared them to one implemented in the Women's Health and Aging Study (WHAS). Using data on men and women ages 65 and older from the CHS, we applied logistic regression models to rank activities by "relative influence" in predicting low physical activity.We considered subsets of the most influential activities as inputs to potential surrogate models (logistic regressions). We evaluated predictive accuracy and predictive validity using the area under receiver operating characteristic curves and assessed criterion validity using proportional hazards models relating frailty status (defined using the surrogate) to mortality. Walking for exercise and moderately strenuous household chores were highly influential for both genders. Women required fewer activities than men for accurate classification. The WHAS model (8 CHS activities) was an effective surrogate, but a surrogate using 6 activities (walking, chores, gardening, general exercise, mowing and golfing) was also highly predictive. We recommend a 6 activity questionnaire to assess physical activity for men and women. If efficiency is essential and the study involves only women, fewer activities can be included.

Molecular markers in bladder cancer: Novel research frontiers.

Science.gov (United States)

Sanguedolce, Francesca; Cormio, Antonella; Bufo, Pantaleo; Carrieri, Giuseppe; Cormio, Luigi

2015-01-01

Bladder cancer (BC) is a heterogeneous disease encompassing distinct biologic features that lead to extremely different clinical behaviors. In the last 20 years, great efforts have been made to predict disease outcome and response to treatment by developing risk assessment calculators based on multiple standard clinical-pathological factors, as well as by testing several molecular markers. Unfortunately, risk assessment calculators alone fail to accurately assess a single patient's prognosis and response to different treatment options. Several molecular markers easily assessable by routine immunohistochemical techniques hold promise for becoming widely available and cost-effective tools for a more reliable risk assessment, but none have yet entered routine clinical practice. Current research is therefore moving towards (i) identifying novel molecular markers; (ii) testing old and new markers in homogeneous patients' populations receiving homogeneous treatments; (iii) generating a multimarker panel that could be easily, and thus routinely, used in clinical practice; (iv) developing novel risk assessment tools, possibly combining standard clinical-pathological factors with molecular markers. This review analyses the emerging body of literature concerning novel biomarkers, ranging from genetic changes to altered expression of a huge variety of molecules, potentially involved in BC outcome and response to treatment. Findings suggest that some of these indicators, such as serum circulating tumor cells and tissue mitochondrial DNA, seem to be easily assessable and provide reliable information. Other markers, such as the phosphoinositide-3-kinase (PI3K)/AKT (serine-threonine kinase)/mTOR (mammalian target of rapamycin) pathway and epigenetic changes in DNA methylation seem to not only have prognostic/predictive value but also, most importantly, represent valuable therapeutic targets. Finally, there is increasing evidence that the development of novel risk assessment tools

Test procedures for polyester immobilized salt-containing surrogate mixed wastes

International Nuclear Information System (INIS)

Biyani, R.K.; Hendrickson, D.W.

1997-01-01

These test procedures are written to meet the procedural needs of the Test Plan for immobilization of salt containing surrogate mixed waste using polymer resins, HNF-SD-RE-TP-026 and to ensure adequacy of conduct and collection of samples and data. This testing will demonstrate the use of four different polyester vinyl ester resins in the solidification of surrogate liquid and dry wastes, similar to some mixed wastes generated by DOE operations

Cardiac embolization of an implanted fiducial marker for hepatic stereotactic body radiotherapy: a case report

Directory of Open Access Journals (Sweden)

Hennessey Hooman

2009-11-01

Full Text Available Abstract Introduction In liver stereotactic body radiotherapy, reduction of normal tissue irradiation requires daily image guidance. This is typically accomplished by imaging a surrogate to the tumor. The surrogate is often an implanted metal fiducial marker. There are few reports addressing the specific risks of hepatic fiducial marker implantation. These risks are assumed to be similar to percutaneous liver biopsies which are associated with a 1-4% complication rate - almost always pain or bleeding. To the best of our knowledge, we present the first case of such a fiducial marker migrating to the heart. Case presentation An 81-year-old Caucasian man (5 years post-gastrectomy for a gastric adenocarcinoma was referred post-second line palliative chemotherapy for radiotherapy of an isolated liver metastasis. It was decided to proceed with treatment and platinum fiducials were chosen for radiation targeting. Under local anesthesia, three Nester embolization coils (Cook Medical Inc., Bloomington, IN, USA were implanted under computed tomography guidance. Before the placement of each coil, the location of the tip of the delivery needle was confirmed by computed tomography imaging. During the procedure, the third coil unexpectedly migrated through the hepatic vein to the inferior vena cava and lodged at the junction of the vena cava and the right atrium. The patient remained asymptomatic. He was immediately referred to angiography for extraction of the coil. Using fluoroscopic guidance, an EN Snare Retrieval System (Hatch Medical L.L.C., Snellville, GA, USA was introduced through a jugular catheter; it successfully grasped the coil and the coil was removed. The patient was kept overnight for observation and no immediate or delayed complications were encountered due to the migration or retrieval of the coil. He subsequently went on to be treated using the remaining fiducials. Conclusion Implanted fiducial markers are increasingly used for stereotactic

Serum interleukin -8 is not a reliable marker for prediction of vesicoureteral reflux in children with febrile urinary tract infection

Directory of Open Access Journals (Sweden)

Abolfazl Mahyar

2015-12-01

Full Text Available Objective: In view of the side effects of voiding cystourethrography (VCUG, identification of noninvasive markers predicting the presence of vesicoureteral reflux (VUR is important. This study was conducted to determine the predictive value of serum interleukin-8 (IL-8 in diagnosis of VUR in children with first febrile urinary tract infection (UTI. Materials and Methods: Eighty children with first febrile UTI were divided into two groups, with and without VUR, based on the results of VCUG. The sensitivity, specificity, positive and negative predictive value positive and negative likelihood ratio, and accuracy of IL-8 for prediction of VUR were investigated. Results: Of the 80 children with febrile UTI, 30 (37.5% had VUR. There was no significant difference between the children with and without VUR and also between low and high-grade VUR groups in terms of serum concentration of IL-8 (P>0.05. Based on ROC curve, the sensitivity, specificity, likelihood ratio positive, and accuracy of serum IL-8 was lower than those of erythrocyte sedimentation rate and C-reactive protein. Multivariate logistic regression analysis showed significant positive correlation only between erythrocyte sedimentation rate and VUR. Conclusions: This study showed no significant difference between the children with and without VUR in terms of the serum concentration of IL-8. Therefore, it seems that serum IL-8 is not a reliable marker for prediction of VUR.

First Trimester Hemolysis, Elevated Liver Enzymes, Low Platelets Syndrome in a Surrogate Pregnancy

OpenAIRE

Myer, Emily; Hill, James

2015-01-01

Background The occurrence of hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome before 20 weeks of gestation is rare. HELLP is a possible but rare syndrome in gestational surrogate pregnancies for surrogates with risk factors for development of preeclampsia. Case A 32-year-old patient with chronic hypertension and positive antinuclear antibody presented for prenatal care at 13 weeks and 1 day. She was a surrogate for the embryo of a 43-year-old couple. By 15 weeks she developed...

Body fluid markers to monitor multiple sclerosis: The assays and the challenges

NARCIS (Netherlands)

Laman, J.D.; Thompson, E.J.; Kappos, L.

1998-01-01

The need for reliable markers of disease activity in multiple sclerosis (MS) to better guide basic research, diagnosis, treatment, and monitoring of therapy is well-recognized. A recent European Charcot Foundation Symposium (Body fluid markers for course and activity of disease in multiple sclerosis

Narrative Interest Standard: A Novel Approach to Surrogate Decision-Making for People With Dementia.

Science.gov (United States)

Wilkins, James M

2017-06-17

Dementia is a common neurodegenerative process that can significantly impair decision-making capacity as the disease progresses. When a person is found to lack capacity to make a decision, a surrogate decision-maker is generally sought to aid in decision-making. Typical bases for surrogate decision-making include the substituted judgment standard and the best interest standard. Given the heterogeneous and progressive course of dementia, however, these standards for surrogate decision-making are often insufficient in providing guidance for the decision-making for a person with dementia, escalating the likelihood of conflict in these decisions. In this article, the narrative interest standard is presented as a novel and more appropriate approach to surrogate decision-making for people with dementia. Through case presentation and ethical analysis, the standard mechanisms for surrogate decision-making for people with dementia are reviewed and critiqued. The narrative interest standard is then introduced and discussed as a dementia-specific model for surrogate decision-making. Through incorporation of elements of a best interest standard in focusing on the current benefit-burden ratio and elements of narrative to provide context, history, and flexibility for values and preferences that may change over time, the narrative interest standard allows for elaboration of an enriched context for surrogate decision-making for people with dementia. More importantly, however, a narrative approach encourages the direct contribution from people with dementia in authoring the story of what matters to them in their lives.

Experimental Validation of Surrogate Models for Predicting the Draping of Physical Interpolating Surfaces

DEFF Research Database (Denmark)

Christensen, Esben Toke; Lund, Erik; Lindgaard, Esben

2018-01-01

This paper concerns the experimental validation of two surrogate models through a benchmark study involving two different variable shape mould prototype systems. The surrogate models in question are different methods based on kriging and proper orthogonal decomposition (POD), which were developed...... to the performance of the studied surrogate models. By comparing surrogate model performance for the two variable shape mould systems, and through a numerical study involving simple finite element models, the underlying cause of this effect is explained. It is concluded that for a variable shape mould prototype...... hypercube approach. This sampling method allows for generating a space filling and high-quality sample plan that respects mechanical constraints of the variable shape mould systems. Through the benchmark study, it is found that mechanical freeplay in the modeled system is severely detrimental...

Surrogate Models for Online Monitoring and Process Troubleshooting of NBR Emulsion Copolymerization

Directory of Open Access Journals (Sweden)

Chandra Mouli R. Madhuranthakam

2016-03-01

Full Text Available Chemical processes with complex reaction mechanisms generally lead to dynamic models which, while beneficial for predicting and capturing the detailed process behavior, are not readily amenable for direct use in online applications related to process operation, optimisation, control, and troubleshooting. Surrogate models can help overcome this problem. In this research article, the first part focuses on obtaining surrogate models for emulsion copolymerization of nitrile butadiene rubber (NBR, which is usually produced in a train of continuous stirred tank reactors. The predictions and/or profiles for several performance characteristics such as conversion, number of polymer particles, copolymer composition, and weight-average molecular weight, obtained using surrogate models are compared with those obtained using the detailed mechanistic model. In the second part of this article, optimal flow profiles based on dynamic optimisation using the surrogate models are obtained for the production of NBR emulsions with the objective of minimising the off-specification product generated during grade transitions.

Baroreflex dysfunction in sick newborns makes heart rate an unreliable surrogate for blood pressure changes.

Science.gov (United States)

Govindan, Rathinaswamy B; Al-Shargabi, Tareq; Massaro, An N; Metzler, Marina; Andescavage, Nickie N; Joshi, Radhika; Dave, Rhiya; du Plessis, Adre

2016-06-01

Cerebral pressure passivity (CPP) in sick newborns can be detected by evaluating coupling between mean arterial pressure (MAP) and cerebral blood flow measured by near infra-red spectroscopy hemoglobin difference (HbD). However, continuous MAP monitoring requires invasive catheterization with its inherent risks. We tested whether heart rate (HR) could serve as a reliable surrogate for MAP in the detection of CPP in sick newborns. Continuous measurements of MAP, HR, and HbD were made and partitioned into 10-min epochs. Spectral coherence (COH) was computed between MAP and HbD (COHMAP-HbD) to detect CPP, between HR and HbD (COHHR-HbD) for comparison, and between MAP and HR (COHMAP-HR) to quantify baroreflex function (BRF). The agreement between COHMAP-HbD and COHHR-HbD was assessed using ROC analysis. We found poor agreement between COHMAP-HbD and COHHR-HbD in left hemisphere (area under the ROC curve (AUC) 0.68) and right hemisphere (AUC 0.71). Baroreflex failure (COHMAP-HR not significant) was present in 79% of epochs. Confining comparison to epochs with intact BRF showed an AUC of 0.85 for both hemispheres. In these sick newborns, HR was an unreliable surrogate for MAP required for the detection of CPP. This is likely due to the prevalence of BRF failure in these infants.

Surrogate fuel formulation for light naphtha combustion in advanced combustion engines

KAUST Repository

Ahmed, Ahfaz

2015-03-30

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.

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

Directory of Open Access Journals (Sweden)

Tveten G. M.

2013-03-01

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 for extracting capture cross sections has to be investigated. In this work we study the reactions 238U(d,p239U, 238U(3He,t238Np, 238U(3He,4He237U as surrogates for neutroninduced 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. First results are presented and discussed.

Regression calibration with more surrogates than mismeasured variables

KAUST Repository

Kipnis, Victor

2012-06-29

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

Regression calibration with more surrogates than mismeasured variables

KAUST Repository

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

2012-01-01

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

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

Directory of Open Access Journals (Sweden)

Hisao Imai

2015-01-01

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

Using an external surrogate for predictor model training in real-time motion management of lung tumors

Energy Technology Data Exchange (ETDEWEB)

Rottmann, Joerg; Berbeco, Ross [Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115 (United States)

2014-12-15

Purpose: Precise prediction of respiratory motion is a prerequisite for real-time motion compensation techniques such as beam, dynamic couch, or dynamic multileaf collimator tracking. Collection of tumor motion data to train the prediction model is required for most algorithms. To avoid exposure of patients to additional dose from imaging during this procedure, the feasibility of training a linear respiratory motion prediction model with an external surrogate signal is investigated and its performance benchmarked against training the model with tumor positions directly. Methods: The authors implement a lung tumor motion prediction algorithm based on linear ridge regression that is suitable to overcome system latencies up to about 300 ms. Its performance is investigated on a data set of 91 patient breathing trajectories recorded from fiducial marker tracking during radiotherapy delivery to the lung of ten patients. The expected 3D geometric error is quantified as a function of predictor lookahead time, signal sampling frequency and history vector length. Additionally, adaptive model retraining is evaluated, i.e., repeatedly updating the prediction model after initial training. Training length for this is gradually increased with incoming (internal) data availability. To assess practical feasibility model calculation times as well as various minimum data lengths for retraining are evaluated. Relative performance of model training with external surrogate motion data versus tumor motion data is evaluated. However, an internal–external motion correlation model is not utilized, i.e., prediction is solely driven by internal motion in both cases. Results: Similar prediction performance was achieved for training the model with external surrogate data versus internal (tumor motion) data. Adaptive model retraining can substantially boost performance in the case of external surrogate training while it has little impact for training with internal motion data. A minimum

Is TrpM5 a reliable marker for chemosensory cells? Multiple types of microvillous cells in the main olfactory epithelium of mice

Directory of Open Access Journals (Sweden)

Finger Thomas E

2008-12-01

Full Text Available Abstract Background In the past, ciliated receptor neurons, basal cells, and supporting cells were considered the principal components of the main olfactory epithelium. Several studies reported the presence of microvillous cells but their function is unknown. A recent report showed cells in the main olfactory epithelium that express the transient receptor potential channel TrpM5 claiming that these cells are chemosensory and that TrpM5 is an intrinsic signaling component of mammalian chemosensory organs. We asked whether the TrpM5-positive cells in the olfactory epithelium are microvillous and whether they belong to a chemosensory system, i.e. are olfactory neurons or trigeminally-innervated solitary chemosensory cells. Results We investigated the main olfactory epithelium of mice at the light and electron microscopic level and describe several subpopulations of microvillous cells. The ultrastructure of the microvillous cells reveals at least three morphologically different types two of which express the TrpM5 channel. None of these cells have an axon that projects to the olfactory bulb. Tests with a large panel of cell markers indicate that the TrpM5-positive cells are not sensory since they express neither neuronal markers nor are contacted by trigeminal nerve fibers. Conclusion We conclude that TrpM5 is not a reliable marker for chemosensory cells. The TrpM5-positive cells of the olfactory epithelium are microvillous and may be chemoresponsive albeit not part of the sensory apparatus. Activity of these microvillous cells may however influence functionality of local elements of the olfactory system.

Love as a regulative ideal in surrogate decision making.

Science.gov (United States)

Stonestreet, Erica Lucast

2014-10-01

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

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

Science.gov (United States)

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

2017-02-01

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

The Pareidolia Test: A Simple Neuropsychological Test Measuring Visual Hallucination-Like Illusions.

Science.gov (United States)

Mamiya, Yasuyuki; Nishio, Yoshiyuki; Watanabe, Hiroyuki; Yokoi, Kayoko; Uchiyama, Makoto; Baba, Toru; Iizuka, Osamu; Kanno, Shigenori; Kamimura, Naoto; Kazui, Hiroaki; Hashimoto, Mamoru; Ikeda, Manabu; Takeshita, Chieko; Shimomura, Tatsuo; Mori, Etsuro

2016-01-01

Visual hallucinations are a core clinical feature of dementia with Lewy bodies (DLB), and this symptom is important in the differential diagnosis and prediction of treatment response. The pareidolia test is a tool that evokes visual hallucination-like illusions, and these illusions may be a surrogate marker of visual hallucinations in DLB. We created a simplified version of the pareidolia test and examined its validity and reliability to establish the clinical utility of this test. The pareidolia test was administered to 52 patients with DLB, 52 patients with Alzheimer's disease (AD) and 20 healthy controls (HCs). We assessed the test-retest/inter-rater reliability using the intra-class correlation coefficient (ICC) and the concurrent validity using the Neuropsychiatric Inventory (NPI) hallucinations score as a reference. A receiver operating characteristic (ROC) analysis was used to evaluate the sensitivity and specificity of the pareidolia test to differentiate DLB from AD and HCs. The pareidolia test required approximately 15 minutes to administer, exhibited good test-retest/inter-rater reliability (ICC of 0.82), and moderately correlated with the NPI hallucinations score (rs = 0.42). Using an optimal cut-off score set according to the ROC analysis, and the pareidolia test differentiated DLB from AD with a sensitivity of 81% and a specificity of 92%. Our study suggests that the simplified version of the pareidolia test is a valid and reliable surrogate marker of visual hallucinations in DLB.

The Pareidolia Test: A Simple Neuropsychological Test Measuring Visual Hallucination-Like Illusions.

Directory of Open Access Journals (Sweden)

Yasuyuki Mamiya

Full Text Available Visual hallucinations are a core clinical feature of dementia with Lewy bodies (DLB, and this symptom is important in the differential diagnosis and prediction of treatment response. The pareidolia test is a tool that evokes visual hallucination-like illusions, and these illusions may be a surrogate marker of visual hallucinations in DLB. We created a simplified version of the pareidolia test and examined its validity and reliability to establish the clinical utility of this test.The pareidolia test was administered to 52 patients with DLB, 52 patients with Alzheimer's disease (AD and 20 healthy controls (HCs. We assessed the test-retest/inter-rater reliability using the intra-class correlation coefficient (ICC and the concurrent validity using the Neuropsychiatric Inventory (NPI hallucinations score as a reference. A receiver operating characteristic (ROC analysis was used to evaluate the sensitivity and specificity of the pareidolia test to differentiate DLB from AD and HCs.The pareidolia test required approximately 15 minutes to administer, exhibited good test-retest/inter-rater reliability (ICC of 0.82, and moderately correlated with the NPI hallucinations score (rs = 0.42. Using an optimal cut-off score set according to the ROC analysis, and the pareidolia test differentiated DLB from AD with a sensitivity of 81% and a specificity of 92%.Our study suggests that the simplified version of the pareidolia test is a valid and reliable surrogate marker of visual hallucinations in DLB.

Neutron-induced capture cross sections via the surrogate reaction method

International Nuclear Information System (INIS)

Boutoux, G.; Jurado, B.; Aiche, M.; Barreau, G.; Capellan, N.; Companis, I.; Czajkowski, S.; Dassie, D.; Haas, B.; Mathieu, L.; Meot, V.; Bail, A.; Bauge, E.; Daugas, J. M.; Faul, T.; Gaudefroy, L.; Morel, P.; Pillet, N.; Roig, O.; Romain, P.; Taieb, J.; Theroine, C.; Burke, J.T.; Companis, I.; Derkx, X.; Gunsing, F.; Matea, I.; Tassan-Got, L.; Porquet, M.G.; Serot, O.

2011-01-01

The surrogate reaction method is an indirect way of determining cross sections for nuclear reactions that proceed through a compound nucleus. This technique enables neutron-induced cross sections to be extracted for nuclear reactions on short-lived unstable nuclei that otherwise can not be measured. This technique has been successfully applied to determine the neutron-induced fission cross sections of several short-lived nuclei. In this work, we investigate whether this powerful technique can also be used to determine of neutron-induced capture cross sections. For this purpose we use the surrogate reaction 174 Yb( 3 He, pγ) 176 Lu to infer the well known 175 Lu(n, γ) cross section and compare the results with the directly measured neutron-induced data. This surrogate experiment has been performed in March 2010. The experimental technique used and the first preliminary results will be presented. (authors)

Validating (d,pγ) as a surrogate for neutron capture

International Nuclear Information System (INIS)

Ratkiewicz, A.; Cizewski, J. A.; Pain, S. D.; Adekola, A. S.; Burke, J. T.; Casperson, R. J.; Fotiadis, Nikolaos; McCleskey, M.; Burcher, S.; Shand, C. M; Austin, R. A. E.; Baugher, T.; Carpenter, M. P.; Devlin, Matthew James; Escher, J. E.; Hardy, S.; Hatarik, R.; Howard, M. E.; Hughes, R. O.; Jones, K. L.; Kozub, R. L.; Lister, C. J.; Manning, B.; O'Donnell, John M.; Peters, W. A.; Ross, T. J.; Scielzo, N. D.; Seweryniak, D.; Zhu, S.

