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

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.

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

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.

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

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

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

TH-B-204-01: Real-Time Tracking with Implanted Markers

International Nuclear Information System (INIS)

Xu, Q.

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-204-01: Real-Time Tracking with Implanted Markers

Energy Technology Data Exchange (ETDEWEB)

Xu, Q. [MD Anderson Cancer Center at Cooper (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

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.

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

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.

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

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.

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

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.

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

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.

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...

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...

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.

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...

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....

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

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

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.

Manipulations with human life and surrogate motherhood: ethical aspects and moral guidelines.

Science.gov (United States)

Boyko, Fr Ihor

2011-06-01

Surrogate motherhood necessarily leads to the question of who is really the mother and what is motherhood. In the judgment of the author, it is necessary to develop a new culture that will bring back to every person the sense of limit and will help humanity develop a more accurate understanding of the duality of scientific and technological progress. Communication between a mother and her unborn child is clearly very close from the biological point of view, but at the same time there exists a mental and spiritual connection. The motherly desire creates the link between a mother and her future child, while the relationship with the child is established at the moment of conception. There is a good alternative to the surrogate motherhood, which most appropriately corresponds to a married couple or family, namely, adoption, which is one of the forms of the valuable service of life. The moral duty of everyone is to protect human race from radical attacks and various forms of manipulation and pass it over intact and preserved for future generations to come.

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

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

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.

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.

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.

Improving selection of markers in nutrition research: evaluation of the criteria proposed by the ILSI Europe Marker Validation Initiative.

Science.gov (United States)

Calder, Philip C; Boobis, Alan; Braun, Deborah; Champ, Claire L; Dye, Louise; Einöther, Suzanne; Greyling, Arno; Matthys, Christophe; Putz, Peter; Wopereis, Suzan; Woodside, Jayne V; Antoine, Jean-Michel

2017-06-01

The conduct of high-quality nutrition research requires the selection of appropriate markers as outcomes, for example as indicators of food or nutrient intake, nutritional status, health status or disease risk. Such selection requires detailed knowledge of the markers, and consideration of the factors that may influence their measurement, other than the effects of nutritional change. A framework to guide selection of markers within nutrition research studies would be a valuable tool for researchers. A multidisciplinary Expert Group set out to test criteria designed to aid the evaluation of candidate markers for their usefulness in nutrition research and subsequently to develop a scoring system for markers. The proposed criteria were tested using thirteen markers selected from a broad range of nutrition research fields. The result of this testing was a modified list of criteria and a template for evaluating a potential marker against the criteria. Subsequently, a semi-quantitative system for scoring a marker and an associated template were developed. This system will enable the evaluation and comparison of different candidate markers within the same field of nutrition research in order to identify their relative usefulness. The ranking criteria of proven, strong, medium or low are likely to vary according to research setting, research field and the type of tool used to assess the marker and therefore the considerations for scoring need to be determined in a setting-, field- and tool-specific manner. A database of such markers, their interpretation and range of possible values would be valuable to nutrition researchers.

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...

Metagenomes provide valuable comparative information on soil microeukaryotes

DEFF Research Database (Denmark)

Jacquiod, Samuel Jehan Auguste; Stenbæk, Jonas; Santos, Susana

2016-01-01

has been identified. Our analyses suggest that publicly available metagenome data can provide valuable information on soil microeukaryotes for comparative purposes when handled appropriately, complementing the current view provided by ribosomal amplicon sequencing methods......., providing microbiologists with substantial amounts of accessible information. We took advantage of public metagenomes in order to investigate microeukaryote communities in a well characterized grassland soil. The data gathered allowed the evaluation of several factors impacting the community structure......, including the DNA extraction method, the database choice and also the annotation procedure. While most studies on soil microeukaryotes are based on sequencing of PCR-amplified taxonomic markers (18S rRNA genes, ITS regions), this work represents, to our knowledge, the first report based solely...

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

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.

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…

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...

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...

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.

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

Plasma tissue inhibitor of metalloproteinases-1 as a biological marker?

DEFF Research Database (Denmark)

Lomholt, Anne F.; Frederiksen, Camilla B.; Christensen, Ib J.

2007-01-01

Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) may be a valuable biological marker in Colorectal Cancer (CRC). However, prospective validation of TIMP-1 as a biological marker should include a series of pre-analytical considerations. TIMP-1 is stored in platelets, which may degranulate during...

Transferability of Rubus Microsatellite Markers for use in Black Raspberry

Science.gov (United States)

Microsatellites or simple sequence repeats (SSRs) are valuable as co-dominant genetic markers with a variety of applications such as DNA fingerprinting, linkage mapping, and population structure analysis. To date, SSR marker development in Rubus has focused on red raspberry (Rubus idaeus L., subgenu...

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.

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.

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

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.

Preliminary Comparative Analysis of Phenological Varieties of Quercus robur by ISSR-Markers

Directory of Open Access Journals (Sweden)

Vasiliy Chokheli

2016-01-01

Full Text Available Quercus robur L. is a valuable wood species having long ontogeny and promising to create long-living artificial plantings of recreational and ameliorative purposes in the steppes zone of Russia and other countries. In this work we have performed the genotyping of varieties of Quercus robur L. obtained from collection of Botanical Garden of Southern Federal University using intersimple sequence repeat (ISSR molecular markers. The most polymorphic ISSR-marker (GA 8YC was found in the collection. The polymorphic DNA markers identified in the present study can be used for the future breeding works to obtain valuable genotypes of Quercus genus. In addition we have performed DNA fingerprinting of the prospective sample of the variety Q. robur var. tardiflora Czern.

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.

System Reliability Analysis Capability and Surrogate Model Application in RAVEN

Energy Technology Data Exchange (ETDEWEB)

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

2015-11-01

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

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.

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

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.

A comprehensive characterization of simple sequence repeats in pepper genomes provides valuable resources for marker development in Capsicum.

Science.gov (United States)

Cheng, Jiaowen; Zhao, Zicheng; Li, Bo; Qin, Cheng; Wu, Zhiming; Trejo-Saavedra, Diana L; Luo, Xirong; Cui, Junjie; Rivera-Bustamante, Rafael F; Li, Shuaicheng; Hu, Kailin

2016-01-07

The sequences of the full set of pepper genomes including nuclear, mitochondrial and chloroplast are now available for use. However, the overall of simple sequence repeats (SSR) distribution in these genomes and their practical implications for molecular marker development in Capsicum have not yet been described. Here, an average of 868,047.50, 45.50 and 30.00 SSR loci were identified in the nuclear, mitochondrial and chloroplast genomes of pepper, respectively. Subsequently, systematic comparisons of various species, genome types, motif lengths, repeat numbers and classified types were executed and discussed. In addition, a local database composed of 113,500 in silico unique SSR primer pairs was built using a homemade bioinformatics workflow. As a pilot study, 65 polymorphic markers were validated among a wide collection of 21 Capsicum genotypes with allele number and polymorphic information content value per marker raging from 2 to 6 and 0.05 to 0.64, respectively. Finally, a comparison of the clustering results with those of a previous study indicated the usability of the newly developed SSR markers. In summary, this first report on the comprehensive characterization of SSR motifs in pepper genomes and the very large set of SSR primer pairs will benefit various genetic studies in Capsicum.

GDdom: An Online Tool for Calculation of Dominant Marker Gene Diversity.

Science.gov (United States)

Abuzayed, Mazen; El-Dabba, Nourhan; Frary, Anne; Doganlar, Sami

2017-04-01

Gene diversity (GD), also called polymorphism information content, is a commonly used measure of molecular marker polymorphism. Calculation of GD for dominant markers such as AFLP, RAPD, and multilocus SSRs is valuable for researchers. To meet this need, we developed a free online computer program, GDdom, which provides easy, quick, and accurate calculation of dominant marker GD with a commonly used formula. Results are presented in tabular form for quick interpretation.

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.

High resolution melting detects sequence polymorphism in rubus occidentalis L. monomorphic microsatellite markers

Science.gov (United States)

Microsatellite, or simple sequence repeat (SSR) markers, are valuable as co-dominant genetic markers with a variety of applications such as DNA fingerprinting, linkage mapping, and population structure analysis. However, primer pairs designed from the regions that flank SSRs often generate fragment...

Alteration of Cartilage Degeneration and Inflammation Markers in Temporomandibular Joint Osteoarthritis Occurs Proportionally

NARCIS (Netherlands)

Vos, Lukas M.; Kuijer, Roel; Slater, James J. R. Huddleston; Stegenga, Boudewijn

2013-01-01

Purpose: There is a growing interest in markers for cartilage degradation in synovial joints because of their potential diagnostic and prognostic value. Therefore, the aim of this study was to identify valuable degradation markers for temporomandibular joint (TMJ) osteoarthritis (OA) by comparing

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

Predicting trace organic compound breakthrough in granular activated carbon using fluorescence and UV absorbance as surrogates.

Science.gov (United States)

Anumol, Tarun; Sgroi, Massimiliano; Park, Minkyu; Roccaro, Paolo; Snyder, Shane A

2015-06-01

This study investigated the applicability of bulk organic parameters like dissolved organic carbon (DOC), UV absorbance at 254 nm (UV254), and total fluorescence (TF) to act as surrogates in predicting trace organic compound (TOrC) removal by granular activated carbon in water reuse applications. Using rapid small-scale column testing, empirical linear correlations for thirteen TOrCs were determined with DOC, UV254, and TF in four wastewater effluents. Linear correlations (R(2) > 0.7) were obtained for eight TOrCs in each water quality in the UV254 model, while ten TOrCs had R(2) > 0.7 in the TF model. Conversely, DOC was shown to be a poor surrogate for TOrC breakthrough prediction. When the data from all four water qualities was combined, good linear correlations were still obtained with TF having higher R(2) than UV254 especially for TOrCs with log Dow>1. Excellent linear relationship (R(2) > 0.9) between log Dow and the removal of TOrC at 0% surrogate removal (y-intercept) were obtained for the five neutral TOrCs tested in this study. Positively charged TOrCs had enhanced removals due to electrostatic interactions with negatively charged GAC that caused them to deviate from removals that would be expected with their log Dow. Application of the empirical linear correlation models to full-scale samples provided good results for six of seven TOrCs (except meprobamate) tested when comparing predicted TOrC removal by UV254 and TF with actual removals for GAC in all the five samples tested. Surrogate predictions using UV254 and TF provide valuable tools for rapid or on-line monitoring of GAC performance and can result in cost savings by extended GAC run times as compared to using DOC breakthrough to trigger regeneration or replacement. Copyright © 2015 Elsevier Ltd. All rights reserved.

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...

Retention of external and internal markers by southern pine beetles (Coleoptera: Scolytidae) during gallery

Science.gov (United States)

Douglas J. Rhodes; Jane Leslie Hayes; Chris Steiner

1998-01-01

If retained, markers used in mark-release-recapture studies of bark beetle dispersal could provide valuable tools in the determination of post-dispersal fate. Retention of the internal marker rubidium (Rb) and of the external marker fluorescent powder during egg gallery construction, oviposition, and feeding were quantified at intervals from 0 to 96 hours by allowing...

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?

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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 production of eggs and sperm by intrapapillary transplantation of germ cells in cytoablated adult fish.

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Sullip Kumar Majhi

Full Text Available Germ cell transplantation (GCT is a promising assisted reproductive technology for the conservation and propagation of endangered and valuable genetic resources. In teleost fish, GCT in adult gonads has been achieved only in male recipients, limiting greatly the usefulness of this technique in situations where both sexes need equal and timely attention for conservation and/or propagation. Here we describe a simplified GCT approach that ultimately leads to production of donor-derived eggs and sperm in considerably short time. Donor germ cells isolated from young pejerrey Odontesthes bonariensis (Atherinopsidae were transplanted non-surgically through the genital papilla into the sexually mature gonads of Patagonian pejerrey O. hatcheri recipients whose gonads have been depleted of endogenous GCs by heat (26°C and chemical treatment (four doses of Busulfan at 30 mg/kg and 40 mg/kg for females and males, respectively. Transplanted spermatogonial and oogonial cells were able to recolonize the recipients' gonads and produce functional donor origin eggs and sperm within 7 months from the GCT. We confirmed the presence of donor-derived gametes by PCR in 17% and 5% of the surrogate O. hatcheri fathers and mothers, respectively. The crosses between surrogate fathers and O. bonariensis mothers yielded 12.6-39.7% pure O. bonariensis and that between a surrogate mother and an O. bonariensis father yielded 52.2% pure O. bonariensis offspring. Our findings confirm that transplantation of germ cells into sexually competent adult fish by non-surgical methods allows the production of functional donor-derived eggs and sperm in a considerably short time. The methods described here could play a vital role in conservation and rapid propagation of endangered fish genetic resources.

Surrogate production of eggs and sperm by intrapapillary transplantation of germ cells in cytoablated adult fish.

