Effects of Fuel-Reduction Techniques on Vegetative Composition of Piedmont Loblolly-Shortleaf Pine Communities: Preliminary Results of the National Fire and Fire Surrogate Study

Treesearch

Ross J. Phillips; Thomas A. Waldrop; Gregg L. Chapman; Helen H. Mohr; Mac A. Callaham; Charles T. Flint

2004-01-01

As part of the National Fire and Fire Surrogate (NFFS) Study, prescribed burning, thinning, and a combination of burning and thinning were conducted in loblolly ( Pinus taeda L.) and shortleaf pine ( P. echinata Mill.) communities in the Piedmont of South Carolina to test the effectiveness of these treatments for fuel reduction. Treatment implementation resulted in an...

Seasonal Avifauna Reponses to Fuel Reduction Treatments in the Upper Piedmont of South Carolina: Results From Phase 1 of the National Fire and Fire Surrogate Study

Treesearch

Laura A. Zebehazy; J. Drew Lanham; Thomas A. Waldrop

2004-01-01

We examined avian species and assemblage responses to prescribed burns and thinning in a southeastern Piedmont pine and mixed pine-hardwood forest as part of the National Fire and Fire Surrogate Study (NFFS) examining the effects of fuel reduction on forest health. Point counts conducted during the non-breeding and breeding seasons of 2000-2002 showed that winter bird...

Response of white-footed mice (Peromyscus leucopus) to fire and fire surrogate fuel reduction treatments in a southern Appalachian hardwood forest

Treesearch

Cathryn H. Greenberg; David L. Otis; Thomas A. Waldrop

2006-01-01

An experiment conducted as part of the multidisciplinary National Fire and Fire Surrogate Study was designed to determine effects of three fuel reduction techniques on small mammals and habitat structure in the southern Appalachian mountains. Four experimental units, each >14-ha were contained within each of three replicate blocks at the Green River Game Land,...

Different interest group views of fuels treatments: survey results from fire and fire surrogate treatments in a Sierran mixed conifer forest, California, USA

Treesearch

Sarah McCaffrey; Jason J. Moghaddas; Scott L. Stephens

2008-01-01

The present paper discusses results from a survey about the acceptance of and preferences for fuels treatments of participants following a field tour of the University of California Blodgett Forest Fire and Fire Surrogate Study Site. Although original expectations were that tours would be composed of general members of the public, individual tour groups ultimately were...

Understory vegetation response in longleaf pine forests to fire and fire surrogate treatments for wildfire hazard reduction and ecological restoration

Treesearch

Dale G. Brockway; Kenneth W Outcalt

2005-01-01

The principal objective is to quantify the responses of the understory plant community to fire and fire surrogate treatments, specifically plant species composition, foliar cover, species richness, diversity, and evenness changes resulting from (1) fire exclusion in the untreated control, (2) prescribed fire, (3) thinning, (4) thinning plus prescribed fire, and (5)...

Soil resources influence vegetation and response to fire and fire-surrogate treatments in Sagebrush-Steppe Ecosystems

Treesearch

Benjamin M. Rau; Jeanne C. Chambers; David A. Pyke; Bruce A. Roundy; Eugene W. Schupp; Paul Doescher; Todd G. Caldwell

2014-01-01

Current paradigm suggests that spatial and temporal competition for resources limit an exotic invader, cheatgrass (Bromus tectorum L.), which once established, alters fire regimes and can result in annual grass dominance in sagebrush steppe. Prescribed fire and fire surrogate treatments (mowing, tebuthiuron, and imazapic) are used to reduce woody...

Effects of fire and fire surrogate treatments on bark beetle-caused tree mortality in the Southern Cascades, California

Treesearch

C.J. Fettig; R.R. Borys; C.P. and Dabney

2010-01-01

We examined bark beetle responses to fire and fire surrogate treatments 2 and 4 years after the application of prescribed fire in a mixed-conifer forest in northern California. Treatments included an untreated control (C), thinning from below (T), and applications of prescribed fire (B) and T + B replicated three times in 10-ha experimental units. A total of 1,822...

A simulation of wildfire behavior in piedmont forests

Treesearch

Helen H. Mohr; Thomas A. Waldrop

2006-01-01

Decades of fire exclusion have increased the need for fuel reduction in U.S. forests. The buildup of excessive fuels has led to uncharacteristically severe fires in areas with historically short-interval, low to moderate intensity fire regimes. The National Fire and Fire Surrogate Study compares the impacts of three fuel reduction treatments on numerous response...

Response of Reptiles and Amphibians to Repeated Fuel Reduction Treatments

Treesearch

Charlotte E. Matthews; Christopher E. Moorman; Cathryn H. Greenberg; Thomas A. Waldrop

2010-01-01

Recent use of prescribed fire and fire surrogates to reduce fuel hazards has spurred interest in their effects on wildlife. Studies of fire in the southern Appalachian Mountains (USA) have documented few effects on reptiles and amphibians. However, these studies were conducted after only one fire and for only a short time (1–3 yr) after the fire. From mid-May to mid-...

