700 resultados para Surrogate


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This thesis details methodology to estimate urban stormwater quality based on a set of easy to measure physico-chemical parameters. These parameters can be used as surrogate parameters to estimate other key water quality parameters. The key pollutants considered in this study are nitrogen compounds, phosphorus compounds and solids. The use of surrogate parameter relationships to evaluate urban stormwater quality will reduce the cost of monitoring and so that scientists will have added capability to generate a large amount of data for more rigorous analysis of key urban stormwater quality processes, namely, pollutant build-up and wash-off. This in turn will assist in the development of more stringent stormwater quality mitigation strategies. The research methodology was based on a series of field investigations, laboratory testing and data analysis. Field investigations were conducted to collect pollutant build-up and wash-off samples from residential roads and roof surfaces. Past research has identified that these impervious surfaces are the primary pollutant sources to urban stormwater runoff. A specially designed vacuum system and rainfall simulator were used in the collection of pollutant build-up and wash-off samples. The collected samples were tested for a range of physico-chemical parameters. Data analysis was conducted using both univariate and multivariate data analysis techniques. Analysis of build-up samples showed that pollutant loads accumulated on road surfaces are higher compared to the pollutant loads on roof surfaces. Furthermore, it was found that the fraction of solids smaller than 150 ìm is the most polluted particle size fraction in solids build-up on both roads and roof surfaces. The analysis of wash-off data confirmed that the simulated wash-off process adopted for this research agrees well with the general understanding of the wash-off process on urban impervious surfaces. The observed pollutant concentrations in wash-off from road surfaces were different to pollutant concentrations in wash-off from roof surfaces. Therefore, firstly, the identification of surrogate parameters was undertaken separately for roads and roof surfaces. Secondly, a common set of surrogate parameter relationships were identified for both surfaces together to evaluate urban stormwater quality. Surrogate parameters were identified for nitrogen, phosphorus and solids separately. Electrical conductivity (EC), total organic carbon (TOC), dissolved organic carbon (DOC), total suspended solids (TSS), total dissolved solids (TDS), total solids (TS) and turbidity (TTU) were selected as the relatively easy to measure parameters. Consequently, surrogate parameters for nitrogen and phosphorus were identified from the set of easy to measure parameters for both road surfaces and roof surfaces. Additionally, surrogate parameters for TSS, TDS and TS which are key indicators of solids were obtained from EC and TTU which can be direct field measurements. The regression relationships which were developed for surrogate parameters and key parameter of interest were of a similar format for road and roof surfaces, namely it was in the form of simple linear regression equations. The identified relationships for road surfaces were DTN-TDS:DOC, TP-TS:TOC, TSS-TTU, TDS-EC and TSTTU: EC. The identified relationships for roof surfaces were DTN-TDS and TSTTU: EC. Some of the relationships developed had a higher confidence interval whilst others had a relatively low confidence interval. The relationships obtained for DTN-TDS, DTN-DOC, TP-TS and TS-EC for road surfaces demonstrated good near site portability potential. Currently, best management practices are focussed on providing treatment measures for stormwater runoff at catchment outlets where separation of road and roof runoff is not found. In this context, it is important to find a common set of surrogate parameter relationships for road surfaces and roof surfaces to evaluate urban stormwater quality. Consequently DTN-TDS, TS-EC and TS-TTU relationships were identified as the common relationships which are capable of providing measurements of DTN and TS irrespective of the surface type.

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This paper presents the outcomes of a research project, which focused on developing a set of surrogate parameters to evaluate urban stormwater quality using simulated rainfall. Use of surrogate parameters has the potential to enhance the rapid generation of urban stormwater quality data based on on-site measurements and thereby reduce resource intensive laboratory analysis. The samples collected from rainfall simulations were tested for a range of physico-chemical parameters which are key indicators of nutrients, solids and organic matter. The analysis revealed that [total dissolved solids (TDS) and dissolved organic carbon (DOC)]; [total solids (TS) and total organic carbon (TOC)]; [turbidity (TTU)]; [electrical conductivity (EC)]; [TTU and EC] as appropriate surrogate parameters for dissolved total nitrogen (DTN), total phosphorus (TP), total suspended solids (TSS), TDS and TS respectively. Relationships obtained for DTN-TDS, DTN-DOC, and TP-TS demonstrated good portability potential. The portability of the relationship developed for TP and TOC was found to be unsatisfactory. The relationship developed for TDS-EC and TS-EC also demonstrated poor portability.