Science.gov (United States)

Majhi, Sullip Kumar; Hattori, Ricardo Shohei; Rahman, Sheikh Mustafizur; Strüssmann, Carlos Augusto

2014-01-01

Germ cell transplantation (GCT) is a promising assisted reproductive technology for the conservation and propagation of endangered and valuable genetic resources. In teleost fish, GCT in adult gonads has been achieved only in male recipients, limiting greatly the usefulness of this technique in situations where both sexes need equal and timely attention for conservation and/or propagation. Here we describe a simplified GCT approach that ultimately leads to production of donor-derived eggs and sperm in considerably short time. Donor germ cells isolated from young pejerrey Odontesthes bonariensis (Atherinopsidae) were transplanted non-surgically through the genital papilla into the sexually mature gonads of Patagonian pejerrey O. hatcheri recipients whose gonads have been depleted of endogenous GCs by heat (26°C) and chemical treatment (four doses of Busulfan at 30 mg/kg and 40 mg/kg for females and males, respectively). Transplanted spermatogonial and oogonial cells were able to recolonize the recipients' gonads and produce functional donor origin eggs and sperm within 7 months from the GCT. We confirmed the presence of donor-derived gametes by PCR in 17% and 5% of the surrogate O. hatcheri fathers and mothers, respectively. The crosses between surrogate fathers and O. bonariensis mothers yielded 12.6-39.7% pure O. bonariensis and that between a surrogate mother and an O. bonariensis father yielded 52.2% pure O. bonariensis offspring. Our findings confirm that transplantation of germ cells into sexually competent adult fish by non-surgical methods allows the production of functional donor-derived eggs and sperm in a considerably short time. The methods described here could play a vital role in conservation and rapid propagation of endangered fish genetic resources.

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.

Detection of Sequence Polymorphism in Rubus Occidentalis L. Monomorphic Microsatellite Markers by High Resolution Melting

Science.gov (United States)

Microsatellite, or simple sequence repeat (SSR) markers, are valuable as co-dominant genetic markers with a variety of applications such as DNA fingerprinting, linkage mapping, and population structure analysis. Development of microsatellite primers through the identification of appropriate repeate...

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) ...

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.

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.

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.

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.

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.

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.

Use of molecular markers in plant breeding = [Het gebruik van moleculaire merkers in de plantenveredeling

NARCIS (Netherlands)

Berloo, van R.

2000-01-01

Molecular markers provide plant breeding with an important and valuable new source of information. Linkage between molecular markers can be translated to genetic linkage maps, which have become an important tool in plant and animal genetics. Linkage between (quantitative) trait-data and

Next generation DNA sequencing technology delivers valuable genetic markers for the genomic orphan legume species, Bituminaria bituminosa

Directory of Open Access Journals (Sweden)

Pazos-Navarro María

2011-12-01

Full Text Available Abstract Background Bituminaria bituminosa is a perennial legume species from the Canary Islands and Mediterranean region that has potential as a drought-tolerant pasture species and as a source of pharmaceutical compounds. Three botanical varieties have previously been identified in this species: albomarginata, bituminosa and crassiuscula. B. bituminosa can be considered a genomic 'orphan' species with very few genomic resources available. New DNA sequencing technologies provide an opportunity to develop high quality molecular markers for such orphan species. Results 432,306 mRNA molecules were sampled from a leaf transcriptome of a single B. bituminosa plant using Roche 454 pyrosequencing, resulting in an average read length of 345 bp (149.1 Mbp in total. Sequences were assembled into 3,838 isotigs/contigs representing putatively unique gene transcripts. Gene ontology descriptors were identified for 3,419 sequences. Raw sequence reads containing simple sequence repeat (SSR motifs were identified, and 240 primer pairs flanking these motifs were designed. Of 87 primer pairs developed this way, 75 (86.2% successfully amplified primarily single fragments by PCR. Fragment analysis using 20 primer pairs in 79 accessions of B. bituminosa detected 130 alleles at 21 SSR loci. Genetic diversity analyses confirmed that variation at these SSR loci accurately reflected known taxonomic relationships in original collections of B. bituminosa and provided additional evidence that a division of the botanical variety bituminosa into two according to geographical origin (Mediterranean region and Canary Islands may be appropriate. Evidence of cross-pollination was also found between botanical varieties within a B. bituminosa breeding programme. Conclusions B. bituminosa can no longer be considered a genomic orphan species, having now a large (albeit incomplete repertoire of expressed gene sequences that can serve as a resource for future genetic studies. This

Epigenetic Markers of Renal Function in African Americans

Directory of Open Access Journals (Sweden)

Samantha M. Bomotti

2013-01-01

Full Text Available Chronic kidney disease (CKD is an increasing concern in the United States due to its rapidly rising prevalence, particularly among African Americans. Epigenetic DNA methylation markers are becoming important biomarkers of chronic diseases such as CKD. To better understand how these methylation markers play a role in kidney function, we measured 26,428 DNA methylation sites in 972 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA study. We then evaluated (1 whether epigenetic markers are associated with estimated glomerular filtration rate (eGFR, (2 whether the significantly associated markers are also associated with traditional risk factors and/or novel biomarkers for eGFR, and (3 how much additional variation in eGFR is explained by epigenetic markers beyond established risk factors and biomarkers. The majority of methylation markers most significantly associated with eGFR (24 out of the top 30 appeared to function, at least in part, through pathways related to aging, inflammation, or cholesterol. However, six epigenetic markers were still able to significantly predict eGFR after adjustment for other risk factors. This work shows that epigenetic markers may offer valuable new insight into the complex pathophysiology of CKD in African Americans.

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.

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.

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...

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 ...

The relationship between tumor markers and pulmonary embolism in lung cancer.

Science.gov (United States)

Xiong, Wei; Zhao, Yunfeng; Xu, Mei; Guo, Jian; Pudasaini, Bigyan; Wu, Xueling; Liu, Jinming

2017-06-20

Tumor markers (TMs) and D-Dimer are both hallmarks of severity and prognosis of lung cancer. Tumor markers could be related to pulmonary embolism (PE) in lung cancer. The number of abnormal tumor markers of lung cancer patients with pulmonary embolism (3.9 ± 1.1vs1.6 ± 0.6,P 0.005) was more than that in patients without pulmonary embolism. TMs panel (P trend tumor markers, TMs panel (OR5.98, P Tumor markers were compared between lung cancer patients complicated with pulmonary embolism and those without pulmonary embolism Then the correlation between each tumor marker as well as panel of combined TMs and D-Dimer as well as pulmonary embolism were analyzed for patients with pulmonary embolism. There is a relationship between tumor markers and pulmonary embolism in patients with lung cancer. The panel of combined tumor markers is a valuable diagnostic marker for pulmonary embolism in lung cancer.

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.

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

Challenging and valuable

NARCIS (Netherlands)

Van Hal, J.D.M.

2008-01-01

Challenging and valuable Inaugural speech given on May 7th 2008 at the occasion of the acceptance of the position of Professor Sustainable Housing Transformation at the faculty of Architeeture of the Delft University of Technology by Prof. J.D.M. van Hal MSc PhD.

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

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.

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.

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."

Recovery and utilization of valuable metals from spent nuclear fuel. 3: Mutual separation of valuable metals

International Nuclear Information System (INIS)

Kirishima, K.; Shibayama, H.; Nakahira, H.; Shimauchi, H.; Myochin, M.; Wada, Y.; Kawase, K.; Kishimoto, Y.

1993-01-01

In the project ''Recovery and Utilization of Valuable Metals from Spent Fuel,'' mutual separation process of valuable metals recovered from spent fuel has been studied by using the simulated solution contained Pb, Ru, Rh, Pd and Mo. Pd was separated successfully by DHS (di-hexyl sulfide) solvent extraction method, while Pb was recovered selectively from the raffinate by neutralization precipitation of other elements. On the other hand, Rh was roughly separated by washing the precipitate with alkaline solution, so that Rh was refined by chelate resin CS-346. Outline of the mutual separation process flow sheet has been established of the combination of these techniques. The experimental results and the process flow sheet of mutual separation of valuable metals are presented in this paper

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?

Development, genetic mapping and QTL association of cotton PHYA, PHYB, and HY5-specific CAPS and dCAPS markers

Science.gov (United States)

Among SNP markers that become increasingly valuable in molecular breeding of crop plants are the CAP and dCAP markers derived from the genes of interest. To date, the number of such gene-based markers is small in polyploid crop plants such as tetraploid cotton that has A and D subgenomes. The obje...

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

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

Mining online genomic resources in Anolis carolinensis facilitates rapid and inexpensive development of cross-species microsatellite markers for the Anolis lizard genus.

Science.gov (United States)

Wordley, Claire; Slate, Jon; Stapley, Jessica

2011-01-01

Online sequence databases can provide valuable resources for the development of cross-species genetic markers. In particular, mining expressed tag sequences (EST) for microsatellites and developing conserved cross-species microsatellite markers can provide a rapid and relatively inexpensive method to develop new markers for a range of species. Here, we adopt this approach to develop cross-species microsatellite markers in Anolis lizards, which is a model genus in evolutionary biology and ecology. Using EST sequences from Anolis carolinensis, we identified 127 microsatellites that satisfied our criteria, and tested 49 of these in five species of Anolis (carolinensis, distichus, apletophallus, porcatus and sagrei). We identified between 8 and 25 new variable genetic markers for five Anolis species. These markers will be a valuable resource for studies of population genetics, comparative mapping, mating systems, behavioural ecology and adaptive radiations in this diverse lineage. © 2010 Blackwell Publishing Ltd.

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...

Parasites as valuable stock markers for fisheries in Australasia, East Asia and the Pacific Islands.

Science.gov (United States)

Lester, R J G; Moore, B R

2015-01-01

Over 30 studies in Australasia, East Asia and the Pacific Islands region have collected and analysed parasite data to determine the ranges of individual fish, many leading to conclusions about stock delineation. Parasites used as biological tags have included both those known to have long residence times in the fish and those thought to be relatively transient. In many cases the parasitological conclusions have been supported by other methods especially analysis of the chemical constituents of otoliths, and to a lesser extent, genetic data. In analysing parasite data, authors have applied multiple different statistical methodologies, including summary statistics, and univariate and multivariate approaches. Recently, a growing number of researchers have found non-parametric methods, such as analysis of similarities and cluster analysis, to be valuable. Future studies into the residence times, life cycles and geographical distributions of parasites together with more robust analytical methods will yield much important information to clarify stock structures in the area.

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.

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....

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

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.

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

Plasma tissue inhibitor of metalloproteinases-1 as a biological marker? Pre-analytical considerations

DEFF Research Database (Denmark)

Lomholt, Anne Fog; Frederiksen, Camilla; Christensen, Ib Jarle

2007-01-01

Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) may be a valuable biological marker in Colorectal Cancer (CRC). However, prospective validation of TIMP-1 as a biological marker should include a series of pre-analytical considerations. TIMP-1 is stored in platelets, which may degranulate during ...... collection and storage. The aim of this study was to evaluate the influence of platelet TIMP-1 contamination on plasma TIMP-1 levels in healthy volunteers....

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

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.

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.

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

Science.gov (United States)

Janardhanan, S.; Datta, B.

2011-12-01

Surrogate models are widely used to develop computationally efficient simulation-optimization models to solve complex groundwater management problems. Artificial intelligence based models are most often used for this purpose where they are trained using predictor-predictand data obtained from a numerical simulation model. Most often this is implemented with the assumption that the parameters and boundary conditions used in the numerical simulation model are perfectly known. However, in most practical situations these values are uncertain. Under these circumstances the application of such approximation surrogates becomes limited. In our study we develop a surrogate model based coupled simulation optimization methodology for determining optimal pumping strategies for coastal aquifers considering parameter uncertainty. An ensemble surrogate modeling approach is used along with multiple realization optimization. The methodology is used to solve a multi-objective coastal aquifer management problem considering two conflicting objectives. Hydraulic conductivity and the aquifer recharge are considered as uncertain values. Three dimensional coupled flow and transport simulation model FEMWATER is used to simulate the aquifer responses for a number of scenarios corresponding to Latin hypercube samples of pumping and uncertain parameters to generate input-output patterns for training the surrogate models. Non-parametric bootstrap sampling of this original data set is used to generate multiple data sets which belong to different regions in the multi-dimensional decision and parameter space. These data sets are used to train and test multiple surrogate models based on genetic programming. The ensemble of surrogate models is then linked to a multi-objective genetic algorithm to solve the pumping optimization problem. Two conflicting objectives, viz, maximizing total pumping from beneficial wells and minimizing the total pumping from barrier wells for hydraulic control of

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.

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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...

Cancer molecular markers: A guide to cancer detection and management.