2015-01-01

The r-process is responsible for creating roughly half of the elements heavier than iron. It has recently become understood that the rates at which neutron capture reactions proceed at late times in the r-process may dramatically affect the final abundance pattern. However, direct measurements of neutron capture reaction rates on exotic nuclei are exceptionally difficult, necessitating the development of indirect approaches such as the surrogate technique. The (d,pγ) reaction at low energies was identified as a promising surrogate for the (n,γ) reaction, as both reactions share many characteristics. We report on a program to validate (d,pγ) as a surrogate for (n,γ) using 95Mo as a target. The experimental campaign includes direct measurements of the γ-ray intensities from the decay of excited states populated in the 95Mo(n,γ) and 95Mo(d,pγ) reactions.

Stability of Markers Used for Real-Time Tumor Tracking After Percutaneous Intrapulmonary Placement

International Nuclear Information System (INIS)

Voort van Zyp, Noelle C. van der; Hoogeman, Mischa S.; Water, Steven van de; Levendag, Peter C.; Holt, Bronno van der; Heijmen, Ben J.M.; Nuyttens, Joost J.

2011-01-01

Purpose: To determine the stability of markers used for real-time tumor tracking after percutaneous intrapulmonary placement. Methods and Materials: A total of 42 patients with 44 lesions, 111 markers, and ≥2 repeat computed tomography (CT) scans were studied. The tumor on the repeat CT scans was registered with the tumor on the planning CT scan. Next, the three-dimensional marker coordinates were determined on the planning CT scan and repeat CT scans. Marker stability was analyzed by the displacement of the markers and the displacement of the center of mass (COM) of the marker configurations. In addition, we assessed the reliability of using the intermarker distance as a check for displacements in the COM of the marker configurations. Results: The median marker displacement was 1.3 mm (range, 0.1-53.6). The marker displacement was >5 mm in 12% of the markers and >10 mm in 5% of the markers. The causes of marker displacement >5 mm included marker migration (2 of 13) and target volume changes (5 of 13). Nonsynchronous tumor and marker movement during breathing might have been responsible for the displacements >5 mm in the other 6 of 13 markers. The median displacement in the COM of the marker configurations was 1.0 mm (range, 0.1-23.3). Displacements in the COM of the marker configurations of ≥2.0 mm were detected by changes in the intermarker distance of >1.5 mm in 96% of the treatment fractions. Conclusion: The median marker displacement was small (1.3 mm). Nevertheless, displacements >5 mm occurred in 12% of the markers. Therefore, we recommend the implantation of multiple markers because multiple markers will enable a quick and reliable check of marker displacement by determining the change in the intermarker distance. A displacement in the COM of the marker configuration of ≥2.0 mm was almost always detected (96%) by a change in the distance between the markers of >1.5 mm. This enabled the displaced marker to be disabled, such that tumor localization was

P53 and cancer-associated sialylated glycans are surrogate markers of cancerization of the bladder associated with Schistosoma haematobium infection.

Directory of Open Access Journals (Sweden)

Júlio Santos

2014-12-01

Full Text Available Bladder cancer is a significant health problem in rural areas of Africa and the Middle East where Schistosoma haematobium is prevalent, supporting an association between malignant transformation and infection by this blood fluke. Nevertheless, the molecular mechanisms linking these events are poorly understood. Bladder cancers in infected populations are generally diagnosed at a late stage since there is a lack of non-invasive diagnostic tools, hence enforcing the need for early carcinogenesis markers.Forty-three formalin-fixed paraffin-embedded bladder biopsies of S. haematobium-infected patients, consisting of bladder tumours, tumour adjacent mucosa and pre-malignant/malignant urothelial lesions, were screened for bladder cancer biomarkers. These included the oncoprotein p53, the tumour proliferation rate (Ki-67>17%, cell-surface cancer-associated glycan sialyl-Tn (sTn and sialyl-Lewisa/x (sLea/sLex, involved in immune escape and metastasis. Bladder tumours of non-S. haematobium etiology and normal urothelium were used as controls. S. haematobium-associated benign/pre-malignant lesions present alterations in p53 and sLex that were also found in bladder tumors. Similar results were observed in non-S. haematobium associated tumours, irrespectively of their histological nature, denoting some common molecular pathways. In addition, most benign/pre-malignant lesions also expressed sLea. However, proliferative phenotypes were more prevalent in lesions adjacent to bladder tumors while sLea was characteristic of sole benign/pre-malignant lesions, suggesting it may be a biomarker of early carcionogenesis associated with the parasite. A correlation was observed between the frequency of the biomarkers in the tumor and adjacent mucosa, with the exception of Ki-67. Most S. haematobium eggs embedded in the urothelium were also positive for sLea and sLex. Reinforcing the pathologic nature of the studied biomarkers, none was observed in the healthy urothelium

Time-varying surrogate data to assess nonlinearity in nonstationary time series: application to heart rate variability.

Science.gov (United States)

Faes, Luca; Zhao, He; Chon, Ki H; Nollo, Giandomenico

2009-03-01

We propose a method to extend to time-varying (TV) systems the procedure for generating typical surrogate time series, in order to test the presence of nonlinear dynamics in potentially nonstationary signals. The method is based on fitting a TV autoregressive (AR) model to the original series and then regressing the model coefficients with random replacements of the model residuals to generate TV AR surrogate series. The proposed surrogate series were used in combination with a TV sample entropy (SE) discriminating statistic to assess nonlinearity in both simulated and experimental time series, in comparison with traditional time-invariant (TIV) surrogates combined with the TIV SE discriminating statistic. Analysis of simulated time series showed that using TIV surrogates, linear nonstationary time series may be erroneously regarded as nonlinear and weak TV nonlinearities may remain unrevealed, while the use of TV AR surrogates markedly increases the probability of a correct interpretation. Application to short (500 beats) heart rate variability (HRV) time series recorded at rest (R), after head-up tilt (T), and during paced breathing (PB) showed: 1) modifications of the SE statistic that were well interpretable with the known cardiovascular physiology; 2) significant contribution of nonlinear dynamics to HRV in all conditions, with significant increase during PB at 0.2 Hz respiration rate; and 3) a disagreement between TV AR surrogates and TIV surrogates in about a quarter of the series, suggesting that nonstationarity may affect HRV recordings and bias the outcome of the traditional surrogate-based nonlinearity test.

A surrogate fuel formulation to characterize heating and evaporation of light naphtha droplets

KAUST Repository

Kabil, I.

2018-03-08

Light naphtha (LN) is gaining interest in internal combustion (IC) engine applications due to its low refining cost and higher heating values compared to commercial gasoline. To properly describe the chemical and physical behavior of the LN fuel under IC engine conditions, a systematic procedure to develop unified physical and chemical surrogates is described. The reduced component models to describe the chemical characteristics of LN are combined with the effective thermal conductivity/effective diffusivity (ETC/ED) model to represent the accurate evaporation behavior. Three surrogate fuels consisting of three to five components are presented and their performance in heating and evaporation of a single LN droplet is compared against the conventional primary reference fuel (PRF65) surrogate which is based on chemical aspects only. Unlike the previous approaches, the new surrogates also target matching the hydrogen-to-carbon ratio and research octane number in order to accurately describe the chemical behavior of the fuel. Subsequently, the performance of the surrogates in describing spray characteristics is tested by computational simulations compared with experimental measurements. The simulations were carried out using CONVERGE CFD package. The ETC/ED model was implemented into CONVERGE using user-defined functions. The predicted spray penetration length for the developed surrogates shows good agreement with the experimental data. At engine-like conditions, the ETC/ED model predicts higher vapor mass than the infinite thermal conductivity/infinite diffusivity model, hence showing the expected trend by incorporating the realistic droplet heating process.

Modeling of Heating and Evaporation of FACE I Gasoline Fuel and its Surrogates

KAUST Repository

Elwardani, Ahmed Elsaid

2016-04-05

The US Department of Energy has formulated different gasoline fuels called \\'\\'Fuels for Advanced Combustion Engines (FACE)\\'\\' to standardize their compositions. FACE I is a low octane number gasoline fuel with research octane number (RON) of approximately 70. The detailed hydrocarbon analysis (DHA) of FACE I shows that it contains 33 components. This large number of components cannot be handled in fuel spray simulation where thousands of droplets are directly injected in combustion chamber. These droplets are to be heated, broken-up, collided and evaporated simultaneously. Heating and evaporation of single droplet FACE I fuel was investigated. The heating and evaporation model accounts for the effects of finite thermal conductivity, finite liquid diffusivity and recirculation inside the droplet, referred to as the effective thermal conductivity/effective diffusivity (ETC/ED) model. The temporal variations of the liquid mass fractions of the droplet components were used to characterize the evaporation process. Components with similar evaporation characteristics were merged together. A representative component was initially chosen based on the highest initial mass fraction. Three 6 components surrogates, Surrogate 1-3, that match evaporation characteristics of FACE I have been formulated without keeping same mass fractions of different hydrocarbon types. Another two surrogates (Surrogate 4 and 5) were considered keeping same hydrocarbon type concentrations. A distillation based surrogate that matches measured distillation profile was proposed. The calculated molar mass, hydrogen-to-carbon (H/C) ratio and RON of Surrogate 4 and distillation based one are close to those of FACE I.

A surrogate fuel formulation to characterize heating and evaporation of light naphtha droplets

KAUST Repository

Kabil, I.; Sim, J.; Badra, J.A.; Eldrainy, Y.; Abdelghaffar, W.; Mubarak Ali, M. Jaasim; Ahmed, Ahfaz; Sarathy, Mani; Im, Hong G.; Elwardani, Ahmed Elsaid

2018-01-01

Light naphtha (LN) is gaining interest in internal combustion (IC) engine applications due to its low refining cost and higher heating values compared to commercial gasoline. To properly describe the chemical and physical behavior of the LN fuel under IC engine conditions, a systematic procedure to develop unified physical and chemical surrogates is described. The reduced component models to describe the chemical characteristics of LN are combined with the effective thermal conductivity/effective diffusivity (ETC/ED) model to represent the accurate evaporation behavior. Three surrogate fuels consisting of three to five components are presented and their performance in heating and evaporation of a single LN droplet is compared against the conventional primary reference fuel (PRF65) surrogate which is based on chemical aspects only. Unlike the previous approaches, the new surrogates also target matching the hydrogen-to-carbon ratio and research octane number in order to accurately describe the chemical behavior of the fuel. Subsequently, the performance of the surrogates in describing spray characteristics is tested by computational simulations compared with experimental measurements. The simulations were carried out using CONVERGE CFD package. The ETC/ED model was implemented into CONVERGE using user-defined functions. The predicted spray penetration length for the developed surrogates shows good agreement with the experimental data. At engine-like conditions, the ETC/ED model predicts higher vapor mass than the infinite thermal conductivity/infinite diffusivity model, hence showing the expected trend by incorporating the realistic droplet heating process.

Results from Second Round of Remediated Nitrate Salt Surrogate Formulation and Testing

Energy Technology Data Exchange (ETDEWEB)

Brown, Geoffrey Wayne [Los Alamos National Laboratory; Leonard, Philip [Los Alamos National Laboratory; Hartline, Ernest Leon [Los Alamos National Laboratory; Tian, Hongzhao [Los Alamos National Laboratory

2016-04-04

High Explosives and Technology (M-7) completed the second round of formulation and testing of Remediated Nitrate Salt (RNS) surrogates on March 17, 2016. This report summarizes the results of the work and also includes additional documentation required under test plan PLAN-TA9-2443 Rev B, "Remediated Nitrate Salt (RNS) Surrogate Formulation and Testing Standard Procedure", released February 16, 2016. All formulation and testing was carried out according to PLAN-TA9-2443 Rev B. Results from the first round of formulation and testing were documented in memorandum M7-16-6042, "Results from First Round of Remediated Nitrate Salt Surrogate Formulation and Testing."

Progress in Chemical Kinetic Modeling for Surrogate Fuels

Energy Technology Data Exchange (ETDEWEB)

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

2008-06-06

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

Elevated CSF-lactate is a reliable marker of mitochondrial disorders in children even after brief seizures.

Science.gov (United States)

Magner, Martin; Szentiványi, Karol; Svandová, Ivana; Ješina, Pavel; Tesařová, Markéta; Honzík, Tomáš; Zeman, Jiří

2011-03-01

Increased lactate is an important biochemical marker in diagnosis of children with suspicion of mitochondrial disorders. A diagnostic dilemma may originate if analyses are performed after seizures, when the increased lactate levels may be considered to result from the seizures. To address this problem, we ascertained the diagnostic value of lactate and alanine in blood (B) and cerebrospinal fluid (CSF) in children with mitochondrial disorders (n = 24), epilepsy (n = 32), psychomotor retardation (n = 23), meningitis (n = 12) and meningism (n = 16). Lactate concentration was measured using a spectrophotometric method. Amino acids in serum and CSF were analyzed by ion exchange chromatography with ninhydrin detection. Average blood and CSF-lactate levels were significantly higher in children with mitochondrial disorders (3.87 ± 0.48 and 4.43 ± 0.55 mmol/l) and meningitis (2.77 ± 0.45 and 8.58 ± 1.08 mmol/l) than in children with epilepsy (1.72 ± 0.13 and 1.62 ± 0.04 mmol/l), psychomotor retardation (1.79 ± 1.40 and 1.68 ± 0.06 mmol/l) or meningism (1.70 ± 0.13 and 1.64 ± 0.07 mmol/l). Blood and CSF-alanine levels were also higher in children with mitochondrial disorders (558 ± 44 and 51 ± 8 μmol/l) than in children with epilepsy (327 ± 23 and 27 ± 3 μmol/l) or psychomotor retardation (323 ± 27 and 26 ± 3 μmol/l). The CSF-lactate levels of children with epilepsy were similar whether the samples were obtained 3 ± 0.6 h after an attack of brief seizures or from children without history of recent seizures. Elevated cerebrospinal fluid lactate level is a reliable marker pointing to mitochondrial origin of disease, even in children who have recently suffered short-lasting seizures. Some children with mitochondrial disorders manifest only mild or intermittent elevation of lactate levels. Copyright © 2010 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Attachment and Detachment Behavior of Human Adenovirus and Surrogates in Fine Granular Limestone Aquifer Material.

Science.gov (United States)

Stevenson, Margaret E; Sommer, Regina; Lindner, Gerhard; Farnleitner, Andreas H; Toze, Simon; Kirschner, Alexander K T; Blaschke, Alfred P; Sidhu, Jatinder P S

2015-09-01

The transport of human adenovirus, nanoparticles, and PRD1 and MS2 bacteriophages was tested in fine granular limestone aquifer material taken from a borehole at a managed aquifer recharge site in Adelaide, South Australia. Comparison of transport and removal of virus surrogates with the pathogenic virus is necessary to understand the differences between the virus and surrogate. Because experiments using pathogenic viruses cannot be done in the field, laboratory tests using flow-through soil columns were used. Results show that PRD1 is the most appropriate surrogate for adenovirus in an aquifer dominated by calcite material but not under high ionic strength or high pH conditions. It was also found that straining due to size and the charge of the colloid were not dominant removal mechanisms in this system. Implications of this study indicate that a certain surrogate may not represent a specific pathogen solely based on similar size, morphology, and/or surface charge. Moreover, if a particular surrogate is representative of a pathogen in one aquifer system, it may not be the most appropriate surrogate in another porous media system. This was apparent in the inferior performance of MS2 as a surrogate, which is commonly used in virus transport studies. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Molecular Markers of Metastasis in Ductal Mammary Carcinoma

National Research Council Canada - National Science Library

Achary, Patnala

2002-01-01

...% of those patients, however, the disease spreads, and they are at risk of death. Our goal is to develop DNA markers that could be reliably used to identify the ductal mammary carcinomas that are prone to develop metastasis...

FENOMENA SURROGATE MOTHER (IBU PENGGANTI DALAM PERSPEKTIF ISLAM DITINJAU DARI HADIS

Directory of Open Access Journals (Sweden)

Nurul Alifah Rahmawati

2018-03-01

Full Text Available In this modern era, there is a finding in technology in the field of genetically changes which try to help the married couple with no children for a long time of marriage. This change can be seen in the existence of an infant with infitro fertilization, sperm banks, or magic box that can save sperm and ovum as they are in the real womb. As the time is gone, the practice of infant with  infitro fertilization and artificial insemination have developed in some forms of activity which are forbidden in Islam. One of the forbidden forms is infitro insemination or artificial insemination which uses the sperm and ovum from a marriage couple and put it in another woman’s womb. This practice is called as Surrogate Mother. Actually there is no verses in the al-Qur’an which strictly stated about the prohibition on the practice of infitro infant using another woman’s womb (Surrogate mother. But it does not mean that al-Qur’an does not give any solution and also guidance in solving the law of this problem. There are some syar’i theorems that can be used as references in the issue of surrogate mother, for example Q.S Maryam verse 3-5 which give us command to keep praying and trying to get descendents, Q.S al-Baqarah verse 223 which states that a wife is the best place for farming and also hadith of the prophet Muhammad SAW which forbid a man to give his sperm to another woman who is not their wife. Moreover, the practice of this surrogate mother is also contradictory with with al-maqasid al-shariah because it can cause a mixed Nasab. Based on those reasons, the writer is interested in analyzing how is the surrogate mother phenomenon in the view of hadith and its contextualization dealing with the children’s position in the law of Waris (inheritance. Based on the literature analysis done by the writer, it can be concluded that the practice of surrogate mother is forbidden according to Ulama because it gives more mudharat (negative effects than

Reliability and Concurrent Validity of the International Personality ...

African Journals Online (AJOL)

Reliability and Concurrent Validity of the International Personality item Pool (IPIP) Big-five Factor Markers in Nigeria. ... Nigerian Journal of Psychiatry ... Aims: The aim of this study was to assess the internal consistency and concurrent validity ...

Demographic changes and marker properties affect detection of human population differentiation

Directory of Open Access Journals (Sweden)

Sanichwankul Kittipong

2007-05-01

Full Text Available Abstract Background Differentiating genetically between populations is valuable for admixture and population stratification detection and in understanding population history. This is easy to achieve for major continental populations, but not for closely related populations. It has been claimed that a large marker panel is necessary to reliably distinguish populations within a continent. We investigated whether empirical genetic differentiation could be accomplished efficiently among three Asian populations (Hmong, Thai, and Chinese using a small set of highly variable markers (15 tetranucleotide and 17 dinucleotide repeats. Results Hmong could be differentiated from Thai and Chinese based on multi-locus genotypes, but Thai and Chinese were indistinguishable from each other. We found significant evidence for a recent population bottleneck followed by expansion in the Hmong that was not present in the Thai or Chinese. Tetranucleotide repeats were less useful than dinucleotide repeat markers in distinguishing between major continental populations (Asian, European, and African while both successfully distinguished Hmong from Thai and Chinese. Conclusion Demographic history contributes significantly to robust detection of intracontinental population structure. Populations having experienced a rapid size reduction may be reliably distinguished as a result of a genetic drift -driven redistribution of population allele frequencies. Tetranucleotide markers, which differ from dinucleotide markers in mutation mechanism and rate, are similar in information content to dinucleotide markers in this situation. These factors should be considered when identifying populations suitable for gene mapping studies and when interpreting interpopulation relationships based on microsatellite markers.

The Decomposition of Surrogate Fuel Molecules During Combustion

National Research Council Canada - National Science Library

Tsang, Wing; Manion, Jeffrey A

2006-01-01

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

An Efficiency Analysis of Augmented Reality Marker Recognition Algorithm

Directory of Open Access Journals (Sweden)

Kurpytė Dovilė

2014-05-01

Full Text Available The article reports on the investigation of augmented reality system which is designed for identification and augmentation of 100 different square markers. Marker recognition efficiency was investigated by rotating markers along x and y axis directions in range from −90° to 90°. Virtual simulations of four environments were developed: a an intense source of light, b an intense source of light falling from the left side, c the non-intensive light source falling from the left side, d equally falling shadows. The graphics were created using the OpenGL graphics computer hardware interface; image processing was programmed in C++ language using OpenCV, while augmented reality was developed in Java programming language using NyARToolKit. The obtained results demonstrate that augmented reality marker recognition algorithm is accurate and reliable in the case of changing lighting conditions and rotational angles - only 4 % markers were unidentified. Assessment of marker recognition efficiency let to propose marker classification strategy in order to use it for grouping various markers into distinct markers’ groups possessing similar recognition properties.

Calibration of an agricultural-hydrological model (RZWQM2) using surrogate global optimization

Science.gov (United States)

Xi, Maolong; Lu, Dan; Gui, Dongwei; Qi, Zhiming; Zhang, Guannan

2017-01-01

Robust calibration of an agricultural-hydrological model is critical for simulating crop yield and water quality and making reasonable agricultural management. However, calibration of the agricultural-hydrological system models is challenging because of model complexity, the existence of strong parameter correlation, and significant computational requirements. Therefore, only a limited number of simulations can be allowed in any attempt to find a near-optimal solution within an affordable time, which greatly restricts the successful application of the model. The goal of this study is to locate the optimal solution of the Root Zone Water Quality Model (RZWQM2) given a limited simulation time, so as to improve the model simulation and help make rational and effective agricultural-hydrological decisions. To this end, we propose a computationally efficient global optimization procedure using sparse-grid based surrogates. We first used advanced sparse grid (SG) interpolation to construct a surrogate system of the actual RZWQM2, and then we calibrate the surrogate model using the global optimization algorithm, Quantum-behaved Particle Swarm Optimization (QPSO). As the surrogate model is a polynomial with fast evaluation, it can be efficiently evaluated with a sufficiently large number of times during the optimization, which facilitates the global search. We calibrate seven model parameters against five years of yield, drain flow, and NO3-N loss data from a subsurface-drained corn-soybean field in Iowa. Results indicate that an accurate surrogate model can be created for the RZWQM2 with a relatively small number of SG points (i.e., RZWQM2 runs). Compared to the conventional QPSO algorithm, our surrogate-based optimization method can achieve a smaller objective function value and better calibration performance using a fewer number of expensive RZWQM2 executions, which greatly improves computational efficiency.

