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Ciani, Oriana, Sarah Davis, Paul Tappenden, Ruth Garside, Ken Stein, Anna Cantrell, Everardo D. Saad, Marc Buyse, and Rod S. Taylor. "VALIDATION OF SURROGATE ENDPOINTS IN ADVANCED SOLID TUMORS: SYSTEMATIC REVIEW OF STATISTICAL METHODS, RESULTS, AND IMPLICATIONS FOR POLICY MAKERS." International Journal of Technology Assessment in Health Care 30, no. 3 (July 2014): 312–24. http://dx.doi.org/10.1017/s0266462314000300.
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Objectives: Licensing of, and coverage decisions on, new therapies should rely on evidence from patient-relevant endpoints such as overall survival (OS). Nevertheless, evidence from surrogate endpoints may also be useful, as it may not only expedite the regulatory approval of new therapies but also inform coverage decisions. It is, therefore, essential that candidate surrogate endpoints be properly validated. However, there is no consensus on statistical methods for such validation and on how the evidence thus derived should be applied by policy makers.Methods: We review current statistical approaches to surrogate-endpoint validation based on meta-analysis in various advanced-tumor settings. We assessed the suitability of two surrogates (progression-free survival [PFS] and time-to-progression [TTP]) using three current validation frameworks: Elston and Taylor's framework, the German Institute of Quality and Efficiency in Health Care's (IQWiG) framework and the Biomarker-Surrogacy Evaluation Schema (BSES3).Results: A wide variety of statistical methods have been used to assess surrogacy. The strength of the association between the two surrogates and OS was generally low. The level of evidence (observation-level versus treatment-level) available varied considerably by cancer type, by evaluation tools and was not always consistent even within one specific cancer type.Conclusions: Not in all solid tumors the treatment-level association between PFS or TTP and OS has been investigated. According to IQWiG's framework, only PFS achieved acceptable evidence of surrogacy in metastatic colorectal and ovarian cancer treated with cytotoxic agents. Our study emphasizes the challenges of surrogate-endpoint validation and the importance of building consensus on the development of evaluation frameworks.
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Rios, Ricardo Araújo, Michael Small, and Rodrigo Fernandes de Mello. "Testing for Linear and Nonlinear Gaussian Processes in Nonstationary Time Series." International Journal of Bifurcation and Chaos 25, no. 01 (January 2015): 1550013. http://dx.doi.org/10.1142/s0218127415500133.
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Surrogate data methods have been widely applied to produce synthetic data, while maintaining the same statistical properties as the original. By using such methods, one can analyze certain properties of time series. In this context, Theiler's surrogate data methods are the most commonly considered approaches. These are based on the Fourier transform, limiting them to be applied only on stationary time series. Consequently, time series including nonstationary behavior, such as trend, produces spurious high frequencies with Theiler's methods, resulting in inconsistent surrogates. To solve this problem, we present two new methods that combine time series decomposition techniques and surrogate data methods. These new methods initially decompose time series into a set of monocomponents and the trend. Afterwards, traditional surrogate methods are applied on those individual monocomponents and a set of surrogates is obtained. Finally, all individual surrogates plus the trend signal are combined in order to create a single surrogate series. Using this method, one can investigate linear and nonlinear Gaussian processes in time series, irrespective of the presence of nonstationary behavior.
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Hernandez-Villafuerte, Karla, Alastair Fischer, and Nicholas Latimer. "CHALLENGES AND METHODOLOGIES IN USING PROGRESSION FREE SURVIVAL AS A SURROGATE FOR OVERALL SURVIVAL IN ONCOLOGY." International Journal of Technology Assessment in Health Care 34, no. 3 (2018): 300–316. http://dx.doi.org/10.1017/s0266462318000338.
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Objectives:A primary outcome in oncology trials is overall survival (OS). However, to estimate OS accurately requires a sufficient number of patients to have died, which may take a long time. If an alternative end point is sufficiently highly correlated with OS, it can be used as a surrogate. Progression-free survival (PFS) is the surrogate most often used in oncology, but does not always satisfy the correlation conditions for surrogacy. We analyze the methodologies used when extrapolating from PFS to OS.Methods:Davis et al. previously reviewed the use of surrogate end points in oncology, using papers published between 2001 and 2011. We extend this, reviewing papers published between 2012 and 2016. We also examine the reporting of statistical methods to assess the strength of surrogacy.Results:The findings from 2012 to 2016 do not differ substantially from those of 2001 to 2011: the same factors are shown to affect the relationship between PFS and OS. The proportion of papers reporting individual patient data (IPD), strongly recommended for full assessment of surrogacy, remains low: 33 percent. A wide range of methods has been used to determine the appropriateness of surrogates. While usually adhering to reporting standards, the standard of scholarship appears sometimes to be questionable and the reporting of results often haphazard.Conclusions:Standards of analysis and reporting PFS to OS surrogate studies should be improved by increasing the rigor of statistical reporting and by agreeing to a minimum set of reporting guidelines. Moreover, the use of IPD to assess surrogacy should increase.
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Lu, Dan, and Daniel Ricciuto. "Efficient surrogate modeling methods for large-scale Earth system models based on machine-learning techniques." Geoscientific Model Development 12, no. 5 (May 6, 2019): 1791–807. http://dx.doi.org/10.5194/gmd-12-1791-2019.
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Abstract. Improving predictive understanding of Earth system variability and change requires data–model integration. Efficient data–model integration for complex models requires surrogate modeling to reduce model evaluation time. However, building a surrogate of a large-scale Earth system model (ESM) with many output variables is computationally intensive because it involves a large number of expensive ESM simulations. In this effort, we propose an efficient surrogate method capable of using a few ESM runs to build an accurate and fast-to-evaluate surrogate system of model outputs over large spatial and temporal domains. We first use singular value decomposition to reduce the output dimensions and then use Bayesian optimization techniques to generate an accurate neural network surrogate model based on limited ESM simulation samples. Our machine-learning-based surrogate methods can build and evaluate a large surrogate system of many variables quickly. Thus, whenever the quantities of interest change, such as a different objective function, a new site, and a longer simulation time, we can simply extract the information of interest from the surrogate system without rebuilding new surrogates, which significantly reduces computational efforts. We apply the proposed method to a regional ecosystem model to approximate the relationship between eight model parameters and 42 660 carbon flux outputs. Results indicate that using only 20 model simulations, we can build an accurate surrogate system of the 42 660 variables, wherein the consistency between the surrogate prediction and actual model simulation is 0.93 and the mean squared error is 0.02. This highly accurate and fast-to-evaluate surrogate system will greatly enhance the computational efficiency of data–model integration to improve predictions and advance our understanding of the Earth system.
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Ciani, Oriana, Bogdan Grigore, Hedwig Blommestein, Saskia de Groot, Meilin Möllenkamp, Stefan Rabbe, Rita Daubner-Bendes, and Rod S. Taylor. "Validity of Surrogate Endpoints and Their Impact on Coverage Recommendations: A Retrospective Analysis across International Health Technology Assessment Agencies." Medical Decision Making 41, no. 4 (March 10, 2021): 439–52. http://dx.doi.org/10.1177/0272989x21994553.