Science.gov (United States)

Nair, Meera; Sandhu, Sardul Singh; Sharma, Anil Kumar

2018-02-08

Cancer is generally caused by the molecular alterations which lead to specific mutations. Advances in molecular biology have provided an impetus to the study of cancers with valuable prognostic and predictive significance. Over the hindsight various attempts have been undertaken by scientists worldwide, in the management of cancer; where, we have witnessed a number of molecular markers which allow the early detection of cancers and lead to a decrease in its mortality rate. Recent advances in oncology have led to the discovery of cancer markers that has allowed early detection and targeted therapy of tumors. In this context, current review provides a detail outlook on various molecular markers for diagnosis, prognosis and management of therapeutic response in cancer patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

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)

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.

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

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...

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...

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.

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.

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

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.

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.

Clinical Evaluation and Cost-Effectiveness Analysis of Serum Tumor Markers in Lung Cancer

Directory of Open Access Journals (Sweden)

Rong Wang

2013-01-01

Full Text Available The detection of serum tumor markers is valuable for the early diagnosis of lung cancer. Tumor markers are frequently used for the management of cancer patients. However, single markers are less efficient but marker combinations increase the cost, which is troublesome for clinics. To find an optimal serum marker combination panel that benefits the patients and the medical management system as well, four routine lung cancer serum markers (SCCA, NSE, CEA, and CYFRA21-1 were evaluated individually and in combination. Meanwhile, the costs and effects of these markers in clinical practice in China were assessed by cost-effectiveness analysis. As expected, combinations of these tumor markers improved their sensitivity for lung cancer and different combination panels had their own usefulness. NSE + CEA + CYFRA21-1 was the optimal combination panel with highest Youden’s index (0.64, higher sensitivity (75.76%, and specificity (88.57%, which can aid the clinical diagnosis of lung cancer. Nevertheless, the most cost-effective combination was SCCA + CEA, which can be used to screen the high-risk group.

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.

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.

Vulnerability of particularly valuable areas. Summary

Energy Technology Data Exchange (ETDEWEB)

NONE

2012-07-01

This report is part of the scientific basis for the management plan for the North Sea and Skagerrak. The report focuses on the vulnerability of particularly valuable areas to petroleum activities, maritime transport, fisheries, land-based and coastal activities and long-range transboundary pollution. A working group with representatives from many different government agencies, headed by the Institute of Marine Research and the Directorate for Nature Management, has been responsible for drawing up the present report on behalf of the Expert Group for the North Sea and Skagerrak. The present report considers the 12 areas that were identified as particularly valuable during an earlier stage of the management plan process on the environment, natural resources and pollution. There are nine areas along the coast and three open sea areas in the North Sea that were identified according to the same predefined criteria as used for the management plans for the Barents Sea: Lofoten area and the Norwegian Sea. The most important criteria for particularly valuable areas are importance for biological production and importance for biodiversity.(Author)

Vulnerability of particularly valuable areas. Summary

International Nuclear Information System (INIS)

2012-01-01

This report is part of the scientific basis for the management plan for the North Sea and Skagerrak. The report focuses on the vulnerability of particularly valuable areas to petroleum activities, maritime transport, fisheries, land-based and coastal activities and long-range transboundary pollution. A working group with representatives from many different government agencies, headed by the Institute of Marine Research and the Directorate for Nature Management, has been responsible for drawing up the present report on behalf of the Expert Group for the North Sea and Skagerrak. The present report considers the 12 areas that were identified as particularly valuable during an earlier stage of the management plan process on the environment, natural resources and pollution. There are nine areas along the coast and three open sea areas in the North Sea that were identified according to the same predefined criteria as used for the management plans for the Barents Sea: Lofoten area and the Norwegian Sea. The most important criteria for particularly valuable areas are importance for biological production and importance for biodiversity.(Author)

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

Radioactive polyethyleneglycol: an intestinal water marker in birds

International Nuclear Information System (INIS)

Mongin, P.

1976-01-01

Polyethyleneglycol (MW=4000) labeled with 14 C remains in the liquid phase whatever the physical conditions are: dilution-alkalinity or acidity. It does not enter the food particles and is not adsorbed by them. When the animals are in state conditions, a four-day balance study in four laying hens shows, that ingested radioactivity is totally recovered in the feces. PEG- 14 C is a valuable water marker in the bird intestine

Application of tumor markers in the immunodiagnosis of cancer

International Nuclear Information System (INIS)

Gelder, F.B.; Barr, L.H.; Goldman, L.I.

1983-01-01

Recently, research directed toward the detection of both tumor-specific and tumor-related products has intensified for several reasons. 1. The growing knowledge of tumor metabolism has lead some investigators to hypothesize that most, if not all, malignant tumors produce these substances. 2. The use of multiple tumor markers appears more valuable than application of single markers. 3. The availability of highly sensitive and specific immunological methods provides the tools to measure substances which previously could not be assayed. 4. As additional information evolves, the events associated with malignant transformation and tumor behaviour may become clear. Tumor-related products include immune markers, altered cell surface membranes, as well as fetal and/or ectopic proteins, to name but a few. The synthesis of fetal and/or ectopic proteins occurs in several cancers. These have served as the basis for most immunodiagnostic tests and comprise the major thrust of this review

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...

Molecular markers: a potential resource for ginger genetic diversity studies.

Science.gov (United States)

Ismail, Nor Asiah; Rafii, M Y; Mahmud, T M M; Hanafi, M M; Miah, Gous

2016-12-01

Ginger is an economically important and valuable plant around the world. Ginger is used as a food, spice, condiment, medicine and ornament. There is available information on biochemical aspects of ginger, but few studies have been reported on its molecular aspects. The main objective of this review is to accumulate the available molecular marker information and its application in diverse ginger studies. This review article was prepared by combing material from published articles and our own research. Molecular markers allow the identification and characterization of plant genotypes through direct access to hereditary material. In crop species, molecular markers are applied in different aspects and are useful in breeding programs. In ginger, molecular markers are commonly used to identify genetic variation and classify the relatedness among varieties, accessions, and species. Consequently, it provides important input in determining resourceful management strategies for ginger improvement programs. Alternatively, a molecular marker could function as a harmonizing tool for documenting species. This review highlights the application of molecular markers (isozyme, RAPD, AFLP, SSR, ISSR and others such as RFLP, SCAR, NBS and SNP) in genetic diversity studies of ginger species. Some insights on the advantages of the markers are discussed. The detection of genetic variation among promising cultivars of ginger has significance for ginger improvement programs. This update of recent literature will help researchers and students select the appropriate molecular markers for ginger-related research.

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.

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.

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

Development of EST-derived markers in Dendrobium from EST of related taxa

Directory of Open Access Journals (Sweden)

Narisa Juejun

2013-04-01

Full Text Available Public databases are useful for molecular marker development. The major aim of this study was to develop expressedsequence tag (EST-derived markers in Dendrobium from available ESTs of Phalaenopsis and Dendrobium. A total of 6063sequences were screened for simple sequence repeats (SSRs and introns. Primers flanking these regions were generated andtested on genomic DNAs of Phalaenopsis and Dendrobium. Twenty-three percent of amplifiable Phalaenopsis EST-derivedmarkers were cross-genera transferable to Dendrobium. Forty-one markers from both Phalaenopsis and Dendrobium thatamplified in Dendrobium were assessed on six commercial cultivars and six wild accessions. All of them were transferableamong Dendrobium species. High polymorphism and heterozygosity were observed within wild accessions. Sixteen polymorphic markers were evaluated for linkage analysis on an F1 segregating population. Seven markers were mapped into threelinkage groups, two of which showed syntenic relationship between dendrobium and rice. This relationship will facilitatefurther quantitative trait loci (QTL mapping and comparative genomic studies of Dendrobium. Our results indicate thatPhalaenopsis EST-derived markers are valuable tools for genetic research and breeding applications in Dendrobium.

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.

Genetic Diversity Analysis of Medicinally Important Horticultural Crop Aegle marmelos by ISSR Markers.

Science.gov (United States)

Mujeeb, Farina; Bajpai, Preeti; Pathak, Neelam; Verma, Smita Rastogi

2017-01-01

Inter simple sequence repeat (ISSR) markers help in identifying and determining the extent of genetic diversity in cultivars. Here, we describe their application in determining the genetic diversity of bael (Aegle marmelos Corr.). Universal ISSR primers are selected and their marker characteristics such as polymorphism information content, effective multiplex ratio and marker index have been evaluated. ISSR-PCR is then performed using universal ISSR primers to generate polymorphic bands. This information is used to determine the degree of genetic similarity among the bael varieties/accessions by cluster analysis using unweighted pair-group method with arithmetic averages (UPGMA). This technology is valuable for biodiversity conservation and for making an efficient choice of parents in breeding programs.

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.

Development of Novel SSR Markers for Flax (Linum usitatissimum L.) Using Reduced-Representation Genome Sequencing.

Science.gov (United States)

Wu, Jianzhong; Zhao, Qian; Wu, Guangwen; Zhang, Shuquan; Jiang, Tingbo

2016-01-01

Flax ( Linum usitatissimum L.) is a major fiber and oil yielding crop grown in northeastern China. Identification of flax molecular markers is a key step toward improving flax yield and quality via marker-assisted breeding. Simple sequence repeat (SSR) markers, which are based on genomic structural variation, are considered the most valuable type of genetic marker for this purpose. In this study, we screened 1574 microsatellites from Linum usitatissimum L. obtained using reduced representation genome sequencing (RRGS) to systematically identify SSR markers. The resulting set of microsatellites consisted mainly of trinucleotide (56.10%) and dinucleotide (35.23%) repeats, with each motif consisting of 5-8 repeats. We then evaluated marker sensitivity and specificity based on samples of 48 flax isolates obtained from northeastern China. Using the new SSR panel, the results demonstrated that fiber flax and oilseed flax varieties clustered into two well separated groups. The novel SSR markers developed in this study show potential value for selection of varieties for use in flax breeding programs.

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.

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.

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

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.

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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

Recovering valuable shale oils, etc

Energy Technology Data Exchange (ETDEWEB)

Engler, C

1922-09-26

A process is described for the recovery of valuable shale oils or tars, characterized in that the oil shale is heated to about 300/sup 0/C or a temperature not exceeding this essentially and then is treated with a solvent with utilization of this heat.

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 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.

Trends in plant research using molecular markers.

Science.gov (United States)

Garrido-Cardenas, Jose Antonio; Mesa-Valle, Concepción; Manzano-Agugliaro, Francisco

2018-03-01

A deep bibliometric analysis has been carried out, obtaining valuable parameters that facilitate the understanding around the research in plant using molecular markers. The evolution of the improvement in the field of agronomy is fundamental for its adaptation to the new exigencies that the current world context raises. In addition, within these improvements, this article focuses on those related to the biotechnology sector. More specifically, the use of DNA markers that allow the researcher to know the set of genes associated with a particular quantitative trait or QTL. The use of molecular markers is widely extended, including: restriction fragment length polymorphism, random-amplified polymorphic DNA, amplified fragment length polymorphism, microsatellites, and single-nucleotide polymorphisms. In addition to classical methodology, new approaches based on the next generation sequencing are proving to be fundamental. In this article, a historical review of the molecular markers traditionally used in plants, since its birth and how the new molecular tools facilitate the work of plant breeders is carried out. The evolution of the most studied cultures from the point of view of molecular markers is also reviewed and other parameters whose prior knowledge can facilitate the approach of researchers to this field of research are analyzed. The bibliometric analysis of molecular markers in plants shows that top five countries in this research are: US, China, India, France, and Germany, and from 2013, this research is led by China. On the other hand, the basic research using Arabidopsis is deeper in France and Germany, while other countries focused its efforts in their main crops as the US for wheat or maize, while China and India for wheat and rice.

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.

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

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

Prioritizing molecular markers to test for in the initial workup of advanced non-small cell lung cancer: wants versus needs.

Science.gov (United States)

West, Howard

2017-09-01

The current standard of care for molecular marker testing in patients with advanced non-small cell lung cancer (NSCLC) has been evolving over several years and is a product of the quality of the evidence supporting a targeted therapy for a specific molecular marker, the pre-test probability of that marker in the population, and the magnitude of benefit seen with that treatment. Among the markers that have one or more matched targeted therapies, only a few are in the subset for which they should be considered as most clearly worthy of prioritizing to detect in the first line setting in order to have them supplant other first line alternatives, and in only a subset of patients, as defined currently by NSCLC histology. Specifically, this currently includes testing for an activating epidermal growth factor receptor ( EGFR ) mutation or an anaplastic lymphoma kinase ( ALK ) or ROS1 rearrangement. This article reviews the history and data supporting the prioritization of these markers in patients with non-squamous NSCLC, a histologically selected population in whom the probability of these markers combined with the anticipated efficacy of targeted therapies against them is high enough to favor these treatments in the first line setting. In reviewing the evidence supporting this very limited core subset of most valuable molecular markers to detect in the initial workup of such patients, we can also see the criteria by which other actionable markers need to reach in order to be widely recognized as reliably valuable enough to warrant prioritization to detect in the initial workup of advanced NSCLC as well.