Forest soil response to fuel reduction treatments in the Southern Appalachian Mountains

Treesearch

T. Adams Coates; Victor B. Shelburne; Thomas A. Waldrop; Bill R. Smith; Hoke S., Jr. Hill; Dean M. Simon

2010-01-01

The National Fire and Fire Surrogate Study (FFS) was established to monitor the impacts of fuel reduction treatments (prescribed fire-only, mechanical fuel reduction-only, and a combination of prescribed fire and mechanical fuel reduction) on a host of ecosystem properties at 13 sites across the United States. Treatment impacts were monitored on the Southern...

Fire and fire surrogate study in the Sierra Nevada: evaluating restoration treatments at Blodgett Forest and Sequoia National Park

Treesearch

Eric E. Knapp; Scott L. Stephens; James D. McIver; Jason J. Moghaddas; Jon E. Keeley

2004-01-01

Management practices have altered both the structure and function of forests throughout the United States. Some of the most dramatic changes have resulted from fire exclusion, especially in forests that historically experienced relatively frequent, low- to moderate-intensity fire regimes. In the Sierra Nevada, fire exclusion is believed to have resulted in widespread...

Fuel reduction treatments affect stand structure of hardwood forests in Western North Carolina and Southern Ohio, USA

Treesearch

Thomas A. Waldrop; Daniel A. Yaussy; Ross J. Phillips; Todd A. Hutchinson; Lucy Brudnak; Ralph E.J. Boerner

2008-01-01

Prescribed fire and mechanical treatments were tested at the two hardwood sites of the National Fire and Fire Surrogate Study (southern and central Appalachian regions) for impacts to stand structure. After two fires and one mechanical treatment, no treatment or treatment combination restored stand structure to historical levels. Burning alone had little impact on...

Short-term response of ground-dwelling arthropods to prescribed fire and mechanical fuel reduction in a Southern Appalachian upland hardwood forest

Treesearch

Cathryn H. Greenberg; T.G. Forrest; Thomas Waldrop

2010-01-01

As part of the multidisciplinary National Fire and Fire Surrogate Study, we used drift fences with pitfall traps to determine how three fuel reduction treatments affected ground-dwelling macroarthropods in the southern Appalachian Mountains of North Carolina. Four experimental units, each

Fuels and predicted fire behavior in the southern Appalachian Mountains and fire and fire surrogate treatments

Treesearch

Thomas Waldrop; Ross J. Phillips; Dean A. Simon

2010-01-01

This study tested the success of fuel reduction treatments for mitigating wildfire behavior in an area that has had little previous research on fire, the southern Appalachian Mountains. A secondary objective of treatments was to restore the community to an open woodland condition. Three blocks of four treatments were installed in a mature hardwood forest in western...

Using BEHAVEPlus for predicting fire behavior in southern Appalachian hardwood stands subjected to fuel reduction treatments

Treesearch

Helen H. Mohr; Thomas A. Waldrop; Dean M. Simon

2010-01-01

There is a crucial need for fuel reduction in United States forests due to decades of fuel accumulation resulting from fire exclusion. The National Fire and Fire Surrogate Study (FFS) addresses this issue by examining the effects of three fuel reduction treatments on numerous response variables. At an FFS site in the southern Appalachian Mountains, fuels were altered...

Delayed mortality of eastern hardwoods after prescribed fire

Treesearch

Daniel A. Yaussy; Thomas A. Waldrop

2010-01-01

The Southern Appalachian Mountain and the Ohio Hills sites of the National Fire and Fire Surrogate Study are located in hardwood dominated forests. Mortality of trees was anticipated the first year after burning but it continued for up to 4 years after burning, which was not expected. Survival analysis showed that the likelihood of mortality was related to prior tree...

Impact of Prescribed Fire and Thinning on Host Resistance to the Southern Pine Beetle: Preliminary Results of the National Fire and Fire Surrogate Study

Treesearch

M. Forbes Boyle; Roy L. Hedden; Thomas A. Waldrop

2004-01-01

The southern pine beetle ( Dendroctonus frontalis Zimm.) is considered one of the most aggressive insect pests in the Southern United States. Resistance to southern pine beetle infestations in southern pines depends largely on oleoresin flow rate and total flow. Treatments, such as prescribed fire and thinning, can be used to reduce stand infestation susceptibil-ity by...

Short-term response of shrews to prescribed fire and mechanical fuelr eduction in a Southern Appalachian upland hardwood forest

Treesearch

Cathryn H. Greenberg; Stanlee Miller; Thomas A. Waldrop

2007-01-01

As part of the multidisciplinary National Fire and Fire Surrogate study, we used drift fences with pitfall traps from May to September 2003 and 2004 to determine how three fuel reduction techniques affected shrews in the Southern Appalachian Mountains of North Carolina. Ground dwelling macroarthropods also were collected from a subset of pitfall traps to assess...