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Background Surrogate endpoints (i.e., intermediate endpoints intended to predict for patient-centered outcomes) are increasingly common. However, little is known about how surrogate evidence is handled in the context of health technology assessment (HTA). Objectives 1) To map methodologies for the validation of surrogate endpoints and 2) to determine their impact on acceptability of surrogates and coverage decisions made by HTA agencies. Methods We sought HTA reports where evaluation relied on a surrogate from 8 HTA agencies. We extracted data on the methods applied for surrogate validation. We assessed the level of agreement between agencies and fitted mixed-effects logistic regression models to test the impact of validation approaches on the agency’s acceptability of the surrogate endpoint and their coverage recommendation. Results Of the 124 included reports, 61 (49%) discussed the level of evidence to support the relationship between the surrogate and the patient-centered endpoint, 27 (22%) reported a correlation coefficient/association measure, and 40 (32%) quantified the expected effect on the patient-centered outcome. Overall, the surrogate endpoint was deemed acceptable in 49 (40%) reports ( k-coefficient 0.10, P = 0.004). Any consideration of the level of evidence was associated with accepting the surrogate endpoint as valid (odds ratio [OR], 4.60; 95% confidence interval [CI], 1.60–13.18, P = 0.005). However, we did not find strong evidence of an association between accepting the surrogate endpoint and agency coverage recommendation (OR, 0.71; 95% CI, 0.23–2.20; P = 0.55). Conclusions Handling of surrogate endpoint evidence in reports varied greatly across HTA agencies, with inconsistent consideration of the level of evidence and statistical validation. Our findings call for careful reconsideration of the issue of surrogacy and the need for harmonization of practices across international HTA agencies.
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Scher, Howard I., Glenn Heller, Arturo Molina, Gerhardt Attard, Daniel C. Danila, Xiaoyu Jia, Weimin Peng, et al. "Circulating Tumor Cell Biomarker Panel As an Individual-Level Surrogate for Survival in Metastatic Castration-Resistant Prostate Cancer." Journal of Clinical Oncology 33, no. 12 (April 20, 2015): 1348–55. http://dx.doi.org/10.1200/jco.2014.55.3487.
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Purpose Trials in castration-resistant prostate cancer (CRPC) need new clinical end points that are valid surrogates for survival. We evaluated circulating tumor cell (CTC) enumeration as a surrogate outcome measure. Patients and Methods Examining CTCs alone and in combination with other biomarkers as a surrogate for overall survival was a secondary objective of COU-AA-301, a multinational, randomized, double-blind phase III trial of abiraterone acetate plus prednisone versus prednisone alone in patients with metastatic CRPC previously treated with docetaxel. The biomarkers were measured at baseline and 4, 8, and 12 weeks, with 12 weeks being the primary measure of interest. The Prentice criteria were applied to test candidate biomarkers as surrogates for overall survival at the individual-patient level. Results A biomarker panel using CTC count and lactate dehydrogenase (LDH) level was shown to satisfy the four Prentice criteria for individual-level surrogacy. Twelve-week surrogate biomarker data were available for 711 patients. The abiraterone acetate plus prednisone and prednisone-alone groups demonstrated a significant survival difference (P = .034); surrogate distribution at 12 weeks differed by treatment (P < .001); the discriminatory power of the surrogate to predict mortality was high (weighted c-index, 0.81); and adding the surrogate to the model eliminated the treatment effect on survival. Overall, 2-year survival of patients with CTCs < 5 (low risk) versus patients with CTCs ≥ 5 cells/7.5 mL of blood and LDH > 250 U/L (high risk) at 12 weeks was 46% and 2%, respectively. Conclusion A biomarker panel containing CTC number and LDH level was shown to be a surrogate for survival at the individual-patient level in this trial of abiraterone acetate plus prednisone versus prednisone alone for patients with metastatic CRPC. Additional trials are ongoing to validate the findings.
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Hu, Zhen, Saideep Nannapaneni, and Sankaran Mahadevan. "Efficient Kriging surrogate modeling approach for system reliability analysis." Artificial Intelligence for Engineering Design, Analysis and Manufacturing 31, no. 2 (May 2017): 143–60. http://dx.doi.org/10.1017/s089006041700004x.
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AbstractCurrent limit state surrogate modeling methods for system reliability analysis usually build surrogate models for failure modes individually or build composite limit states. In practical engineering applications, multiple system responses may be obtained from a single setting of inputs. In such cases, building surrogate models individually will ignore the correlation between different system responses and building composite limit states may be computationally expensive because the nonlinearity of composite limit state is usually higher than individual limit states. This paper proposes a new efficient Kriging surrogate modeling approach for system reliability analysis by constructing composite Kriging surrogates through selection of Kriging surrogates constructed individually and Kriging surrogates built based on singular value decomposition. The resulting composite surrogate model will combine the advantages of both types of Kriging surrogate models and thus reduce the number of required training points. A new stopping criterion and a new surrogate model refinement strategy are proposed to further improve the efficiency of this approach. The surrogate models are refined adaptively with high accuracy near the active failure boundary until the proposed new stopping criterion is satisfied. Three numerical examples including a series, a parallel, and a combined system are used to demonstrate the effectiveness of the proposed method.
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Oko, S. O. "Surrogate methods for linear inequalities." Journal of Optimization Theory and Applications 72, no. 2 (February 1992): 247–68. http://dx.doi.org/10.1007/bf00940518.
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Kim, Hyejin, Janet A. Deatrick, and Connie M. Ulrich. "Ethical frameworks for surrogates’ end-of-life planning experiences." Nursing Ethics 24, no. 1 (August 3, 2016): 46–69. http://dx.doi.org/10.1177/0969733016638145.
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Background: Despite the growing body of knowledge about surrogate decision making, we know very little about the use of ethical frameworks (including ethical theories, principles, and concepts) to understand surrogates’ day-to-day experiences in end-of-life care planning for incapacitated adults. Objectives and Methods: This qualitative systematic review was conducted to identify the types of ethical frameworks used to address surrogates’ experiences in end-of-life care planning for incapacitated adults as well as the most common themes or patterns found in surrogate decision-making research. Findings: Seven research papers explicitly identified ethical theories, principles, or concepts, such as autonomy, substituted judgment, and best interest standards as guidelines for the research. Surrogate decision making themes included the responsibilities and goals of being a surrogate, factors influencing surrogates’ decision making, outcomes for surrogates, and an overarching theme of “wanting to do the right thing” for their loved one and/or themselves. Discussion: Understanding the complexity of surrogates’ experiences of end-of-life care planning is beyond the scope of conventional ethical frameworks. Conclusion: Ethical frameworks that address individuality and contextual variations related to decision making may more appropriately guide surrogate decision-making research that explores surrogates’ end-of-life care planning experiences.
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Royce, Trevor Joseph, Ming-Hui Chen, Jing Wu, Marian Loffredo, Andrew A. Renshaw, Philip W. Kantoff, and Anthony Victor D'Amico. "A comparison of surrogate endpoints for all cause mortality in men with localized unfavorable-risk prostate cancer." Journal of Clinical Oncology 35, no. 6_suppl (February 20, 2017): 21. http://dx.doi.org/10.1200/jco.2017.35.6_suppl.21.
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21 Background: Several surrogates for prostate cancer-specific mortality exist, but whether these are surrogates for all cause mortality (ACM), and how their performance compares, is unknown. We investigated the relative efficacy of 4 candidate surrogates for ACM using the proportion of treatment effect (PTE) metric. Methods: Two-hundred and six men with localized unfavorable-risk prostate cancer were randomized to radiation therapy (RT) or RT and 6 months of androgen-deprivation therapy (ADT) from 1995 to 2001 and followed for a median of 16.62 years. Among the 159 men with no or minimal comorbidity, a significant reduction in the risk of death was observed in those randomized to RT and ADT versus RT alone; these 159 men formed the study cohort. In order to assess whether the candidate surrogated satisfied Prentice’s criteria for surrogacy, Cox regression analyses were performed to assess the risk of death for each of the candidate surrogates and treatment before and after adjusting for prostate-specific antigen (PSA), age at randomization, T category, and Gleason score. Results: PSA nadir > 0.5 ng/mL, PSA doubling time < 9 months and interval to PSA failure < 30 months met Prentice’s criteria for surrogacy (P = 0.01, 0.003, and 0.03 for the surrogate covariate in the multivariable model, respectively) for ACM, while PSA failure did not (P = 0.10). For the three surrogates, the PTE values were 103.86%, 43.09%, and 41.26%, respectively. Conclusions: A PSA nadir value of > 0.5 ng/mL following RT and ADT identified men prior to PSA failure who were at high-risk for death and therefore could be used to select men for entry, at the time of PSA nadir and before PSA failure, onto randomized trials evaluating the impact on survival of salvage ADT with or without agents shown to prolong survival in men with castrate-resistant metastatic prostate cancer. By enriching study cohorts with men who have achieved a surrogate endpoint for ACM, one can enhance the likelihood that the study will be able to observe whether survival is prolonged when novel treatment is added to ADT, as compared to ADT alone, in an abbreviated time period. Clinical Trial Number: NCT00116220
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MEEKER, MARY ANN, and MARY ANN JEZEWSKI. "Family decision making at end of life." Palliative and Supportive Care 3, no. 2 (June 2005): 131–42. http://dx.doi.org/10.1017/s1478951505050212.