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.

Segregation analysis of microsatellite (SSR) markers in sugarcane polyploids.

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Lu, X; Zhou, H; Pan, Y-B; Chen, C Y; Zhu, J R; Chen, P H; Li, Y-R; Cai, Q; Chen, R K

2015-12-28

No information is available on segregation analysis of DNA markers involving both pollen and self-progeny. Therefore, we used capillary electrophoresis- and fluorescence-based DNA fingerprinting together with single pollen collection and polymerase chain reaction (PCR) to investigate simple sequence repeat (SSR) marker segregation among 964 single pollens and 288 self-progenies (S1) of sugarcane cultivar LCP 85-384. Twenty SSR DNA fragments (alleles) were amplified by five polymorphic SSR markers. Only one non-parental SSR allele was observed in 2392 PCRs. SSR allele inheritance was in accordance with Mendelian laws of segregation and independent assortment. Highly significant correlation coefficients were found between frequencies of observed and expected genotypes in pollen and S1 populations. Within the S1 population, the most frequent genotype of each SSR marker was the parental genotype of the same marker. The number of genotypes was higher in pollen than S1 population. PIC values of the five SSR markers were greater in pollen than S1 populations. Eleven of 20 SSR alleles (55%) were segregated in accordance with Mendelian segregation ratios expected from pollen and S1 populations of a 2n = 10x polyploid. Six of 20 SSR alleles were segregated in a 3:1 (presence:absence) ratio and were simplex markers. Four and one alleles were segregated in 77:4 and 143:1 ratios and considered duplex and triplex markers, respectively. Segregation ratios of remaining alleles were unexplainable. The results provide information about selection of crossing parents, estimation of seedling population optimal size, and promotion of efficient selection, which may be valuable for sugarcane breeders.

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

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.

Development and Molecular Characterization of Novel Polymorphic Genomic DNA SSR Markers in Lentinula edodes.

Science.gov (United States)

Moon, Suyun; Lee, Hwa-Yong; Shim, Donghwan; Kim, Myungkil; Ka, Kang-Hyeon; Ryoo, Rhim; Ko, Han-Gyu; Koo, Chang-Duck; Chung, Jong-Wook; Ryu, Hojin

2017-06-01

Sixteen genomic DNA simple sequence repeat (SSR) markers of Lentinula edodes were developed from 205 SSR motifs present in 46.1-Mb long L. edodes genome sequences. The number of alleles ranged from 3-14 and the major allele frequency was distributed from 0.17-0.96. The values of observed and expected heterozygosity ranged from 0.00-0.76 and 0.07-0.90, respectively. The polymorphic information content value ranged from 0.07-0.89. A dendrogram, based on 16 SSR markers clustered by the paired hierarchical clustering' method, showed that 33 shiitake cultivars could be divided into three major groups and successfully identified. These SSR markers will contribute to the efficient breeding of this species by providing diversity in shiitake varieties. Furthermore, the genomic information covered by the markers can provide a valuable resource for genetic linkage map construction, molecular mapping, and marker-assisted selection in the shiitake mushroom.

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...

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.

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.

Evaluating β Diversity as a Surrogate for Species Representation at Fine Scale.

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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.

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

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

Semantic Document Image Classification Based on Valuable Text Pattern

Directory of Open Access Journals (Sweden)

Hossein Pourghassem

2011-01-01

Full Text Available Knowledge extraction from detected document image is a complex problem in the field of information technology. This problem becomes more intricate when we know, a negligible percentage of the detected document images are valuable. In this paper, a segmentation-based classification algorithm is used to analysis the document image. In this algorithm, using a two-stage segmentation approach, regions of the image are detected, and then classified to document and non-document (pure region regions in the hierarchical classification. In this paper, a novel valuable definition is proposed to classify document image in to valuable or invaluable categories. The proposed algorithm is evaluated on a database consisting of the document and non-document image that provide from Internet. Experimental results show the efficiency of the proposed algorithm in the semantic document image classification. The proposed algorithm provides accuracy rate of 98.8% for valuable and invaluable document image classification problem.

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

Valuable Internet Advertising and Customer Satisfaction Cycle(VIACSC)

OpenAIRE

Muhammad Awais; Tanzila Samin; Muhammad Bilal

2012-01-01

Now-a-days it is very important for the business persons to attract their target customers towards their products through valuable mode of promotion and communication. Increasing use of World Wide Web has completely changed the scenario of business sector. Customized products and services, customers preferences, @ and dot com craze have elevated the importance of internet advertising. This research paper investigates valuable internet advertising which will help to enhance the value of intern...

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.

Antibody Arrays Identify Potential Diagnostic Markers of Hepatocellular Carcinoma

Directory of Open Access Journals (Sweden)

Brian J. Peter

2008-01-01

Full Text Available Hepatocellular carcinoma (HCC is the third leading cause of cancer deaths worldwide. Effective treatment of HCC patients is hampered by the lack of sensitive and specific diagnostic markers of HCC. Alpha-fetoprotein (AFP, the currently used HCC marker, misses 30%–50% of HCC patients, who therefore remain undiagnosed and untreated. In order to identify novel diagnostic markers that can be used individually or in combination with AFP, we used an antibody array platform to detect the levels of candidate proteins in the plasma of HCC patients (n = 48 and patients with chronic hepatitis B or C viral infections (n = 19 (both of which are the major risk factors of HCC. We identified 7 proteins that significantly differentiate HCC patients from hepatitis patients (p < 0.05 (AFP, CTNNB, CSF1, SELL, IGFBP6, IL6R, and VCAM1.Importantly, we also identified 8 proteins that significantly differentiate HCC patients with ‘normal’ levels of AFP (<20 ng/ml from hepatitis patients (p < 0.05 (IL1RN, IFNG, CDKN1A, RETN, CXCL14, CTNNB, FGF2, and SELL. These markers are potentially important complementary markers to AFP. Using an independent immunoassay method in an independent group of 23 HCC patients and 22 hepatitis patients, we validated that plasma levels of CTNNB were significantly higher in the HCC group (p = 0.020. In conclusion, we used an antibody array platform to identify potential circulating diagnostic markers of HCC, some of which may be valuable when used in combination with AFP. The clinical utility of these newly identified HCC diagnostic markers needs to be systematically evaluated.

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.

Reduction of Human Norovirus GI, GII, and Surrogates by Peracetic Acid and Monochloramine in Municipal Secondary Wastewater Effluent.

Science.gov (United States)

Dunkin, Nathan; Weng, ShihChi; Coulter, Caroline G; Jacangelo, Joseph G; Schwab, Kellogg J

2017-10-17

The objective of this study was to characterize human norovirus (hNoV) GI and GII reductions during disinfection by peracetic acid (PAA) and monochloramine in secondary wastewater (WW) and phosphate buffer (PB) as assessed by reverse transcription-qPCR (RT-qPCR). Infectivity and RT-qPCR reductions are also presented for surrogate viruses murine norovirus (MNV) and bacteriophage MS2 under identical experimental conditions to aid in interpretation of hNoV molecular data. In WW, RT-qPCR reductions were less than 0.5 log 10 for all viruses at concentration-time (CT) values up to 450 mg-min/L except for hNoV GI, where 1 log 10 reduction was observed at CT values of less than 50 mg-min/L for monochloramine and 200 mg-min/L for PAA. In PB, hNoV GI and MNV exhibited comparable resistance to PAA and monochloramine with CT values for 2 log 10 RT-qPCR reduction between 300 and 360 mg-min/L. Less than 1 log 10 reduction was observed for MS2 and hNoV GII in PB at CT values for both disinfectants up to 450 mg-min/L. Our results indicate that hNoVs exhibit genogroup dependent resistance and that disinfection practices targeting hNoV GII will result in equivalent or greater reductions for hNoV GI. These data provide valuable comparisons between hNoV and surrogate molecular signals that can begin the process of informing regulators and engineers on WW treatment plant design and operational practices necessary to inactivate hNoVs.

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.

Efficient surrogate models for reliability analysis of systems with multiple failure modes

International Nuclear Information System (INIS)

Bichon, Barron J.; McFarland, John M.; Mahadevan, Sankaran

2011-01-01

Despite many advances in the field of computational reliability analysis, the efficient estimation of the reliability of a system with multiple failure modes remains a persistent challenge. Various sampling and analytical methods are available, but they typically require accepting a tradeoff between accuracy and computational efficiency. In this work, a surrogate-based approach is presented that simultaneously addresses the issues of accuracy, efficiency, and unimportant failure modes. The method is based on the creation of Gaussian process surrogate models that are required to be locally accurate only in the regions of the component limit states that contribute to system failure. This approach to constructing surrogate models is demonstrated to be both an efficient and accurate method for system-level reliability analysis. - Highlights: → Extends efficient global reliability analysis to systems with multiple failure modes. → Constructs locally accurate Gaussian process models of each response. → Highly efficient and accurate method for assessing system reliability. → Effectiveness is demonstrated on several test problems from the literature.

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

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

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.

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

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.

Evaluation of a multi-marker immunomagnetic enrichment assay for the quantification of circulating melanoma cells

Directory of Open Access Journals (Sweden)

Freeman James B

2012-09-01

Full Text Available Abstract Background Circulating melanoma cells (CMCs are thought to be valuable in improving measures of prognosis in melanoma patients and may be a useful marker of residual disease to identify non-metastatic patients requiring adjuvant therapy. We investigated whether immunomagnetic enrichment targeting multiple markers allows more efficient enrichment of CMCs from patient peripheral blood than targeting a single marker. Furthermore, we aimed to determine whether the number of CMCs in patient blood was associated with disease stage. Methods We captured CMCs by targeting the melanoma associated markers MCSP and MCAM as well as the melanoma stem cell markers ABCB5 and CD271, both individually and in combination, by immunomagnetic enrichment. CMCs were enriched and quantified from the peripheral blood of 10 non-metastatic and 13 metastatic melanoma patients. Results Targeting all markers in combination resulted in the enrichment of more CMCs than when any individual marker was targeted (p  Conclusions Our results demonstrated that a combination of markers should be targeted for optimal isolation of CMCs. In addition, there are significantly more CMCs in metastatic patients compared with non-metastatic patients and therefore quantification of CMCs may prove to be a useful marker of disease progression.

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.

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.

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

Recovering valuable liquid hydrocarbons

Energy Technology Data Exchange (ETDEWEB)

Pier, M

1931-06-11

A process for recovering valuable liquid hydrocarbons from coking coal, mineral coal, or oil shale through treatment with hydrogen under pressure at elevated temperature is described. Catalysts and grinding oil may be used in the process if necessary. The process provides for deashing the coal prior to hydrogenation and for preventing the coking and swelling of the deashed material. During the treatment with hydrogen, the coal is either mixed with coal low in bituminous material, such as lean coal or active coal, as a diluent or the bituminous constituents which cause the coking and swelling are removed by extraction with solvents. (BLM)

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.

Ravens reconcile after aggressive conflicts with valuable partners.

Science.gov (United States)

Fraser, Orlaith N; Bugnyar, Thomas

2011-03-25

Reconciliation, a post-conflict affiliative interaction between former opponents, is an important mechanism for reducing the costs of aggressive conflict in primates and some other mammals as it may repair the opponents' relationship and reduce post-conflict distress. Opponents who share a valuable relationship are expected to be more likely to reconcile as for such partners the benefits of relationship repair should outweigh the risk of renewed aggression. In birds, however, post-conflict behavior has thus far been marked by an apparent absence of reconciliation, suggested to result either from differing avian and mammalian strategies or because birds may not share valuable relationships with partners with whom they engage in aggressive conflict. Here, we demonstrate the occurrence of reconciliation in a group of captive subadult ravens (Corvus corax) and show that it is more likely to occur after conflicts between partners who share a valuable relationship. Furthermore, former opponents were less likely to engage in renewed aggression following reconciliation, suggesting that reconciliation repairs damage caused to their relationship by the preceding conflict. Our findings suggest not only that primate-like valuable relationships exist outside the pair bond in birds, but that such partners may employ the same mechanisms in birds as in primates to ensure that the benefits afforded by their relationships are maintained even when conflicts of interest escalate into aggression. These results provide further support for a convergent evolution of social strategies in avian and mammalian species.

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

How taxonomic diversity, community structure, and sample size determine the reliability of higher taxon surrogates.