Short-term effects of fuel reduction treatments on herpetofauna from the southeastern United States

Treesearch

Eran S. Kilpatrick; Thomas A. Waldrop; Joseph D. Lanham; Cathryn H. Greenberg; Tom H. Contreras

2010-01-01

Path analysis of fuel reduction treatments on herpetofauna across four southeastern sites of the National Fire and Fire Surrogate Study provided quantitative evidence relating changes in vegetation and fuels to herpetofauna response. Fuel reduction treatments included prescribed burning (B), a mechanical treatment (M), mechanical treatment followed by prescribed...

Effects of fuel reduction treatments on avian nest density in the upper piedmont of South Carolina

Treesearch

E.S. Kilpatrick; J.D. Lanham; T.A. Waldrop

2010-01-01

The Fire and Fire Surrogate Study is a national study installed at 13 sites across the United States. One goal of the southeastern Piedmont FFS installation was to assess the effects of fuel reduction treatments such as prescribed burning and thinning on avian nest density. Nest searching and monitoring took place within twelve 10-hectare study plots during the...

Preliminary Effects of Prescribed Burning and Thinning as Fuel Reduction Treatments on the Piedmont Soils of the Clemson Experimental Forest

Treesearch

Victor B. Shelburne; M. Forbes Boyle; Darren J. Lione; Thomas A. Waldrop

2004-01-01

This study is a component of the National Fire and Fire Surrogate (NFFS) Study which is an integrated national network of long-term interdisciplinary research to facilitate broad applicability of fuel impacts. This part of the NFFS study in the Piedmont of South Carolina studied three ways of reducing fuel loads (prescribed burning, thinning, and the two in combination...

Thinning and burning in dry coniferous forests of the Western United States: effectiveness in altering diameter distributions

Treesearch

Andrew Youngblood

2010-01-01

Western United States land managers are conducting fuel reduction and forest restoration treatments in forests with altered structural conditions. As part of the National Fire and Fire Surrogate (FFS) study, thinning and burning treatments were evaluated for changing forest structure. Shifts between pretreatment and posttreatment diameter distributions at seven western...

Fuel-reduction treatments for restoration in eastern hardwoods: impacts on multiple ecosystem components

Treesearch

Thomas A. Waldrop; Daniel A. Yaussy; Ralph E.J. Boerner; Cathryn H. Greenberg; Dean M. Simon

2013-01-01

The Southern Appalachian Mountains and Ohio Hills sites are unique within the National Fire and Fire Surrogate Study because they are in hardwood-dominated forests. The efficacy of four fuel-reduction treatments was evaluated to restore these unmanaged hardwood forests to the structure and function of open woodland habitats. Treatments included control, prescribed...

A review of fire effects on vegetation and soils in the Great Basin region: response and ecological site characteristics

USGS Publications Warehouse

Miller, Richard F.; Chambers, Jeanne C.; Pyke, David A.; Pierson, Fred B.; Williams, C. Jason

2013-01-01

This review synthesizes the state of knowledge on fire effects on vegetation and soils in semi-arid ecosystems in the Great Basin Region, including the central and northern Great Basin and Range, Columbia River Basin, and the Snake River Plain. We summarize available literature related to: (1) the effects of environmental gradients, ecological site, and vegetation characteristics on resilience to disturbance and resistance to invasive species; (2) the effects of fire on individual plant species and communities, biological soil crusts, seed banks, soil nutrients, and hydrology; and (3) the role of fire severity, fire versus fire surrogate treatments, and post-fire grazing in determining ecosystem response. From this, we identify knowledge gaps and present a framework for predicting plant successional trajectories following wild and prescribed fires and fire surrogate treatments. Possibly the three most important ecological site characteristics that influence a site’s resilience (ability of the ecological site to recover from disturbance) and resistance to invasive species are soil temperature/moisture regimes and the composition and structure of vegetation on the ecological site just prior to the disturbance event.

Effects of Fuel Reduction Treatments on Incidence of Phytophthora Species in Soil of a Southern Appalachian Mountain Forest

Treesearch

I.M. Meadows; D.C. Zwart; S.N. Jeffers; T.A. Waldrop; W.C. Bridges

2011-01-01

The National Fire and Fire Surrogate Study was initiated to study the effects of fuel reduction treatments on forest ecosystems. Four fuel reduction treatments were applied to three sites in a southern Appalachian Mountain forest in western North Carolina: prescribed burning, mechanical fuel reduction, mechanical fuel reduction followed by prescribed burning, and a non...

Sources, sinks, and spatial ecology of cotton mice in longleaf pine stands undergoing restoration

USGS Publications Warehouse

Sharp, N.W.; Mitchell, M.S.; Grand, J.B.