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Objective: To enhance understanding of the phenomenon of family surrogate decision-making at the end of life (EOL) by means of a systematic review and synthesis of published research reports that address this phenomenon.Methods: Garrard's (1999) methods for conducting a systematic review of the literature were followed. Fifty-one studies focusing on family decision-making experiences, needs, and processes when assisting a dying family member were selected following electronic database searches and ancestry searches.Results: In studies using hypothetical scenarios to compare patients' choices and surrogates' predictions of those choices, surrogates demonstrated low to moderate predictive accuracy. Increased accuracy occurred in more extreme scenarios, under conditions of forced choice, and when the surrogate was specifically directed to use substituted judgment. In qualitative explorations of their perspectives, family members voiced their desire to be involved and to accept the moral responsibility attendant to being a surrogate. Quality of communication available with providers significantly influenced family satisfaction with decision-making and EOL care. Group or consensual decision-making involving multiple family members was preferred over individual surrogate decision-making. Surrogates experienced long-term physical and psychological outcomes from being decision-makers.Significance of results: Functioning as a surrogate decision-maker typically places great moral, emotional, and cognitive demands on the family surrogate. Clinicians can provide improved care to both patients and families with better understanding of surrogates' needs and experiences.
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Armstrong, A. J., M. A. Eisenberger, E. S. Garrett-Mayer, Y. Ou Yang, M. A. Carducci, R. de Wit, and I. Tannock. "Analysis of prostate-specific antigen decline as a surrogate for overall survival in metastatic hormone-refractory prostate cancer (HRPC)." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 5009. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.5009.
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5009 Background: A 30% PSA decline following initiation of cytotoxic chemotherapy has been identified as a potential surrogate for overall survival in metastatic HRPC. We sought to examine whether various levels of PSA decline were surrogates for overall survival in TAX327, a randomized trial of q3w docetaxel and prednisone (DP), q1w DP, and q3w mitoxantrone and prednisone (MP). Methods: In this trial of 1006 men with HRPC, 943 men had sufficient data on 3-month post-treatment PSA decline for analysis, and 646 had sufficient data for analysis for a change in PSA kinetics with therapy. Surrogacy was examined for a range of PSA decline from 0% to 90% and PSA normalization, and for post-treatment changes in PSA kinetics. We investigated the Prentice Criteria for surrogacy using Cox proportional hazards models and calculated the proportion of treatment effect explained (PTE) by each surrogate marker. Results: In this analysis, a 30% or greater PSA decline with therapy was identified as the optimal cutoff that correlated with overall survival, based on the highest PTE point estimate (0.66, 95% CI 0.23–1.0), with 1.0 being a perfect surrogate. A 30% decline in PSA in the first 3 months after treatment occurred in 65% of subjects receiving q3w DP, 67% q1w DP, and 44% q3w MP, despite the significant survival benefits seen only with q3w DP. A 30% PSA decline was associated with a hazard ratio (HR) of 0.43 (95% CI 0.36–0.51) for overall survival after adjusting for treatment effect, while treatment effect itself lost significance, indicating surrogacy. Additionally, PSA normalization, changes in PSA kinetics, and pain response were significant prognostic variables, yet were only modest surrogates for the survival benefit seen with q3w DP therapy. Conclusions: In this trial of two schedules of DP as compared to MP for HRPC, a PSA decline of 30% in the first three months following initiation of cytotoxic chemotherapy was found to have the highest degree of surrogacy for overall survival, thus confirming data from the SWOG 9916 trial. However, given that the confidence interval for the estimate of this surrogate effect is wide, overall survival should remain the preferred endpoint for phase III trials of cytotoxic agents in HRPC. No significant financial relationships to disclose.
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Foo, Aaron SC, Tze Wee Lee, and Chai Rick Soh. "Discrepancies in End-of-life Decisions Between Elderly Patients and Their Named Surrogates." Annals of the Academy of Medicine, Singapore 41, no. 4 (April 15, 2012): 141–53. http://dx.doi.org/10.47102/annals-acadmedsg.v41n4p141.
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Introduction: This study aims to determine the attitudes of Asian elderly patients towards invasive life support measures, the degree of patient-surrogate concordance in end-of-life decision making, the extent to which patients desire autonomy over end-of-life medical decisions, the reasons behind patients’ and surrogates’ decisions, and the main factors influencing patients’ and surrogates’ decision-making processes. We hypothesize that there is significant patient-surrogate discordance in end-of-life decision making in our community. Materials and Methods: The patient and surrogate were presented with a hypothetical scenario in which the patient experienced gradual functional decline in the community before being admitted for life-threatening pneumonia. It was explained that the outcome was likely to be poor even with intensive care and each patient-surrogate pair was subsequently interviewed separately on their opinions of extraordinary life support using a standardised questionnaire. Both parties were blinded to each other’s replies. Results: In total, 30 patients and their surrogate decision-makers were interviewed. Twenty-eight (93.3%) patients and 20 (66.7%) surrogates rejected intensive care. Patient-surrogate concurrence was found in 20 pairs (66.7%). Twenty-four (80.0%) patients desired autonomy over their decision. The patients’ and surrogates’ top reasons for rejecting intensive treatment were treatment-related discomfort, poor prognosis and financial cost. Surrogates’ top reasons for selecting intensive treatment were the hope of recovery, the need to complete final tasks and the sanctity of life. Conclusion: The majority of patients desire autonomy over critical care issues. Relying on the surrogates’ decisions to initiate treatment may result in treatment against patients’ wishes in up to one-third of critically ill elderly patients. Key words: Advanced medical directive, Intensive care
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Ebner, Brendan C., Mark Lintermans, Mark Jekabsons, Mark Dunford, and William Andrews. "A cautionary tale: surrogates for radio-tagging practice do not always simulate the responses of closely related species." Marine and Freshwater Research 60, no. 4 (2009): 371. http://dx.doi.org/10.1071/mf08159.
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Telemetry is useful for monitoring rare and threatened species if they can be effectively tagged. Relatively abundant, closely related species are sometimes used as surrogates in refining tagging methods or testing the suitability of methods before transfer to rare and threatened species. A decision framework for developing a radio-tagging method of an endangered fish (Macquaria australasica; Percichthyidae) is presented based on experiences with tagging a closely related, surrogate species (Macquaria ambigua). Aquaria and field-based trials demonstrated the suitability of internally implanting a radio-tag with an externally exited antenna on the surrogate species. However, transferring this method to the endangered species under field conditions was unsuccessful in terms of mortality and/or radio-tag rejection. In this case, a surrogate species served to refine radio-tagging methods, but did not successfully indicate the suitability of these methods for a closely related species. This cautionary tale illustrates that surrogate species are not always effective and extrapolation of methods, even across closely related species, may be perilous.
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Armstrong, Andrew J., Elizabeth Garrett-Mayer, Yi-Chun Ou Yang, Michael A. Carducci, Ian Tannock, Ronald de Wit, and Mario Eisenberger. "Prostate-Specific Antigen and Pain Surrogacy Analysis in Metastatic Hormone-Refractory Prostate Cancer." Journal of Clinical Oncology 25, no. 25 (September 1, 2007): 3965–70. http://dx.doi.org/10.1200/jco.2007.11.4769.