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Background Research involving incapacitated persons with dementia entails complex scientific, legal, and ethical issues, making traditional surveys of layperson views on the ethics of such research challenging. We therefore assessed the impact of democratic deliberation (DD), involving balanced, detailed education and peer deliberation, on the views of those responsible for persons with dementia. Methods One hundred and seventy-eight community-recruited caregivers or primary decision-makers for persons with dementia were randomly assigned to either an all-day DD session group or a control group. Educational materials used for the DD session were vetted for balance and accuracy by an interdisciplinary advisory panel. We assessed the acceptability of family-surrogate consent for dementia research (“surrogate-based research”) from a societal policy perspective as well as from the more personal perspectives of deciding for a loved one or for oneself (surrogate and self-perspectives), assessed at baseline, immediately post-DD session, and 1 month after DD date, for four research scenarios of varying risk-benefit profiles. Results At baseline, a majority in both the DD and control groups supported a policy of family consent for dementia research in all research scenarios. The support for a policy of family consent for surrogate-based research increased in the DD group, but not in the control group. The change in the DD group was maintained 1 month later. In the DD group, there were transient changes in attitudes from surrogate or self-perspectives. In the control group, there were no changes from baseline in attitude toward surrogate consent from any perspective. Conclusions Intensive, balanced, and accurate education, along with peer deliberation provided by democratic deliberation, led to a sustained increase in support for a societal policy of family consent in dementia research among those responsible for dementia patients.

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Stormwater is a potential and readily available alternative source for potable water in urban areas. However, its direct use is severely constrained by the presence of toxic pollutants, such as heavy metals (HMs). The presence of HMs in stormwater is of concern because of their chronic toxicity and persistent nature. In addition to human health impacts, metals can contribute to adverse ecosystem health impact on receiving waters. Therefore, the ability to predict the levels of HMs in stormwater is crucial for monitoring stormwater quality and for the design of effective treatment systems. Unfortunately, the current laboratory methods for determining HM concentrations are resource intensive and time consuming. In this paper, applications of multivariate data analysis techniques are presented to identify potential surrogate parameters which can be used to determine HM concentrations in stormwater. Accordingly, partial least squares was applied to identify a suite of physicochemical parameters which can serve as indicators of HMs. Datasets having varied characteristics, such as land use and particle size distribution of solids, were analyzed to validate the efficacy of the influencing parameters. Iron, manganese, total organic carbon, and inorganic carbon were identified as the predominant parameters that correlate with the HM concentrations. The practical extension of the study outcomes to urban stormwater management is also discussed.

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The importance of community resilience to natural disasters is being increasingly recognised. This paper presents an approach for the development of surrogate indicators for comprehensive assessment of community resilience, which is crucial in the context of predicted increase in natural disasters resulting from extreme weather events due to climate change. The use of surrogate indicators is advocated because a comprehensive assessment of community resilience across various thematic areas and associated key areas requires the measurement of a large number of resilience indicators which is not always feasible due to time and resource constraints, To overcome this, researchers tend to use secondary data sources, which are easily available but not always reliable. This highlights the need for surrogate indicators that are easy to measure from reliable primary data sources and are adequate to capture the resilience of a community. Firstly, the paper discusses the two approaches for defining and conceptualising community resilience and the need to account for the complex interrelationships between thematic areas, key areas and resilience indicators and their implications for research. Secondly, a comprehensive framework for the assessment of community resilience is proposed and the difficulties associated with the measurement of overall resilience of the community are discussed. Thirdly, the paper explains a two-step approach to develop surrogate indicators highlighting the necessity and challenges associated with it. Finally, the proposed approach is elaborated with a simple example for better understanding.