A Diagnostic Marker to Discriminate Childhood Apraxia of Speech from Speech Delay: III. Theoretical Coherence of the Pause Marker with Speech Processing Deficits in Childhood Apraxia of Speech

Science.gov (United States)

Shriberg, Lawrence D.; Strand, Edythe A.; Fourakis, Marios; Jakielski, Kathy J.; Hall, Sheryl D.; Karlsson, Heather B.; Mabie, Heather L.; McSweeny, Jane L.; Tilkens, Christie M.; Wilson, David L.

2017-01-01

Purpose: Previous articles in this supplement described rationale for and development of the pause marker (PM), a diagnostic marker of childhood apraxia of speech (CAS), and studies supporting its validity and reliability. The present article assesses the theoretical coherence of the PM with speech processing deficits in CAS. Method: PM and other…

First Trimester Hemolysis, Elevated Liver Enzymes, Low Platelets Syndrome in a Surrogate Pregnancy.

Science.gov (United States)

Myer, Emily; Hill, James

2015-10-01

Background The occurrence of hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome before 20 weeks of gestation is rare. HELLP is a possible but rare syndrome in gestational surrogate pregnancies for surrogates with risk factors for development of preeclampsia. Case A 32-year-old patient with chronic hypertension and positive antinuclear antibody presented for prenatal care at 13 weeks and 1 day. She was a surrogate for the embryo of a 43-year-old couple. By 15 weeks she developed uncontrolled hypertension requiring hospitalization. She was expectantly managed until her condition deteriorated. At 16 weeks and 1 day she developed hemolysis, elevated liver enzymes, thrombocytopenia, and fetal demise. Conclusions HELLP syndrome is rare and carries a significant morbidity and mortality for the mother and fetus. Clinicians should encourage the surrogate to share her medical history with the embryo donor for appropriate counseling on pregnancy risks.

Committee-Based Active Learning for Surrogate-Assisted Particle Swarm Optimization of Expensive Problems.

Science.gov (United States)

Wang, Handing; Jin, Yaochu; Doherty, John

2017-09-01

Function evaluations (FEs) of many real-world optimization problems are time or resource consuming, posing a serious challenge to the application of evolutionary algorithms (EAs) to solve these problems. To address this challenge, the research on surrogate-assisted EAs has attracted increasing attention from both academia and industry over the past decades. However, most existing surrogate-assisted EAs (SAEAs) either still require thousands of expensive FEs to obtain acceptable solutions, or are only applied to very low-dimensional problems. In this paper, a novel surrogate-assisted particle swarm optimization (PSO) inspired from committee-based active learning (CAL) is proposed. In the proposed algorithm, a global model management strategy inspired from CAL is developed, which searches for the best and most uncertain solutions according to a surrogate ensemble using a PSO algorithm and evaluates these solutions using the expensive objective function. In addition, a local surrogate model is built around the best solution obtained so far. Then, a PSO algorithm searches on the local surrogate to find its optimum and evaluates it. The evolutionary search using the global model management strategy switches to the local search once no further improvement can be observed, and vice versa. This iterative search process continues until the computational budget is exhausted. Experimental results comparing the proposed algorithm with a few state-of-the-art SAEAs on both benchmark problems up to 30 decision variables as well as an airfoil design problem demonstrate that the proposed algorithm is able to achieve better or competitive solutions with a limited budget of hundreds of exact FEs.

Counterfactual reasoning in surrogate decision making -- another look.

Science.gov (United States)

Johansson, Mats; Broström, Linus

2011-06-01

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

Umbrellas can work under water: Using threatened species as indicator and management surrogates can improve coastal conservation

Science.gov (United States)

Gilby, Ben L.; Olds, Andrew D.; Connolly, Rod M.; Yabsley, Nicholas A.; Maxwell, Paul S.; Tibbetts, Ian R.; Schoeman, David S.; Schlacher, Thomas A.

2017-12-01

Species surrogates, the use of particular species to index habitat condition or to represent ecological assemblages are commonly identified in many ecosystems, but are less tested, and therefore less employed in estuaries. Estuaries provide important ecosystem goods (e.g. harvestable species) and services (e.g. carbon processing, coastal armouring), but require protection from multiple human activities, meaning that finding surrogates for estuarine condition or faunal assemblages is a significant knowledge gap. In this study, we test the efficacy of the threatened estuary ray Hemitrygon fluviorum, as a suitable indicator of ecosystem condition and management umbrella surrogate species for conservation prioritisation and monitoring purposes within estuaries. We surveyed fish assemblages and ray presence at ten sites within each of 22 estuaries in southeast Queensland, Australia, using one hour deployments of baited video arrays. We then tested for correlations between ray presence, a series of environmental variables considered important to ecosystem management within estuaries (i.e. testing rays as indicator species), and the co-occurring fish species (i.e. testing rays as umbrella species). Estuary rays function as both umbrella species and ecological indicators of habitat status in subtropical Australian estuaries. As umbrellas, ray occurrence concords with elevated species richness. As ecological indicators, ray distribution concords with habitats of good water quality (especially low turbidity) and more natural vegetation remaining in the catchment. These results highlight the potential for other threatened aquatic vertebrates that are both readily detectable and that are reliable proxies for ecosystems status to be become useful management tools in estuaries. The protection of such large, threatened species in coastal seascapes allows managers to address multiple targets for conservation, especially; (1) protecting species of conservation concern; (2

Smart markers for watershed-based cell segmentation.

Directory of Open Access Journals (Sweden)

Can Fahrettin Koyuncu

Full Text Available Automated cell imaging systems facilitate fast and reliable analysis of biological events at the cellular level. In these systems, the first step is usually cell segmentation that greatly affects the success of the subsequent system steps. On the other hand, similar to other image segmentation problems, cell segmentation is an ill-posed problem that typically necessitates the use of domain-specific knowledge to obtain successful segmentations even by human subjects. The approaches that can incorporate this knowledge into their segmentation algorithms have potential to greatly improve segmentation results. In this work, we propose a new approach for the effective segmentation of live cells from phase contrast microscopy. This approach introduces a new set of "smart markers" for a marker-controlled watershed algorithm, for which the identification of its markers is critical. The proposed approach relies on using domain-specific knowledge, in the form of visual characteristics of the cells, to define the markers. We evaluate our approach on a total of 1,954 cells. The experimental results demonstrate that this approach, which uses the proposed definition of smart markers, is quite effective in identifying better markers compared to its counterparts. This will, in turn, be effective in improving the segmentation performance of a marker-controlled watershed algorithm.

Smart markers for watershed-based cell segmentation.

Science.gov (United States)

Koyuncu, Can Fahrettin; Arslan, Salim; Durmaz, Irem; Cetin-Atalay, Rengul; Gunduz-Demir, Cigdem

2012-01-01

Automated cell imaging systems facilitate fast and reliable analysis of biological events at the cellular level. In these systems, the first step is usually cell segmentation that greatly affects the success of the subsequent system steps. On the other hand, similar to other image segmentation problems, cell segmentation is an ill-posed problem that typically necessitates the use of domain-specific knowledge to obtain successful segmentations even by human subjects. The approaches that can incorporate this knowledge into their segmentation algorithms have potential to greatly improve segmentation results. In this work, we propose a new approach for the effective segmentation of live cells from phase contrast microscopy. This approach introduces a new set of "smart markers" for a marker-controlled watershed algorithm, for which the identification of its markers is critical. The proposed approach relies on using domain-specific knowledge, in the form of visual characteristics of the cells, to define the markers. We evaluate our approach on a total of 1,954 cells. The experimental results demonstrate that this approach, which uses the proposed definition of smart markers, is quite effective in identifying better markers compared to its counterparts. This will, in turn, be effective in improving the segmentation performance of a marker-controlled watershed algorithm.

Combustion Kinetic Studies of Gasolines and Surrogates

KAUST Repository

Javed, Tamour

2016-01-01

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

Decision conflict and regret among surrogate decision makers in the medical intensive care unit.

Science.gov (United States)

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

2016-04-01

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

Biomedically assisted reproduction and child birth: Surrogate motherhood in comparative European law and Serbia

Directory of Open Access Journals (Sweden)

Kovaček-Stanić Gordana

2013-01-01

Full Text Available Surrogate motherhood is an arrangement in which a woman agrees to carry and deliver a child for another couple who ordered the pregnancy. This procedure is applied today in Great Britain, Holland (although without legal regulations, Israel, Greece, Ukraine, Armenia, Georgia, the USA and Australia, and it is forbidden in France, Austria, Spain, Germany, Switzerland and Slovenia. There are two types of surrogacy, one when the woman gives birth to a child who is genetically her own ("partial", genetic surrogacy, and the other where the surrogate mother only carries and gives birth to a child, whereby the child is genetically from the couple that wanted the child, or the fertilized egg is from a third woman (donor, or the embryo was donated ("full", "total", gestational surrogacy. In these cases two women take part in conception and birth of the child while in the last case there is a third woman who will raise the child. Biologically observed, the woman whose egg has been fertilized may be called the genetic mother, while the woman who carried the pregnancy and gave birth to the child - the gestational carrier. Taking into consideration that the Preliminary Draft of the Serbian Civil Law anticipates the introduction of surrogate motherhood into domestic law, we believe restrictive solutions should first be taken into consideration. This would mean that only full surrogating should be allowed, namely the egg should be from the woman who wants the child and not the surrogate mother. In domestic conditions, genetic surrogation should not be allowed as it leads to confusion in family relations, and kinships still have an important social and legal significance in our country. The surrogate mother should be a woman who has already given birth, because in that way any possible shocks which might arise after birth when the woman who has to handover the child to the intended couple would be avoided. The next condition would be that persons involved in this

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

Directory of Open Access Journals (Sweden)

Ducasse Q.

2013-12-01

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.

Identification and assessment of markers of biotin status in healthy adults

Science.gov (United States)

Eng, Wei Kay; Giraud, David; Schlegel, Vicki L.; Wang, Dong; Lee, Bo Hyun; Zempleni, Janos

2016-01-01

Human biotin requirements are unknown and the identification of reliable markers of biotin status is necessary to fill this knowledge gap. Here, we used an outpatient feeding protocol to create states of biotin deficiency, sufficiency and supplementation in sixteen healthy men and women. A total of twenty possible markers of biotin status were assessed, including the abundance of biotinylated carboxylases in lymphocytes, the expression of genes from biotin metabolism and the urinary excretion of biotin and organic acids. Only the abundance of biotinylated 3-methylcrotonyl-CoA carboxylase (holo-MCC) and propionyl-CoA carboxylase (holo-PCC) allowed for distinguishing biotin-deficient and biotin-sufficient individuals. The urinary excretion of biotin reliably identified biotin-supplemented subjects, but did not distinguish between biotin-depleted and biotin-sufficient individuals. The urinary excretion of 3-hydroxyisovaleric acid detected some biotin-deficient subjects, but produced a meaningful number of false-negative results and did not distinguish between biotin-sufficient and biotin-supplemented individuals. None of the other organic acids that were tested were useful markers of biotin status. Likewise, the abundance of mRNA coding for biotin transporters, holocarboxylase synthetase and biotin-dependent carboxylases in lymphocytes were not different among the treatment groups. Generally, datasets were characterised by variations that exceeded those seen in studies in cell cultures. We conclude that holo-MCC and holo-PCC are the most reliable, single markers of biotin status tested in the present study. PMID:23302490

Time-variant reliability assessment through equivalent stochastic process transformation

International Nuclear Information System (INIS)

Wang, Zequn; Chen, Wei

2016-01-01

Time-variant reliability measures the probability that an engineering system successfully performs intended functions over a certain period of time under various sources of uncertainty. In practice, it is computationally prohibitive to propagate uncertainty in time-variant reliability assessment based on expensive or complex numerical models. This paper presents an equivalent stochastic process transformation approach for cost-effective prediction of reliability deterioration over the life cycle of an engineering system. To reduce the high dimensionality, a time-independent reliability model is developed by translating random processes and time parameters into random parameters in order to equivalently cover all potential failures that may occur during the time interval of interest. With the time-independent reliability model, an instantaneous failure surface is attained by using a Kriging-based surrogate model to identify all potential failure events. To enhance the efficacy of failure surface identification, a maximum confidence enhancement method is utilized to update the Kriging model sequentially. Then, the time-variant reliability is approximated using Monte Carlo simulations of the Kriging model where system failures over a time interval are predicted by the instantaneous failure surface. The results of two case studies demonstrate that the proposed approach is able to accurately predict the time evolution of system reliability while requiring much less computational efforts compared with the existing analytical approach. - Highlights: • Developed a new approach for time-variant reliability analysis. • Proposed a novel stochastic process transformation procedure to reduce the dimensionality. • Employed Kriging models with confidence-based adaptive sampling scheme to enhance computational efficiency. • The approach is effective for handling random process in time-variant reliability analysis. • Two case studies are used to demonstrate the efficacy

The long-term experiences of surrogates: relationships and contact with surrogacy families in genetic and gestational surrogacy arrangements.

Science.gov (United States)

Imrie, Susan; Jadva, Vasanti

2014-10-01

This study examined the contact arrangements and relationships between surrogates and surrogacy families and whether these outcomes differed according to the type of surrogacy undertaken. Surrogates' motivations for carrying out multiple surrogacy arrangements were also examined, and surrogates' psychological health was assessed. Semi-structured interviews were administered to 34 women who had given birth to a child conceived through surrogacy approximately 7 years prior to interview. Some surrogates had carried out multiple surrogacy arrangements, and data were collected on the frequency, type of contact, and surrogate's feelings about the level of contact in each surrogacy arrangement, the surrogate's relationship with each child and parent, and her experience of, and motivation for, each surrogacy. Questionnaire measures of psychological health were administered. Surrogates had completed a total of 102 surrogacy arrangements and remained in contact with the majority of families, and reported positive relationships in most cases. Surrogates were happy with their level of contact in the majority of arrangements and most were viewed as positive experiences. Few differences were found according to surrogacy type. The primary motivation given for multiple surrogacy arrangements was to help couples have a sibling for an existing child. Most surrogates showed no psychological health problems at the time of data collection. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Use of surrogate travel to lower training costs and reduce person-rems

International Nuclear Information System (INIS)

Scully, M.C.; Porter, N.J.; Scott, J.W.

1985-01-01

In the commercial nuclear power industry where access on site may be prohibited by regulations, procedures, or the potential of extremely high radiation levels, a surrogate travel system has potential for the reduction of both exposure and personnel training time. A prototype surrogate travel system using a microcomputer-assisted laser optical video disc has been developed by Southern California Edison and Combustion Engineering

A conceptual model of the role of communication in surrogate decision making for hospitalized adults.

Science.gov (United States)

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

2012-04-01

To build a conceptual model of the role of communication in decision making, based on literature from medicine, communication studies and medical ethics. We proposed a model and described each construct in detail. We review what is known about interpersonal and patient-physician communication, described literature about surrogate-clinician communication, and discussed implications for our developing model. The communication literature proposes two major elements of interpersonal communication: information processing and relationship building. These elements are composed of constructs such as information disclosure and emotional support that are likely to be relevant to decision making. We propose these elements of communication impact decision making, which in turn affects outcomes for both patients and surrogates. Decision making quality may also mediate the relationship between communication and outcomes. Although many elements of the model have been studied in relation to patient-clinician communication, there is limited data about surrogate decision making. There is evidence of high surrogate distress associated with decision making that may be alleviated by communication-focused interventions. More research is needed to test the relationships proposed in the model. Good communication with surrogates may improve both the quality of medical decisions and outcomes for the patient and surrogate. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Effects of rotation and systematic occlusion on fiducial marker recognition

Directory of Open Access Journals (Sweden)

Sagitov Artur

2017-01-01

Full Text Available Fiducial marker systems consist of patterns that are placed in environment for miscellaneous applications and are further automatically detected with cameras. A variety of applications determines the criteria, which characterize qualitative properties of a marker and include such evaluation benchmarks as resilience to occlusion, distance to a marker, false positive and false negative rates, sensitivity to illumination, and others. The paper compares existing ARTag, AprilTag, and CALTag systems utilizing a high fidelity camera, which is a main vision sensor of a full-size Russian humanoid robot AR-601M. In experiments the comparison of the three marker systems reliability and detection rate in occlusions of various types and intensities was verified. Finally, a preferable for AR-601M robot visual applications marker system was selected.

Surrogate analysis and index developer (SAID) tool and real-time data dissemination utilities

Science.gov (United States)

Domanski, Marian M.; Straub, Timothy D.; Wood, Molly S.; Landers, Mark N.; Wall, Gary R.; Brady, Steven J.

2015-01-01

The use of acoustic and other parameters as surrogates for suspended-sediment concentrations (SSC) in rivers has been successful in multiple applications across the Nation. Critical to advancing the operational use of surrogates are tools to process and evaluate the data 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 in operation. The Surrogate Analysis and Index Developer (SAID) standalone tool, under development by the U.S. Geological Survey (USGS), assists in the creation of regression models that relate response and explanatory variables by providing visual and quantitative diagnostics to the user. SAID also processes acoustic parameters to be used as explanatory variables for suspended-sediment concentrations. The sediment acoustic method utilizes acoustic parameters from fixed-mount stationary equipment. The background theory and method used by the tool have been described in recent publications, and the tool also serves to support sediment-acoustic-index methods being drafted by the multi-agency Sediment Acoustic Leadership Team (SALT), and other surrogate guidelines like USGS Techniques and Methods 3-C4 for turbidity and SSC. The regression models in SAID can be used in utilities that have been developed to work with the USGS National Water Information System (NWIS) and for the USGS National Real-Time Water Quality (NRTWQ) Web site. The real-time dissemination of predicted SSC and prediction intervals for each time step has substantial potential to improve understanding of sediment-related water-quality and associated engineering and ecological management decisions.

Technologies for Assessing Behavioral and Cognitive Markers of Suicide Risk

Science.gov (United States)

2017-10-01

assessing behavioral and cognitive markers of risk for suicide among U.S. Army National Guard personnel. Journal of Environmental Research and Public Policy...effective ways to prevent injury and death from suicide • No reliable method for predicting suicide risk in military personnel • Behavioral (e.g...AWARD NUMBER: W81XWH-15-1-0632 TITLE: Technologies for Assessing Behavioral and Cognitive Markers of Suicide Risk PRINCIPAL INVESTIGATOR: Brian

Evaluation of markers for CpG island methylator phenotype (CIMP) in colorectal cancer by a large population-based sample.

Science.gov (United States)

Ogino, Shuji; Kawasaki, Takako; Kirkner, Gregory J; Kraft, Peter; Loda, Massimo; Fuchs, Charles S

2007-07-01

The CpG island methylator phenotype (CIMP or CIMP-high) with extensive promoter methylation is a distinct phenotype in colorectal cancer. However, a choice of markers for CIMP has been controversial. A recent extensive investigation has selected five methylation markers (CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1) as surrogate markers for epigenomic aberrations in tumor. The use of these markers as a CIMP-specific panel needs to be validated by an independent, large dataset. Using MethyLight assays on 920 colorectal cancers from two large prospective cohort studies, we quantified DNA methylation in eight CIMP-specific markers [the above five plus CDKN2A (p16), CRABP1, and MLH1]. A CIMP-high cutoff was set at > or = 6/8 or > or = 5/8 methylated promoters, based on tumor distribution and BRAF/KRAS mutation frequencies. All but two very specific markers [MLH1 (98% specific) and SOCS1 (93% specific)] demonstrated > or = 85% sensitivity and > or = 80% specificity, indicating overall good concordance in methylation patterns and good performance of these markers. Based on sensitivity, specificity, and false positives and negatives, the eight markers were ranked in order as: RUNX3, CACNA1G, IGF2, MLH1, NEUROG1, CRABP1, SOCS1, and CDKN2A. In conclusion, a panel of markers including at least RUNX3, CACNA1G, IGF2, and MLH1 can serve as a sensitive and specific marker panel for CIMP-high.

Surrogacy families 10 years on: relationship with the surrogate, decisions over disclosure and children's understanding of their surrogacy origins

Science.gov (United States)

Jadva, V.; Blake, L.; Casey, P.; Golombok, S.