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Purpose It is currently unclear if early prostate-specific antigen (PSA) or pain improvements are adequate surrogates for overall survival in men with metastatic hormone-refractory prostate cancer (HRPC). Here we examined various degrees of PSA decline and pain response as surrogates for the survival benefit observed in the TAX327 trial. Patients and Methods In the TAX327 trial, 1,006 men with HRPC were randomly assigned to receive docetaxel in two schedules, or mitoxantrone, each with prednisone: 989 men provided data on 3-month PSA decline. Surrogacy was examined for post-treatment changes in PSA and pain response using Cox proportional hazards models to calculate the proportion of treatment effect (PTE) explained by each potential surrogate. Results A ≥ 30% PSA decline within 3 months of treatment initiation provides the highest degree of surrogacy, with a PTE of 0.66 (95% CI, 0.23 to 1.0), and was associated with a hazard ratio (HR) of 0.50 (95% CI, 0.43 to 0.58) for overall survival after adjusting for treatment effect. Introduction of a ≥ 30% PSA decline is predictive of survival regardless of treatment arm. Other changes in PSA or PSA kinetics, PSA normalization, and pain responses were highly prognostic but weaker surrogates for survival. Conclusion In the TAX327 trial, a PSA decline of ≥ 30% within 3 months of chemotherapy initiation had the highest degree of surrogacy for overall survival, confirming data from the Southwest Oncology Group 9916 trial. However, given the wide CIs around the estimate of this moderate surrogate effect, overall survival should remain the preferred end point for phase III trials of cytotoxic agents in HRPC.
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Geng, Zhi, Yue Liu, Chunchen Liu, and Wang Miao. "Evaluation of Causal Effects and Local Structure Learning of Causal Networks." Annual Review of Statistics and Its Application 6, no. 1 (March 7, 2019): 103–24. http://dx.doi.org/10.1146/annurev-statistics-030718-105312.
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Causal effect evaluation and causal network learning are two main research areas in causal inference. For causal effect evaluation, we review the two problems of confounders and surrogates. The Yule-Simpson paradox is the idea that the association between two variables may be changed dramatically due to ignoring confounders. We review criteria for confounders and methods of adjustment for observed and unobserved confounders. The surrogate paradox occurs when a treatment has a positive causal effect on a surrogate endpoint, which, in turn, has a positive causal effect on a true endpoint, but the treatment may have a negative causal effect on the true endpoint. Some of the existing criteria for surrogates are subject to the surrogate paradox, and we review criteria for consistent surrogates to avoid the surrogate paradox. Causal networks are used to depict the causal relationships among multiple variables. Rather than discovering a global causal network, researchers are often interested in discovering the causes and effects of a given variable. We review some algorithms for local structure learning of causal networks centering around a given variable.
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Poad, Heather, Sam Khan, Lorna Wheaton, Anne Thomas, Michael Sweeting, and Sylwia Bujkiewicz. "The Validity of Surrogate Endpoints in Sub Groups of Metastatic Colorectal Cancer Patients Defined by Treatment Class and KRAS Status." Cancers 14, no. 21 (November 1, 2022): 5391. http://dx.doi.org/10.3390/cancers14215391.
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Background and Aim: Findings from the literature suggest that the validity of surrogate endpoints in metastatic colorectal cancer (mCRC) may depend on a treatments’ mechanism of action. We explore this and the impact of Kirsten rat sarcoma (KRAS) status on surrogacy patterns in mCRC. Methods: A systematic review was undertaken to identify randomized controlled trials (RCTs) for pharmacological therapies in mCRC. Bayesian meta-analytic methods for surrogate endpoint evaluation were used to evaluate surrogate relationships across all RCTs, by KRAS status and treatment class. Surrogate endpoints explored were progression free survival (PFS) as a surrogate endpoint for overall survival (OS), and tumour response (TR) as a surrogate for PFS and OS. Results: 66 RCTs were identified from the systematic review. PFS showed a strong surrogate relationship with OS across all data and in subgroups by KRAS status. The relationship appeared stronger within individual treatment classes compared to the overall analysis. The TR-PFS and TR-OS relationships were found to be weak overall but stronger within the Epidermal Growth Factor Receptor + Chemotherapy (EGFR + Chemo) treatment class; both overall and in the wild type (WT) patients for TR-PFS, but not in patients with the mutant (MT) KRAS status where data were limited. Conclusions: PFS appeared to be a good surrogate endpoint for OS. TR showed a moderate surrogate relationship with PFS and OS for the EGFR + Chemo treatment class. There was some evidence of impact of the mechanism of action on the strength of the surrogacy patterns in mCRC, but little evidence of the impact of KRAS status on the validity of surrogate endpoints.
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Kunde, Christian, Tobias Keßler, Steffen Linke, Kevin McBride, Kai Sundmacher, and Achim Kienle. "Surrogate Modeling for Liquid–Liquid Equilibria Using a Parameterization of the Binodal Curve." Processes 7, no. 10 (October 16, 2019): 753. http://dx.doi.org/10.3390/pr7100753.
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Computational effort and convergence problems can pose serious challenges when employing advanced thermodynamic models in process simulation and optimization. Data-based surrogate modeling helps to overcome these problems at the cost of additional modeling effort. The present work extends the range of methods for efficient data-based surrogate modeling of liquid–liquid equilibria. A new model formulation is presented that enables smaller surrogates with box-constrained input domains and reduced input dimensions. Sample data are generated efficiently by using numerical continuation. The new methods are demonstrated for the surrogate modeling and optimization of a process for the hydroformylation of 1-decene in a thermomorphic multiphase system.
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Escher, Jutta E., Frank S. Dietrich, and Christian Forssén. "Surrogate nuclear reaction methods for astrophysics." Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms 261, no. 1-2 (August 2007): 1075–78. http://dx.doi.org/10.1016/j.nimb.2007.04.223.
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Vesting, Florian, and Rickard E. Bensow. "On surrogate methods in propeller optimisation." Ocean Engineering 88 (September 2014): 214–27. http://dx.doi.org/10.1016/j.oceaneng.2014.06.024.
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Li, Muxi, and Jian Zhang. "A Novel Alternate Point-taking Strategy for Surrogate-Assisted Evolutionary Algorithm." Journal of Advances in Mathematics and Computer Science 38, no. 7 (May 29, 2023): 181–88. http://dx.doi.org/10.9734/jamcs/2023/v38i71783.
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The essence of surrogate model is a low-cost alternative, which mainly replaces the computationally heavy simulation process to reduce the time cost consumed. In the past two decades, this approximation based optimization method has made remarkable progress, and surrogate models are widely used in computationally expensive simulation model analysis and optimization. In addition, with the development of technology, the surrogate model is no longer a simple substitute, but can drive new sample points to join the training process based on historical data, so as to gradually approach the global optimal solution of the problem. For optimization problems, there are many surrogates-assisted optimization algorithm methods. However, the selection of sample points has great influence on the accuracy of the surrogate model. In order to obtain a more accurate surrogate model, the newly added sample points should meet the sample diversity criterion of the specified distance, and at the same time, corresponding strategies should be adopted to fully explore sparse regions, so as to avoid falling into the local optimal phenomenon in the optimization process. Therefore, an ensemble of surrogates based on alternate point-taking strategy (APTS) is proposed, and a hierarchical search framework is designed, using different algorithms at each stage. The effectiveness of APTS is verified on three benchmark examples with different dimensions and compared with several advanced methods. The results show that this method has better accuracy and robustness than other methods on most test problems.
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Angione, Claudio, Eric Silverman, and Elisabeth Yaneske. "Using machine learning as a surrogate model for agent-based simulations." PLOS ONE 17, no. 2 (February 10, 2022): e0263150. http://dx.doi.org/10.1371/journal.pone.0263150.