2009-01-01

The Fire and Fire Surrogate studya replicated, manipulative experimentsought the most economically and ecologically efficient way to restore the nation's fire-maintained ecosystems. As part of this study, we conducted a 3-year markrecapture study, comprising 105,000 trap-nights, to assess demographic responses of cotton mice (Peromyscus gossypinus) to Fire and Fire Surrogate treatments at the Gulf Coastal Plain site, where longleaf pine was the ecosystem to be restored. We compared competing models to evaluate restoration effects on variation in apparent survival and recruitment over time, space, and treatment, and incorporated measures of available source habitat for cotton mice with reverse-time modeling to infer immigration from outside the study area. The top-ranked survival model contained only variation over time, but the closely ranked 2nd and 3rd models included variation over space and treatment, respectively. The top 4 recruitment models all included effects for availability of source habitat and treatments. Burning appeared to degrade habitat quality for cotton mice, showing demographic characteristics of a sink, but treatments combining fire with thinning of trees or application of herbicide to the understory appeared to improve habitat quality, possibly creating sources. Bottomland hardwoods outside the study also acted as sources by providing immigrants to experimental units. Models suggested that population dynamics operated over multiple spatial scales. Treatments applied to 15-ha stands probably only caused local variation in vital rates within the larger population. ?? 2009 American Society of Mammalogists.

Evaluation of novel thermally enhanced spectral indices for mapping fire perimeters and comparisons with fire atlas data

Treesearch

Z.A Holden; P. Morgan; A.M.S. Smith; M Rollins; P.E. Gessler

2005-01-01

We evaluated the potential of two novel thermally enhanced Landsat Thematic Mapper (TM)-derived spectral indices for discriminating burned areas and for producing fire perimeter data (as a potential surrogate to digital fire atlas data) within two wildland fires (1985 and 1993) in ponderosa pine (Pinus ponderosa) forests of the Gila Wilderness, New...

Structure of diffusion flames from a vertical burner

Treesearch

Mark A. Finney; Dan Jimenez; Jack D. Cohen; Isaac C. Grenfell; Cyle Wold

2010-01-01

Non-steady and turbulent flames are commonly observed to produce flame contacts with adjacent fuels during fire spread in a wide range of fuel bed depths. A stationary gas-fired burner (flame wall) was developed to begin study of flame edge variability along an analagous vertical fuel source. This flame wall is surrogate for a combustion interface at the edge of a deep...

The Sagebrush Steppe Treatment Evaluation Project (SageSTEP): a test of state-and-transition theory

Treesearch

James D. McIver; Mark Brunson; Steve C. Bunting; Jeanne Chambers; Nora Devoe; Paul Doescher; James Grace; Dale Johnson; Steve Knick; Richard Miller; Mike Pellant; Fred Pierson; David Pyke; Kim Rollins; Bruce Roundy; Eugene Schupp; Robin Tausch; David Turner

2010-01-01

The Sagebrush Steppe Treatment Evaluation Project (SageSTEP) is a comprehensive, integrated, long-term study that evaluates the ecological effects of fire and fire surrogate treatments designed to reduce fuel and to restore sagebrush (Artemisia spp.) communities of the Great Basin and surrounding areas. SageSTEP has several features that make it ideal for testing...

Litter Decomposition and Soil Respiration Responses to Fuel-Reduction Treatments in Piedmond Loblolly Pine Forests

Treesearch

Mac A. Callaham; Peter H. Anderson; Thomas A. Waldrop; Darren J. Lione; Victor B. Shelburne

2004-01-01

As part of the National Fire and Fire Surrogate Study, we measured the short-term effects of different fuel-management practices on leaf litter decomposition and soil respiration in loblolly pine stands on the upper Piedmont of South Carolina. These stands had been subjected to a factorial arrangement of experimental fuel-management treatments that included prescribed...

Effects of prescribed fire and fire surrogates on Saproxylic coleoptera in the Southern Appalachians of North Carolina

Treesearch

Joshua W. Campbell; James L. Hanula; Thomas A. Waldrop

2008-01-01

We examined the effects of forest management practices (prescribed burning, mechanical, and prescribed burn plus mechanical) on saproxylic forest Coleoptera in the southern Appalachian Mountains of North Carolina. During the 2-yr study, we captured 37,191 Coleoptera with baited multiple- unnel traps and pipe traps, comprising 20 families and 122 species that were used...

Exposure–response relationships for select cancer and non-cancer health outcomes in a cohort of US firefighters from San Francisco, Chicago and Philadelphia (1950–2009)

PubMed Central

Daniels, Robert D.; Bertke, Stephen; Dahm, Matthew M.; Yiin, James H.; Kubale, Travis L.; Hales, Thomas R.; Baris, Dalsu; Zahm, Shelia H.; Beaumont, James J.; Waters, Kathleen M.; Pinkerton, Lynne E.