2012-01-01

BACKGROUND This study aimed to prospectively examine families created using surrogacy over a 10-year period in the UK with respect to intending parents' and children's relationship with the surrogate mother, parents' decisions over disclosure and children's understanding of the nature of their conception. METHODS Semi-structured interviews were administered by trained researchers to intending mothers, intending fathers and children on four occasions over a 10-year period. Forty-two families (19 with a genetic surrogate mother) participated when the child was 1-year old and by age 10 years, 33 families remained in the study. Data were collected on the frequency of contact with the surrogate mother, relationship with the surrogate, disclosure of surrogacy to the child and the child's understanding of their surrogacy birth. RESULTS Frequency of contact between surrogacy families and their surrogate mother decreased over time, particularly for families whose surrogate was a previously unknown genetic carrier (P surrogate mother's egg was used to conceive the child). Most families reported harmonious relationships with their surrogate mother. At age 10 years, 19 (90%) children who had been informed of the nature of their conception had a good understanding of this and 13 of the 14 children who were in contact with their surrogate reported that they liked her. CONCLUSIONS Surrogacy families maintained good relationships with the surrogate mother over time. Children felt positive about their surrogate mother and their surrogacy birth. The sample size of this study was small and further, larger investigations are needed before firm conclusions can be drawn. PMID:22814484

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

Science.gov (United States)

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

2008-05-01

A biological mother's movement appears necessary for optimal development in infant monkeys. However, nursery-reared monkeys are typically provided with inanimate surrogate mothers that move very little. The purpose of this study was to evaluate the effects of a novel, highly mobile surrogate mother on motor development, exploration, and reactions to novelty. Six infant rhesus macaques (Macaca mulatta) were reared on mobile hanging surrogates (MS) and compared to six infants reared on standard stationary rocking surrogates (RS) and to 9-15 infants reared with their biological mothers (MR) for early developmental outcome. We predicted that MS infants would develop more similarly to MR infants than RS infants. In neonatal assessments conducted at Day 30, both MS and MR infants showed more highly developed motor activity than RS infants on measures of grasping (p = .009), coordination (p = .038), spontaneous crawl (p = .009), and balance (p = .003). At 2-3 months of age, both MS and MR infants displayed higher levels of exploration in the home cage than RS infants (p = .016). In a novel situation in which only MS and RS infants were tested, MS infants spent less time near their surrogates in the first five minutes of the test session than RS infants (p = .05), indicating a higher level of comfort. Collectively, these results suggest that when nursery-rearing of infant monkeys is necessary, a mobile hanging surrogate may encourage more normative development of gross motor skills and exploratory behavior and may serve as a useful alternative to stationary or rocking surrogates.

Robust best linear estimation for regression analysis using surrogate and instrumental variables.

Science.gov (United States)

Wang, C Y

2012-04-01

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.

MEASUREMENT OF CONTROLLED ATTENUATION PARAMETER: A SURROGATE MARKER OF HEPATIC STEATOSIS IN PATIENTS OF NONALCOHOLIC FATTY LIVER DISEASE ON LIFESTYLE MODIFICATION - A PROSPECTIVE FOLLOW-UP STUDY

Directory of Open Access Journals (Sweden)

Jayanta PAUL

Full Text Available ABSTRACT BACKGROUND: Liver biopsy is a gold standard method for hepatic steatosis assessment. However, liver biopsy is an invasive and painful procedure and can cause severe complications therefore it cannot be frequently used in case of follow-up of patients. Non-invasive assessment of steatosis and fibrosis is of growing relevance in non-alcoholic fatty liver disease (NAFLD. To evaluate hepatic steatosis, transient elastography with controlled attenuation parameter (CAP measurement is an option now days. OBJECTIVE: Aim of this study is to evaluate role of measurement of controlled attenuation parameter, a surrogate marker of hepatic steatosis in patients of nonalcoholic fatty liver disease on lifestyle modification. METHODS: In this study, initially 37 participants were included who were followed up after 6 months with transient elastography, blood biochemical tests and anthropometric measurements. The results were analyzed by Multivariate linear regression analysis and paired samples t-test (Dependent t-test with 95% confidence interval. Correlation is calculated by Pearson correlation coefficients. RESULTS: Mean CAP value for assessing hepatic steatosis during 1st consultation (278.57±49.13 dB/m was significantly improved (P=0.03 after 6 months of lifestyle modification (252.91±62.02 dB/m. Only fasting blood sugar (P=0.008, weight (P=0.000, body mass index (BMI (P=0.000 showed significant positive correlation with CAP. Only BMI (P=0.034 and weight (P=0.035 were the independent predictor of CAP value in NAFLD patients. CONCLUSION: Lifestyle modification improves the hepatic steatosis, and CAP can be used to detect the improvement of hepatic steatosis during follow-up in patients with NAFLD on lifestyle modification. There is no relation between CAP and Fibroscan score in NAFLD patients. Only BMI and weight can predict CAP value independently.

MEASUREMENT OF CONTROLLED ATTENUATION PARAMETER: A SURROGATE MARKER OF HEPATIC STEATOSIS IN PATIENTS OF NONALCOHOLIC FATTY LIVER DISEASE ON LIFESTYLE MODIFICATION - A PROSPECTIVE FOLLOW-UP STUDY.

Science.gov (United States)

Paul, Jayanta; Venugopal, Raj Vigna; Peter, Lorance; Shetty, Kula Naresh Kumar; Shetti, Mohit P

2018-01-01

Liver biopsy is a gold standard method for hepatic steatosis assessment. However, liver biopsy is an invasive and painful procedure and can cause severe complications therefore it cannot be frequently used in case of follow-up of patients. Non-invasive assessment of steatosis and fibrosis is of growing relevance in non-alcoholic fatty liver disease (NAFLD). To evaluate hepatic steatosis, transient elastography with controlled attenuation parameter (CAP) measurement is an option now days. Aim of this study is to evaluate role of measurement of controlled attenuation parameter, a surrogate marker of hepatic steatosis in patients of nonalcoholic fatty liver disease on lifestyle modification. In this study, initially 37 participants were included who were followed up after 6 months with transient elastography, blood biochemical tests and anthropometric measurements. The results were analyzed by Multivariate linear regression analysis and paired samples t-test (Dependent t-test) with 95% confidence interval. Correlation is calculated by Pearson correlation coefficients. Mean CAP value for assessing hepatic steatosis during 1st consultation (278.57±49.13 dB/m) was significantly improved (P=0.03) after 6 months of lifestyle modification (252.91±62.02 dB/m). Only fasting blood sugar (P=0.008), weight (P=0.000), body mass index (BMI) (P=0.000) showed significant positive correlation with CAP. Only BMI (P=0.034) and weight (P=0.035) were the independent predictor of CAP value in NAFLD patients. Lifestyle modification improves the hepatic steatosis, and CAP can be used to detect the improvement of hepatic steatosis during follow-up in patients with NAFLD on lifestyle modification. There is no relation between CAP and Fibroscan score in NAFLD patients. Only BMI and weight can predict CAP value independently.

Annual sediment flux estimates in a tidal strait using surrogate measurements

Science.gov (United States)

Ganju, N.K.; Schoellhamer, D.H.

2006-01-01

Annual suspended-sediment flux estimates through Carquinez Strait (the seaward boundary of Suisun Bay, California) are provided based on surrogate measurements for advective, dispersive, and Stokes drift flux. The surrogates are landward watershed discharge, suspended-sediment concentration at one location in the Strait, and the longitudinal salinity gradient. The first two surrogates substitute for tidally averaged discharge and velocity-weighted suspended-sediment concentration in the Strait, thereby providing advective flux estimates, while Stokes drift is estimated with suspended-sediment concentration alone. Dispersive flux is estimated using the product of longitudinal salinity gradient and the root-mean-square value of velocity-weighted suspended-sediment concentration as an added surrogate variable. Cross-sectional measurements validated the use of surrogates during the monitoring period. During high freshwater flow advective and dispersive flux were in the seaward direction, while landward dispersive flux dominated and advective flux approached zero during low freshwater flow. Stokes drift flux was consistently in the landward direction. Wetter than average years led to net export from Suisun Bay, while dry years led to net sediment import. Relatively low watershed sediment fluxes to Suisun Bay contribute to net export during the wet season, while gravitational circulation in Carquinez Strait and higher suspended-sediment concentrations in San Pablo Bay (seaward end of Carquinez Strait) are responsible for the net import of sediment during the dry season. Annual predictions of suspended-sediment fluxes, using these methods, will allow for a sediment budget for Suisun Bay, which has implications for marsh restoration and nutrient/contaminant transport. These methods also provide a general framework for estimating sediment fluxes in estuarine environments, where temporal and spatial variability of transport are large. ?? 2006 Elsevier Ltd. All rights

Surrogate Based Uni/Multi-Objective Optimization and Distribution Estimation Methods

Science.gov (United States)

Gong, W.; Duan, Q.; Huo, X.

2017-12-01

Parameter calibration has been demonstrated as an effective way to improve the performance of dynamic models, such as hydrological models, land surface models, weather and climate models etc. Traditional optimization algorithms usually cost a huge number of model evaluations, making dynamic model calibration very difficult, or even computationally prohibitive. With the help of a serious of recently developed adaptive surrogate-modelling based optimization methods: uni-objective optimization method ASMO, multi-objective optimization method MO-ASMO, and probability distribution estimation method ASMO-PODE, the number of model evaluations can be significantly reduced to several hundreds, making it possible to calibrate very expensive dynamic models, such as regional high resolution land surface models, weather forecast models such as WRF, and intermediate complexity earth system models such as LOVECLIM. This presentation provides a brief introduction to the common framework of adaptive surrogate-based optimization algorithms of ASMO, MO-ASMO and ASMO-PODE, a case study of Common Land Model (CoLM) calibration in Heihe river basin in Northwest China, and an outlook of the potential applications of the surrogate-based optimization methods.

Meet the surrogate fish

International Nuclear Information System (INIS)

Johnson, Bob; Neitzel, Duane; Moxon, Suzanne

1999-01-01

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

Fabrication and Characterization of Surrogate Glasses Aimed to Validate Nuclear Forensic Techniques

Science.gov (United States)

2017-12-01

the glass formed during a nuclear event, trinitite [14]. The SiO2 composition is generally greater than 50% for trinitite and can vary appreciably...CHARACTERIZATION OF SURROGATE GLASSES AIMED TO VALIDATE NUCLEAR FORENSIC TECHNIQUES by Ken G. Foos December 2017 Thesis Advisor: Claudia...December 2017 3. REPORT TYPE AND DATES COVERED Master’s thesis 4. TITLE AND SUBTITLE FABRICATION AND CHARACTERIZATION OF SURROGATE GLASSES AIMED TO

Silver-Catalyzed [2+1] Cyclopropenation of Alkynes with Unstable Diazoalkanes: N-Nosylhydrazones as Room-Temperature Decomposable Diazo Surrogates.

Science.gov (United States)

Liu, Zhaohong; Li, Qiangqiang; Liao, Peiqiu; Bi, Xihe

2017-04-06

The [2+1] cycloaddition of alkynes with diazo compounds represents one of the most powerful and reliable methods for the construction of cyclopropenes. However, it remains a formidable challenge to accomplish the cyclopropenation of alkynes with non-stabilized diazoalkanes, owing to the fact that such compounds are unstable and prone to detonation. Herein, we report a general silver-catalyzed cyclopropenation reaction of alkynes with unstable diazoalkanes, by for the first time the discovery and application of N-nosylhydrazones as room-temperature decomposiable diazo surrogates. This method allows for the efficient assembly a wide variety of cyclopropene derivatives that are otherwise difficult to access by conventional methods. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Assessing the clinical significance of tumor markers in common neoplasms.

Science.gov (United States)

Beketic-Oreskovic, Lidija; Maric, Petra; Ozretic, Petar; Oreskovic, Darko; Ajdukovic, Mia; Levanat, Sonja

2012-06-01

The term tumor markers include a spectrum of molecules and substances with widely divergent characteristics whose presence in the significant amount can be related to the malignant disease. An ideal tumor marker should have high specificity and sensitivity, which would allow its use in early diagnosis and prognosis of malignant disease, as well as in prediction of therapeutic response and follow-up of the patients. Numerous biochemical entities have emerged as potentially valuable tumor markers so far, but only few markers showed to be of considerable clinical reliability and have been accepted into standard clinical practice. Recent development of genomics and proteomics has enabled the examination of many new potential tumor markers. Scientific studies on discovery, development, and application of tumor markers have been proceeding quite rapidly providing great opportunities for improving the management of cancer patients. This review is focusing on the clinical usefulness of various tumor markers already in clinical practice as well as certain potential markers, giving a brief description of their prognostic and predictive significance in most common malignancies.

Ultrasonographic Optic Nerve Sheath Diameter as a Surrogate Measure of Raised Intracranial Pressure in Severe Pregnancy-induced Hypertension Patients.

Science.gov (United States)

Singh, Shiv Kumar; Bhatia, Kiran

2018-01-01

It is a well-known fact that severe pregnancy-induced hypertension (PIH) can be disastrous at times as it can cause a lot of complications to both pregnant women and her baby. Hence, it is always desirable to know the extent of severity by a real-time and easily accessible modality like ultrasound. The aim of the study was to evaluate the incidence of raised intracranial pressure (ICP) in severe preeclampsia and eclampsia patients using ocular ultrasonography with optic nerve sheath diameter (ONSD) measurement. This study design was a prospective and clinically controlled blinded observational study. After taking necessary permissions from the Institution Ethical Committee, 75 patients were enrolled for the study. However, finally, 25 patients in severe preeclampsia and 24 in eclampsia group were compared with 25 normal term antenatal women. Demographic profiles, hemodynamic parameters, laboratory markers for severity of PIH, and ultrasonographic OSND were measured. They were statistically analyzed and compared using one-way ANOVA and Tukey's test. Value of P surrogate marker for raised ICP in severe PIH patients. It is a rapid, bedside, noninvasive, and readily accessible tool and could be a part of a holistic approach for managing such patients.

A double-loop adaptive sampling approach for sensitivity-free dynamic reliability analysis

International Nuclear Information System (INIS)

Wang, Zequn; Wang, Pingfeng

2015-01-01

Dynamic reliability measures reliability of an engineered system considering time-variant operation condition and component deterioration. Due to high computational costs, conducting dynamic reliability analysis at an early system design stage remains challenging. This paper presents a confidence-based meta-modeling approach, referred to as double-loop adaptive sampling (DLAS), for efficient sensitivity-free dynamic reliability analysis. The DLAS builds a Gaussian process (GP) model sequentially to approximate extreme system responses over time, so that Monte Carlo simulation (MCS) can be employed directly to estimate dynamic reliability. A generic confidence measure is developed to evaluate the accuracy of dynamic reliability estimation while using the MCS approach based on developed GP models. A double-loop adaptive sampling scheme is developed to efficiently update the GP model in a sequential manner, by considering system input variables and time concurrently in two sampling loops. The model updating process using the developed sampling scheme can be terminated once the user defined confidence target is satisfied. The developed DLAS approach eliminates computationally expensive sensitivity analysis process, thus substantially improves the efficiency of dynamic reliability analysis. Three case studies are used to demonstrate the efficacy of DLAS for dynamic reliability analysis. - Highlights: • Developed a novel adaptive sampling approach for dynamic reliability analysis. • POD Developed a new metric to quantify the accuracy of dynamic reliability estimation. • Developed a new sequential sampling scheme to efficiently update surrogate models. • Three case studies were used to demonstrate the efficacy of the new approach. • Case study results showed substantially enhanced efficiency with high accuracy

A rapid situation assessment of the market for surrogate and illegal alcohols in Tallinn, Estonia.

Science.gov (United States)

Pärna, Kersti; Lang, Katrin; Raju, Kadi; Väli, Marika; McKee, Martin

2007-01-01

To understand the phenomenon of consumption of surrogate and illegal alcohols in Tallinn, capital of Estonia. This study, conducted in Tallinn in May 2006, used rapid situation assessment. Interviews with key informants in relevant settings such as emergency departments of hospitals, accommodation for the homeless, police etc. (n = 22), with alcohol abusers (n = 33), natural observations of surrogate sale and consumption venues (n = 46), and tracking of trade data were carried out. Key informants confirmed that consumption of illegal and surrogate alcohols are widely used by alcohol abusers, a finding confirmed by the alcohol abusers. Availability of surrogates varied by area of the city, mainly sold from street kiosks. Illegally produced spirits were also easily available. Sales of surrogates appear to have increased in recent years. A range of alcohol-containing substances that appear to be easily available at low cost, and that have high concentration of ethanol or contaminants known to be toxic, were identified in Tallinn. Alcohol policies in Estonia should address the consumption and availability of these substances.

Overview of Biomarkers and Surrogate Endpoints in Drug Development

Directory of Open Access Journals (Sweden)

John A. Wagner

2002-01-01

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

Carbon Particles in Airway Macrophage as a Surrogate Marker in the Early Detection of Lung Diseases

Directory of Open Access Journals (Sweden)

NK Kalappanavar

2012-03-01

Full Text Available Background: It has been shown that inhalation of carbonaceous particulate matter may impair lung function in children. Objective: Using the carbon content of airway macrophages as a marker of individual exposure to particulate matter derived from fossil fuel, we sought direct evidence for this association. Methods: 300 children from puffed rice industrial areas and 300 children from population living in green zone were selected randomly. Airway macrophages were obtained from healthy children through sputum induction, and the grading of ultrafine carbon particles in airway macrophages was measured. Pulmonary function was also measured by spirometry. Results: Pulmonary function tests showed that in industrial area 42.6% and 20.3% of children had moderate obstructive airway disease and restrictive airway disease, respectively. In the green zone area, 7% of children had obstructive airway disease and 6% had restrictive airway disease. Evaluation of airway macrophages for ultrafine carbon particles revealed that in industrial area there were ultrafine carbon particles of grade 2 in 23% of subjects and grade 3 in 8.33% of individuals with obstructive airway disease. In the green zone area, the rates were 1.67% and 0.7%, respectively. Conclusion: The study provides a first evidence of the strong association between air pollution and development of airway diseases. Carbon particles in the sputum can be used as a marker for air pollution.

Simultaneous tumor and surrogate motion tracking with dynamic MRI for radiation therapy planning

Science.gov (United States)

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

2018-01-01

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.

EVALUATION OF IMMUNOHISTOCHEMISTRY (IHC MARKER HER2 IN BREAST CANCER

Directory of Open Access Journals (Sweden)

Prasanna G. Shete

2016-08-01

Full Text Available The paper discusses a novel approach involving algorithm implementation and hardware Devkit processing for estimating the extent of cancer in a breast tissue sample. The process aims at providing a reliable, repeatable, and fast method that could replace the traditional method of manual examination and estimation. Immunohistochemistry (IHC and Fluorescence in situ Hybridization (FISH are the two main methods used to detect the marker status in clinical practice. FISH is though more reliable than IHC, but IHC is widely used as it is cheaper, convenient to operate and conserve, the morphology is clear. The IHC markers are Estrogen receptor (ER, Progesterone receptor (PR, Human Epidermal Growth Factor (HER2 that give clear indications of the presence of cancer cells in the tissue sample. HER2 remains the most reliable marker for the detection of breast cancer. The Human Epidermal Growth Factor Receptor (HER2 markers are discussed in the paper, as it gives clear indications of the presence of cancer cells in the tissue sample. HER2 is identified based on the color and intensity of the cell membrane staining. The color and intensity is obviously based on the thresholding for classifying the cancerous cells into severity levels in terms of score to estimate the extent of spread of cancer in breast tissue. For HER2 evaluation, the percentage of staining is calculated in terms of ratio of stain pixel count to the total pixel count. The evaluation of HER2 is obtained through simulation software (MATLAB using intensity based algorithm and same is run on embedded processor evaluation board Devkit 8500. The results are validated with doctors.

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

Science.gov (United States)

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

2014-04-01

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

Critical review of norovirus surrogates in food safety research: rationale for considering volunteer studies.

Science.gov (United States)

Richards, Gary P

2012-03-01

The inability to propagate human norovirus (NoV) or to clearly differentiate infectious from noninfectious virus particles has led to the use of surrogate viruses, like feline calicivirus (FCV) and murine norovirus-1 (MNV), which are propagatable in cell culture. The use of surrogates is predicated on the assumption that they generally mimic the viruses they represent; however, studies are proving this concept invalid. In direct comparisons between FCV and MNV, their susceptibility to temperatures, environmental and food processing conditions, and disinfectants are dramatically different. Differences have also been noted between the inactivation of NoV and its surrogates, thus questioning the validity of surrogates. Considerable research funding is provided globally each year to conduct surrogate studies on NoVs; however, there is little demonstrated benefit derived from these studies in regard to the development of virus inactivation techniques or food processing strategies. Human challenge studies are needed to determine which processing techniques are effective in reducing NoVs in foods. A major obstacle to clinical trials on NoVs is the perception that such trials are too costly and risky, but in reality, there is far more cost and risk in allowing millions of unsuspecting consumers to contract NoV illness each year, when practical interventions are only a few volunteer studies away. A number of clinical trials have been conducted, providing important insights into NoV inactivation. A shift in research priorities from surrogate research to volunteer studies is essential if we are to identify realistic, practical, and scientifically valid processing approaches to improve food safety.

Comparative study of surrogate models for groundwater contamination source identification at DNAPL-contaminated sites

Science.gov (United States)

Hou, Zeyu; Lu, Wenxi

2018-05-01

Knowledge of groundwater contamination sources is critical for effectively protecting groundwater resources, estimating risks, mitigating disaster, and designing remediation strategies. Many methods for groundwater contamination source identification (GCSI) have been developed in recent years, including the simulation-optimization technique. This study proposes utilizing a support vector regression (SVR) model and a kernel extreme learning machine (KELM) model to enrich the content of the surrogate model. The surrogate model was itself key in replacing the simulation model, reducing the huge computational burden of iterations in the simulation-optimization technique to solve GCSI problems, especially in GCSI problems of aquifers contaminated by dense nonaqueous phase liquids (DNAPLs). A comparative study between the Kriging, SVR, and KELM models is reported. Additionally, there is analysis of the influence of parameter optimization and the structure of the training sample dataset on the approximation accuracy of the surrogate model. It was found that the KELM model was the most accurate surrogate model, and its performance was significantly improved after parameter optimization. The approximation accuracy of the surrogate model to the simulation model did not always improve with increasing numbers of training samples. Using the appropriate number of training samples was critical for improving the performance of the surrogate model and avoiding unnecessary computational workload. It was concluded that the KELM model developed in this work could reasonably predict system responses in given operation conditions. Replacing the simulation model with a KELM model considerably reduced the computational burden of the simulation-optimization process and also maintained high computation accuracy.