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In this proof-of-concept work, we evaluate the performance of multiple machine-learning methods as surrogate models for use in the analysis of agent-based models (ABMs). Analysing agent-based modelling outputs can be challenging, as the relationships between input parameters can be non-linear or even chaotic even in relatively simple models, and each model run can require significant CPU time. Surrogate modelling, in which a statistical model of the ABM is constructed to facilitate detailed model analyses, has been proposed as an alternative to computationally costly Monte Carlo methods. Here we compare multiple machine-learning methods for ABM surrogate modelling in order to determine the approaches best suited as a surrogate for modelling the complex behaviour of ABMs. Our results suggest that, in most scenarios, artificial neural networks (ANNs) and gradient-boosted trees outperform Gaussian process surrogates, currently the most commonly used method for the surrogate modelling of complex computational models. ANNs produced the most accurate model replications in scenarios with high numbers of model runs, although training times were longer than the other methods. We propose that agent-based modelling would benefit from using machine-learning methods for surrogate modelling, as this can facilitate more robust sensitivity analyses for the models while also reducing CPU time consumption when calibrating and analysing the simulation.
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Kuchynska, Oksana P., Oksana Yu Kashyntseva, and Oleh V. Shchyhol. "CURRENT ISSUES OF LEGAL REGULATION OF SURROGATE MATERNITY AND ENFORCEMENT OF RIGHTS OF SURROGATE MOTHERS." Wiadomości Lekarskie 73, no. 12 (2020): 2871–76. http://dx.doi.org/10.36740/wlek202012228.
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The aim: To propose effective jurisdictional methods in the field of legal regulation of surrogacy and ensuring the rights of surrogate mothers in the EU. Materials and methods: The research is based on international documents in the field of surrogacy, Ukrainian legislation, decisions of the European Court of Human Rights, scientists' works in the field of legal regulation of surrogacy, etc. General scientific methods (synthesis, induction, system method) and specific scientific methods (comparative legal and special legal methods) are used. Conclusions: The study found that today some issues related to the surrogacy legal nature, conditions and procedure for its implementation remain out of the EU's attention. It is established that the adoption of a separate regional (within the EU) legal act will fully solve the existing problems, ensuring the effectiveness and transparency of surrogacy, will unify the medical tourism's mechanisms in the field of surrogacy. The authors have developed and proposed to enshrine the main provisions on surrogacy in the EU Regulation / Directive.
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Yevtieieva, Daryna P., Andrii V. Lapkin, and Vladyslav V. Karelin. "EAST SLAVIC SURROGATE MOTHERHOOD: STATE OF LEGAL REGULATION AND RISK OF HUMAN RIGHTS VIOLATION." Wiadomości Lekarskie 73, no. 12 (2020): 2882–89. http://dx.doi.org/10.36740/wlek202012230.
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The aim: The aim of the study is to determine the state of legal regulation of surrogacy in Ukraine, Russian Federation and Belarus, to identify risks of human rights violations, to identify legal and medical mechanisms to combat the exploitation of women, and to outline a portrait of a surrogate mother. Materials and methods: The empirical basis is the legislation of Ukraine, Russian Federation and Belarus, which regulates the service of surrogacy, information from the websites of agencies and clinics in this area, as well as personal stories of 41 surrogate mothers, set out in open sources. The following methods were used: dialectical, comparative, statistical, induction and deduction, questionnaire, analysis and synthesis, content analysis. Conclusions: The results of the study clarify both the common features of the legal regulation of surrogacy in the East Slavic countries, and the specifics of each of them; the main problems in the field of its application are outlined; the risks of violation of the rights of genetic parents, children and surrogate mothers are characterized. Legal and medical mechanisms for counteracting the exploitation of surrogate mothers have been identified.
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Mendzhul, Marija V., Viktoriia V. Nadon, and Zhanna O. Rekova. "PROTECTION OF THE RIGHTS OF CHILDREN BORN BY SURROGATE MOTHERS DURING THE COVID-19 PANDEMIC." Wiadomości Lekarskie 74, no. 11 (2021): 2999–3003. http://dx.doi.org/10.36740/wlek202111223.
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The aim: Analyze the practice of resolving the problems of protecting the rights of children born to surrogate mothers in the context of the COVID-19 pandemic. Materials and methods: In carrying out the study, an interdisciplinary approach was applied to the analysis of the problem of protecting the rights of children born to surrogate mothers in the context of the COVID-19 pandemic. This approach includes dialectical, comparative-legal, statistical, and systemic methods. The research used scientific developments in the field of problems of protecting the rights of children born to surrogate mothers, international acts, legislation, statistical data. It has been established that although the understanding of surrogacy is the same for all states, there is a rather different approach to the possibility of its application. The issue of providing a child born to a surrogate mother with data on his genetic origin (in the absence of a genetic link with legal parents) should be resolved on the basis of this approach: maintaining a balance of interests between parents and the child, taking into account the principle of the best interests of the child. Conclusions: It was concluded that the inadmissibility of closing borders and restricting the entry of foreigners to reunite with children born of surrogate mothers. It is proposed to create a register of persons those wishing to apply the surrogacy procedure, as well as the register of children born from surrogate mothers in Ukraine.
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Almalkie, Saba, and Stephen M. de Bruyn Kops. "Energy dissipation rate surrogates in incompressible Navier–Stokes turbulence." Journal of Fluid Mechanics 697 (March 6, 2012): 204–36. http://dx.doi.org/10.1017/jfm.2012.53.
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AbstractHigh-resolution direct numerical simulations of isotropic homogeneous turbulence are used to understand the differences between the effects of spatial intermittency on the energy dissipation rate and on surrogates for the dissipation rate that are based on measurements of a subset of the strain rate tensor. In particular, the one-dimensional longitudinal and transverse surrogates, as well as a surrogate based on the asymmetric part of the strain rate tensor, are considered. The instantaneous surrogates are studied locally, locally averaged in space and conditionally averaged to see what statistics of the dissipation rate might accurately be inferred given measurements of the surrogates. The simulations with the Reynolds numbers based on the Taylor microscale of 102–235 are highly resolved for accurate evaluation of higher-order statistics. The probability densities of the local and locally averaged surrogates are significantly different from the corresponding statistics for the dissipation rate itself. All of the surrogates are more intermittent than the dissipation rate, the transverse surrogate is more intermittent than the longitudinal and these trends are still prominent even when the fields are spatially averaged at length scales close to the integral length scale. As a consequence, the intermittency exponent computed from the moments of the locally averaged longitudinal and transverse surrogates is approximately 1.5 and 2.2 times higher, respectively, than that computed by the same method from the dissipation rate field. In addition, while different methods of computing intermittency exponent from the dissipation rate field yield the same result, different methods applied to a surrogate are inconsistent.
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Mohamed, Mohamed Gomaa, and Nicolas Saunier. "Motion Prediction Methods for Surrogate Safety Analysis." Transportation Research Record: Journal of the Transportation Research Board 2386, no. 1 (January 2013): 168–78. http://dx.doi.org/10.3141/2386-19.
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Uçar, Bora, Cevdet Aykanat, Mustafa Ç. Pınar, and Tahir Malas. "Parallel image restoration using surrogate constraint methods." Journal of Parallel and Distributed Computing 67, no. 2 (February 2007): 186–204. http://dx.doi.org/10.1016/j.jpdc.2006.10.001.
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Vu, Ky Khac, Claudia D'Ambrosio, Youssef Hamadi, and Leo Liberti. "Surrogate-based methods for black-box optimization." International Transactions in Operational Research 24, no. 3 (April 20, 2016): 393–424. http://dx.doi.org/10.1111/itor.12292.
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Manner, David, John W. Seaman, and Dean M. Young. "Bayesian Methods for Regression Using Surrogate Variables." Biometrical Journal 46, no. 6 (December 2004): 750–59. http://dx.doi.org/10.1002/bimj.200210073.