Science.gov (United States)

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

2013-07-01

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

High content screening for G protein-coupled receptors using cell-based protein translocation assays

DEFF Research Database (Denmark)

Grånäs, Charlotta; Lundholt, Betina Kerstin; Heydorn, Arne

2005-01-01

G protein-coupled receptors (GPCRs) have been one of the most productive classes of drug targets for several decades, and new technologies for GPCR-based discovery promise to keep this field active for years to come. While molecular screens for GPCR receptor agonist- and antagonist-based drugs...... will continue to be valuable discovery tools, the most exciting developments in the field involve cell-based assays for GPCR function. Some cell-based discovery strategies, such as the use of beta-arrestin as a surrogate marker for GPCR function, have already been reduced to practice, and have been used...... as valuable discovery tools for several years. The application of high content cell-based screening to GPCR discovery has opened up additional possibilities, such as direct tracking of GPCRs, G proteins and other signaling pathway components using intracellular translocation assays. These assays provide...

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

Psychological trait and state characteristics, social support and attitudes to the surrogate pregnancy and baby.

Science.gov (United States)

van den Akker, Olga B A

2007-08-01

Personality differences between surrogate mothers (SMs) who gestate and relinquish and intended mothers (IMs) who commission a genetically related or unrelated baby have been unexplored in the UK. Furthermore, the psychological effects of the arrangement have not been determined in a prospective longitudinal study, making this the first quantitative report of psychological functioning in SMs and IMs. SMs and IMs (n = 81: 61 surrogate, 20 intended) undergoing genetic or gestational surrogacy (4 groups) were assessed by postal questionnaire during the first, second and third trimesters of pregnancy. Those with a positive outcome were assessed again in the first week, at 6 weeks and 6 months post-delivery of the surrogate baby. There were no significant differences between or within SM and IM groups on personality characteristics. Social support, marital harmony and state anxiety differed significantly (to P pregnancy and the baby were also observed between groups during pregnancy (to P surrogate arrangement are notable and occur over an extended period of time. It also shows that psychological screening and support prior to, during and following surrogacy is indicated.

Environmental and geographic variables are effective surrogates for genetic variation in conservation planning.

Science.gov (United States)

Hanson, Jeffrey O; Rhodes, Jonathan R; Riginos, Cynthia; Fuller, Richard A

2017-11-28

Protected areas buffer species from anthropogenic threats and provide places for the processes that generate and maintain biodiversity to continue. However, genetic variation, the raw material for evolution, is difficult to capture in conservation planning, not least because genetic data require considerable resources to obtain and analyze. Here we show that freely available environmental and geographic distance variables can be highly effective surrogates in conservation planning for representing adaptive and neutral intraspecific genetic variation. We obtained occurrence and genetic data from the IntraBioDiv project for 27 plant species collected over the European Alps using a gridded sampling scheme. For each species, we identified loci that were potentially under selection using outlier loci methods, and mapped their main gradients of adaptive and neutral genetic variation across the grid cells. We then used the cells as planning units to prioritize protected area acquisitions. First, we verified that the spatial patterns of environmental and geographic variation were correlated, respectively, with adaptive and neutral genetic variation. Second, we showed that these surrogates can predict the proportion of genetic variation secured in randomly generated solutions. Finally, we discovered that solutions based only on surrogate information secured substantial amounts of adaptive and neutral genetic variation. Our work paves the way for widespread integration of surrogates for genetic variation into conservation planning.

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

KAUST Repository

Shankar, Vijai S B

2015-03-30

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

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

KAUST Repository

Shankar, Vijai S B; Al-Qurashi, Khalid; Ahmed, Ahfaz; Atef, Nour; Chung, Suk-Ho; Roberts, William L.; Sarathy, Mani

2015-01-01

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

Laminar Flame Speeds of Gasoline Surrogates Measured with the Flat Flame Method

KAUST Repository

Liao, Y.-H.

2016-01-27

© 2016 American Chemical Society. The adiabatic, laminar flame speeds of gasoline surrogates at atmospheric pressure over a range of equivalence ratios of = 0.8-1.3 and unburned gas temperatures of 298-400 K are measured with the flat flame method, which produces a one-dimensional flat flame free of stretch. Surrogates used in the current work are the primary reference fuels (PRFs, mixtures of n-heptane and isooctane), the toluene reference fuels (TRFs, mixtures of toluene and PRFs), and the ethanol reference fuels (ERFs, mixtures of ethanol and PRFs). In general, there is good agreement between the present work and the literature data for single-component fuel and PRF mixtures. Surrogates of TRF mixtures are found to exhibit comparable flame speeds to a real gasoline, while there is discrepancy observed between isooctane and gasoline. Moreover, the laminar flame speeds of TRF mixtures with similar fractions of n-heptane are found to be insensitive to the quantity of toluene in the mixture. Mixtures of ERFs exhibit comparable flame speeds to those of TRFs with similar mole fractions of n-heptane and isooctane.

Surrogate mothers 10 years on: A longitudinal study of psychological wellbeing and relationships with the parents and child

OpenAIRE

Jadva, Vasanti Harish; Imrie, S; Golombok, Susan Esther

2014-01-01

Study Question: How do surrogates psychological health and experiences of surrogacy change from one year to ten years following the birth of the surrogacy child? Summary answer: Surrogates’ psychological well-being did not change ten years following the birth, with the majority continuing to report good mental health andall surrogates remained positive about the surrogacy arrangement. What is known already: Studies have found that surrogates may find the weeks following the birth difficu...

Fast and Accurate Prediction of Numerical Relativity Waveforms from Binary Black Hole Coalescences Using Surrogate Models.

Science.gov (United States)

Blackman, Jonathan; Field, Scott E; Galley, Chad R; Szilágyi, Béla; Scheel, Mark A; Tiglio, Manuel; Hemberger, Daniel A

2015-09-18

Simulating a binary black hole coalescence by solving Einstein's equations is computationally expensive, requiring days to months of supercomputing time. Using reduced order modeling techniques, we construct an accurate surrogate model, which is evaluated in a millisecond to a second, for numerical relativity (NR) waveforms from nonspinning binary black hole coalescences with mass ratios in [1, 10] and durations corresponding to about 15 orbits before merger. We assess the model's uncertainty and show that our modeling strategy predicts NR waveforms not used for the surrogate's training with errors nearly as small as the numerical error of the NR code. Our model includes all spherical-harmonic _{-2}Y_{ℓm} waveform modes resolved by the NR code up to ℓ=8. We compare our surrogate model to effective one body waveforms from 50M_{⊙} to 300M_{⊙} for advanced LIGO detectors and find that the surrogate is always more faithful (by at least an order of magnitude in most cases).

Premixed flame chemistry of a gasoline primary reference fuel surrogate

KAUST Repository

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

2017-01-01

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

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

Directory of Open Access Journals (Sweden)

Patrick P J Phillips

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

Development of a post-intensive care unit storytelling intervention for surrogates involved in decisions to limit life-sustaining treatment.

Science.gov (United States)

Schenker, Yael; Dew, Mary Amanda; Reynolds, Charles F; Arnold, Robert M; Tiver, Greer A; Barnato, Amber E

2015-06-01

Surrogates involved in decisions to limit life-sustaining treatment for a loved one in the intensive care unit (ICU) are at increased risk for adverse psychological outcomes that can last for months to years after the ICU experience. Post-ICU interventions to reduce surrogate distress have not yet been developed. We sought to (1) describe a conceptual framework underlying the beneficial mental health effects of storytelling, and (2) present formative work developing a storytelling intervention to reduce distress for recently bereaved surrogates. An interdisciplinary team conceived the idea for a storytelling intervention based on evidence from narrative theory that storytelling reduces distress from traumatic events through emotional disclosure, cognitive processing, and social connection. We developed an initial storytelling guide based on this theory and the clinical perspectives of team members. We then conducted a case series with recently bereaved surrogates to iteratively test and modify the guide. The storytelling guide covered three key domains of the surrogate's experience of the patient's illness and death: antecedents, ICU experience, and aftermath. The facilitator focused on the parts of a story that appeared to generate strong emotions and used nonjudgmental statements to attend to these emotions. Between September 2012 and May 2013, we identified 28 eligible surrogates from a medical ICU and consented 20 for medical record review and recontact; 10 became eligible, of whom 6 consented and completed the storytelling intervention. The single-session storytelling intervention lasted from 40 to 92 minutes. All storytelling participants endorsed the intervention as acceptable, and five of six reported it as helpful. Surrogate storytelling is an innovative and acceptable post-ICU intervention for recently bereaved surrogates and should be evaluated further.

Accelerated Monte Carlo system reliability analysis through machine-learning-based surrogate models of network connectivity

International Nuclear Information System (INIS)

Stern, R.E.; Song, J.; Work, D.B.

2017-01-01

The two-terminal reliability problem in system reliability analysis is known to be computationally intractable for large infrastructure graphs. Monte Carlo techniques can estimate the probability of a disconnection between two points in a network by selecting a representative sample of network component failure realizations and determining the source-terminal connectivity of each realization. To reduce the runtime required for the Monte Carlo approximation, this article proposes an approximate framework in which the connectivity check of each sample is estimated using a machine-learning-based classifier. The framework is implemented using both a support vector machine (SVM) and a logistic regression based surrogate model. Numerical experiments are performed on the California gas distribution network using the epicenter and magnitude of the 1989 Loma Prieta earthquake as well as randomly-generated earthquakes. It is shown that the SVM and logistic regression surrogate models are able to predict network connectivity with accuracies of 99% for both methods, and are 1–2 orders of magnitude faster than using a Monte Carlo method with an exact connectivity check. - Highlights: • Surrogate models of network connectivity are developed by machine-learning algorithms. • Developed surrogate models can reduce the runtime required for Monte Carlo simulations. • Support vector machine and logistic regressions are employed to develop surrogate models. • Numerical example of California gas distribution network demonstrate the proposed approach. • The developed models have accuracies 99%, and are 1–2 orders of magnitude faster than MCS.

Surrogacy: outcomes for surrogate mothers, children and the resulting families-a systematic review.

Science.gov (United States)

Söderström-Anttila, Viveca; Wennerholm, Ulla-Britt; Loft, Anne; Pinborg, Anja; Aittomäki, Kristiina; Romundstad, Liv Bente; Bergh, Christina

2016-01-01

Surrogacy is a highly debated method mainly used for treating women with infertility caused by uterine factors. This systematic review summarizes current levels of knowledge of the obstetric, medical and psychological outcomes for the surrogate mothers, the intended parents and children born as a result of surrogacy. PubMed, Cochrane and Embase databases up to February 2015 were searched. Cohort studies and case series were included. Original studies published in English and the Scandinavian languages were included. In case of double publications, the latest study was included. Abstracts only and case reports were excluded. Studies with a control group and case series (more than three cases) were included. Cohort studies, but not case series, were assessed for methodological quality, in terms of risk of bias. We examined a variety of main outcomes for the surrogate mothers, children and intended mothers, including obstetric outcome, relationship between surrogate mother and intended couple, surrogate's experiences after relinquishing the child, preterm birth, low birthweight, birth defects, perinatal mortality, child psychological development, parent-child relationship, and disclosure to the child. The search returned 1795 articles of which 55 met the inclusion criteria. The medical outcome for the children was satisfactory and comparable to previous results for children conceived after fresh IVF and oocyte donation. The rate of multiple pregnancies was 2.6-75.0%. Preterm birth rate in singletons varied between 0 and 11.5% and low birthweight occurred in between 0 and 11.1% of cases. At the age of 10 years there were no major psychological differences between children born after surrogacy and children born after other types of assisted reproductive technology (ART) or after natural conception. The obstetric outcomes for the surrogate mothers were mainly reported from case series. Hypertensive disorders in pregnancy were reported in between 3.2 and 10% of cases and

A CROSS SECTIONAL STUDY TO FIND THE DIFFERENCE IN SYSTOLIC BLOOD PRESSURE BETWEEN ARMS AS A RISK MARKER FOR DIABETIC NEPHROPATHY IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

OpenAIRE

Uday Subhash Bande; Anish Anthony Tekkinadath

2016-01-01

BACKGROUND Diabetic nephropathy is the commonest cause of end-stage renal disease in the developed world. Recent studies have demonstrated that a difference in systolic blood pressure between arms is associated with cardiovascular disease and microalbuminuria. It is considered a predictor for cardiovascular disease and a surrogate marker for early kidney damage among patients with both type 2 diabetes and hypertension. AIMS AND OBJECTIVES The aim was to investigate an associ...

Development and pilot testing of a decision aid for surrogates of patients with prolonged mechanical ventilation

Science.gov (United States)

Cox, Christopher E.; Lewis, Carmen L.; Hanson, Laura C.; Hough, Catherine L.; Kahn, Jeremy M.; White, Douglas B.; Song, Mi-Kyung; Tulsky, James A.; Carson, Shannon S.