2015-01-01

Objectives To examine exposure–response relationships between surrogates of firefighting exposure and select outcomes among previously studied US career firefighters. Methods Eight cancer and four non-cancer outcomes were examined using conditional logistic regression. Incidence density sampling was used to match each case to 200 controls on attained age. Days accrued in firefighting assignments (exposed-days), run totals (fire-runs) and run times (fire-hours) were used as exposure surrogates. HRs comparing 75th and 25th centiles of lagged cumulative exposures were calculated using loglinear, linear, log-quadratic, power and restricted cubic spline general relative risk models. Piecewise constant models were used to examine risk differences by time since exposure, age at exposure and calendar period. Results Among 19 309 male firefighters eligible for the study, there were 1333 cancer deaths and 2609 cancer incidence cases. Significant positive associations between fire-hours and lung cancer mortality and incidence were evident. A similar relation between leukaemia mortality and fire-runs was also found. The lung cancer associations were nearly linear in cumulative exposure, while the association with leukaemia mortality was attenuated at higher exposure levels and greater for recent exposures. Significant negative associations were evident for the exposure surrogates and colorectal and prostate cancers, suggesting a healthy worker survivor effect possibly enhanced by medical screening. Conclusions Lung cancer and leukaemia mortality risks were modestly increasing with firefighter exposures. These findings add to evidence of a causal association between firefighting and cancer. Nevertheless, small effects merit cautious interpretation. We plan to continue to follow the occurrence of disease and injury in this cohort. PMID:25673342

Implementation of the fire and fire surrogate study— a national research effort to evaluate the consequences of fuel reduction treatments

Treesearch

Andrew Youngblood; Kerry L. Metlen; Eric E. Knapp; Kenneth W. Outcalt; Scott L. Stephens; Thomas A. Waldrop; Daniel Yaussy

2005-01-01

Many fire-dependent forests today are denser, contain fewer large trees, have higher fuel loads, and greater fuel continuity than occurred under historical fire regimes. These conditions increase the probability of unnaturally severe wildfires. Silviculturists are increasingly being asked to design fuel reduction treatments to help protect existing and future forest...

Mechanical mid-story reduction treatments for forest fuel management

Treesearch

B. Rummer; K. Outcalt; D. Brockway

2002-01-01

There are many forest stands where exclusion of fire or lack of management has led to dense understorys and fuel accumulation. Generally, the least expensive treatment is to introduce a regime of prescribed fire as a surrogate for natural forest fire processes in these stands. However, in some cases prescribed fire is not an option. For example, heavy fuel loadings may...

Soil nitrogen mineralization and enzymatic activities in fire and fire surrogate treatments in California

Treesearch

J. R. Miesel; R. E. J. Boerner; C. N. Skinner

2011-01-01

Forest thinning and prescribed fire are management strategies used to reduce hazardous fuel loads and catastrophic wildfires in western mixed-conifer forests. We evaluated effects of thinning (Thin) and prescribed fire (Burn), alone and in combination (Thin+Burn), on N transformations and microbial enzyme activities relative to an untreated control (Control) at 1 and 3...

Evaluating productivity-biodiversity relationship and spectral diversity in prairie grasslands under different fire management treatments using in-situ and remote sensing hyperspectral data

NASA Astrophysics Data System (ADS)

Gholizadeh, H.; Gamon, J. A.; Zygielbaum, A. I.; Schweiger, A. K.; Cavender-Bares, J.; Yang, Y.; Knops, J. M. H.

2017-12-01

Grasslands cover as much as 25% of the Earth's surface and account for approximately 20% of overall terrestrial productivity and contribute to global biodiversity. To optimize the status of grasslands and to counteract their degradation, different management practices have been adopted. Fire has been shown to be an important management practice in the maintenance of grasslands. Our main goals were 1) to evaluate the productivity-biodiversity relationship in grasslands under fire treatment, and 2) to evaluate the capability of hyperspectral remote sensing in estimating biodiversity using spectral data (i.e. spectral diversity). We used above-ground biomass (as a surrogate for productivity), species richness (SR; as a surrogate for biodiversity), and airborne hyperspectral data from a natural grassland with fire treatment (20 plots), and a natural grassland without fire treatment (21 plots), all located at the Cedar Creek Ecosystem Science Reserve in Central Minnesota, USA. The productivity-biodiversity relationship for the fire treatment plots showed a hump-shaped model with adjusted R2=0.37, whereas the relationship for the non-burned plots were non-significant. The relationship between SR and spectral diversity (SD) were positive linear for both treatments; however, the relationship for plots with fire treatment was higher (adjusted R2 = 0.34 vs. 0.19). It is assumed that post-fire foliar nutrients increase soil nitrogen and phosphorus which facilitate post-fire growth and induce higher above-ground biomass and chlorophyll content in plants. Overall, the results of this study showed that management practices affect the productivity-biodiversity relationship and illustrated the effect of fire treatment on remote sensing of biodiversity.

Prescribed fires as ecological surrogates for wildfires: A stream and riparian perspective

USGS Publications Warehouse

Arkle, R.S.; Pilliod, D.S.