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Purpose To evaluate carbonic anhydrase (CA) IX as a surrogate marker of hypoxia and investigate the prognostic significance of different patterns of expression in non-small-cell lung cancer (NSCLC). Methods Standard immunohistochemical techniques were used to study CA IX expression in 175 resected NSCLC tumors. CA IX expression was determined by Western blotting in A549 cell lines grown under normoxic and hypoxic conditions. Measurements from microvessels to CA IX positivity were obtained. Results CA IX immunostaining was detected in 81.8% of patients. Membranous (m) (P = .005), cytoplasmic (c) (P = .018), and stromal (P < .001) CA IX expression correlated with the extent of tumor necrosis (TN). The mean distance from vascular endothelium to the start of tumor cell positivity was 90 μm, which equates to an oxygen pressure of 5.77 mmHg. The distance to blood vessels from individual tumor cells or tumor cell clusters was greater if they expressed mCA IX than if they did not (P < .001). Hypoxic exposure of A549 cells for 16 hours enhanced CAIX expression in the nuclear and cytosolic extracts. Perinuclear (p) CA IX (P = .035) was associated with a poor prognosis. In multivariate analysis, pCA IX (P = .004), stage (P = .001), platelet count (P = .011), sex (P = .027), and TN (P = .035) were independent poor prognostic factors. Conclusion These results add weight to the contention that mCA IX is a marker of tumor cell hypoxia. The absence of CA IX staining close to microvessels suggests that these vessels are functionally active. pCA IX expression is representative of an aggressive phenotype. © 2003 by American Society of Clinical Oncology.

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Work zone safety studies have traditionally relied on historical crash records—an approach which is reactive in nature as it requires crashes to accumulate first before taking any preventive actions. However, detailed and accurate data on work zone crashes are often not available, as is the case for Australian road work zones. The lack of reliable safety records and the reactive nature of the crash-based safety analysis approach motivated this research to seek alternative and proactive measures of safety. Various surrogate measures of safety have been developed in the traffic safety literature including time to collision, time to accident, gap time, post encroachment time, required deceleration rate, proportion of stopping distances, lateral distance to departure, and time to departure. These measures express how close road-user(s) are from a potential crash by analysing their movement trajectories. A review of this fast-growing literature is presented in this paper from the viewpoint of applying the measures to untangle work zone safety issues. The review revealed that the use of the surrogate measures is very limited for analysing work zone safety, although numerous studies have used these measures for analysing safety in other parts of the road network, such as intersections and motorway ramps. There exist great opportunities for adopting this proactive safety assessment approach to transform work zone safety for both roadworkers and motorists.

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A multi-objective design optimization study has been conducted for upstream fuel injection through porous media applied to the first ramp of a two-dimensional scramjet intake. The optimization has been performed by coupling evolutionary algorithms assisted by surrogate modeling and computational fluid dynamics with respect to three design criteria, that is, the maximization of the absolute mixing quantity, total pressure saving, and fuel penetration. A distinct Pareto optimal front has been obtained, highlighting the counteracting behavior of the total pressure against the mixing efficiency and fuel penetration. The injector location and size have been identified as the key design parameters as a result of a sensitivity analysis, with negligible influence of the porous properties in the configurations and conditions considered in the present study. Flowfield visualization has revealed the underlying physics associated with the effects of these dominant parameters on the shock structure and intensity.

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Introduction: Agonists of glucagon-like peptide-1 (GLP-1) receptors are used in the treatment of type 2 diabetes. Albiglutide is a new long acting GLP-1 receptor agonist being developed for once-weekly use. Areas covered: This evaluation is of 2 clinical trials in the HARMONY clinical trials series. HARMONY 3 compares albiglutide to sitagliptin and glimepiride in subjects with type 2 diabetes poorly controlled with metformin, and HARMONY 6 compares albiglutide to insulin lispro in subjects poorly controlled with slow/medium release preparations of insulin. Expert opinion: Both studies showed that albiglutide lowered HbA1c, and had advantages over its comparator drugs. However, questions remain about the safety of albiglutide. Albiglutide is not being used in subjects with a history of thyroid cancer, as it is not known whether this is a rare adverse effect with albiglutide. Also, the safety of albiglutide in subjects with type 2 diabetes and high cardiovascular risk is unknown.

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The fatty acid composition of ground nuts (Arachis hypogaea L.) commonly known as peanuts, is an important consideration when a new variety is being released. The composition impacts on nutrition and, importantly, self-life of peanut products. To select for suitable breeding material, it was necessary to develop a rapid, non-derstructive and cost-efficient method. Near infrared spectroscopy was chosen as that methodology. Calibrations were developed for two major fatty-acid components, oleic and linoleic acids and two minor components, palmitic and stearic acids, as well as total oil content. Partial least squares models indicated a high level of precision with a squared multiple correlation coefficient of greater than 0.90 for each constitutent. Standard errors for prediction for oleic, linoleic, palmitic, stearic acids and total oil content were 6.4%, 4.5%, 0.8%, 0.9% and 1.3% respectively. The results demonstrated that reasonable calibrations could be developed to predict oil composition and content of peanuts for a breeding programme.