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Checherskiy, Viktor. "Human trafficking and surrogate motherhood: challenges." Constitutional and legal academic studies, no. 1 (October 11, 2021): 35–43. http://dx.doi.org/10.24144/2663-5399.2021.1.04.
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Owing to modern scientific advances prospective parents, among other opportunities, enjoy the opportunity, which has not been available before. It consists in giving birth to a child by using another woman’s reproductive capacity when the situation seems hardly improvable.
The paper examines surrogate motherhood as one of the reproductive methods through the prism of human trafficking. It aims at studying and differentiating such legal phenomena as the sale of human beings and surrogate motherhood, which is provided primarily on a paid-for basis, whose consequences (transferring irrevocably a child from one person to another), are externally similar.
The comparative legal and formal legal methods have been employed to provide a general description of international experience in regulating surrogate motherhood. Examples of absolutely opposite ways of pursuing state policy on the legalization of this type of reproductive methods in foreign countries are suggested: from a complete ban to legislative approval and even further simplification of the applying procedure.
It has been proved that there is no connection between acknowledgement of the legality of this procedure and the geographical location of states, the level of their economic development, the specifics of the legal system, and the like. It has been stated that none of the countries can be considered a universal example of solving these issues.
Based on the example of Ukrainian legislation, the author suggests distinguishing between the objective aspect of selling human beings and surrogate motherhood, which is provided, first of all, for a fee. It is emphasized that due to the peculiarities of reproductive technologies only a child should be the object of trade, not a person’s gametes, zygote, embryo or fetus. When a child is sold, in view of the objective aspect, the child is illegally transferred from one person to another. In legal surrogate motherhood agreements the object of the agreement concluded between the surrogate mother and the future parents is not the child, but the service related to embryo implantation, pregnancy and childbirth, id est, a long process.
Based on criminal law, there have been modelled the peculiarities of surrogate motherhood and its assessment used in determining the signs of human trafficking largely depending on genetic relationship between a child and customers (potential parents), as well as a child and a surrogate mother.
The mental element making the distinction between surrogacy and the trafficking of newborns is described. It is emphasized that qualifying as «trafficking in human beings» necessitates the proof of direct intent to unlawfully «transfer» a child, primarily in return for a fee.
It has been concluded that the legal regulation of surrogacy requires further improvement and consolidation at the legislative level. Investigators and prosecutors should investigate all the circumstances that were associated with the surrogacy methods applied in order to establish whether child trafficking occurred in each specific case.
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Araújo, Marisa Almeida. "The Portuguese law on Surrogacy – Promises and Perils." Frontiers in Law 2 (October 9, 2023): 82–94. http://dx.doi.org/10.6000/2817-2302.2023.02.10.
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After years of intense debate, on August 22, 2016 the Portuguese Assisted Reproductive Technologies (ART) Law was altered, and altruistic gestational surrogacy was made legal in Portugal. Although the journey has not been easy since then. The Portuguese Constitutional Court was called twice (in 2018 and 2019) to analyse the legal provisions of the surrogacy legal regime. The judges concluded that altruistic surrogacy was not in violation of the Portuguese Constitution, although the legal solution, and later amendment, was, in some of its provisions, unconstitutional. The judges found that the law needed to guarantee the right of the surrogate to regret the arrangement after the child was born. Considering the rulings of the Constitutional Court, surrogacy contracts in Portugal are not enforceable and the surrogate can, after the child is born, revoke her consent and become the legal mother of the child. The Parliament altered the Law accordingly in 2021, although, for the time being, it is still to be regulated.
Using qualitative methods, including legal, and bioethical analyses and a review of literature, this paper introduces an overview of the Portuguese legal solution on surrogacy and discusses, in particular, the right to regret of the surrogate after the child is born. The conclusion is that the Portuguese law on surrogacy does not yet have a clear and needed position about who are, in fact, the parents or mother(s) of the child in contested surrogacy contracts if the surrogate regrets the arrangement and revokes her consent after the child is born.
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Cunha, Barbara Zaparoli, Abdel-Malek Zine, Mohamed Ichchou, Christophe Droz, and Stéphane Foulard. "On Machine-Learning-Driven Surrogates for Sound Transmission Loss Simulations." Applied Sciences 12, no. 21 (October 23, 2022): 10727. http://dx.doi.org/10.3390/app122110727.
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Surrogate models are data-based approximations of computationally expensive simulations that enable efficient exploration of the model’s design space and informed decision making in many physical domains. The usage of surrogate models in the vibroacoustic domain, however, is challenging due to the non-smooth, complex behavior of wave phenomena. This paper investigates four machine learning (ML) approaches in the modelling of surrogates of sound transmission loss (STL). Feature importance and feature engineering are used to improve the models’ accuracy while increasing their interpretability and physical consistency. The transfer of the proposed techniques to other problems in the vibroacoustic domain and possible limitations of the models are discussed. Experiments show that neural network surrogates with physics-guided features have better accuracy than other ML models across different STL models. Furthermore, sensitivity analysis methods are used to assess how physically coherent the analyzed surrogates are.
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Wang, Chong, Xin Qiang, Menghui Xu, and Tao Wu. "Recent Advances in Surrogate Modeling Methods for Uncertainty Quantification and Propagation." Symmetry 14, no. 6 (June 13, 2022): 1219. http://dx.doi.org/10.3390/sym14061219.
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Surrogate-model-assisted uncertainty treatment practices have been the subject of increasing attention and investigations in recent decades for many symmetrical engineering systems. This paper delivers a review of surrogate modeling methods in both uncertainty quantification and propagation scenarios. To this end, the mathematical models for uncertainty quantification are firstly reviewed, and theories and advances on probabilistic, non-probabilistic and hybrid ones are discussed. Subsequently, numerical methods for uncertainty propagation are broadly reviewed under different computational strategies. Thirdly, several popular single surrogate models and novel hybrid techniques are reviewed, together with some general criteria for accuracy evaluation. In addition, sample generation techniques to improve the accuracy of surrogate models are discussed for both static sampling and its adaptive version. Finally, closing remarks are provided and future prospects are suggested.
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Bogdan, V. V., and M. N. Urda. "SURROGACY & HUMAN TRAFFICKING: INTERBRANCH CONFLICT." Вестник Пермского университета. Юридические науки, no. 4(58) (2022): 628–57. http://dx.doi.org/10.17072/1995-4190-2022-58-628-657.
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Introduction: the article discusses the challenging problem of the interbranch conflict between the legal institution of surrogacy and a criminally punishable act – human trafficking. The normative minimalism of regulatory legislation, the lack of understanding of the essence of surrogacy as a legal institution, insufficient understanding of the legal essence of the contract for child bearing and birth, are the factors that necessitate defining the boundaries of what is permissible through drawing a distinction between the application of surrogacy technology and the crime mentioned. Resolution of this issue is of particular importance for ensuring legal certainty that would exclude both abusive practices in legal relations involving surrogate motherhood and unlawful prosecution against the participants in these relations. Purpose: to create a conceptual framework for the interbranch relationship between the institution of surrogacy and the criminal law prohibition of human trafficking. Methods: empirical methods of comparison, description, interpretation; theoretical methods of formal and dialectical logic; special scientific methods: legal-dogmatic and the method of interpretation of legal norms. Results: the research into interbranch interaction of the institutions in question showed that the root cause of contradictions in the practice of applying the norms under study is the lack of a uniform systemic approach, both at the international and domestic level, to determining the legal boundaries of surrogacy technology and to the protection of relations generated by this technology by the norms on human trafficking. Conclusions: we have formulated doctrinal definitions of the institution of surrogate motherhood and the contract for child bearing and birth, which is interpreted as an interbranch contract; identified the legal nature of the surrogate mother’s consent to record the potential (genetic) parents in relation to the child born by her; described the specific nature of contractual structures included in the subject area of surrogate motherhood, with the identification of defects that transfer private-law relations regulated by them into the field of criminal law; formulated recommendations on the application of Article 127.1 of the Criminal Code of the Russian Federation. At present, there are no means in international law to resolve the conflict between legal surrogacy and human trafficking; the transnational nature of the phenomena under study dictates the need for the development of such means.