2010-01-01

Forest managers use prescribed fire to reduce wildfire risk and to provide resource benefits, yet little information is available on whether prescribed fires can function as ecological surrogates for wildfire in fire-prone landscapes. Information on impacts and benefits of this management tool on stream and riparian ecosystems is particularly lacking. We used a beyond-BACI (Before, After, Control, Impact) design to investigate the effects of a prescribed fire on a stream ecosystem and compared these findings to similar data collected after wildfire. For 3 years after prescribed fire treatment, we found no detectable changes in periphyton, macroinvertebrates, amphibians, fish, and riparian and stream habitats compared to data collected over the same time period in four unburned reference streams. Based on changes in fuels, plant and litter cover, and tree scorching, this prescribed fire was typical of those being implemented in ponderosa pine forests throughout the western U.S. However, we found that the extent and severity of riparian vegetation burned was substantially lower after prescribed fire compared to nearby wildfires. The early-season prescribed fire did not mimic the riparian or in-stream ecological effects observed following a nearby wildfire, even in catchments with burn extents similar to the prescribed fire. Little information exists on the effects of long-term fire exclusion from riparian forests, but a "prescribed fire regime" of repeatedly burning upland forests while excluding fire in adjacent riparian forests may eliminate an important natural disturbance from riparian and stream habitats.

Catalytic Destruction of a Surrogate Organic Hazardous Air Pollutant as a Potential Co-benefit for Coal-fired Selective Catalyst Reduction Systems

EPA Science Inventory

Catalytic destruction of benzene (C6H6), a surrogate for organic hazardous air pollutants (HAPs) produced from coal combustion, was investigated using a commercial selective catalytic reduction (SCR) catalyst for evaluating the potential co-benefit of the SCR technology for reduc...

Effects of prescribed fire on conditions inside a Cuban parrot (Amazona Leucocephala) surrogate nesting cavity on Great Abaco, Bahamas

Treesearch

Joseph O' Brien; Caroline Stahala; Gina P. Mori; Mac Callaham; Chris M. Bergh

2006-01-01

Cuban Parrots (Amazona leucocephala) on the island of Great Abaco in the Bahamas forage and nest in native pine forests. The population is unique in that the birds nest in limestone solution holes on the forest floor. Bahamian pine forests are fire-dependent with a frequent surface fire regime. The effects of fire on the parrots, especially while nesting, are not well...

Fire performance in traditional silvicultural and fire and fire surrogate treatments in Sierran mixed-conifer forests: a brief summary

Treesearch

Jason J. Moghaddas; Scott L. Stephens

2007-01-01

Mixed conifer forests cover 7.9 million acres of California’s total land base. Forest structure in these forests has been influenced by harvest practices and silvicultural systems implemented since the beginning of the California Gold Rush in 1849. Today, the role of fire in coniferous forests, both in shaping past stand structure and its ability to shape future...

Using bark char codes to predict post-fire cambium mortality

Treesearch

Sharon M. Hood; Danny R. Cluck; Sheri L. Smith; Kevin C. Ryan

2008-01-01

Cambium injury is an important factor in post-fire tree survival. Measurements that quantify the degree of bark charring on tree stems after fire are often used as surrogates for direct cambium injury because they are relatively easy to assign and are non-destructive. However, bark char codes based on these measurements have been inadequately tested to determine how...

Exposure-response relationships for select cancer and non-cancer health outcomes in a cohort of U.S. firefighters from San Francisco, Chicago and Philadelphia (1950-2009).

PubMed

Daniels, Robert D; Bertke, Stephen; Dahm, Matthew M; Yiin, James H; Kubale, Travis L; Hales, Thomas R; Baris, Dalsu; Zahm, Shelia H; Beaumont, James J; Waters, Kathleen M; Pinkerton, Lynne E

2015-10-01

To examine exposure-response relationships between surrogates of firefighting exposure and select outcomes among previously studied US career firefighters. Eight cancer and four non-cancer outcomes were examined using conditional logistic regression. Incidence density sampling was used to match each case to 200 controls on attained age. Days accrued in firefighting assignments (exposed-days), run totals (fire-runs) and run times (fire-hours) were used as exposure surrogates. HRs comparing 75th and 25th centiles of lagged cumulative exposures were calculated using loglinear, linear, log-quadratic, power and restricted cubic spline general relative risk models. Piecewise constant models were used to examine risk differences by time since exposure, age at exposure and calendar period. Among 19,309 male firefighters eligible for the study, there were 1333 cancer deaths and 2609 cancer incidence cases. Significant positive associations between fire-hours and lung cancer mortality and incidence were evident. A similar relation between leukaemia mortality and fire-runs was also found. The lung cancer associations were nearly linear in cumulative exposure, while the association with leukaemia mortality was attenuated at higher exposure levels and greater for recent exposures. Significant negative associations were evident for the exposure surrogates and colorectal and prostate cancers, suggesting a healthy worker survivor effect possibly enhanced by medical screening. Lung cancer and leukaemia mortality risks were modestly increasing with firefighter exposures. These findings add to evidence of a causal association between firefighting and cancer. Nevertheless, small effects merit cautious interpretation. We plan to continue to follow the occurrence of disease and injury in this cohort. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Soil resources influence vegetation and response to fire and fire-surrogate treatments in sagebrush-steppe ecosystems

USGS Publications Warehouse

Rau, Benjamin M.; Chambers, Jeanne C.; Pyke, David A.; Roundy, Bruce A.; Schupp, Eugene W.; Doescher, Paul; Caldwell, Todd G.