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Three major changes in drink driving enforcement have occurred in South Australia since 1981. The effect of these changes on a number of surrogate measures of alcohol involvement in accidents were investigated. The surrogates included alcohol involvement of driver fatalities, and combinations of casualty, serious casualty, single vehicle and nighttime accidents. Data from previous studies were also cited. It was found that relationships between surrogate measures were inconsistent, and incompatible with assumptions about drink driving levels and related accidents. It was concluded that until these effects are understood the use of surrogate measures should be treated with caution.

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Objective To quantify and compare the treatment effect and risk of bias of trials reporting biomarkers or intermediate outcomes (surrogate outcomes) versus trials using final patient relevant primary outcomes. Design Meta-epidemiological study. Data sources All randomised clinical trials published in 2005 and 2006 in six high impact medical journals: Annals of Internal Medicine, BMJ, Journal of the American Medical Association, Lancet, New England Journal of Medicine, and PLoS Medicine. Study selection Two independent reviewers selected trials. Data extraction Trial characteristics, risk of bias, and outcomes were recorded according to a predefined form. Two reviewers independently checked data extraction. The ratio of odds ratios was used to quantify the degree of difference in treatment effects between the trials using surrogate outcomes and those using patient relevant outcomes, also adjusted for trial characteristics. A ratio of odds ratios >1.0 implies that trials with surrogate outcomes report larger intervention effects than trials with patient relevant outcomes. Results 84 trials using surrogate outcomes and 101 using patient relevant outcomes were considered for analyses. Study characteristics of trials using surrogate outcomes and those using patient relevant outcomes were well balanced, except for median sample size (371 v 741) and single centre status (23% v 9%). Their risk of bias did not differ. Primary analysis showed trials reporting surrogate endpoints to have larger treatment effects (odds ratio 0.51, 95% confidence interval 0.42 to 0.60) than trials reporting patient relevant outcomes (0.76, 0.70 to 0.82), with an unadjusted ratio of odds ratios of 1.47 (1.07 to 2.01) and adjusted ratio of odds ratios of 1.46 (1.05 to 2.04). This result was consistent across sensitivity and secondary analyses. Conclusions Trials reporting surrogate primary outcomes are more likely to report larger treatment effects than trials reporting final patient relevant primary outcomes. This finding was not explained by differences in the risk of bias or characteristics of the two groups of trials.

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Objectives In 2012, the National Institute for Health and Care Excellence assessed dasatinib, nilotinib, and standard-dose imatinib as first-line treatment of chronic phase chronic myelogenous leukemia (CML). Licensing of these alternative treatments was based on randomized controlled trials assessing complete cytogenetic response (CCyR) and major molecular response (MMR) at 12 months as primary end points. We use this case study to illustrate the validation of CCyR and MMR as surrogate outcomes for overall survival in CML and how this evidence was used to inform National Institute for Health and Care Excellence’s recommendation on the public funding of these first-line treatments for CML. Methods We undertook a systematic review and meta-analysis to quantify the association between CCyR and MMR at 12 months and overall survival in patients with chronic phase CML. We estimated life expectancy by extrapolating long-term survival from the weighted overall survival stratified according to the achievement of CCyR and MMR. Results Five studies provided data on the observational association between CCyR or MMR and overall survival. Based on the pooled association between CCyR and MMR and overall survival, our modeling showed comparable predicted mean duration of survival (21–23 years) following first-line treatment with imatinib, dasatinib, or nilotinib. Conclusions This case study illustrates the consideration of surrogate outcome evidence in health technology assessment. Although it is often recommended that the acceptance of surrogate outcomes be based on randomized controlled trial data demonstrating an association between the treatment effect on both the surrogate outcome and the final outcome, this case study shows that policymakers may be willing to accept a lower level of evidence (i.e., observational association).

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Multimetric ecological condition assessment has become an important biodiversity management tool. This study was the first to examine the reliability of these ecological surrogates across variable environments, and the implications for surrogate efficacy. It was demonstrated that through strategic application and design of the multimetric ecological condition index, the effects of environmental gradients and disturbance regimes can be mitigated, and that ecological condition assessment may serve as a scientifically rigorous approach for conservation planning.