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DASHKOVSKA, Olena, and Vladyslav VASIUTIN. "Monetary surrogate as a legal category: general theoretical characteristics." Economics. Finances. Law, no. 6 (June 18, 2021): 18–21. http://dx.doi.org/10.37634/efp.2021.6.4.
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The emergence of monetary surrogates is a consequence of the inability to comprehensively meet the public needs for servicing the turnover of various objects (property, rights, etc.) solely with the help of money. Bringing a short-term positive economic effect, monetary surrogates compete with state money, disrupting money circulation. An important role in limiting monetary surrogates is played by legal remedies, the effective use of which is possible only if the content of the legal category «monetary surrogate» is determined. At the same time, the norms of law do not disclose its content, and in the scientific community there is a discussion on this issue, while its vector is shifted towards understanding the monetary surrogate only as a means of payment, unnecessarily narrowing it. The reliability and validity of the results are achieved through the integrated application of the comparative legal method (when comparing the concepts of money and monetary surrogate, as well as other single-order legal categories), logical-theoretical methods, and other research methods. As a result of the study, the authors tried to determine the content of the legal category «monetary surrogate» from the standpoint of his main economic functions of money, which allows not only to distinguish this category from related concepts, but effectively apply various legal restrictions, which the use of monetary surrogates. Theoretical bases of research of private monetary systems are developed, in particular, their classification on the following signs is carried out: appointment, the status of the issuer, sphere of distribution. It is determined that the main reasons for the emergence of private money are the insufficiency or unsuitability of public currencies to service economic relations. The place of electronic money in the modern globalized economy is highlighted. It was found that the emergence of cryptocurrencies initiated a new stage in the development of the monetary system, which is characterized by the lack of a single issuer and the inability of the state to regulate them.
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Liew, Jaime, Riccardo Riva, and Tuhfe Göçmen. "Efficient Mann turbulence generation for offshore wind farms with applications in fatigue load surrogate modelling." Journal of Physics: Conference Series 2626, no. 1 (October 1, 2023): 012050. http://dx.doi.org/10.1088/1742-6596/2626/1/012050.
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Abstract Surrogate models are vital for offshore wind farm optimisation, or digital twin for rapid execution. Reliable surrogates are difficult to make, especially for large wind farms and for fatigue loads. One limitation is the high resolution of turbulence needed for fatigue calculations and the vast size of a wind farm. We present code optimisations for implementing the Mann model for farm-sized flows, which are infeasible otherwise. Additionally, we present a case study of a full load surrogate for the Lillgrund offshore wind farm using large turbulence box generation in aeroelastic wind farm simulations using HAWC2Farm. Various mappings between the wind field in front of a turbine and the corresponding turbine structural fatigue loads are presented. The best-performing surrogate model, using a proper orthogonal decomposition of the input space with an artificial neural network, is able to significantly reduce the error in fatigue load estimates by as much as a factor of 5 compared to conventional methods. The presented recommendations are crucial to generating reliable wind farm load surrogates for wind farm optimisation purposes.
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Shin, Seung-Soo, and Yong-Hyuk Kim. "Optimal Agent Search Using Surrogate-Assisted Genetic Algorithms." Mathematics 11, no. 1 (January 2, 2023): 230. http://dx.doi.org/10.3390/math11010230.
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An intelligent agent is a program that can make decisions or perform a service based on its environment, user input, and experiences. Due to the complexity of its state and action spaces, agents are approximated by deep neural networks (DNNs), and it can be optimized using methods such as deep reinforcement learning and evolution strategies. However, these methods include simulation-based evaluations in the optimization process, and they are inefficient if the simulation cost is high. In this study, we propose surrogate-assisted genetic algorithms (SGAs), whose surrogate models are used in the fitness evaluation of genetic algorithms, and the surrogates also predict cumulative rewards for an agent’s DNN parameters. To improve the SGAs, we applied stepwise improvements that included multiple surrogates, data standardization, and sampling with dimensional reduction. We conducted experiments using the proposed SGAs in benchmark environments such as cart-pole balancing and lunar lander, and successfully found optimal solutions and significantly reduced computing time. The computing time was reduced by 38% and 95%, in the cart-pole balancing and lunar lander problems, respectively. For the lunar lander problem, an agent with approximately 4% better quality than that found by a gradient-based method was even found.
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Vasquez, Taylor S., Carma L. Bylund, Jordan Alpert, Julia Close, Tien Le, Merry Jennifer Markham, Greenberry B. Taylor, and Samantha R. Paige. "Comparing Transactional eHealth Literacy of Individuals With Cancer and Surrogate Information Seekers: Mixed Methods Study." JMIR Formative Research 6, no. 9 (September 28, 2022): e36714. http://dx.doi.org/10.2196/36714.
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Background The number of adults entering higher-risk age groups for receiving a cancer diagnosis is rising, with predicted numbers of cancer cases expected to increase by nearly 50% by 2050. Living with cancer puts exceptional burdens on individuals and families during treatment and survivorship, including how they navigate their relationships with one another. One role that a member of a support network may enact is that of a surrogate seeker, who seeks information in an informal capacity on behalf of others. Individuals with cancer and surrogate seekers often use the internet to learn about cancer, but differences in their skills and strategies have received little empirical attention. Objective This study aimed to examine the eHealth literacy of individuals with cancer and surrogate information seekers, including an investigation of how each group evaluates the credibility of web-based cancer information. As a secondary aim, we sought to explore the differences that exist between individuals with cancer and surrogate seekers pertaining to eHealth literacies and sociodemographic contexts. Methods Between October 2019 and January 2020, we conducted a web-based survey of 282 individuals with cancer (n=185) and surrogate seekers (n=97). We used hierarchical linear regression analyses to explore differences in functional, communicative, critical, and translational eHealth literacy between individuals with cancer and surrogate seekers using the Transactional eHealth Literacy Instrument. Using a convergent, parallel mixed methods design, we also conducted a thematic content analysis of an open-ended survey response to qualitatively examine how each group evaluates web-based cancer information. Results eHealth literacy scores did not differ between individuals with cancer and surrogate seekers, even after adjusting for sociodemographic variables. Individuals with cancer and surrogate seekers consider the credibility of web-based cancer information based on its channel (eg, National Institutes of Health). However, in evaluating web-based information, surrogate seekers were more likely than individuals with cancer to consider the presence and quality of scientific references supporting the information. Individuals with cancer were more likely than surrogate seekers to cross-reference other websites and web-based sources to establish consensus. Conclusions Web-based cancer information accessibility and evaluation procedures differ among individuals with cancer and surrogate seekers and should be considered in future efforts to design web-based cancer education interventions. Future studies may also benefit from more stratified recruitment approaches and account for additional contextual factors to better understand the unique circumstances experienced within this population.
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Meltzer, Ellen C., Zhenzhen Shi, Alexandra Suppes, Jennifer E. Hersh, Jay D. Orlander, Aaron W. Calhoun, Judy Tung, et al. "Improving Communication With Surrogate Decision-Makers: A Pilot Initiative." Journal of Graduate Medical Education 9, no. 4 (August 1, 2017): 461–66. http://dx.doi.org/10.4300/jgme-d-17-00035.1.
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ABSTRACT Background 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. Objective 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. Methods 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. Results 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 < .001; effect size r = 0.52). After the workshop, the majority of participants self-reported feeling “more confident.” Conclusions Residents' communication skills specific to surrogate 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.
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Bhatnagar, Saakaar. "Investigating the Surrogate Modeling Capabilities of Continuous Time Echo State Networks." Mathematical and Computational Applications 29, no. 1 (January 24, 2024): 9. http://dx.doi.org/10.3390/mca29010009.