2014-01-01

Current paradigm suggests that spatial and temporal competition for resources limit an exotic invader, cheatgrass (Bromus tectorum L.), which once established, alters fire regimes and can result in annual grass dominance in sagebrush steppe. Prescribed fire and fire surrogate treatments (mowing, tebuthiuron, and imazapic) are used to reduce woody fuels and increase resistance to exotic annuals, but may alter resource availability and inadvertently favor invasive species. We used four study sites within the Sagebrush Steppe Treatment Evaluation Project (SageSTEP) to evaluate 1) how vegetation and soil resources were affected by treatment, and 2) how soil resources influenced native herbaceous perennial and exotic annual grass cover before and following treatment. Treatments increased resin exchangeable NH4+, NO3−, H2PO4−, and K+, with the largest increases caused by prescribed fire and prolonged by application of imazapic. Burning with imazapic application also increased the number of wet growing degree days. Tebuthiuron and imazapic reduced exotic annual grass cover, but imazapic also reduced herbaceous perennial cover when used with prescribed fire. Native perennial herbaceous species cover was higher where mean annual precipitation and soil water resources were relatively high. Exotic annual grass cover was higher where resin exchangeable H2PO4− was high and gaps between perennial plants were large. Prescribed fire, mowing, and tebuthiuron were successful at increasing perennial herbaceous cover, but the results were often ephemeral and inconsistent among sites. Locations with sandy soil, low mean annual precipitation, or low soil water holding capacity were more likely to experience increased exotic annual grass cover after treatment, and treatments that result in slow release of resources are needed on these sites. This is one of few studies that correlate abiotic variables to native and exotic species cover across a broad geographic setting, and that demonstrates how soil resources potentially influence the outcome of management treatments.

The national Fire and Fire Surrogate study: Effects of fuel reduction methods on forest vegetation structure and fuels

USGS Publications Warehouse

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

2009-01-01

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

Lithium-Ion Battery Failure: Effects of State of Charge and Packing Configuration

DTIC Science & Technology

2016-08-22

and failure characteristics. Internal temperatures were obtained by designing and fabricating 18650 surrogate cells with embedded thermocouples which...Council Postdoctoral Associate Lithium-ion cell Lithium-ion battery fire Battery state of charge Packing configuration iii Contents 1.0 Background...and fabricating 18650 surrogate cells with embedded thermocouples which contained no active materials and were reused for multiple failure tests

Effects of forest fuel-reduction treatments in the United States

Treesearch

Scott L. Stephens; James D. McIver; Ralph E.J. Boerner; Christopher J. Fettig; Joseph B. Fontaine; Bruce R. Hartsough; Patricia L. Kennedy; Dylan W. Schwilk

2012-01-01

The current conditions of many seasonally dry forests in the western and southern United States, especially those that once experienced low- to moderate-intensity fire regimes, leave them uncharacteristically susceptible to high-severity wildfire. Both prescribed fire and its mechanical surrogates are generally successful in meeting short-term fuel-reduction objectives...

A PILOT-SCALE STUDY OF THE PRECURSORS LEADING TO THE FORMATION OF MIXED BROMO-CHLORO DIOXINS AND FURANS

EPA Science Inventory

The paper gives results of experiments in a pilot-scale rotary kiln incinerator simulator where a mixture of chlorinated and brominated surrogate waste was burned in the presence of injected fly-ash from a coal-fired utility boiler. Measurements were made of semivolatile products...

Relationships between annual plant productivity, nitrogen deposition and fire size in low-elevation California desert scrub

USGS Publications Warehouse

Rao, Leela E.; Matchett, John R.; Brooks, Matthew L.; Johns, Robert; Minnich, Richard A.; Allen, Edith B.

2014-01-01

Although precipitation is correlated with fire size in desert ecosystems and is typically used as an indirect surrogate for fine fuel load, a direct link between fine fuel biomass and fire size has not been established. In addition, nitrogen (N) deposition can affect fire risk through its fertilisation effect on fine fuel production. In this study, we examine the relationships between fire size and precipitation, N deposition and biomass with emphasis on identifying biomass and N deposition thresholds associated with fire spreading across the landscape. We used a 28-year fire record of 582 burns from low-elevation desert scrub to evaluate the relationship of precipitation, N deposition and biomass with the distribution of fire sizes using quantile regression. We found that models using annual biomass have similar predictive ability to those using precipitation and N deposition at the lower to intermediate portions of the fire size distribution. No distinct biomass threshold was found, although within the 99th percentile of the distribution fire size increased with greater than 125 g m–2 of winter fine fuel production. The study did not produce an N deposition threshold, but did validate the value of 125 g m–2 of fine fuel for spread of fires.