Surrogate consent to non-beneficial research: erring on the right side when substituted judgments may be inaccurate.

Science.gov (United States)

Johansson, Mats; Broström, Linus

2016-04-01

Part of the standard protection of decisionally incapacitated research subjects is a prohibition against enrolling them unless surrogate decision makers authorize it. A common view is that surrogates primarily ought to make their decisions based on what the decisionally incapacitated subject would have wanted regarding research participation. However, empirical studies indicate that surrogate predictions about such preferences are not very accurate. The focus of this article is the significance of surrogate accuracy in the context of research that is not expected to benefit the research subject. We identify three morally relevant asymmetries between being enrolled and not being enrolled in such non-beneficial research, and conclude that when there is a non-negligible probability that surrogates' predictions are wrong, it will generally be better to err on the side of not authorizing enrollment.

The ethics of commercial surrogate mothering: a response to Casey Humbyrd.

Science.gov (United States)

Omonzejele, Peter F

2011-01-01

This article critically examines the argument advanced by Casey Humbyrd in support of international commercial surrogate mothering. It finds her arguments unconvincing especially at the point of implementation. This is because the author was unable to demonstrate how regulation and her notion offair compensation would not lead to undue inducement and exploitation in resource-poor settings where urgent needs often exist. In fact, the argument advanced in this article is that commercial surrogate mothering cannot but be exploitative in so far as urgent and compelling needs exist. To logically drive home this point, the elements of exploitation were discussed in order to show that regulation and fair compensation cannot prevent exploitative transaction in commercial surrogate mothering arrangements. This may happen in the same way as regulation and compensation framework have not been successful in preventing the allegations of exploitation in the research context especially where studies are conducted in resource-poor countries.

Interfractional Positional Variability of Fiducial Markers and Primary Tumors in Locally Advanced Non-Small-Cell Lung Cancer During Audiovisual Biofeedback Radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Roman, Nicholas O., E-mail: nroman@mcvh-vcu.edu [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA (United States); Shepherd, Wes [Department of Pulmonology, Virginia Commonwealth University, Richmond, VA (United States); Mukhopadhyay, Nitai [Department of Biostatistics, Virginia Commonwealth University, Richmond, VA (United States); Hugo, Geoffrey D.; Weiss, Elisabeth [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA (United States)

2012-08-01

Purpose: To evaluate implanted markers as a surrogate for tumor-based setup during image-guided lung cancer radiotherapy with audiovisual biofeedback. Methods and Materials: Seven patients with locally advanced non-small-cell lung cancer were implanted bronchoscopically with gold coils. Markers, tumor, and a reference bony structure (vertebra) were contoured for all 10 phases of the four-dimensional respiration-correlated fan-beam computed tomography and weekly four-dimensional cone-beam computed tomography. Results: The systematic/random interfractional marker-to-tumor centroid displacements were 2/3, 2/2, and 3/3 mm in the x (lateral), y (anterior-posterior), and z (superior-inferior) directions, respectively. The systematic/random interfractional marker-to-bone displacements were 2/3, 2/3, and 2/3 mm in the x, y, and z directions, respectively. The systematic/random tumor-to-bone displacements were 2/3, 2/4, and 4/4 mm in the x, y, and z directions, respectively. All displacements changed significantly over time (p < 0.0001). Conclusions: Although marker-based image guidance may decrease the risk for geometric miss compared with bony anatomy-based positioning, the observed displacements between markers and tumor centroids indicate the need for repeated soft tissue imaging, particularly in situations with large tumor volume change and large initial marker-to-tumor centroid distance.

Interfractional Positional Variability of Fiducial Markers and Primary Tumors in Locally Advanced Non-Small-Cell Lung Cancer During Audiovisual Biofeedback Radiotherapy

International Nuclear Information System (INIS)

Roman, Nicholas O.; Shepherd, Wes; Mukhopadhyay, Nitai; Hugo, Geoffrey D.; Weiss, Elisabeth

2012-01-01

Purpose: To evaluate implanted markers as a surrogate for tumor-based setup during image-guided lung cancer radiotherapy with audiovisual biofeedback. Methods and Materials: Seven patients with locally advanced non-small-cell lung cancer were implanted bronchoscopically with gold coils. Markers, tumor, and a reference bony structure (vertebra) were contoured for all 10 phases of the four-dimensional respiration-correlated fan-beam computed tomography and weekly four-dimensional cone-beam computed tomography. Results: The systematic/random interfractional marker-to-tumor centroid displacements were 2/3, 2/2, and 3/3 mm in the x (lateral), y (anterior–posterior), and z (superior–inferior) directions, respectively. The systematic/random interfractional marker-to-bone displacements were 2/3, 2/3, and 2/3 mm in the x, y, and z directions, respectively. The systematic/random tumor-to-bone displacements were 2/3, 2/4, and 4/4 mm in the x, y, and z directions, respectively. All displacements changed significantly over time (p < 0.0001). Conclusions: Although marker-based image guidance may decrease the risk for geometric miss compared with bony anatomy–based positioning, the observed displacements between markers and tumor centroids indicate the need for repeated soft tissue imaging, particularly in situations with large tumor volume change and large initial marker-to-tumor centroid distance.

Surrogacy families 10 years on: relationship with the surrogate, decisions over disclosure and children's understanding of their surrogacy origins.

Science.gov (United States)

Jadva, V; Blake, L; Casey, P; Golombok, S

2012-10-01

This study aimed to prospectively examine families created using surrogacy over a 10-year period in the UK with respect to intending parents' and children's relationship with the surrogate mother, parents' decisions over disclosure and children's understanding of the nature of their conception. Semi-structured interviews were administered by trained researchers to intending mothers, intending fathers and children on four occasions over a 10-year period. Forty-two families (19 with a genetic surrogate mother) participated when the child was 1-year old and by age 10 years, 33 families remained in the study. Data were collected on the frequency of contact with the surrogate mother, relationship with the surrogate, disclosure of surrogacy to the child and the child's understanding of their surrogacy birth. Frequency of contact between surrogacy families and their surrogate mother decreased over time, particularly for families whose surrogate was a previously unknown genetic carrier (P Surrogacy families maintained good relationships with the surrogate mother over time. Children felt positive about their surrogate mother and their surrogacy birth. The sample size of this study was small and further, larger investigations are needed before firm conclusions can be drawn.

Someone to Lean on: Assessment and Implications of Social Surrogate Use in Childhood

Science.gov (United States)

Arbeau, Kimberley A.; Coplan, Robert J.; Matheson, Adrienne

2012-01-01

A social surrogate is a person who helps a shy individual deal with the stresses of a social situation. Previous research has only investigated social surrogate use in adults. The purpose of the current study was to develop and evaluate a new self-report measure of social surrogacy in middle childhood and to explore the implications of this…

Gay father surrogacy families: relationships with surrogates and egg donors and parental disclosure of children's origins.

Science.gov (United States)

Blake, Lucy; Carone, Nicola; Slutsky, Jenna; Raffanello, Elizabeth; Ehrhardt, Anke A; Golombok, Susan

2016-11-01

To study the nature and quality of relationships between gay father families and their surrogates and egg donors and parental disclosure of children's origins. Cross-sectional study. Family homes. Parents in 40 gay father families with 3-9-year-old children born through surrogacy. Administration of a semistructured interview. Relationships between parents, children, surrogates, and egg donors and parental disclosure of children's origins were examined using a semistructured interview. The majority of fathers were content with the level of contact they had with the surrogate, with those who were discontent wanting more contact. Fathers were more likely to maintain relationships with surrogates than egg donors, and almost all families had started the process of talking to their children about their origins, with the level of detail and children's understanding increasing with the age of the child. In gay father surrogacy families with young children, relationships between parents, children, surrogates, and egg donors are generally positive. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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)

2015-08-15

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.

Videotrees: Improving video surrogate presentation using hierarchy

NARCIS (Netherlands)

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

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

Reliability of sagittal plane hip, knee, and ankle joint angles from a single frame of video data using the GAITRite camera system.

Science.gov (United States)

Ross, Sandy A; Rice, Clinton; Von Behren, Kristyn; Meyer, April; Alexander, Rachel; Murfin, Scott

2015-01-01

The purpose of this study was to establish intra-rater, intra-session, and inter-rater, reliability of sagittal plane hip, knee, and ankle angles with and without reflective markers using the GAITRite walkway and single video camera between student physical therapists and an experienced physical therapist. This study included thirty-two healthy participants age 20-59, stratified by age and gender. Participants performed three successful walks with and without markers applied to anatomical landmarks. GAITRite software was used to digitize sagittal hip, knee, and ankle angles at two phases of gait: (1) initial contact; and (2) mid-stance. Intra-rater reliability was more consistent for the experienced physical therapist, regardless of joint or phase of gait. Intra-session reliability was variable, the experienced physical therapist showed moderate to high reliability (intra-class correlation coefficient (ICC) = 0.50-0.89) and the student physical therapist showed very poor to high reliability (ICC = 0.07-0.85). Inter-rater reliability was highest during mid-stance at the knee with markers (ICC = 0.86) and lowest during mid-stance at the hip without markers (ICC = 0.25). Reliability of a single camera system, especially at the knee joint shows promise. Depending on the specific type of reliability, error can be attributed to the testers (e.g. lack of digitization practice and marker placement), participants (e.g. loose fitting clothing) and camera systems (e.g. frame rate and resolution). However, until the camera technology can be upgraded to a higher frame rate and resolution, and the software can be linked to the GAITRite walkway, the clinical utility for pre/post measures is limited.

Black-footed ferrets and Siberian polecats as ecological surrogates and ecological equivalents

Science.gov (United States)

Biggins, D.E.; Hanebury, L.R.; Miller, B.J.; Powell, R.A.

2011-01-01

Ecologically equivalent species serve similar functions in different communities, and an ecological surrogate species can be used as a substitute for an equivalent species in a community. Siberian polecats (Mustela eversmanii) and black-footed ferrets (M. nigripes) have long been considered ecological equivalents. Polecats also have been used as investigational surrogates for black-footed ferrets, yet the similarities and differences between the 2 species are poorly understood. We contrasted activity patterns of radiotagged polecats and ferrets released onto ferret habitat. Ferrets tended to be nocturnal and most active after midnight. Polecats were not highly selective for any period of the day or night. Ferrets and polecats moved most during brightly moonlit nights. The diel activity pattern of ferrets was consistent with avoidance of coyotes (Canis latrans) and diurnal birds of prey. Similarly, polecat activity was consistent with avoidance of red foxes (Vulpes vulpes) in their natural range. Intraguild predation (including interference competition) is inferred as a selective force influencing behaviors of these mustelines. Examination of our data suggests that black-footed ferrets and Siberian polecats might be ecological equivalents but are not perfect surrogates. Nonetheless, polecats as surrogates for black-footed ferrets have provided critical insight needed, especially related to predation, to improve the success of ferret reintroductions. ?? 2011 American Society of Mammalogists.

Can urinary exosomes act as treatment response markers in prostate cancer?

Directory of Open Access Journals (Sweden)

Tabi Zsuzsanna

2009-01-01

Full Text Available Abstract Background Recently, nanometer sized vesicles (termed exosomes have been described as a component of urine. Such vesicles may be a useful non-invasive source of markers in renal disease. Their utility as a source of markers in urological cancer remains unstudied. Our aim in this study was to investigate the feasibility and value of analysing urinary exosomes in prostate cancer patients undergoing standard therapy. Methods Ten patients (with locally advanced PCa provided spot urine specimens at three time points during standard therapy. Patients received 3–6 months neoadjuvant androgen deprivation therapy prior to radical radiotherapy, comprising a single phase delivering 55 Gy in 20 fractions to the prostate and 44 Gy in 20 fractions to the pelvic nodes. Patients were continued on adjuvant ADT according to clinical need. Exosomes were purified, and the phenotype compared to exosomes isolated from the prostate cancer cell line LNcaP. A control group of 10 healthy donors was included. Serum PSA was used as a surrogate treatment response marker. Exosomes present in urine were quantified, and expression of prostate markers (PSA and PSMA and tumour-associated marker 5T4 was examined. Results The quantity and quality of exosomes present in urine was highly variable, even though we handled all materials freshly and used methods optimized for obtaining highly pure exosomes. There was approx 2-fold decrease in urinary exosome content following 12 weeks ADT, but this was not sustained during radiotherapy. Nevertheless, PSA and PSMA were present in 20 of 24 PCa specimens, and not detected in healthy donor specimens. There was a clear treatment-related decrease in exosomal prostate markers in 1 (of 8 patient. Conclusion Evaluating urinary-exosomes remains difficult, given the variability of exosomes in urine specimens. Nevertheless, this approach holds promise as a non-invasive source of multiple markers of malignancy that could provide

Validation of candidate gene markers for marker-assisted selection of potato cultivars with improved tuber quality.

Science.gov (United States)

Li, Li; Tacke, Eckhard; Hofferbert, Hans-Reinhardt; Lübeck, Jens; Strahwald, Josef; Draffehn, Astrid M; Walkemeier, Birgit; Gebhardt, Christiane

2013-04-01

Tuber yield, starch content, starch yield and chip color are complex traits that are important for industrial uses and food processing of potato. Chip color depends on the quantity of reducing sugars glucose and fructose in the tubers, which are generated by starch degradation. Reducing sugars accumulate when tubers are stored at low temperatures. Early and efficient selection of cultivars with superior yield, starch yield and chip color is hampered by the fact that reliable phenotypic selection requires multiple year and location trials. Application of DNA-based markers early in the breeding cycle, which are diagnostic for superior alleles of genes that control natural variation of tuber quality, will reduce the number of clones to be evaluated in field trials. Association mapping using genes functional in carbohydrate metabolism as markers has discovered alleles of invertases and starch phosphorylases that are associated with tuber quality traits. Here, we report on new DNA variants at loci encoding ADP-glucose pyrophosphorylase and the invertase Pain-1, which are associated with positive or negative effect with chip color, tuber starch content and starch yield. Marker-assisted selection (MAS) and marker validation were performed in tetraploid breeding populations, using various combinations of 11 allele-specific markers associated with tuber quality traits. To facilitate MAS, user-friendly PCR assays were developed for specific candidate gene alleles. In a multi-parental population of advanced breeding clones, genotypes were selected for having different combinations of five positive and the corresponding negative marker alleles. Genotypes combining five positive marker alleles performed on average better than genotypes with four negative alleles and one positive allele. When tested individually, seven of eight markers showed an effect on at least one quality trait. The direction of effect was as expected. Combinations of two to three marker alleles were

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

Marker-controlled watershed for lymphoma segmentation in sequential CT images

International Nuclear Information System (INIS)

Yan Jiayong; Zhao Binsheng; Wang, Liang; Zelenetz, Andrew; Schwartz, Lawrence H.

2006-01-01

Segmentation of lymphoma containing lymph nodes is a difficult task because of multiple variables associated with the tumor's location, intensity distribution, and contrast to its surrounding tissues. In this paper, we present a reliable and practical marker-controlled watershed algorithm for semi-automated segmentation of lymphoma in sequential CT images. Robust determination of internal and external markers is the key to successful use of the marker-controlled watershed transform in the segmentation of lymphoma and is the focus of this work. The external marker in our algorithm is the circle enclosing the lymphoma in a single slice. The internal marker, however, is determined automatically by combining techniques including Canny edge detection, thresholding, morphological operation, and distance map estimation. To obtain tumor volume, the segmented lymphoma in the current slice needs to be propagated to the adjacent slice to help determine the external and internal markers for delineation of the lymphoma in that slice. The algorithm was applied to 29 lymphomas (size range, 9-53 mm in diameter; mean, 23 mm) in nine patients. A blinded radiologist manually delineated all lymphomas on all slices. The manual result served as the ''gold standard'' for comparison. Several quantitative methods were applied to objectively evaluate the performance of the segmentation algorithm. The algorithm received a mean overlap, overestimation, and underestimation ratios of 83.2%, 13.5%, and 5.5%, respectively. The mean average boundary distance and Hausdorff boundary distance were 0.7 and 3.7 mm. Preliminary results have shown the potential of this computer algorithm to allow reliable segmentation and quantification of lymphomas on sequential CT images

Tc-99m Hydroxymethylene Diphosphonate (HMDP) Renal Uptake as a Surrogate Marker of Postoperative Impairment of the Glomerular Filtration Rate in Renal Tumor Patients Following Nephron-Sparing Surgery.

Science.gov (United States)

Choi, Hongyoon; Lee, Won Woo; So, Young; Ha, Seunggyun; Byun, Seok-Soo; Kim, Sang Eun

2014-12-01

We investigated Tc-99m hydroxymethylene diphosphonate (HMDP) scintigraphy findings in renal tumor patients from the perspective of postoperative renal dysfunction following nephron-sparing surgery (NSS). Forty-three renal tumor patients (M:F = 28:15, age 53.9 ± 12.5 years) who had undergone Tc-99m HMDP scintigraphy after NSS were enrolled. The patients were divided into HMDP(+) or HMDP(-) groups by visual assessment, and the asymmetric index (ASI) was calculated using a region-of-interest analysis. In 16 patients, the total and split glomerular filtration rate (GFR) was assessed using Tc-99m diethylenetriaminepentaacetic acid (DTPA) scintigraphy at baseline and at 3 and 6 months post-NSS. High Tc-99m HMDP uptake was observed in the operated kidneys, but this did not persist later than 7 days post-NSS. Split GFR of the operated kidneys at baseline (58.5 ± 9.3 ml/min) was significantly reduced at 6 months post-NSS (40.1 ± 5.9 ml/min, p Tc-99m HMDP. Declines in both total GFR (p = 0.010 and p = 0.002 for 3 and 6 months, respectively) and split GFR of the operated kidneys (p Tc-99m HMDP in the operated kidneys. The ASI was negatively correlated with %change in the split GFR of these operated kidneys at 6 months post-NSS (rho =-0.578, p = 0.0304). Tc-99m HMDP uptake within 1 week following NSS is a surrogate marker of GFR impairment over 6 months post-NSS.

Surrogate model approach for improving the performance of reactive transport simulations

Science.gov (United States)

Jatnieks, Janis; De Lucia, Marco; Sips, Mike; Dransch, Doris

2016-04-01

Reactive transport models can serve a large number of important geoscientific applications involving underground resources in industry and scientific research. It is common for simulation of reactive transport to consist of at least two coupled simulation models. First is a hydrodynamics simulator that is responsible for simulating the flow of groundwaters and transport of solutes. Hydrodynamics simulators are well established technology and can be very efficient. When hydrodynamics simulations are performed without coupled geochemistry, their spatial geometries can span millions of elements even when running on desktop workstations. Second is a geochemical simulation model that is coupled to the hydrodynamics simulator. Geochemical simulation models are much more computationally costly. This is a problem that makes reactive transport simulations spanning millions of spatial elements very difficult to achieve. To address this problem we propose to replace the coupled geochemical simulation model with a surrogate model. A surrogate is a statistical model created to include only the necessary subset of simulator complexity for a particular scenario. To demonstrate the viability of such an approach we tested it on a popular reactive transport benchmark problem that involves 1D Calcite transport. This is a published benchmark problem (Kolditz, 2012) for simulation models and for this reason we use it to test the surrogate model approach. To do this we tried a number of statistical models available through the caret and DiceEval packages for R, to be used as surrogate models. These were trained on randomly sampled subset of the input-output data from the geochemical simulation model used in the original reactive transport simulation. For validation we use the surrogate model to predict the simulator output using the part of sampled input data that was not used for training the statistical model. For this scenario we find that the multivariate adaptive regression splines

Failed surrogate conceptions: social and ethical aspects of preconception disruptions during commercial surrogacy in India.

Science.gov (United States)

Mitra, Sayani; Schicktanz, Silke

2016-09-19

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

Surrogate-based optimization of hydraulic fracturing in pre-existing fracture networks

Science.gov (United States)

Chen, Mingjie; Sun, Yunwei; Fu, Pengcheng; Carrigan, Charles R.; Lu, Zhiming; Tong, Charles H.; Buscheck, Thomas A.

2013-08-01

Hydraulic fracturing has been used widely to stimulate production of oil, natural gas, and geothermal energy in formations with low natural permeability. Numerical optimization of fracture stimulation often requires a large number of evaluations of objective functions and constraints from forward hydraulic fracturing models, which are computationally expensive and even prohibitive in some situations. Moreover, there are a variety of uncertainties associated with the pre-existing fracture distributions and rock mechanical properties, which affect the optimized decisions for hydraulic fracturing. In this study, a surrogate-based approach is developed for efficient optimization of hydraulic fracturing well design in the presence of natural-system uncertainties. The fractal dimension is derived from the simulated fracturing network as the objective for maximizing energy recovery sweep efficiency. The surrogate model, which is constructed using training data from high-fidelity fracturing models for mapping the relationship between uncertain input parameters and the fractal dimension, provides fast approximation of the objective functions and constraints. A suite of surrogate models constructed using different fitting methods is evaluated and validated for fast predictions. Global sensitivity analysis is conducted to gain insights into the impact of the input variables on the output of interest, and further used for parameter screening. The high efficiency of the surrogate-based approach is demonstrated for three optimization scenarios with different and uncertain ambient conditions. Our results suggest the critical importance of considering uncertain pre-existing fracture networks in optimization studies of hydraulic fracturing.