2013-01-01

Objective Shared decision making is inadequate in intensive care units (ICUs). Decision aids can improve decision making quality, though their role in an ICU setting is unclear. We aimed to develop and pilot test a decision aid for shared decision makers of patients undergoing prolonged mechanical ventilation. Setting ICUs at three medical centers. Subjects 53 surrogate decision makers and 58 physicians. Design and interventions We developed the decision aid using defined methodological guidelines. After an iterative revision process, formative cognitive testing was performed among surrogate-physician dyads. Next, we compared the decision aid to usual care control in a prospective, before/after design study. Measurements and main results Primary outcomes were physician-surrogate discordance for expected patient survival, comprehension of relevant medical information, and the quality of communication. Compared to control, the intervention group had lower surrogate-physician discordance (7 [10] vs 43 [21]), greater comprehension (11.4 [0.7] vs 6.1 [3.7]), and improved quality of communication (8.7 [1.3] vs 8.4 [1.3]) (all ppost-intervention. Hospital costs were lower in the intervention group ($110,609 vs $178,618; p=0.044); mortality did not differ by group (38% vs 50%, p=0.95). 94% of surrogates and 100% of physicians reported that the decision aid was useful in decision making. Conclusion We developed a prolonged mechanical ventilation decision aid that is feasible, acceptable, and associated with both improved decision making quality and less resource utilization. Further evaluation using a randomized controlled trial design is needed to evaluate the decision aid's effect on long-term patient and surrogate outcomes. PMID:22635048

Airfoil Shape Optimization based on Surrogate Model

Science.gov (United States)

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

2018-02-01

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

Germ cell transplantation using sexually competent fish: an approach for rapid propagation of endangered and valuable germlines.

Directory of Open Access Journals (Sweden)

Sullip K Majhi

Full Text Available The transplantation of germ cells into adult recipient gonads is a tool with wide applications in animal breeding and conservation of valuable and/or endangered species; it also provides a means for basic studies involving germ cell (GC proliferation and differentiation. Here we describe the establishment of a working model for xenogeneic germ cell transplantation (GCT in sexually competent fish. Spermatogonial cells isolated from juveniles of one species, the pejerrey Odontesthes bonariensis (Atherinopsidae, were surgically transplanted into the gonads of sexually mature Patagonian pejerrey O. hatcheri, which have been partially depleted of endogenous GCs by a combination of Busulfan (40 mg/kg and high water temperature (25 degrees C treatments. The observation of the donor cells' behavior showed that transplanted spermatogonial cells were able to recolonize the recipients' gonads and resume spermatogenesis within 6 months from the GCT. The presence of donor-derived gametes was confirmed by PCR in 20% of the surrogate O. hatcheri fathers at 6 months and crosses with O. bonariensis mothers produced hybrids and pure O. bonariensis, with donor-derived germline transmission rates of 1.2-13.3%. These findings indicate that transplantation of spermatogonial cells into sexually competent fish can shorten considerably the production time of donor-derived gametes and offspring and could play a vital role in germline conservation and propagation of valued and/or endangered fish species.

CmMDb: a versatile database for Cucumis melo microsatellite markers and other horticulture crop research.

Science.gov (United States)

Bhawna; Chaduvula, Pavan K; Bonthala, Venkata S; Manjusha, Verma; Siddiq, Ebrahimali A; Polumetla, Ananda K; Prasad, Gajula M N V

2015-01-01

Cucumis melo L. that belongs to Cucurbitaceae family ranks among one of the highest valued horticulture crops being cultivated across the globe. Besides its economical and medicinal importance, Cucumis melo L. is a valuable resource and model system for the evolutionary studies of cucurbit family. However, very limited numbers of molecular markers were reported for Cucumis melo L. so far that limits the pace of functional genomic research in melon and other similar horticulture crops. We developed the first whole genome based microsatellite DNA marker database of Cucumis melo L. and comprehensive web resource that aids in variety identification and physical mapping of Cucurbitaceae family. The Cucumis melo L. microsatellite database (CmMDb: http://65.181.125.102/cmmdb2/index.html) encompasses 39,072 SSR markers along with its motif repeat, motif length, motif sequence, marker ID, motif type and chromosomal locations. The database is featured with novel automated primer designing facility to meet the needs of wet lab researchers. CmMDb is a freely available web resource that facilitates the researchers to select the most appropriate markers for marker-assisted selection in melons and to improve breeding strategies.

Physical and mechanical properties of degraded waste surrogate material

International Nuclear Information System (INIS)

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

1998-03-01

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

Surrogate reservoir models for CSI well probabilistic production forecast

Directory of Open Access Journals (Sweden)

Saúl Buitrago

2017-09-01

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

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

DEFF Research Database (Denmark)

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

2013-01-01

The aim of this study is to evaluate the existing chemical kinetic mechanism reduction techniques. From here, an appropriate reduction scheme was developed to create compact yet comprehensive surrogate models for both diesel and biodiesel fuels for diesel engine applications. The reduction...... techniques applied here were Directed Relation Graph (DRG), DRG with Error Propagation, DRG-aided Sensitivity Analysis, and DRG with Error Propagation and Sensitivity Analysis. Nonetheless, the reduced mechanisms generated via these techniques were not sufficiently small for application in multi......-dimensional computational fluid dynamics (CFD) study. A new reduction scheme was therefore formulated. A 68-species mechanism for biodiesel surrogate and a 49-species mechanism for diesel surrogate were successfully derived from the respective detailed mechanisms. An overall 97% reduction in species number...

Genetic Diversity Analysis of South and East Asian Duck Populations Using Highly Polymorphic Microsatellite Markers

Directory of Open Access Journals (Sweden)

Dongwon Seo

2016-04-01

Full Text Available Native duck populations have lower productivity, and have not been developed as much as commercials duck breeds. However, native ducks have more importance in terms of genetic diversity and potentially valuable economic traits. For this reason, population discriminable genetic markers are needed for conservation and development of native ducks. In this study, 24 highly polymorphic microsatellite (MS markers were investigated using commercial ducks and native East and South Asian ducks. The average polymorphic information content (PIC value for all MS markers was 0.584, indicating high discrimination power. All populations were discriminated using 14 highly polymorphic MS markers by genetic distance and phylogenetic analysis. The results indicated that there were close genetic relationships among populations. In the structure analysis, East Asian ducks shared more haplotypes with commercial ducks than South Asian ducks, and they had more independent haplotypes than others did. These results will provide useful information for genetic diversity studies in ducks and for the development of duck traceability systems in the market.

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

OpenAIRE

Bonnetain Franck; Bedenne Laurent; Methy Nicolas

2010-01-01

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

Efficient stochastic EMC/EMI analysis using HDMR-generated surrogate models

KAUST Repository

Yücel, Abdulkadir C.

2011-08-01

Stochastic methods have been used extensively to quantify effects due to uncertainty in system parameters (e.g. material, geometrical, and electrical constants) and/or excitation on observables pertinent to electromagnetic compatibility and interference (EMC/EMI) analysis (e.g. voltages across mission-critical circuit elements) [1]. In recent years, stochastic collocation (SC) methods, especially those leveraging generalized polynomial chaos (gPC) expansions, have received significant attention [2, 3]. SC-gPC methods probe surrogate models (i.e. compact polynomial input-output representations) to statistically characterize observables. They are nonintrusive, that is they use existing deterministic simulators, and often cost only a fraction of direct Monte-Carlo (MC) methods. Unfortunately, SC-gPC-generated surrogate models often lack accuracy (i) when the number of uncertain/random system variables is large and/or (ii) when the observables exhibit rapid variations. © 2011 IEEE.

Italian gay fathers' experiences of transnational surrogacy and their relationship with the surrogate pre- and post-birth.

Science.gov (United States)

Carone, Nicola; Baiocco, Roberto; Lingiardi, Vittorio

2017-02-01

This study aims to explore the experience of transnational surrogacy and the relationship with the surrogate pre- and post-birth in Italian gay father families. Couple and individual semi-structured interviews were carried out with 30 Italian gay partnered fathers with at least one child born through gestational surrogacy in California or Canada. No couples had known their surrogates or egg donors previously. The Interpretative Phenomenological Analysis indicated that three interrelated themes could be helpful for understanding the gay fathers' experience of their geographical distance from the surrogate: the perceived loss of control over the pregnancy; the surrogate as a person who facilitates the fathers' feelings of being emotionally connected to their developing child; the surrogate as an 'aunty' who, along with her family, maintains a relationship with the fathers. None of the fathers mentioned the egg donor during the interview. The study inspires reflections in offshore fertility practitioners on how pre- and ongoing surrogacy counselling for prospective gay fathers should be tailored. It further calls for the necessity of offering psychological counselling in gay fathers' resident countries in order to promote informed decisions before starting surrogacy abroad and to elaborate on potential difficulties related to surrogacy after the child's birth. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

A Parallel and Distributed Surrogate Model Implementation for Computational Steering

KAUST Repository

Butnaru, Daniel; Buse, Gerrit; Pfluger, Dirk

2012-01-01

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

Efficient stochastic EMC/EMI analysis using HDMR-generated surrogate models

KAUST Repository

Yü cel, Abdulkadir C.; Bagci, Hakan; Michielssen, Eric

2011-01-01

of direct Monte-Carlo (MC) methods. Unfortunately, SC-gPC-generated surrogate models often lack accuracy (i) when the number of uncertain/random system variables is large and/or (ii) when the observables exhibit rapid variations. © 2011 IEEE.

TU-CD-BRA-05: Atlas Selection for Multi-Atlas-Based Image Segmentation Using Surrogate Modeling

International Nuclear Information System (INIS)

Zhao, T; Ruan, D

2015-01-01

Purpose: The growing size and heterogeneity in training atlas necessitates sophisticated schemes to identify only the most relevant atlases for the specific multi-atlas-based image segmentation problem. This study aims to develop a model to infer the inaccessible oracle geometric relevance metric from surrogate image similarity metrics, and based on such model, provide guidance to atlas selection in multi-atlas-based image segmentation. Methods: We relate the oracle geometric relevance metric in label space to the surrogate metric in image space, by a monotonically non-decreasing function with additive random perturbations. Subsequently, a surrogate’s ability to prognosticate the oracle order for atlas subset selection is quantified probabilistically. Finally, important insights and guidance are provided for the design of fusion set size, balancing the competing demands to include the most relevant atlases and to exclude the most irrelevant ones. A systematic solution is derived based on an optimization framework. Model verification and performance assessment is performed based on clinical prostate MR images. Results: The proposed surrogate model was exemplified by a linear map with normally distributed perturbation, and verified with several commonly-used surrogates, including MSD, NCC and (N)MI. The derived behaviors of different surrogates in atlas selection and their corresponding performance in ultimate label estimate were validated. The performance of NCC and (N)MI was similarly superior to MSD, with a 10% higher atlas selection probability and a segmentation performance increase in DSC by 0.10 with the first and third quartiles of (0.83, 0.89), compared to (0.81, 0.89). The derived optimal fusion set size, valued at 7/8/8/7 for MSD/NCC/MI/NMI, agreed well with the appropriate range [4, 9] from empirical observation. Conclusion: This work has developed an efficacious probabilistic model to characterize the image-based surrogate metric on atlas selection

Testing serial dependence by Random-shuffle surrogates and the Wayland method

Energy Technology Data Exchange (ETDEWEB)

Hirata, Yoshito [Department of Mathematical Informatics, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan); Aihara Complexity Modelling Project, ERATO, JST (Japan); Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505 (Japan)], E-mail: yoshito@sat.t.u-tokyo.ac.jp; Horai, Shunsuke [Aihara Complexity Modelling Project, ERATO, JST (Japan); Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505 (Japan); Suzuki, Hideyuki [Department of Mathematical Informatics, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan); Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505 (Japan); Aihara, Kazuyuki [Department of Mathematical Informatics, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan); Aihara Complexity Modelling Project, ERATO, JST (Japan); Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505 (Japan)

2007-10-22

Given time series, a primary concern is existence of serial dependence and determinism. They are often tested with Random-shuffle surrogates, which totally break serial dependence, and the Wayland method. Since the statistic of the Wayland method fundamentally shows a smaller value for a more deterministic time series, for real-world data, we usually expect that the statistic for the original data is smaller than or equal to those of Random-shuffle surrogates. However, we show herewith an opposite result with wind data in high time resolution. We argue that this puzzling phenomenon can be produced by observational or dynamical noise, both of which may be produced by a low-dimensional deterministic system. Thus the one-sided test is dangerous.