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Continuous Time Echo State Networks (CTESNs) are a promising yet under-explored surrogate modeling technique for dynamical systems, particularly those governed by stiff Ordinary Differential Equations (ODEs). A key determinant of the generalization accuracy of a CTESN surrogate is the method of projecting the reservoir state to the output. This paper shows that of the two common projection methods (linear and nonlinear), the surrogates developed via the nonlinear projection consistently outperform those developed via the linear method. CTESN surrogates are developed for several challenging benchmark cases governed by stiff ODEs, and for each case, the performance of the linear and nonlinear projections is compared. The results of this paper demonstrate the applicability of CTESNs to a variety of problems while serving as a reference for important algorithmic and hyper-parameter choices for CTESNs.
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Ragan, Mark A. "On surrogate methods for detecting lateral gene transfer." FEMS Microbiology Letters 201, no. 2 (July 2001): 187–91. http://dx.doi.org/10.1111/j.1574-6968.2001.tb10755.x.
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Nino-Ruiz, Elias D. "Implicit surrogate models for trust region based methods." Journal of Computational Science 26 (May 2018): 264–74. http://dx.doi.org/10.1016/j.jocs.2018.02.003.
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KNUD-HANSEN, CAROL R., GINA A. DALLABETTA, CINDY REICHART, KATHERINE M. PABST, EDWARD W. HOOK, and JUDITH N. WASSERHEIT. "Surrogate Methods to Diagnose Gonococcal and Chlamydial Cervicitis." Sexually Transmitted Diseases 18, no. 4 (October 1991): 211–16. http://dx.doi.org/10.1097/00007435-199110000-00003.
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Ruscoe, Rebecca E., Jeremy I. Ramsden, and Nicholas J. Turner. "Redox surrogate methods for sustainable amine N-alkylation." Current Opinion in Chemical Engineering 30 (December 2020): 60–68. http://dx.doi.org/10.1016/j.coche.2020.08.005.
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Wirtz, D., N. Karajan, and B. Haasdonk. "Surrogate modeling of multiscale models using kernel methods." International Journal for Numerical Methods in Engineering 101, no. 1 (November 11, 2014): 1–28. http://dx.doi.org/10.1002/nme.4767.
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Borovkova, Violetta V., Aleksandr V. Zubko, Tamara P. Sabgayda, Konstantin E. Khomanov, and Gleb S. Krasnov. "The opinion of the medical community on the legal issues of surrogate maternity." HEALTH CARE OF THE RUSSIAN FEDERATION 66, no. 1 (March 4, 2022): 76–84. http://dx.doi.org/10.47470/0044-197x-2022-66-1-76-84.
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Introduction. Surrogacy is a method of infertility treatment involving the conclusion of an agreement between potential parents, a surrogate mother and a medical institution. Until now, lawyers have not been able to develop a unified approach to forming the regulatory framework for surrogacy. Whether healthcare providers have developed a standard view of this problem is not clear. The purpose is to summarise the medical community representatives’ views on the surrogacy program’s managing issues and their participants’ rights and obligations. Material and methods. The Internet survey was conducted among medical workers of various specialisations from different regions of Russia and among future specialists (students of medical universities and interns). 7504 questionnaire was analysed. The questions concerned the indications for surrogate motherhood, the sources of its funding, the citizenship of the participants in surrogacy and their contractual obligations, the rights of the surrogate mother and the ordering parents. Results. medical specialists assign a pivotal role to the surrogacy program’s legal aspects, despite being implemented using high-tech medical technologies. They give priority rights to a newborn child to the ordering parents. During pregnancy and childbirth, decisions regarding lifestyle, hospitalisation, and delivery methods should be made only in conjunction with specialists from the medical institution that signed the contract. As the level of professional responsibility of medical specialists grows, the share of answers about the inadmissibility of state funding of surrogacy, the implementation of surrogacy programs for foreign citizens and single men and women as genetic donors increases, and the share of answers about the admissibility of altruistic surrogacy decrease. Conclusion. Having decided on the legal issues of managing medical care in surrogacy programs, representatives of the medical community do not consider this type of high-tech medical care a common way to solve the problem of infertility, considering it as an exclusive method of medical care for married couples with infertility of women.
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Wang, Ching-Yun, Jean de Dieu Tapsoba, Catherine Duggan, and Anne McTiernan. "Generalized Linear Models with Covariate Measurement Error and Zero-Inflated Surrogates." Mathematics 12, no. 2 (January 17, 2024): 309. http://dx.doi.org/10.3390/math12020309.
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Epidemiological studies often encounter a challenge due to exposure measurement error when estimating an exposure–disease association. A surrogate variable may be available for the true unobserved exposure variable. However, zero-inflated data are encountered frequently in the surrogate variables. For example, many nutrient or physical activity measures may have a zero value (or a low detectable value) among a group of individuals. In this paper, we investigate regression analysis when the observed surrogates may have zero values among some individuals of the whole study cohort. A naive regression calibration without taking into account a probability mass of the surrogate variable at 0 (or a low detectable value) will be biased. We developed a regression calibration estimator which typically can have smaller biases than the naive regression calibration estimator. We propose an expected estimating equation estimator which is consistent under the zero-inflated surrogate regression model. Extensive simulations show that the proposed estimator performs well in terms of bias correction. These methods are applied to a physical activity intervention study.
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Petkau, J., SC Reingold, U. Held, GR Cutter, TR Fleming, MD Hughes, DH Miller, HF McFarland, and JS Wolinsky. "Magnetic resonance imaging as a surrogate outcome for multiple sclerosis relapses." Multiple Sclerosis Journal 14, no. 6 (July 2008): 770–78. http://dx.doi.org/10.1177/1352458507088104.
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Background Magnetic resonance imaging (MRI) of lesions in the brain may be the best current candidate for a surrogate biological marker of clinical outcomes in relapsing remitting multiple sclerosis (MS), based on its role as an objective indicator of disease pathology. No biological surrogate marker has yet been validated for MS clinical outcomes. Objective The objective of this study was to use a multi-phased study to determine if a valid surrogate relationship could be demonstrated between counts of contrast enhancing lesions (CELs) and occurrence of relapses in MS. Methods We examined correlations for the concurrent and predictive relationship between CELs over 6 months and MS relapses over the same 6 months and an additional 6 months (total: 12 months), using available data on untreated patients from a large clinical trial and natural history database. Results Concurrent and predictive correlations were inadequate to justify continuation of this study to the planned additional phases required to demonstrate a surrogate relationship between CELs and MS relapses. Conclusions Confidence intervals for correlations between CELs and MS relapses exclude the possibility that CELs can be a good surrogate for relapses over the time scales we investigated. Further exploration of surrogacy between MRI measures and MS clinical outcomes may require improved datasets, the development of MRI techniques that couple better to clinical disease, and the ability to test a wide range of imaging- and clinically-based hypotheses for surrogacy.
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Doskočil, Ondřej. "“Any surrogate mothers?” A Debate on surrogacy in internet discussion forums." Human Affairs 30, no. 1 (January 28, 2020): 10–26. http://dx.doi.org/10.1515/humaff-2020-0002.
Full textAbstract:
AbstractSurrogacy has long been discussed in reproductive medicine. In the Czech Republic, surrogacy is not legally regulated. Because of this legal vacuum, there are no official procedures or organizations that openly deal with surrogacy. Potential surrogate mothers and applicants do not have many options for obtaining or sharing information. The only source is the Internet. Online forums are a popular tool for gaining information and contacts regarding surrogacy. The goal of this research was to use qualitative research methods to survey the most searched and discussed topics on Czech online discussion forum websites. We used discussions that we found on www.emimino.cz between 2009 and 2019. This article analyses the comments of the Internet forum discussants/participants, their involvement, knowledge of surrogacy, the information sought and their opinions. In particular, the participants discussed where to find a surrogate mother or how to become one. This article attempts to outline the discussions ordinary people have about surrogacy outside official expert forums.