Incorporating surrogate species and seascape connectivity to improve marine conservation outcomes.

Science.gov (United States)

Olds, Andrew D; Connolly, Rod M; Pitt, Kylie A; Maxwell, Paul S; Aswani, Shankar; Albert, Simon

2014-08-01

Conservation focuses on maintaining biodiversity and ecosystem functioning, but gaps in our knowledge of species biology and ecological processes often impede progress. For this reason, focal species and habitats are used as surrogates for multispecies conservation, but species-based approaches are not widely adopted in marine ecosystems. Reserves in the Solomon Islands were designed on the basis of local ecological knowledge to conserve bumphead parrotfish (Bolbometopon muricatum) and to protect food security and ecosystem functioning. Bumphead parrotfish are an iconic threatened species and may be a useful surrogate for multispecies conservation. They move across tropical seascapes throughout their life history, in a pattern of habitat use that is shared with many other species. We examined their value as a conservation surrogate and assessed the importance of seascape connectivity (i.e., the physical connectedness of patches in the seascape) among reefs, mangroves, and seagrass to marine reserve performance. Reserves were designed for bumphead parrotfish, but also enhanced the abundance of other species. Integration of local ecological knowledge and seascape connectivity enhanced the abundance of 17 other harvested fish species in local reserves. This result has important implications for ecosystem functioning and local villagers because many of these species perform important ecological processes and provide the foundation for extensive subsistence fisheries. Our findings suggest greater success in maintaining and restoring marine ecosystems may be achieved when they are managed to conserve surrogate species and preserve functional seascape connections. © 2014 Society for Conservation Biology.

Partnership for Edge Physics (EPSI), University of Texas Final Report

International Nuclear Information System (INIS)

Moser, Robert; Carey, Varis; Michoski, Craig; Faghihi, Danial

2017-01-01

Simulations of tokamak plasmas require a number of inputs whose values are uncertain. The effects of these input uncertainties on the reliability of model predictions is of great importance when validating predictions by comparison to experimental observations, and when using the predictions for design and operation of devices. However, high fidelity simulation of tokamak plasmas, particular those aimed at characterization of the edge plasma physics, are computationally expensive, so lower cost surrogates are required to enable practical uncertainty estimates. Two surrogate modeling techniques have been explored in the context of tokamak plasma simulations using the XGC family of plasma simulation codes. The first is a response surface surrogate, and the second is an augmented surrogate relying on scenario extrapolation. In addition, to reduce the costs of the XGC simulations, a particle resampling algorithm was developed, which allows marker particle distributions to be adjusted to maintain optimal importance sampling. This means that the total number of particles in and therefore the cost of a simulation can be reduced while maintaining the same accuracy.

Partnership for Edge Physics (EPSI), University of Texas Final Report

Energy Technology Data Exchange (ETDEWEB)

Moser, Robert [Univ. of Texas, Austin, TX (United States); Carey, Varis [Univ. of Texas, Austin, TX (United States); Michoski, Craig [Univ. of Texas, Austin, TX (United States); Faghihi, Danial [Univ. of Texas, Austin, TX (United States)

2017-11-03

Simulations of tokamak plasmas require a number of inputs whose values are uncertain. The effects of these input uncertainties on the reliability of model predictions is of great importance when validating predictions by comparison to experimental observations, and when using the predictions for design and operation of devices. However, high fidelity simulation of tokamak plasmas, particular those aimed at characterization of the edge plasma physics, are computationally expensive, so lower cost surrogates are required to enable practical uncertainty estimates. Two surrogate modeling techniques have been explored in the context of tokamak plasma simulations using the XGC family of plasma simulation codes. The first is a response surface surrogate, and the second is an augmented surrogate relying on scenario extrapolation. In addition, to reduce the costs of the XGC simulations, a particle resampling algorithm was developed, which allows marker particle distributions to be adjusted to maintain optimal importance sampling. This means that the total number of particles in and therefore the cost of a simulation can be reduced while maintaining the same accuracy.

Concordance Between Veterans' Self-Report and Documentation of Surrogate Decision Makers: Implications for Quality Measurement.

Science.gov (United States)

Garner, Kimberly K; Dubbert, Patricia; Lensing, Shelly; Sullivan, Dennis H

2017-01-01

The Measuring What Matters initiative of the American Academy of Hospice and Palliative Medicine and the Hospice and Palliative Nurses Association identified documentation of a surrogate decision maker as one of the top 10 quality indicators in the acute hospital and hospice settings. To better understand the potential implementation of this Measuring What Matters quality measure #8, Documentation of Surrogate in outpatient primary care settings by describing primary care patients' self-reported identification and documentation of a surrogate decision maker. Examination of patient responses to self-assessment questions from advance health care planning educational groups conducted in one medical center primary care clinic and seven community-based outpatient primary care clinics. We assessed the concordance between patient reports of identifying and naming a surrogate decision maker and having completed an advance directive (AD) with presence of an AD in the electronic medical record. Of veterans without a documented AD on file, more than half (66%) reported that they had talked with someone they trusted and nearly half (52%) reported that they had named someone to communicate their preferences. Our clinical project data suggest that many more veterans may have initiated communications with surrogate decision makers than is evident in the electronic medical record. System changes are needed to close the gap between veterans' plans for a surrogate decision maker and the documentation available to acute care health care providers. Published by Elsevier Inc.

Evaluation of bone surrogates for indirect and direct ballistic fractures.

Science.gov (United States)

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

2016-04-01

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

Humoral markers of active Epstein-Barr virus infection associate with anti-extractable nuclear antigen autoantibodies and plasma galectin-3 binding protein in systemic lupus erythematosus

DEFF Research Database (Denmark)

Rasmussen, N S; Nielsen, C T; Houen, G

2016-01-01

We investigated if signs of active Epstein-Barr virus and cytomegalovirus infections associate with certain autoantibodies and a marker of type I interferon activity in patients with systemic lupus erythematosus. IgM and IgG plasma levels against Epstein-Barr virus early antigen diffuse...... and cytomegalovirus pp52 were applied as humoral markers of ongoing/recently active Epstein-Barr virus and cytomegalovirus infections, respectively. Plasma galectin-3 binding protein served as a surrogate marker of type I interferon activity. The measurements were conducted in 57 systemic lupus erythematosus patients...... concentrations were significantly higher in systemic lupus erythematosus patients (P = 0.009) and associated positively with Epstein-Barr virus early antigen diffuse-directed antibodies and the presence of autoantibodies against extractable nuclear antigens in adjusted linear regressions (B = 2.02 and 2.02, P...

Basic mechanisms of urgency: preclinical and clinical evidence.

Science.gov (United States)

Michel, Martin C; Chapple, Christopher R

2009-08-01

Urgency is the core symptom of the overactive bladder symptom complex, but the underlying mechanisms are not fully understood. To review clinical and experimental studies related to how bladder filling and urgency are sensed and what causes urgency and to discuss how this process affects potential therapeutic strategies. Review of published reports. The definition of urgency as a desire implies that it can only be assessed in cognitively intact patients and that animal studies have to rely on surrogate markers thereof, such as detrusor overactivity (DO); however, DO and urgency are not always associated. While the precise mechanisms of how urgency is sensed remain unclear, accumulating evidence suggests that they may differ from the physiologic sensation of bladder filling. Studies on the neurophysiology of urgency sensing are hampered by reliance on the surrogate marker DO. Functional brain imaging may help to understand the central neurophysiology, but, until now, it has not specifically focused on urgency. With regard to causes of urgency, multiple theories have been forwarded. While none of them has been proven, it should be noted that they are not mutually exclusive, and, in specific patients, different causes may be present. The development of improved therapeutic strategies against urgency will be helped by a better understanding of how urgency is perceived and the underlying causes. Rigorous use of existing definitions and the search for reliable surrogate markers will aid such attempts.

Simultaneous Thermal Analysis of Remediated Nitrate Salt Surrogates

Energy Technology Data Exchange (ETDEWEB)

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

2016-05-13

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

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

Science.gov (United States)

Andrew Youngblood; Heidi Bigler-Cole; Christopher J. Fettig; Carl Fiedler; Eric E. Knapp; John F. Lehmkuhl; Kenneth W. Outcalt; Carl N. Skinner; Scott L. Stephens; Thomas A. Waldrop

2007-01-01

Operational-scale experiments that evaluate the consequences of fire and mechanical "surrogates" for natural disturbance events are essential to better understand strategies for reducing the incidence and severity of wildfire. The national Fire and Fire Surrogate (FFS) study was initiated in 1999 to establish an integrated network of long-term studies...

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

Science.gov (United States)

Baker, Stuart G

2018-02-20

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

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

Science.gov (United States)

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

2008-03-01

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

Invisible marker based augmented reality system

Science.gov (United States)

Park, Hanhoon; Park, Jong-Il

2005-07-01

Augmented reality (AR) has recently gained significant attention. The previous AR techniques usually need a fiducial marker with known geometry or objects of which the structure can be easily estimated such as cube. Placing a marker in the workspace of the user can be intrusive. To overcome this limitation, we present an AR system using invisible markers which are created/drawn with an infrared (IR) fluorescent pen. Two cameras are used: an IR camera and a visible camera, which are positioned in each side of a cold mirror so that their optical centers coincide with each other. We track the invisible markers using IR camera and visualize AR in the view of visible camera. Additional algorithms are employed for the system to have a reliable performance in the cluttered background. Experimental results are given to demonstrate the viability of the proposed system. As an application of the proposed system, the invisible marker can act as a Vision-Based Identity and Geometry (VBIG) tag, which can significantly extend the functionality of RFID. The invisible tag is the same as RFID in that it is not perceivable while more powerful in that the tag information can be presented to the user by direct projection using a mobile projector or by visualizing AR on the screen of mobile PDA.

Laboratory stabilization/solidification of surrogate and actual mixed-waste sludge in glass and grout

International Nuclear Information System (INIS)

Spence, R.D.; Gilliam, T.M.; Mattus, C.H.; Mattus, A.J.

1998-01-01

Grouting and vitrification are currently the most likely stabilization/solidification technologies for mixed wastes. Grouting has been used to stabilize and solidify hazardous and low-level waste for decades. Vitrification has long been developed as a high-level-waste alternative and has been under development recently as an alternative treatment technology for low-level mixed waste. Laboratory testing has been performed to develop grout and vitrification formulas for mixed-waste sludges currently stored in underground tanks at Oak Ridge National Laboratory (ORNL) and to compare these waste forms. Envelopes, or operating windows, for both grout and soda-lime-silica glass formulations for a surrogate sludge were developed. One formulation within each envelope was selected for testing the sensitivity of performance to variations (±10 wt%) in the waste form composition and variations in the surrogate sludge composition over the range previously characterized in the sludges. In addition, one sludge sample of an actual mixed-waste tank was obtained, a surrogate was developed for this sludge sample, and grout and glass samples were prepared and tested in the laboratory using both surrogate and the actual sludge. The sensitivity testing of a surrogate tank sludge in selected glass and grout formulations is discussed in this paper, along with the hot-cell testing of an actual tank sludge sample

The relationships of markers of cholesterol homeostasis with carotid intima-media thickness.

Directory of Open Access Journals (Sweden)

Oliver Weingärtner

Full Text Available BACKGROUND: The relationship of cholesterol homeostasis and carotid intima-media thickness (cIMT is unknown. To address this, we assessed markers of cholesterol homeostasis (serum plant sterols and cholesterol precursor concentrations as surrogate measures of cholesterol absorption and synthesis, respectively and cIMT in a middle-aged, statin-naive population. METHODS: In this prospective study of primary prevention cIMT was measured by ultrasound in 583 hospital employees aged 25-60 years without prevalent cardiovascular disease or lipid-modifying medication. The serum concentrations of plant sterols (as markers of cholesterol absorption were measured by gas-liquid chromatography. Lathosterol serum concentrations were quantitated to assess hepatic cholesterol synthesis. RESULTS: cIMT correlated positively with serum cholesterol (r = 0.22, P<0.0005 and lathosterol-to-cholesterol (r = 0.18, P<0.001. In contrast, plant sterols, as markers of cholesterol absorption, showed a weak negative correlation to cIMT measurements (r = -0.18; P<0.001 for campesterol-to-cholesterol. Stratifying subjects by serum sterol levels, we found that cIMT increased continuously over quintiles of serum cholesterol (P<0.0005 and was positively associated to serum lathosterol-to-cholesterol levels (P = 0.007, on the other hand, plant sterol levels showed a weak negative association to cIMT (P<0.001 for campesterol-to-cholesterol. CONCLUSIONS: In this population without prevalent cardiovascular diseases or lipid-modifying medication, markers of increased endogenous cholesterol synthesis correlated positively with cIMT, while markers of cholesterol absorption showed a weakly negative correlation. These data suggest that not only total serum cholesterol levels but also differences in cholesterol homeostasis are associated with cIMT.

A novel method for monitoring high-risk breast cancer with tumor markers

DEFF Research Database (Denmark)

Sölétormos, G; Nielsen, D; Schiøler, V

1993-01-01

cancer. METHODS: Ninety females with high-risk breast cancer were included in the study. Response evaluation was based upon clinical examination, x-rays or histology and elaborated marker criteria. RESULTS: During the marker monitoring period, metastases in four patients were confined to skin or lymph......BACKGROUND: An early and reliable diagnosis of metastatic spread has increased interest in serum tumor markers. This study investigated the ability of CA 15.3, CEA, and TPA to identify, predict, and exclude metastases in bone/viscera during adjuvant treatment and follow-up of high-risk breast...

Evaluating β Diversity as a Surrogate for Species Representation at Fine Scale.

Directory of Open Access Journals (Sweden)

Paul Beier

Full Text Available Species turnover or β diversity is a conceptually attractive surrogate for conservation planning. However, there has been only 1 attempt to determine how well sites selected to maximize β diversity represent species, and that test was done at a scale too coarse (2,500 km2 sites to inform most conservation decisions. We used 8 plant datasets, 3 bird datasets, and 1 mammal dataset to evaluate whether sites selected to span β diversity will efficiently represent species at finer scale (sites sizes < 1 ha to 625 km2. We used ordinations to characterize dissimilarity in species assemblages (β diversity among plots (inventory data or among grid cells (atlas data. We then selected sites to maximize β diversity and used the Species Accumulation Index, SAI, to evaluate how efficiently the surrogate (selecting sites for maximum β diversity represented species in the same taxon. Across all 12 datasets, sites selected for maximum β diversity represented species with a median efficiency of 24% (i.e., the surrogate was 24% more effective than random selection of sites, and an interquartile range of 4% to 41% efficiency. β diversity was a better surrogate for bird datasets than for plant datasets, and for atlas datasets with 10-km to 14-km grid cells than for atlas datasets with 25-km grid cells. We conclude that β diversity is more than a mere descriptor of how species are distributed on the landscape; in particular β diversity might be useful to maximize the complementarity of a set of sites. Because we tested only within-taxon surrogacy, our results do not prove that β diversity is useful for conservation planning. But our results do justify further investigation to identify the circumstances in which β diversity performs well, and to evaluate it as a cross-taxon surrogate.

Induction of lactation in the intended mother of a surrogate pregnancy: case report.

Science.gov (United States)

Biervliet, F P; Maguiness, S D; Hay, D M; Killick, S R; Atkin, S L

2001-03-01

A case of a successful induction of lactation in a commissioning mother of a surrogate pregnancy is reported. Induction of lactation was achieved with oral metoclopramide which was well tolerated. Alternative methods to induce lactation are reviewed. The advantages of breast-feeding and the relative ease with which lactation can be induced after a surrogate pregnancy would suggest that this could be offered to all commissioning mothers.

Reliabilities of genomic estimated breeding values in Danish Jersey

DEFF Research Database (Denmark)

Thomasen, Jørn Rind; Guldbrandtsen, Bernt; Su, Guosheng

2012-01-01

In order to optimize the use of genomic selection in breeding plans, it is essential to have reliable estimates of the genomic breeding values. This study investigated reliabilities of direct genomic values (DGVs) in the Jersey population estimated by three different methods. The validation methods...... were (i) fivefold cross-validation and (ii) validation on the most recent 3 years of bulls. The reliability of DGV was assessed using squared correlations between DGV and deregressed proofs (DRPs). In the recent 3-year validation model, estimated reliabilities were also used to assess the reliabilities...... of DGV. The data set consisted of 1003 Danish Jersey bulls with conventional estimated breeding values (EBVs) for 14 different traits included in the Nordic selection index. The bulls were genotyped for Single-nucleotide polymorphism (SNP) markers using the Illumina 54 K chip. A Bayesian method was used...

Prostate position relative to pelvic bony anatomy based on intraprostatic gold markers and electronic portal imaging

International Nuclear Information System (INIS)

Schallenkamp, John M.; Herman, Michael G.; Kruse, Jon J.; Pisansky, Thomas M.

2005-01-01

Purpose: To describe the relative positions and motions of the prostate, pelvic bony anatomy, and intraprostatic gold fiducial markers during daily electronic portal localization of the prostate. Methods and Materials: Twenty prostate cancer patients were treated supine with definitive external radiotherapy according to an on-line target localization protocol using three or four intraprostatic gold fiducial markers and an electronic portal imaging device. Daily pretherapy and through-treatment electronic portal images (EPIs) were obtained for each of four treatment fields. The patients' pelvic bony anatomy, intraprostatic gold markers, and a best visual match to the target (i.e., prostate) were identified on simulation digitally reconstructed radiographs and during daily treatment setup and delivery. These data provided quantitative inter- and intrafractional analysis of prostate motion, its position relative to the bony anatomy, and the individual intraprostatic fiducial markers. Treatment planning margins, with and without on-line localization, were subsequently compared. Results: A total of 22,266 data points were obtained from daily pretherapy and through-treatment EPIs. The pretherapy three-dimensional (3D) average displacement of the fiducial markers, as a surrogate for the prostate, was 5.6 mm, which improved to 2.8 mm after use of the localization protocol. The bony anatomy 3D average displacement was 4.4 mm both before and after localization to the prostate (p = 0.46). Along the superior-inferior (SI), anterior-posterior (AP), and right-left (RL) axes, the average prostate displacement improved from 2.5, 3.7, and 1.9 mm, respectively, before localization to 1.4, 1.6, and 1.1 mm after (all p < 0.001). The pretherapy to through-treatment position of the bony landmarks worsened from 1.7 to 2.5 mm (p < 0.001) in the SI axis, remained statistically unchanged at 2.8 mm (p = 0.39) in the AP axis, and improved from 2.0 to 1.2 mm in the RL axis (p < 0.001). There

Embedding filtering criteria into a wrapper marker selection method for brain tumor classification: an application on metabolic peak area ratios

International Nuclear Information System (INIS)

Kounelakis, M G; Zervakis, M E; Giakos, G C; Postma, G J; Buydens, L M C; Kotsiakis, X

2011-01-01

The purpose of this study is to identify reliable sets of metabolic markers that provide accurate classification of complex brain tumors and facilitate the process of clinical diagnosis. Several ratios of metabolites are tested alone or in combination with imaging markers. A wrapper feature selection and classification methodology is studied, employing Fisher's criterion for ranking the markers. The set of extracted markers that express statistical significance is further studied in terms of biological behavior with respect to the brain tumor type and grade. The outcome of this study indicates that the proposed method by exploiting the intrinsic properties of data can actually reveal reliable and biologically relevant sets of metabolic markers, which form an important adjunct toward a more accurate type and grade discrimination of complex brain tumors

The Proposed Use of Unmanned Aerial System Surrogate Research Aircraft for National Airspace System Integration Research

Science.gov (United States)

Howell, Charles T., III

2011-01-01

Research is needed to determine what procedures, aircraft sensors and other systems will be required to allow Unmanned Aerial Systems (UAS) to safely operate with manned aircraft in the National Airspace System (NAS). This paper explores the use of Unmanned Aerial System (UAS) Surrogate research aircraft to serve as platforms for UAS systems research, development, and flight testing. These aircraft would be manned with safety pilots and researchers that would allow for flight operations almost anywhere in the NAS without the need for a Federal Aviation Administration (FAA) Certificate of Authorization (COA). With pilot override capability, these UAS Surrogate aircraft would be controlled from ground stations like true UAS s. It would be possible to file and fly these UAS Surrogate aircraft in the NAS with normal traffic and they would be better platforms for real world UAS research and development over existing vehicles flying in restricted ranges or other sterilized airspace. These UAS surrogate aircraft could be outfitted with research systems as required such as computers, state sensors, video recording, data acquisition, data link, telemetry, instrumentation, and Automatic Dependent Surveillance-Broadcast (ADS-B). These surrogate aircraft could also be linked to onboard or ground based simulation facilities to further extend UAS research capabilities. Potential areas for UAS Surrogate research include the development, flight test and evaluation of sensors to aide in the process of air traffic "see-and-avoid". These and other sensors could be evaluated in real-time and compared with onboard human evaluation pilots. This paper examines the feasibility of using UAS Surrogate research aircraft as test platforms for a variety of UAS related research.