Testing serial dependence by Random-shuffle surrogates and the Wayland method

International Nuclear Information System (INIS)

Hirata, Yoshito; Horai, Shunsuke; Suzuki, Hideyuki; Aihara, Kazuyuki

2007-01-01

Given time series, a primary concern is existence of serial dependence and determinism. They are often tested with Random-shuffle surrogates, which totally break serial dependence, and the Wayland method. Since the statistic of the Wayland method fundamentally shows a smaller value for a more deterministic time series, for real-world data, we usually expect that the statistic for the original data is smaller than or equal to those of Random-shuffle surrogates. However, we show herewith an opposite result with wind data in high time resolution. We argue that this puzzling phenomenon can be produced by observational or dynamical noise, both of which may be produced by a low-dimensional deterministic system. Thus the one-sided test is dangerous

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

Science.gov (United States)

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

2014-01-01

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

Corpus callosum thickness on mid-sagittal MRI as a marker of brain volume: a pilot study in children with HIV-related brain disease and controls

Energy Technology Data Exchange (ETDEWEB)

Andronikou, Savvas [University of the Witwatersrand, Department of Radiology, Faculty of Health Sciences, Cape Town (South Africa); Ackermann, Christelle [University of Stellenbosch, Department of Radiology, Stellenbosch (South Africa); Laughton, Barbara; Cotton, Mark [Stellenbosch University and Tygerberg Children' s Hospital, Children' s Infectious Diseases Research Unit, Stellenbosch (South Africa); Tomazos, Nicollette [University of Cape Town, Faculty of Commerce, Department of Management Studies, Cape Town (South Africa); Spottiswoode, Bruce [University of Cape Town, MRC/UCT Medical Imaging Research Unit, Department of Human Biology, Cape Town (South Africa); Mauff, Katya [University of Cape Town, Department of Statistical Sciences, Cape Town (South Africa); Pettifor, John M. [University of the Witwatersrand, MRC/Wits Developmental Pathways for Health Research Unit, Department of Paediatrics, Faculty of Health Sciences, Witwatersrand (South Africa)

2015-07-15

Corpus callosum thickness measurement on mid-sagittal MRI may be a surrogate marker of brain volume. This is important for evaluation of diseases causing brain volume gain or loss, such as HIV-related brain disease and HIV encephalopathy. To determine if thickness of the corpus callosum on mid-sagittal MRI is a surrogate marker of brain volume in children with HIV-related brain disease and in controls without HIV. A retrospective MRI analysis in children (<5 years old) with HIV-related brain disease and controls used a custom-developed semi-automated tool, which divided the midline corpus callosum and measured its thickness in multiple locations. Brain volume was determined using volumetric analysis. Overall corpus callosum thickness and thickness of segments of the corpus callosum were correlated with overall and segmented (grey and white matter) brain volume. Forty-four children (33 HIV-infected patients and 11 controls) were included. Significant correlations included overall corpus callosum (mean) and total brain volume (P = 0.05); prefrontal corpus callosum maximum with white matter volume (P = 0.02); premotor corpus callosum mean with total brain volume (P = 0.04) and white matter volume (P = 0.02), premotor corpus callosum maximum with white matter volume (P = 0.02) and sensory corpus callosum mean with total brain volume (P = 0.02). Corpus callosum thickness correlates with brain volume both in HIV-infected patients and controls. (orig.)

Corpus callosum thickness on mid-sagittal MRI as a marker of brain volume: a pilot study in children with HIV-related brain disease and controls

International Nuclear Information System (INIS)

Andronikou, Savvas; Ackermann, Christelle; Laughton, Barbara; Cotton, Mark; Tomazos, Nicollette; Spottiswoode, Bruce; Mauff, Katya; Pettifor, John M.

2015-01-01

Corpus callosum thickness measurement on mid-sagittal MRI may be a surrogate marker of brain volume. This is important for evaluation of diseases causing brain volume gain or loss, such as HIV-related brain disease and HIV encephalopathy. To determine if thickness of the corpus callosum on mid-sagittal MRI is a surrogate marker of brain volume in children with HIV-related brain disease and in controls without HIV. A retrospective MRI analysis in children (<5 years old) with HIV-related brain disease and controls used a custom-developed semi-automated tool, which divided the midline corpus callosum and measured its thickness in multiple locations. Brain volume was determined using volumetric analysis. Overall corpus callosum thickness and thickness of segments of the corpus callosum were correlated with overall and segmented (grey and white matter) brain volume. Forty-four children (33 HIV-infected patients and 11 controls) were included. Significant correlations included overall corpus callosum (mean) and total brain volume (P = 0.05); prefrontal corpus callosum maximum with white matter volume (P = 0.02); premotor corpus callosum mean with total brain volume (P = 0.04) and white matter volume (P = 0.02), premotor corpus callosum maximum with white matter volume (P = 0.02) and sensory corpus callosum mean with total brain volume (P = 0.02). Corpus callosum thickness correlates with brain volume both in HIV-infected patients and controls. (orig.)

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

African Journals Online (AJOL)

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

Toward a psychology of surrogate decision-making

OpenAIRE

Tunney, Richard J.; Ziegler, Fenja

2016-01-01

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

The effect of emotion and physician communication behaviors on surrogates' life-sustaining treatment decisions: a randomized simulation experiment.

Science.gov (United States)

Barnato, Amber E; Arnold, Robert M

2013-07-01

Surrogate decision makers for critically ill patients experience strong negative emotional states. Emotions influence risk perception, risk preferences, and decision making. We sought to explore the effect of emotional state and physician communication behaviors on surrogates' life-sustaining treatment decisions. 5 × 2 between-subject randomized factorial experiment. Web-based simulated interactive video meeting with an intensivist to discuss code status. Community-based participants 35 and older who self-identified as the surrogate for a parent or spouse recruited from eight U.S. cities through public advertisements. Block random assignment to emotion arousal manipulation and each of the four physician communication behaviors. Surrogate's code status decision (cardiopulmonary resuscitation vs do not resuscitate/allow natural death). Two hundred fifty-six of 373 respondents (69%) logged-in and were randomized: average age was 50; 70% were surrogates for a parent; 63.5% were women; 76% were white, 11% black, and 9% Asian; and 81% were college educated. When asked about code status, 56% chose cardiopulmonary resuscitation. The emotion arousal manipulation increased the score on depression-dejection scale (β = 1.76 [0.58 - 2.94]) but did not influence cardiopulmonary resuscitation choice. Physician attending to emotion and framing the decision as the patient's rather than the surrogate's did not influence cardiopulmonary resuscitation choice. Framing no cardiopulmonary resuscitation as the norm rather than cardiopulmonary resuscitation resulted in fewer surrogates choosing cardiopulmonary resuscitation (48% vs 64%, odds ratio, 0.52 [95% CI, 0.32-0.87]), as did framing the alternative to cardiopulmonary resuscitation as "allow natural death" rather than do not resuscitate (49% vs 61%, odds ratio, 0.58 [95% CI, 0.35-0.96]). Experimentally induced emotional state did not influence code status decisions, although small changes in physician communication behaviors

Family matters: effects of birth order, culture, and family dynamics on surrogate decision-making.

Science.gov (United States)

Su, Christopher T; McMahan, Ryan D; Williams, Brie A; Sharma, Rashmi K; Sudore, Rebecca L

2014-01-01

Cultural attitudes about medical decision-making and filial expectations may lead some surrogates to experience stress and family conflict. Thirteen focus groups with racially and ethnically diverse English and Spanish speakers from county and Veterans Affairs hospitals, senior centers, and cancer support groups were conducted to describe participants' experiences making serious or end-of-life decisions for others. Filial expectations and family dynamics related to birth order and surrogate decision-making were explored using qualitative, thematic content analysis, and overarching themes from focus group transcripts were identified. The mean age of the 69 participants was 69 ± 14, and 29% were African American, 26% were white, 26% were Asian or Pacific Islander, and 19% were Latino. Seventy percent of participants engaged in unprompted discussions about birth order and family dynamics. Six subthemes were identified within three overarching categories: communication (unspoken expectations and discussion of death as taboo), emotion (emotional stress and feelings of loneliness), and conflict (family conflict and potential solutions to prevent conflict). These findings suggest that birth order and family dynamics can have profound effects on surrogate stress and coping. Clinicians should be aware of potential unspoken filial expectations for firstborns and help facilitate communication between the patient, surrogate, and extended family to reduce stress and conflict. © Published 2013. This article is a U.S. Government work and is in the public domain in the U.S.A.

Family Matters: Effects of Birth Order, Culture, and Family Dynamics on Surrogate Decision Making

Science.gov (United States)

Su, Christopher T.; McMahan, Ryan D.; Williams, Brie A.; Sharma, Rashmi K.; Sudore, Rebecca L.

2014-01-01

Cultural attitudes about medical decision making and filial expectations may lead some surrogates to experience stress and family conflict. Thirteen focus groups with racially and ethnically diverse English- and Spanish-speakers from county and Veterans hospitals, senior centers, and cancer support groups were conducted to describe participants’ experiences making serious or end-of-life decisions for others. Filial expectations and family dynamics related to birth order and surrogate decision making were explored using qualitative, thematic content analysis and overarching themes from focus group transcripts were identified. The mean age of the 69 participants was 69 years ± 14 and 29% were African American, 26% were White, 26% were Asian/Pacific Islander, and 19% were Latino. Seventy percent of participants engaged in unprompted discussions about birth order and family dynamics. Six subthemes were identified within 3 overarching categories of communication, emotion, and conflict: Communication – (1) unspoken expectations and (2) discussion of death as taboo; Emotion – (3) emotional stress and (4) feelings of loneliness; and Conflict – (5) family conflict and (6) potential solutions to prevent conflict. These findings suggest that birth order and family dynamics can have profound effects on surrogate stress and coping. Clinicians should be aware of potential unspoken filial expectations for firstborns and help facilitate communication between the patient, surrogate, and extended family to reduce stress and conflict. PMID:24383459

Spermatogonial stem cell markers and niche in equids.

Directory of Open Access Journals (Sweden)

Guilherme M J Costa

Full Text Available Spermatogonial stem cells (SSCs are the foundation of spermatogenesis and are located in a highly dynamic microenvironment called "niche" that influences all aspects of stem cell function, including homing, self-renewal and differentiation. Several studies have recently identified specific proteins that regulate the fate of SSCs. These studies also aimed at identifying surface markers that would facilitate the isolation of these cells in different vertebrate species. The present study is the first to investigate SSC physiology and niche in stallions and to offer a comparative evaluation of undifferentiated type A spermatogonia (Aund markers (GFRA1, PLZF and CSF1R in three different domestic equid species (stallions, donkeys, and mules. Aund were first characterized according to their morphology and expression of the GFRA1 receptor. Our findings strongly suggest that in stallions these cells were preferentially located in the areas facing the interstitium, particularly those nearby blood vessels. This distribution is similar to what has been observed in other vertebrate species. In addition, all three Aund markers were expressed in the equid species evaluated in this study. These markers have been well characterized in other mammalian species, which suggests that the molecular mechanisms that maintain the niche and Aund/SSCs physiology are conserved among mammals. We hope that our findings will help future studies needing isolation and cryopreservation of equids SSCs. In addition, our data will be very useful for studies that aim at preserving the germplasm of valuable animals, and involve germ cell transplantation or xenografts of equids testis fragments/germ cells suspensions.

Advance care planning and end-of-life decision making in dialysis: a randomized controlled trial targeting patients and their surrogates.

Science.gov (United States)

Song, Mi-Kyung; Ward, Sandra E; Fine, Jason P; Hanson, Laura C; Lin, Feng-Chang; Hladik, Gerald A; Hamilton, Jill B; Bridgman, Jessica C

2015-11-01

Few trials have examined long-term outcomes of advance care planning (ACP) interventions. We examined the efficacy of an ACP intervention on preparation for end-of-life decision making for dialysis patients and surrogates and for surrogates' bereavement outcomes. A randomized trial compared an ACP intervention (Sharing Patient's Illness Representations to Increase Trust [SPIRIT]) to usual care alone, with blinded outcome assessments. 420 participants (210 dyads of prevalent dialysis patients and their surrogates) from 20 dialysis centers. Every dyad received usual care. Those randomly assigned to SPIRIT had an in-depth ACP discussion at the center and a follow-up session at home 2 weeks later. preparation for end-of-life decision making, assessed for 12 months, included dyad congruence on goals of care at end of life, patient decisional conflict, surrogate decision-making confidence, and a composite of congruence and surrogate decision-making confidence. bereavement outcomes, assessed for 6 months, included anxiety, depression, and posttraumatic distress symptoms completed by surrogates after patient death. adjusting for time and baseline values, dyad congruence (OR, 1.89; 95% CI, 1.1-3.3), surrogate decision-making confidence (β=0.13; 95% CI, 0.01-0.24), and the composite (OR, 1.82; 95% CI, 1.0-3.2) were better in SPIRIT than controls, but patient decisional conflict did not differ between groups (β=-0.01; 95% CI, -0.12 to 0.10). 45 patients died during the study. Surrogates in SPIRIT had less anxiety (β=-1.13; 95% CI, -2.23 to -0.03), depression (β=-2.54; 95% CI, -4.34 to -0.74), and posttraumatic distress (β=-5.75; 95% CI, -10.9 to -0.64) than controls. Study was conducted in a single US region. SPIRIT was associated with improvements in dyad preparation for end-of-life decision making and surrogate bereavement outcomes. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Soot formation characteristics of gasoline surrogate fuels in counterflow diffusion flames

KAUST Repository

Choi, Byungchul; Choi, Sangkyu; Chung, Suk-Ho

2011-01-01

The characteristics of polycyclic aromatic hydrocarbon (PAH) and soot for gasoline surrogate fuels have been investigated in counterflow diffusion flames by adopting laser-induced fluorescence (LIF) and laser-induced incandescence (LII) techniques

A Successful Induction of Lactation in Surrogate Pregnancy with Metoclopramide and Review of Lactation Induction

OpenAIRE

Elahe Mirzaaga; Arezoo Arabipoor; Mitra Frotan; Marzieh Shiva

2010-01-01

In surrogate pregnancies genetic parents have little opportunity for early bonding with their infants,either prenatally (in utero) or during the immediate postnatal period. Procedures commonlyused to induce lactation include both pharmacologic and nonpharmacologic methods, often incombination. Studies reporting induced lactation are sparse, due to the rarity of augmentedlactation. Here we report a case of lactation induction following a surrogate pregnancy. Othermethods that can be used to au...

Ignition of alkane-rich FACE gasoline fuels and their surrogate mixtures

KAUST Repository

Sarathy, Mani

2015-01-01

Petroleum derived gasoline is the most used transportation fuel for light-duty vehicles. In order to better understand gasoline combustion, this study investigated the ignition propensity of two alkane-rich FACE (Fuels for Advanced Combustion Engines) gasoline test fuels and their corresponding PRF (primary reference fuel) blend in fundamental combustion experiments. Shock tube ignition delay times were measured in two separate facilities at pressures of 10, 20, and 40 bar, temperatures from 715 to 1500 K, and two equivalence ratios. Rapid compression machine ignition delay times were measured for fuel/air mixtures at pressures of 20 and 40 bar, temperatures from 632 to 745 K, and two equivalence ratios. Detailed hydrocarbon analysis was also performed on the FACE gasoline fuels, and the results were used to formulate multi-component gasoline surrogate mixtures. Detailed chemical kinetic modeling results are presented herein to provide insights into the relevance of utilizing PRF and multi-component surrogate mixtures to reproduce the ignition behavior of the alkane-rich FACE gasoline fuels. The two FACE gasoline fuels and their corresponding PRF mixture displayed similar ignition behavior at intermediate and high temperatures, but differences were observed at low temperatures. These trends were mimicked by corresponding surrogate mixture models, except for the amount of heat release in the first stage of a two-stage ignition events, when observed. © 2014 The Combustion Institute.

Surrogate mothers, surrogate mistresses, and surrogate memories : a comparative study of the re-presentation of the feminine possessed in “The Bear” by William Faulkner and Borderline by Janette Turner Hospital

OpenAIRE

Heggelund, Marte

2008-01-01

The thesis aims to investigate the feminine surrogates in the worlds of Ike McCaslin (“The Bear”) and Jean-Marc Seymour (Borderline). Thematically speaking, the main problems facing the protagonists of ”The Bear” and Borderline revolve around their constant struggle for self-definition. The lack of strong mother figures in childhood creates obvious and deep problems for both protagonists’ attempts to construct a self, a foundation from which to interpret their surroundings. They hence constru...

Frequency response as a surrogate eigenvalue problem in topology optimization

DEFF Research Database (Denmark)

Andreassen, Erik; Ferrari, Federico; Sigmund, Ole

2018-01-01

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

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.

Development and Characterization of Microsatellite Markers for Central American Begonia sect. Gireoudia (Begoniaceae

Directory of Open Access Journals (Sweden)

Alex D. Twyford

2013-05-01

Full Text Available Premise of the study: Transcriptome sequence data were used to design microsatellite primers for two widespread Central American Begonia species, B. heracleifolia and B. nelumbiifolia, to investigate population structure and hybridization. Methods and Results: The transcriptome from vegetative meristem tissue from the related B. plebeja was mined for microsatellite loci, and 31 primer pairs amplified in the target species. Fifteen primer pairs were combined in two multiplex PCR reactions, which amplified an average of four alleles per locus. Conclusions: The markers developed will be a valuable genetic resource for medium-throughput genotyping of Central American species of Begonia sect. Gireoudia. A subset of these markers have perfect sequence matches to Asian B. venusta, and are promising for studies in other Begonia sections.

Investigation of the change in marker geometry during respiration motion: a preliminary study for dynamic-multi-leaf real-time tumor tracking

International Nuclear Information System (INIS)

Yamazaki, Rie; Nishioka, Seiko; Date, Hiroyuki; Shirato, Hiroki; Koike, Takao; Nishioka, Takeshi

2012-01-01

The use of stereotactic body radiotherapy (SBRT) is rapidly increasing. Presently, the most accurate method uses fiducial markers implanted near the tumor. A shortcoming of this method is that the beams turn off during the majority of the respiratory cycle, resulting in a prolonged treatment time. Recent advances in collimation technology have enabled continuous irradiation to a moving tumor. However, the lung is a dynamic organ characterized by inhalation exhalation cycles, during which marker/tumor geometry may change (i.e., misalignment), resulting in under-dosing to the tumor. Eight patients with lung cancer who were candidates for stereotactic radiotherapy were examined with 4D high-resolution CT. As a marker surrogate, virtual bronchoscopy using the pulmonary artery (VBPA) was conducted. To detect possible marker/tumor misalignment during the respiration cycle, the distance between the peripheral bronchus, where a marker could be implanted, and the center of gravity of a tumor were calculated for each respiratory phase. When the respiration cycle was divided into 10 phases, the median value was significantly larger for the 30%-70% respiratory phases compared to that for the 10% respiratory phase (P<0.05, Mann–Whitney U-test). These results demonstrate that physiological aspect must be considered when continuous tumor tracking is applied to a moving tumor. To minimize an “additional” internal target volume (ITV) margin, a marker should be placed approximately 2.5 cm from the tumor

Pulmonary and symptom threshold effects of ozone in airline passenger and cockpit crew surrogates

Energy Technology Data Exchange (ETDEWEB)

Lategola, M.T.; Melton, C.E.; Higgins, E.A.

1980-09-01

Previous studies showed that the ozone concentration for pulmonary and symptom threshold effects in flight attendant surrogates lies between 0.20 and 0.30 ppMv for a 3-h exposure with intermittent treadmill exercise at 1829 m (MSL) stimulated cabin altitude. In the present study of sedentary occupants of the in-flight airline cabin, the same protocol was used except for omitting all treadmill exercise. Symptoms were assessed with a standardized questionnaire. Pulmonary function was assessed using standardized quantitative spirometry. Male smoker and nonsmoker airline passenger and cockpit crew surrogates 40 to 59 years of age were used. Small but statistically significant displacements occurred in symptoms and in some spirometry parameters. In general, the younger subjects appeared more sensitive to ozone than the older subjects. No significant differences appeared between smokers' and nonsmokers' responses to ozone exposure. It is concluded that the ozone threshold of these sedentary surrogates under these experimental conditions is right at 0.30 ppMv.

High-resolution computed tomography of the chest in children with cystic fibrosis: support for use as an outcome surrogate

Energy Technology Data Exchange (ETDEWEB)

Brody, A.S. [Departments of Radiology and Pediatrics, Children`s Hospital Medical Center, Cincinnati, OH (United States)]|[University of Cincinnati School of Medicine, Children`s Hospital Medical Center, Cincinnati, OH (United States)]|[Department of Radiology, Cincinnati, OH (United States); Molina, P.L. [Department of Radiology, University of North Carolina at Chapel Hill, North Carolina (United States); Klein, J.S. [Department of Radiology, University of Vermont, Burlington, Vermont (United States); Rothman, B.S. [University of Cincinnati School of Medicine, Children`s Hospital Medical Center, Cincinnati, OH (United States); Ramagopal, M.; Swartz, D.R. [Department of Pediatrics, University of Vermont, Burlington, Vermont (United States)

1999-10-01

Background. Outcome surrogates are indicators that reflect, rather than directly measure, patient benefit. In order to provide useful results, however, outcome surrogates must be carefully chosen and must meet specific criteria. Objective. To support development of high-resolution computed tomography (HRCT) as an outcome surrogate in cystic fibrosis (CF) by demonstrating the ability of HRCT to show short-term improvement in the appearance of the lungs in children with CF. Materials and methods. HRCT was performed at admission and after discharge on 8 children during 15 admissions for acute pulmonary exacerbation of CF. Three radiologists scored each study separately, then compared admission and discharge pairs. Results. HRCT scores improved in 13/15 admissions. Mean score decreased from 25 to 22. The decrease was significant (P = 0.014). Comparison of admission and discharge scans showed improvement in peribronchial thickening (P = 0.007), mucous plugging (P = 0.002), and overall appearance (P = 0.025). Conclusion. HRCT has the potential to be a useful outcome surrogate in CF. A necessary attribute of an outcome surrogate is that it improves rapidly with effective therapy. Despite widespread belief among radiologists and pulmonologists that HRCT meets this criterion, no previous report has demonstrated this ability in children. These findings support further development of HRCT as an outcome surrogate in children with CF. (orig.) With 2 figs., 2 tabs., 18 refs.

[The Intentions Affecting the Medical Decision-Making Behavior of Surrogate Decision Makers of Critically Ill Patients and Related Factors].

Science.gov (United States)

Su, Szu-Huei; Wu, Li-Min

2018-04-01

The severity of diseases and high mortality rates that typify the intensive care unit often make it difficult for surrogate decision makers to make decisions for critically ill patients regarding whether to continue medical treatments or to accept palliative care. To explore the behavioral intentions that underlie the medical decisions of surrogate decision makers of critically ill patients and the related factors. A cross-sectional, correlation study design was used. A total of 193 surrogate decision makers from six ICUs in a medical center in southern Taiwan were enrolled as participants. Three structured questionnaires were used, including a demographic datasheet, the Family Relationship Scale, and the Behavioral Intention of Medical Decisions Scale. Significantly positive correlations were found between the behavioral intentions underlying medical decisions and the following variables: the relationship of the participant to the patient (Eta = .343, p = .020), the age of the patient (r = .295, p medical decisions of the surrogate decision makers, explaining 13.9% of the total variance. In assessing the behavioral intentions underlying the medical decisions of surrogate decision makers, health providers should consider the relationship between critical patients and their surrogate decision makers, patient age, the length of ICU stay, and whether the patient has a pre-signed advance healthcare directive in order to maximize the effectiveness of medical care provided to critically ill patients.

High-resolution computed tomography of the chest in children with cystic fibrosis: support for use as an outcome surrogate

International Nuclear Information System (INIS)

Brody, A.S.; Molina, P.L.; Klein, J.S.; Rothman, B.S.; Ramagopal, M.; Swartz, D.R.

1999-01-01

Background. Outcome surrogates are indicators that reflect, rather than directly measure, patient benefit. In order to provide useful results, however, outcome surrogates must be carefully chosen and must meet specific criteria. Objective. To support development of high-resolution computed tomography (HRCT) as an outcome surrogate in cystic fibrosis (CF) by demonstrating the ability of HRCT to show short-term improvement in the appearance of the lungs in children with CF. Materials and methods. HRCT was performed at admission and after discharge on 8 children during 15 admissions for acute pulmonary exacerbation of CF. Three radiologists scored each study separately, then compared admission and discharge pairs. Results. HRCT scores improved in 13/15 admissions. Mean score decreased from 25 to 22. The decrease was significant (P = 0.014). Comparison of admission and discharge scans showed improvement in peribronchial thickening (P = 0.007), mucous plugging (P = 0.002), and overall appearance (P = 0.025). Conclusion. HRCT has the potential to be a useful outcome surrogate in CF. A necessary attribute of an outcome surrogate is that it improves rapidly with effective therapy. Despite widespread belief among radiologists and pulmonologists that HRCT meets this criterion, no previous report has demonstrated this ability in children. These findings support further development of HRCT as an outcome surrogate in children with CF. (orig.)

Fabrication and Characterization of Surrogate TRISO Particles Using 800μm ZrO₂ Kernels

Energy Technology Data Exchange (ETDEWEB)

Jolly, Brian C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Helmreich, Grant [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Cooley, Kevin M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Dyer, John [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Terrani, Kurt [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2016-07-01

In support of fully ceramic microencapsulated (FCM) fuel development, coating development work is ongoing at Oak Ridge National Laboratory (ORNL) to produce tri-structural isotropic (TRISO) coated fuel particles with both UN kernels and surrogate (uranium-free) kernels. The nitride kernels are used to increase fissile density in these SiC-matrix fuel pellets with details described elsewhere. The surrogate TRISO particles are necessary for separate effects testing and for utilization in the consolidation process development. This report focuses on the fabrication and characterization of surrogate TRISO particles which use 800μm in diameter ZrO₂ microspheres as the kernel.