SU-C-BRF-07: A Pattern Fusion Algorithm for Multi-Step Ahead Prediction of Surrogate Motion

International Nuclear Information System (INIS)

Zawisza, I; Yan, H; Yin, F

2014-01-01

Purpose: To assure that tumor motion is within the radiation field during high-dose and high-precision radiosurgery, real-time imaging and surrogate monitoring are employed. These methods are useful in providing real-time tumor/surrogate motion but no future information is available. In order to anticipate future tumor/surrogate motion and track target location precisely, an algorithm is developed and investigated for estimating surrogate motion multiple-steps ahead. Methods: The study utilized a one-dimensional surrogate motion signal divided into three components: (a) training component containing the primary data including the first frame to the beginning of the input subsequence; (b) input subsequence component of the surrogate signal used as input to the prediction algorithm: (c) output subsequence component is the remaining signal used as the known output of the prediction algorithm for validation. The prediction algorithm consists of three major steps: (1) extracting subsequences from training component which best-match the input subsequence according to given criterion; (2) calculating weighting factors from these best-matched subsequence; (3) collecting the proceeding parts of the subsequences and combining them together with assigned weighting factors to form output. The prediction algorithm was examined for several patients, and its performance is assessed based on the correlation between prediction and known output. Results: Respiratory motion data was collected for 20 patients using the RPM system. The output subsequence is the last 50 samples (∼2 seconds) of a surrogate signal, and the input subsequence was 100 (∼3 seconds) frames prior to the output subsequence. Based on the analysis of correlation coefficient between predicted and known output subsequence, the average correlation is 0.9644±0.0394 and 0.9789±0.0239 for equal-weighting and relative-weighting strategies, respectively. Conclusion: Preliminary results indicate that the prediction

Integrating surrogate models into subsurface simulation framework allows computation of complex reactive transport scenarios

Science.gov (United States)

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

2017-04-01

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

Dynamic impact indentation of hydrated biological tissues and tissue surrogate gels

Science.gov (United States)

Ilke Kalcioglu, Z.; Qu, Meng; Strawhecker, Kenneth E.; Shazly, Tarek; Edelman, Elazer; VanLandingham, Mark R.; Smith, James F.; Van Vliet, Krystyn J.

2011-03-01

For both materials engineering research and applied biomedicine, a growing need exists to quantify mechanical behaviour of tissues under defined hydration and loading conditions. In particular, characterisation under dynamic contact-loading conditions can enable quantitative predictions of deformation due to high rate 'impact' events typical of industrial accidents and ballistic insults. The impact indentation responses were examined of both hydrated tissues and candidate tissue surrogate materials. The goals of this work were to determine the mechanical response of fully hydrated soft tissues under defined dynamic loading conditions, and to identify design principles by which synthetic, air-stable polymers could mimic those responses. Soft tissues from two organs (liver and heart), a commercially available tissue surrogate gel (Perma-Gel™) and three styrenic block copolymer gels were investigated. Impact indentation enabled quantification of resistance to penetration and energy dissipative constants under the rates and energy densities of interest for tissue surrogate applications. These analyses indicated that the energy dissipation capacity under dynamic impact increased with increasing diblock concentration in the styrenic gels. Under the impact rates employed (2 mm/s to 20 mm/s, corresponding to approximate strain energy densities from 0.4 kJ/m3 to 20 kJ/m3), the energy dissipation capacities of fully hydrated soft tissues were ultimately well matched by a 50/50 triblock/diblock composition that is stable in ambient environments. More generally, the methodologies detailed here facilitate further optimisation of impact energy dissipation capacity of polymer-based tissue surrogate materials, either in air or in fluids.

Combining endangered plants and animals as surrogates to identify priority conservation areas in Yunnan, China

Science.gov (United States)

Yang, Feiling; Hu, Jinming; Wu, Ruidong

2016-08-01

Suitable surrogates are critical for identifying optimal priority conservation areas (PCAs) to protect regional biodiversity. This study explored the efficiency of using endangered plants and animals as surrogates for identifying PCAs at the county level in Yunnan, southwest China. We ran the Dobson algorithm under three surrogate scenarios at 75% and 100% conservation levels and identified four types of PCAs. Assessment of the protection efficiencies of the four types of PCAs showed that endangered plants had higher surrogacy values than endangered animals but that the two were not substitutable; coupled endangered plants and animals as surrogates yielded a higher surrogacy value than endangered plants or animals as surrogates; the plant-animal priority areas (PAPAs) was the optimal among the four types of PCAs for conserving both endangered plants and animals in Yunnan. PAPAs could well represent overall species diversity distribution patterns and overlap with critical biogeographical regions in Yunnan. Fourteen priority units in PAPAs should be urgently considered as optimizing Yunnan’s protected area system. The spatial pattern of PAPAs at the 100% conservation level could be conceptualized into three connected conservation belts, providing a valuable reference for optimizing the layout of the in situ protected area system in Yunnan.

Study on de novo collagen biosynthesis and degradation markers of bone

International Nuclear Information System (INIS)

Hanna, L.S.; Matta, T.F.; Ibrahim, I.; Meky, N.H.

2003-01-01

This investigation was carried out to study the performance of de novo biochemical markers of serum pro collagen type-1 amino terminal extension (PINP), as a marker of collagen biosynthesis, and urinary collagen crosslink free deoxypyridinoline (DPD) as a marker of collagen degradation. Moreover, urinary calcium C Ca) and inorganic phosphorus (P), as markers of bone demineralization, in addition to urinary creatinine (Cr), to reflect status of renal function, were also studied in order to assess the activity of bone turnover in osteoporotic (OST), postmenopausal (POST), peri menopausal(PERI), premenopausal (PRE) women and also in young adult (YON) ones. The obtained results showed that urinary creatinine levels were within the normal ranges in all women even in the elderly osteoporotic and postmenopausal women. Serum PINP did not reflect osteoblastic activity. Urinary DPD proved to be a good marker in monitoring the postmenopausal bone resorption and urinary Ca was a reliable marker for bone loss in osteoporosis and bone turnover in the postmenopausal status

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

Science.gov (United States)

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

2004-07-01

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

Pregnancy after breast cancer: a case study resolving the reproductive challenge with a gestational surrogate.

Science.gov (United States)

Krychman, Michael L; King, Tari

2006-01-01

Pregnancy and fertility issues are substantial concerns for the young breast cancer survivor, yet the available literature is hampered by a lack of prospective clinical studies and meaningful long-term outcome data. A lack of reliable information often leads to physician discomfort and patients may be left to navigate the world of fertility preservation and reproductive technology on their own. This case exemplifies some of the many issues that breast cancer survivors may face and adds another dimension to the survivor's dilemma; once fertility options have been preserved, what is the best method to sustain the pregnancy--self or surrogate? For many, the goal of balancing optimal treatment and long-term survival with restoration of a complete quality of life, including childbearing, may be attainable. This discussion highlights the importance of offering young breast cancer patients an opportunity to discuss these issues with their health care providers prior to initiating therapy.

Adaptive surrogate modeling for response surface approximations with application to bayesian inference

KAUST Repository

Prudhomme, Serge; Bryant, Corey M.

2015-01-01

Parameter estimation for complex models using Bayesian inference is usually a very costly process as it requires a large number of solves of the forward problem. We show here how the construction of adaptive surrogate models using a posteriori error estimates for quantities of interest can significantly reduce the computational cost in problems of statistical inference. As surrogate models provide only approximations of the true solutions of the forward problem, it is nevertheless necessary to control these errors in order to construct an accurate reduced model with respect to the observables utilized in the identification of the model parameters. Effectiveness of the proposed approach is demonstrated on a numerical example dealing with the Spalart–Allmaras model for the simulation of turbulent channel flows. In particular, we illustrate how Bayesian model selection using the adapted surrogate model in place of solving the coupled nonlinear equations leads to the same quality of results while requiring fewer nonlinear PDE solves.

Adaptive surrogate modeling for response surface approximations with application to bayesian inference

KAUST Repository

Prudhomme, Serge

2015-09-17

Parameter estimation for complex models using Bayesian inference is usually a very costly process as it requires a large number of solves of the forward problem. We show here how the construction of adaptive surrogate models using a posteriori error estimates for quantities of interest can significantly reduce the computational cost in problems of statistical inference. As surrogate models provide only approximations of the true solutions of the forward problem, it is nevertheless necessary to control these errors in order to construct an accurate reduced model with respect to the observables utilized in the identification of the model parameters. Effectiveness of the proposed approach is demonstrated on a numerical example dealing with the Spalart–Allmaras model for the simulation of turbulent channel flows. In particular, we illustrate how Bayesian model selection using the adapted surrogate model in place of solving the coupled nonlinear equations leads to the same quality of results while requiring fewer nonlinear PDE solves.

Dosimetric impact of gold markers implanted closely to lung tumors: a Monte Carlo simulation.

Science.gov (United States)

Shiinoki, Takehiro; Sawada, Akira; Ishihara, Yoshitomo; Miyabe, Yuki; Matsuo, Yukinori; Mizowaki, Takashi; Kokubo, Masaki; Hiraoka, Masahiro

2014-05-08

We are developing an innovative dynamic tumor tracking irradiation technique using gold markers implanted around a tumor as a surrogate signal, a real-time marker detection system, and a gimbaled X-ray head in the Vero4DRT. The gold markers implanted in a normal organ will produce uncertainty in the dose calculation during treatment planning because the photon mass attenuation coefficient of a gold marker is much larger than that of normal tissue. The purpose of this study was to simulate the dose variation near the gold markers in a lung irradiated by a photon beam using the Monte Carlo method. First, the single-beam and the opposing-beam geometries were simulated using both water and lung phantoms. Subsequently, the relative dose profiles were calculated using a stereotactic body radiotherapy (SBRT) treatment plan for a lung cancer patient having gold markers along the anterior-posterior (AP) and right-left (RL) directions. For the single beam, the dose at the gold marker-phantom interface laterally along the perpendicular to the beam axis increased by a factor of 1.35 in the water phantom and 1.58 in the lung phantom, respectively. Furthermore, the entrance dose at the interface along the beam axis increased by a factor of 1.63 in the water phantom and 1.91 in the lung phantom, while the exit dose increased by a factor of 1.00 in the water phantom and 1.12 in the lung phantom, respectively. On the other hand, both dose escalations and dose de-escalations were canceled by each beam for opposing portal beams with the same beam weight. For SBRT patient data, the dose at the gold marker edge located in the tumor increased by a factor of 1.30 in both AP and RL directions. In clinical cases, dose escalations were observed at the small area where the distance between a gold marker and the lung tumor was ≤ 5 mm, and it would be clinically negligible in multibeam treatments, although further investigation may be required.

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

KAUST Repository

Elwardani, Ahmed Elsaid; Sazhin, S.S.; Im, Hong G.

2016-01-01

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

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

KAUST Repository

Elwardani, Ahmed Elsaid

2016-02-19

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

Cryptochrome-1 expression: a new prognostic marker in B-cell chronic lymphocytic leukemia.

Science.gov (United States)

Lewintre, Eloisa Jantus; Martín, Cristina Reinoso; Ballesteros, Carlos García; Montaner, David; Rivera, Rosa Farrás; Mayans, José Ramón; García-Conde, Javier

2009-02-01

Chronic lymphocytic leukemia is an adult-onset leukemia with a heterogeneous clinical behavior. When chronic lymphocytic leukemia cases were divided on the basis of IgV(H) mutational status, widely differing clinical courses were revealed. Since IgV(H) sequencing is difficult to perform in a routine diagnostic laboratory, finding a surrogate for IgV(H) mutational status seems an important priority. In the present study, we proposed the use of Cryptochrome-1 as a new prognostic marker in early-stage chronic lymphocytic leukemia. Seventy patients (Binet stage A, without treatment) were included in the study. We correlated Cryptochrome-1 mRNA with well established prognostic markers such as IgV(H) mutations, ZAP70, LPL or CD38 expression and chromosomal abnormalities. High Cryptochrome-1 expression correlated with IgV(H) unmutated samples. In addition, Cryptochrome-1 was a valuable predictor of disease progression in early-stage chronic lymphocytic leukemia, therefore it can be introduced in clinical practice with the advantage of a simplified method of quantification.

Experimental gingivitis induces systemic inflammatory markers in young healthy individuals: a single-subject interventional study.

Science.gov (United States)

Eberhard, Jörg; Grote, Karsten; Luchtefeld, Maren; Heuer, Wieland; Schuett, Harald; Divchev, Dimitar; Scherer, Ralph; Schmitz-Streit, Ruth; Langfeldt, Daniela; Stumpp, Nico; Staufenbiel, Ingmar; Schieffer, Bernhard; Stiesch, Meike

2013-01-01

We here investigated whether experimental gingivitis enhances systemic markers of inflammation which are also known as surrogate markers of atherosclerotic plaque development. Gingivitis is a low-level oral infection induced by bacterial deposits with a high prevalence within Western populations. A potential link between the more severe oral disease periodontitis and cardiovascular disease has already been shown. 37 non-smoking young volunteers with no inflammatory disease or any cardiovascular risk factors participated in this single-subject interventional study with an intra-individual control. Intentionally experimental oral inflammation was induced by the interruption of oral hygiene for 21 days, followed by a 21-days resolving phase after reinitiation of oral hygiene. Primary outcome measures at baseline, day 21 and 42 were concentrations of hsCRP, IL-6, and MCP-1, as well as adhesion capacity and oxLDL uptake of isolated blood monocytes. The partial cessation of oral hygiene procedures was followed by the significant increase of gingival bleeding (34.0%, Pgingivitis. Bacterial-induced gingival low-level inflammation induced a systemic increase in inflammatory markers. Dental hygiene almost completely reversed this experimental inflammatory process, suggesting that appropriate dental prophylaxis may also limit systemic markers of inflammation in subjects with natural gingivitis. International Clinical Trials Register Platform of the World Health Organization, registry number: DRKS00003366, URL: http://apps.who.int/trialsearch/Default.aspx.

Mapping surrogate gasoline compositions into RON/MON space

NARCIS (Netherlands)

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

2010-01-01

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

Phenotypic and functional markers for 1alpha,25-dihydroxyvitamin D(3)-modified regulatory dendritic cells

DEFF Research Database (Denmark)

Pedersen, A W; Holmstrøm, K; Jensen, S S

2009-01-01

The clinical use of dendritic cells (DCs) to induce antigen-specific immune tolerance has been hampered by the lack of a widely acknowledged method for generating human regulatory DCs but even more so by the non-existence of reliable markers. Thus, we set out to find reliable markers that can...... CD14 and reduced CD1a on the cell surface. These VD3-treated DCs exert a long-lasting inefficient T cell stimulation and induce T cell hyporesponsiveness with regulatory potential. Importantly, such VD3-treated DCs were readily distinguishable from untreated DCs by low levels of interleukin-23...

A new set of mulberry-specific SSR markers for application in ...

Indian Academy of Sciences (India)

Marian Vincent Pinto

have used these markers to characterize a set of 216 diverse mulberry germplasm and ..... tinctness of a new cultivar or for reliable, cost-effective and quick germplasm ... Morus boninensis Koidz., to establish conservation program. Mol. Ecol.

Real-time tumor motion estimation using respiratory surrogate via memory-based learning

International Nuclear Information System (INIS)

Li Ruijiang; Xing Lei; Lewis, John H; Berbeco, Ross I

2012-01-01

Respiratory tumor motion is a major challenge in radiation therapy for thoracic and abdominal cancers. Effective motion management requires an accurate knowledge of the real-time tumor motion. External respiration monitoring devices (optical, etc) provide a noninvasive, non-ionizing, low-cost and practical approach to obtain the respiratory signal. Due to the highly complex and nonlinear relations between tumor and surrogate motion, its ultimate success hinges on the ability to accurately infer the tumor motion from respiratory surrogates. Given their widespread use in the clinic, such a method is critically needed. We propose to use a powerful memory-based learning method to find the complex relations between tumor motion and respiratory surrogates. The method first stores the training data in memory and then finds relevant data to answer a particular query. Nearby data points are assigned high relevance (or weights) and conversely distant data are assigned low relevance. By fitting relatively simple models to local patches instead of fitting one single global model, it is able to capture highly nonlinear and complex relations between the internal tumor motion and external surrogates accurately. Due to the local nature of weighting functions, the method is inherently robust to outliers in the training data. Moreover, both training and adapting to new data are performed almost instantaneously with memory-based learning, making it suitable for dynamically following variable internal/external relations. We evaluated the method using respiratory motion data from 11 patients. The data set consists of simultaneous measurement of 3D tumor motion and 1D abdominal surface (used as the surrogate signal in this study). There are a total of 171 respiratory traces, with an average peak-to-peak amplitude of ∼15 mm and average duration of ∼115 s per trace. Given only 5 s (roughly one breath) pretreatment training data, the method achieved an average 3D error of 1.5 mm and 95

Real-time tumor motion estimation using respiratory surrogate via memory-based learning

Science.gov (United States)

Li, Ruijiang; Lewis, John H.; Berbeco, Ross I.; Xing, Lei

2012-08-01

Respiratory tumor motion is a major challenge in radiation therapy for thoracic and abdominal cancers. Effective motion management requires an accurate knowledge of the real-time tumor motion. External respiration monitoring devices (optical, etc) provide a noninvasive, non-ionizing, low-cost and practical approach to obtain the respiratory signal. Due to the highly complex and nonlinear relations between tumor and surrogate motion, its ultimate success hinges on the ability to accurately infer the tumor motion from respiratory surrogates. Given their widespread use in the clinic, such a method is critically needed. We propose to use a powerful memory-based learning method to find the complex relations between tumor motion and respiratory surrogates. The method first stores the training data in memory and then finds relevant data to answer a particular query. Nearby data points are assigned high relevance (or weights) and conversely distant data are assigned low relevance. By fitting relatively simple models to local patches instead of fitting one single global model, it is able to capture highly nonlinear and complex relations between the internal tumor motion and external surrogates accurately. Due to the local nature of weighting functions, the method is inherently robust to outliers in the training data. Moreover, both training and adapting to new data are performed almost instantaneously with memory-based learning, making it suitable for dynamically following variable internal/external relations. We evaluated the method using respiratory motion data from 11 patients. The data set consists of simultaneous measurement of 3D tumor motion and 1D abdominal surface (used as the surrogate signal in this study). There are a total of 171 respiratory traces, with an average peak-to-peak amplitude of ∼15 mm and average duration of ∼115 s per trace. Given only 5 s (roughly one breath) pretreatment training data, the method achieved an average 3D error of 1.5 mm and 95

Multivariate analysis for the estimation of target localization errors in fiducial marker-based radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Takamiya, Masanori [Department of Nuclear Engineering, Graduate School of Engineering, Kyoto University, Kyoto 606-8501, Japan and Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Nakamura, Mitsuhiro, E-mail: m-nkmr@kuhp.kyoto-u.ac.jp; Akimoto, Mami; Ueki, Nami; Yamada, Masahiro; Matsuo, Yukinori; Mizowaki, Takashi; Hiraoka, Masahiro [Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Tanabe, Hiroaki [Division of Radiation Oncology, Institute of Biomedical Research and Innovation, Kobe 650-0047 (Japan); Kokubo, Masaki [Division of Radiation Oncology, Institute of Biomedical Research and Innovation, Kobe 650-0047, Japan and Department of Radiation Oncology, Kobe City Medical Center General Hospital, Kobe 650-0047 (Japan); Itoh, Akio [Department of Nuclear Engineering, Graduate School of Engineering, Kyoto University, Kyoto 606-8501 (Japan)

2016-04-15

Purpose: To assess the target localization error (TLE) in terms of the distance between the target and the localization point estimated from the surrogates (|TMD|), the average of respiratory motion for the surrogates and the target (|aRM|), and the number of fiducial markers used for estimating the target (n). Methods: This study enrolled 17 lung cancer patients who subsequently underwent four fractions of real-time tumor tracking irradiation. Four or five fiducial markers were implanted around the lung tumor. The three-dimensional (3D) distance between the tumor and markers was at maximum 58.7 mm. One of the markers was used as the target (P{sub t}), and those markers with a 3D |TMD{sub n}| ≤ 58.7 mm at end-exhalation were then selected. The estimated target position (P{sub e}) was calculated from a localization point consisting of one to three markers except P{sub t}. Respiratory motion for P{sub t} and P{sub e} was defined as the root mean square of each displacement, and |aRM| was calculated from the mean value. TLE was defined as the root mean square of each difference between P{sub t} and P{sub e} during the monitoring of each fraction. These procedures were performed repeatedly using the remaining markers. To provide the best guidance on the answer with n and |TMD|, fiducial markers with a 3D |aRM ≥ 10 mm were selected. Finally, a total of 205, 282, and 76 TLEs that fulfilled the 3D |TMD| and 3D |aRM| criteria were obtained for n = 1, 2, and 3, respectively. Multiple regression analysis (MRA) was used to evaluate TLE as a function of |TMD| and |aRM| in each n. Results: |TMD| for n = 1 was larger than that for n = 3. Moreover, |aRM| was almost constant for all n, indicating a similar scale for the marker’s motion near the lung tumor. MRA showed that |aRM| in the left–right direction was the major cause of TLE; however, the contribution made little difference to the 3D TLE because of the small amount of motion in the left–right direction. The TLE

Enhancing product robustness in reliability-based design optimization

International Nuclear Information System (INIS)

Zhuang, Xiaotian; Pan, Rong; Du, Xiaoping

2015-01-01

Different types of uncertainties need to be addressed in a product design optimization process. In this paper, the uncertainties in both product design variables and environmental noise variables are considered. The reliability-based design optimization (RBDO) is integrated with robust product design (RPD) to concurrently reduce the production cost and the long-term operation cost, including quality loss, in the process of product design. This problem leads to a multi-objective optimization with probabilistic constraints. In addition, the model uncertainties associated with a surrogate model that is derived from numerical computation methods, such as finite element analysis, is addressed. A hierarchical experimental design approach, augmented by a sequential sampling strategy, is proposed to construct the response surface of product performance function for finding optimal design solutions. The proposed method is demonstrated through an engineering example. - Highlights: • A unifying framework for integrating RBDO and RPD is proposed. • Implicit product performance function is considered. • The design problem is solved by sequential optimization and reliability assessment. • A sequential sampling technique is developed for improving design optimization. • The comparison with traditional RBDO is provided

Cancer stem cell markers in common cancers - therapeutic implications

DEFF Research Database (Denmark)

Klonisch, Thomas; Wiechec, Emilia; Hombach-Klonisch, Sabine

2008-01-01

Rapid advance in the cancer stem cell field warrants optimism for the development of more reliable cancer therapies within the next 2-3 decades. Below, we characterize and compare the specific markers that are present on stem cells, cancer cells and cancer stem cells (CSC) in selected tissues...

Surrogate mothers 10 years on: a longitudinal study of psychological well-being and relationships with the parents and child.

Science.gov (United States)

Jadva, V; Imrie, S; Golombok, S

2015-02-01

How do the psychological health and experiences of surrogate mothers change from 1 year to 10 years following the birth of the surrogacy child? The psychological well-being of surrogate mothers did not change 10 years following the birth, with all remaining positive about the surrogacy arrangement and the majority continuing to report good mental health. Studies have found that surrogates may find the weeks following the birth difficult, but do not experience psychological problems 6 months or 1 year later. Research has also shown that surrogates can form close relationships with the intended parents during the pregnancy which may continue after the birth. This study used a prospective longitudinal design, in which 20 surrogates were seen at two time points: 1 year following the birth of the surrogacy child and 10 years later. The 20 surrogates (representing 59% of the original sample) participated in a semi-structured interview and completed self-report questionnaires. Eleven surrogates were gestational carriers and nine surrogates had used their own oocyte (genetic surrogacy). Four were previously known to the intended parents and 16 were previously not known. Ten years following the birth of the surrogacy child, surrogate mothers scored within the normal range for self-esteem and did not show signs of depression as measured by the Beck Depression Inventory. Marital quality remained positive over time. All surrogates reported that their expectations of their relationship with the intended parents had been either met or exceeded and most reported positive feelings towards the child. In terms of expectations for the future, most surrogates reported that they would like to maintain contact or would be available to the child if the child wished to contact them. None expressed regrets about their involvement in surrogacy. The sample size of this study was small and the women may not be representative of all surrogates. Therefore the extent to which these findings can

Fog Density Estimation and Image Defogging Based on Surrogate Modeling for Optical Depth.

Science.gov (United States)

Jiang, Yutong; Sun, Changming; Zhao, Yu; Yang, Li

2017-05-03

In order to estimate fog density correctly and to remove fog from foggy images appropriately, a surrogate model for optical depth is presented in this paper. We comprehensively investigate various fog-relevant features and propose a novel feature based on the hue, saturation, and value color space which correlate well with the perception of fog density. We use a surrogate-based method to learn a refined polynomial regression model for optical depth with informative fog-relevant features such as dark-channel, saturation-value, and chroma which are selected on the basis of sensitivity analysis. Based on the obtained accurate surrogate model for optical depth, an effective method for fog density estimation and image defogging is proposed. The effectiveness of our proposed method is verified quantitatively and qualitatively by the experimental results on both synthetic and real-world foggy images.

Developing the role of the social worker as coordinator of services at the surrogate parenting center.

Science.gov (United States)

Gagin, Roni; Cohen, Miri; Greenblatt, Lee; Solomon, Hanah; Itskovitz-Eldor, Joseph

2004-01-01

A law permitting couples to conceive biological children through surrogacy was legislated in Israel in March 1996. The Rambam Medical Center has established the only nonprofit Surrogate Parenting Center at a public hospital in Israel. The multidisciplinary teamwork at the Center is case managed by a social worker. An important role of the social work intervention is consultation and support for the couple and the surrogate at all stages of the process. The case study presented in the article illustrates the need for sensitive and professional intervention due to the complexity of the surrogacy process and the crisis it involves for both the surrogate and the couple. In light of the growing parenting surrogacy cases in the United States, Europe, and Israel, a structured social work intervention model is described, which may be implemented at public or private surrogate parenting centers.

The Pareidolia Test: A Simple Neuropsychological Test Measuring Visual Hallucination-Like Illusions

OpenAIRE

Mamiya, Yasuyuki; Nishio, Yoshiyuki; Watanabe, Hiroyuki; Yokoi, Kayoko; Uchiyama, Makoto; Baba, Toru; Iizuka, Osamu; Kanno, Shigenori; Kamimura, Naoto; Kazui, Hiroaki; Hashimoto, Mamoru; Ikeda, Manabu; Takeshita, Chieko; Shimomura, Tatsuo; Mori, Etsuro

2016-01-01

Background Visual hallucinations are a core clinical feature of dementia with Lewy bodies (DLB), and this symptom is important in the differential diagnosis and prediction of treatment response. The pareidolia test is a tool that evokes visual hallucination-like illusions, and these illusions may be a surrogate marker of visual hallucinations in DLB. We created a simplified version of the pareidolia test and examined its validity and reliability to establish the clinical utility of this test....

Predicting freshwater habitat integrity using land-use surrogates

African Journals Online (AJOL)

2007-04-02

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

SURROGATE SPECIES IN ASSESSING CONTAMINANT RISK FOR ENDANGERED FISHES

Science.gov (United States)

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

Triazole-linked DNA as a primer surrogate in the synthesis of first-strand cDNA.

Science.gov (United States)

Fujino, Tomoko; Yasumoto, Ken-ichi; Yamazaki, Naomi; Hasome, Ai; Sogawa, Kazuhiro; Isobe, Hiroyuki

2011-11-04

A phosphate-eliminated nonnatural oligonucleotide serves as a primer surrogate in reverse transcription reaction of mRNA. Despite of the nonnatural triazole linkages in the surrogate, the reverse transcriptase effectively elongated cDNA sequences on the 3'-downstream of the primer by transcription of the complementary sequence of mRNA. A structure-activity comparison with the reference natural oligonucleotides shows the superior priming activity of the surrogate containing triazole-linkages. The nonnatural linkages also protect the transcribed cDNA from digestion reactions with 5'-exonuclease and enable us to remove noise transcripts of unknown origins. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Intraprostatic fiducials for localization of the prostate gland: Monitoring intermarker distances during radiation therapy to test for marker stability

International Nuclear Information System (INIS)

Kupelian, Patrick A.; Willoughby, Twyla R.; Meeks, Sanford L.; Forbes, Alan; Wagner, Thomas; Maach, Mourad; Langen, Katja M.

2005-01-01

Purpose: The use of intraprostatic fiducials as surrogates for prostate gland position assumes that the markers are rigidly positioned within the prostate. To test this assumption, the intermarker distances (IMD) of implanted markers was monitored during the full course of radiation therapy to determine marker stability within the prostate gland. Methods and Materials The analysis is performed on 56 patients treated with intensity-modulated radiotherapy. A total of 168 markers (3 markers per patient) were implanted. Two high-resolution X-rays were acquired before treatment delivery to visualize the position of the implanted markers. A total of 2,037 daily alignments were performed on the 56 cases (average: 36 alignments per patient). Each pair of X-ray images allows the computation of the 3 IMDs. A total of 6,111 IMDs were available for analysis. To study variations in marker position, daily IMDs were compared with the IMD that was observed during the first alignment. We defined the variation in the IMD as the important measure of intrinsic marker position variation. The standard deviation (SD) of IMD variations was studied as a measure of the extent of marker position variation. Particular attention was given to cases in which significant intermarker variations were observed. Results The average directional variation of all IMDs (± SD) was -0.31 (±1.41) mm. The average absolute variation of all IMDs (± SD) was 1.01 (±1.03) mm. The largest observed variation in IMD was 10.2 mm. Among the individual 56 patients, the SDs of the IMD variations were computed and found to range from 0.4 to 4.2 mm. In 54 of the 56 patients (96%), the variations of all 3 IMDs had SD of 4.0 mm or less, which indicates little variation in the relative position of the markers. Only in 2 patients did any of the IMDs vary, with SD that exceeded 4.0 mm, which indicated noticeable and consistent marker-position variation. The maximum observed SD in the IMD variation was 4.2 mm. In each of

Coastal aquifer management based on surrogate models and multi-objective optimization

Science.gov (United States)

Mantoglou, A.; Kourakos, G.

2011-12-01

The demand for fresh water in coastal areas and islands can be very high, especially in summer months, due to increased local needs and tourism. In order to satisfy demand, a combined management plan is proposed which involves: i) desalinization (if needed) of pumped water to a potable level using reverse osmosis and ii) injection of biologically treated waste water into the aquifer. The management plan is formulated into a multiobjective optimization framework, where simultaneous minimization of economic and environmental costs is desired; subject to a constraint to satisfy demand. The method requires modeling tools, which are able to predict the salinity levels of the aquifer in response to different alternative management scenarios. Variable density models can simulate the interaction between fresh and saltwater; however, they are computationally intractable when integrated in optimization algorithms. In order to alleviate this problem, a multi objective optimization algorithm is developed combining surrogate models based on Modular Neural Networks [MOSA(MNN)]. The surrogate models are trained adaptively during optimization based on a Genetic Algorithm. In the crossover step of the genetic algorithm, each pair of parents generates a pool of offspring. All offspring are evaluated based on the fast surrogate model. Then only the most promising offspring are evaluated based on the exact numerical model. This eliminates errors in Pareto solution due to imprecise predictions of the surrogate model. Three new criteria for selecting the most promising offspring were proposed, which improve the Pareto set and maintain the diversity of the optimum solutions. The method has important advancements compared to previous methods, e.g. alleviation of propagation of errors due to surrogate model approximations. The method is applied to a real coastal aquifer in the island of Santorini which is a very touristy island with high water demands. The results show that the algorithm

Using surrogate biomarkers to improve measurement error models in nutritional epidemiology

Science.gov (United States)

Keogh, Ruth H; White, Ian R; Rodwell, Sheila A

2013-01-01

Nutritional epidemiology relies largely on self-reported measures of dietary intake, errors in which give biased estimated diet–disease associations. Self-reported measurements come from questionnaires and food records. Unbiased biomarkers are scarce; however, surrogate biomarkers, which are correlated with intake but not unbiased, can also be useful. It is important to quantify and correct for the effects of measurement error on diet–disease associations. Challenges arise because there is no gold standard, and errors in self-reported measurements are correlated with true intake and each other. We describe an extended model for error in questionnaire, food record, and surrogate biomarker measurements. The focus is on estimating the degree of bias in estimated diet–disease associations due to measurement error. In particular, we propose using sensitivity analyses to assess the impact of changes in values of model parameters which are usually assumed fixed. The methods are motivated by and applied to measures of fruit and vegetable intake from questionnaires, 7-day diet diaries, and surrogate biomarker (plasma vitamin C) from over 25000 participants in the Norfolk cohort of the European Prospective Investigation into Cancer and Nutrition. Our results show that the estimated effects of error in self-reported measurements are highly sensitive to model assumptions, resulting in anything from a large attenuation to a small amplification in the diet–disease association. Commonly made assumptions could result in a large overcorrection for the effects of measurement error. Increased understanding of relationships between potential surrogate biomarkers and true dietary intake is essential for obtaining good estimates of the effects of measurement error in self-reported measurements on observed diet–disease associations. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23553407

Iran's experience with surrogate motherhood: an Islamic view and ethical concerns.

Science.gov (United States)

Aramesh, K

2009-05-01

Gestational surrogacy as a treatment for infertility is being practised in some well-known medical institutions in Tehran and some other cities in Iran. While the majority of Muslims in the world are Sunni, the majority of Iranians are Shiite. Most Sunni scholars do not permit surrogate motherhood, since it involves introducing the sperm of a man into the uterus of a woman to whom he is not married. Most Shiite scholars, however, have issued jurisprudential decrees (fatwas) that allow surrogate motherhood as a treatment for infertility, albeit only for legal couples. They regard this practice as transferring an embryo or fetus from one womb to another, which is not forbidden in Shiite jurisprudence. Nevertheless, there are some controversies concerning some issues such as kinship and inheritance. The main ethical concern of Iran's experience with gestational surrogacy is the monetary relation between the intended couple and the surrogate mother. While monetary remuneration is practised in Iran and allowed by religious authorities, it seems to suffer from ethical problems. This article proposes that this kind of monetary relation should be modified and limited to reimbursement of normal costs. Such modification requires new legislation and religious decrees.

A longitudinal pre-pregnancy to post-delivery comparison of genetic and gestational surrogate and intended mothers: confidence and genealogy.

Science.gov (United States)

Van Den Akker, Olga B A

2005-12-01

For women opting to use surrogacy to overcome subfertility, a choice can be made to have a genetically related or unrelated baby. Similarly, women opting to become surrogate mothers also have to choose to gestate and relinquish a genetically related or unrelated baby. This study explored the cognitions behind the initial choices made and determined the strength of those cognitions six months post-delivery of the surrogate baby. Surrogate and Intended mothers (N=81) undergoing Artificial Insemination (AI, genetic) or Embryo Transfer (ET, gestational) were studied separately (four groups) at the start of their surrogate arrangement and those with a positive outcome (n=34) were re-interviewed at six months post-relinquishment. There were significant differences between surrogate and intended mothers in their confidence about the arrangement. Beliefs about the importance of a genetic link were predictors of ET arrangements. Responses were consistent over a one and a half-year study period. The ethical and clinical implications of the results are discussed in relation to appropriate self-selection and confidence with the surrogate process and the importance of genetic offspring.

Effects of a Mechanical Response-Contingent Surrogate on the Development of Behaviors in Nursery-Reared Rhesus Macaques (Macaca mulatta)

Science.gov (United States)

Brunelli, Rebecca L; Blake, Jennifer; Willits, Neil; Rommeck, Ina; McCowan, Brenda

2014-01-01

Nursery-reared infants have several behavioral and physiologic differences from their mother-reared counterparts. We investigated whether a response-contingent surrogate mitigated some of those differences by decreasing fearfulness and partner-clinging and increasing environmental exploration in nursery-reared infants continuously paired with a peer. Six nursery-reared infant rhesus macaques (in pairs) were given a mechanical responsive surrogate (RS), and 6 (in pairs) were given an identical but nonresponsive surrogate (NRS). The 2 treatment groups were compared and then combined into a single group of all 12 of surrogate-exposed animals (CS) that was compared with a nonsurrogate control group (NS) of 10 nursery-reared infants. Results showed significant differences between CS and NS infants but no significant differences between the RS and NRS infants. As compared with NS infants, CS infants showed less partner-clinging, less affiliation directed toward only partner, and more foraging and tactile–oral exploration of the environment. These advantageous effects support additional research to develop improved surrogate and the implementation of surrogate programs for nursery-reared infants. PMID:25255068

Treatment studies of plutonium-bearing INEEL waste surrogates in a bench-scale arc furnace

International Nuclear Information System (INIS)

Freeman, C.J.

1997-05-01

Since 1989, the Subsurface Disposal Area (SDA) at the Idaho National Environmental and Engineering Laboratory (INEEL) has been included on the National Priority List for remediation. Arc- and plasma-heated furnaces are being considered for converting the radioactive mixed waste buried in the SDA to a stabilized-vitreous form. Nonradioactive, surrogate SDA wastes have been melted during tests in these types of furnaces, but data are needed on the behavior of transuranic (TRU) constituents, primarily plutonium, during thermal treatment. To begin collecting this data, plutonium-spiked SDA surrogates were processed in a bench-scale arc furnace to quantify the fate of the plutonium and other hazardous and nonhazardous metals. Test conditions included elevating the organic, lead, chloride, and sodium contents of the surrogates. Blends having higher organic contents caused furnace power levels to fluctuate. An organic content corresponding to 50% INEEL soil in a soil-waste blend was the highest achievable before power fluctuations made operating conditions unacceptable. The glass, metal, and off-gas solids produced from each surrogate blend tested were analyzed for elemental (including plutonium) content and the partitioning of each element to the corresponding phase was calculated

Treatment studies of plutonium-bearing INEEL waste surrogates in a bench-scale arc furnace

Energy Technology Data Exchange (ETDEWEB)

Freeman, C.J.

1997-05-01

Since 1989, the Subsurface Disposal Area (SDA) at the Idaho National Environmental and Engineering Laboratory (INEEL) has been included on the National Priority List for remediation. Arc- and plasma-heated furnaces are being considered for converting the radioactive mixed waste buried in the SDA to a stabilized-vitreous form. Nonradioactive, surrogate SDA wastes have been melted during tests in these types of furnaces, but data are needed on the behavior of transuranic (TRU) constituents, primarily plutonium, during thermal treatment. To begin collecting this data, plutonium-spiked SDA surrogates were processed in a bench-scale arc furnace to quantify the fate of the plutonium and other hazardous and nonhazardous metals. Test conditions included elevating the organic, lead, chloride, and sodium contents of the surrogates. Blends having higher organic contents caused furnace power levels to fluctuate. An organic content corresponding to 50% INEEL soil in a soil-waste blend was the highest achievable before power fluctuations made operating conditions unacceptable. The glass, metal, and off-gas solids produced from each surrogate blend tested were analyzed for elemental (including plutonium) content and the partitioning of each element to the corresponding phase was calculated.

Monte Carlo simulations on marker grouping and ordering.

Science.gov (United States)

Wu, J; Jenkins, J; Zhu, J; McCarty, J; Watson, C

2003-08-01

Four global algorithms, maximum likelihood (ML), sum of adjacent LOD score (SALOD), sum of adjacent recombinant fractions (SARF) and product of adjacent recombinant fraction (PARF), and one approximation algorithm, seriation (SER), were used to compare the marker ordering efficiencies for correctly given linkage groups based on doubled haploid (DH) populations. The Monte Carlo simulation results indicated the marker ordering powers for the five methods were almost identical. High correlation coefficients were greater than 0.99 between grouping power and ordering power, indicating that all these methods for marker ordering were reliable. Therefore, the main problem for linkage analysis was how to improve the grouping power. Since the SER approach provided the advantage of speed without losing ordering power, this approach was used for detailed simulations. For more generality, multiple linkage groups were employed, and population size, linkage cutoff criterion, marker spacing pattern (even or uneven), and marker spacing distance (close or loose) were considered for obtaining acceptable grouping powers. Simulation results indicated that the grouping power was related to population size, marker spacing distance, and cutoff criterion. Generally, a large population size provided higher grouping power than small population size, and closely linked markers provided higher grouping power than loosely linked markers. The cutoff criterion range for achieving acceptable grouping power and ordering power differed for varying cases; however, combining all situations in this study, a cutoff criterion ranging from 50 cM to 60 cM was recommended for achieving acceptable grouping power and ordering power for different cases.

RAD-seq derived genome-wide nuclear markers resolve the phylogeny of tunas

KAUST Repository

Dí az-Arce, Natalia; Arrizabalaga, Haritz; Murua, Hilario; Irigoien, Xabier; Rodrí guez-Ezpeleta, Naiara

2016-01-01

conservation and management strategies for these species. Previous attempts based on mitochondrial and nuclear markers were unsuccessful in inferring a congruent and reliable phylogeny, probably due to mitochondrial introgression events and lack of enough

Long-term follow-up after cervical cancer treatment and subsequent successful surrogate pregnancy.

Science.gov (United States)

Agorastos, T; Zafrakas, M; Mastrominas, M

2009-08-01

Preservation of fertility is a major concern for premenopausal women after diagnosis of cervical cancer. Successful surrogate pregnancy after treatment for cervical cancer has very rarely been reported. In the present report, a case of successful surrogate pregnancy after radical hysterectomy, lymphadenectomy and ovarian transposition for cervical cancer, followed by radiation therapy, is presented. After stimulation of the transposed ovaries using the short gonadotrophin-releasing hormone (GnRH) analogue protocol, four oocytes were retrieved transabdominally from the genetic mother. IVF followed and two embryos were transferred to the surrogate mother, leading to an uneventful singleton pregnancy, and ultimately normal vaginal delivery of a healthy female infant at term. The unique aspect in this case is the long-lasting favourable outcome for both genetic mother and child, observed during 8.5 years of follow-up, the longest follow-up period reported to date in such cases.

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

Directory of Open Access Journals (Sweden)

Groot-Kormelink Paul J

2012-10-01

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

An Evaluation of Two Internal Surrogates for Determining the Three-Dimensional Position of Peripheral Lung Tumors

NARCIS (Netherlands)

Spoelstra, F.O.B.; Sornsen de Koste, van J.R.; Vincent, A.D.; Cuijpers, J.P.; Slotman, B.J.; Senan, S.

2009-01-01

Purpose: Both carina and diaphragm positions have been used as surrogates during respiratory-gated radiotherapy. We studied the correlation of both surrogates with three-dimensional (3D) tumor position. Methods and Materials: A total of 59 repeat artifact-free four-dimensional (4D) computed

Differences in behaviour and physiology between adult surrogate-reared and mother-reared Cynomolgous monkeys (Macaca fascicularis)

NARCIS (Netherlands)

Luijk, I.A.F. van; Timmermans, P.J.A.; Sweep, C.G.J.; Willems, J.; Vossen, J.M.H.

2000-01-01

Previous studies of the effects of rearing conditions on exploratory behaviour revealed that 80% of monkeys reared in peer groups with surrogate mothers developed neophobia, whereas only 15 % of mother-reared monkeys did. Young surrogate-reared and, especially, isolated rhesus monkeys are known to