Bat activity in relation to fire and fire surrogate treatments in southern pine stands

Treesearch

Susan C. Loeb; Thomas A. Waldrop

2008-01-01

Forest managers often use thinning and prescribed burning to reduce the risk of wildfire and insect outbreaks. Because thinning and burning alter the structure of forest stands and may affect insect prey abundance, they may change the suitability of stands for bats. Our objective was to test the effects of thinning and burning on bat foraging and commuting activity in...

Effects of prescribed fire and fire surrogates on floral visiting insects of the blue ridge province in North Carolina

Treesearch

J.W. Campbell; J.L. Hanula; T.A. Waldrop

2007-01-01

Pollination by insects in forests is an extremely important process that should be conserved. Not only do pollinating insects help to maintain a diversity of plants within forests, but they also aid in pollinating crops found near forested land. Currently, the effects of various forest management practices on floral visiting insect abundance or diversity is unknown, so...

Feasibility of Developing a Surrogate Missile System for the Purpose of Combat Systems Testing, Evaluation, and Watchstander Proficiency

DTIC Science & Technology

2014-06-01

Certification The USS Comte De Grasse, DDG 125, is weeks away from commissioning. As a new Baseline Flight III DDG, her AEGIS Weapon system has...The part is replaced, and the next STM firing is a complete success. Comte De Grasse is cleared to conduct follow-on SM firings. a. Scenario...17 “Solid Rocket Boosters,” NASA, last modified August 31, 2000, http://science.ksc.nasa.gov/shuttle/technology/sts-newsref/srb.html 53 Another

MERCURY(II) ADSORPTION FROM WASTEWATERS USING A THIOL FUNCTIONAL ADSORBENT

EPA Science Inventory

The removal of mercury(II) from wastewaters (coal-fired utility plant scrubber solutions) using a thiol functional organoceramic composite (SOL-AD-IV) is investigated. A simulant is employed as a surrogate to demonstrate the removal of mercury from real waste solutions. Equilibri...

Dynamic loads on human and animal surrogates at different test locations in compressed-gas-driven shock tubes

NASA Astrophysics Data System (ADS)

Alay, E.; Skotak, M.; Misistia, A.; Chandra, N.

2018-01-01

Dynamic loads on specimens in live-fire conditions as well as at different locations within and outside compressed-gas-driven shock tubes are determined by both static and total blast overpressure-time pressure pulses. The biomechanical loading on the specimen is determined by surface pressures that combine the effects of static, dynamic, and reflected pressures and specimen geometry. Surface pressure is both space and time dependent; it varies as a function of size, shape, and external contour of the specimens. In this work, we used two sets of specimens: (1) anthropometric dummy head and (2) a surrogate rodent headform instrumented with pressure sensors and subjected them to blast waves in the interior and at the exit of the shock tube. We demonstrate in this work that while inside the shock tube the biomechanical loading as determined by various pressure measures closely aligns with live-fire data and shock wave theory, significant deviations are found when tests are performed outside.

Simultaneous Thermal Analysis of Remediated Nitrate Salt Surrogates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wayne, David Matthew

The actinide engineering and science group (MET-1) have completed simultaneous thermal analysis and offgas analysis by mass spectrometry (STA-MS) of remediated nitrate salt (RNS) surrogates formulated by the high explosives science and technology group (M-7). The 1.0 to 1.5g surrogate samples were first analyzed as received, then a new set was analyzed with 100-200mL 10M HNO 3 +0.3 MHF added, and a third set was analyzed after 200 mL of a concentrated Pu-AM spike (in 10M HNO 3 +0.3 MHF) was added. The acid and spike solutions were formulated by the actinide analytical chemistry group (C-AAC) using reagent-grade HNO 3more » and HF, which was also used to dissolve a small quantity of mixed, high-fired PuO 2/ AmO 2 oxide.« less

Bird assemblage response to restoration of fire-suppressed longleaf pine sandhills.

PubMed

Steen, David A; Conner, L M; Smith, Lora L; Provencher, Louis; Hiers, J Kevin; Pokswinski, Scott; Helms, Brian S; Guyer, Craig

2013-01-01

The ecological restoration of fire-suppressed habitats may require a multifaceted approach. Removal of hardwood trees together with reintroduction of fire has been suggested as a method of restoring fire-suppressed longleaf pine (Pinus palustris) forests; however, this strategy, although widespread, has not been evaluated on large spatial and temporal scales. We used a landscape-scale experimental design to examine how bird assemblages in fire-suppressed longleaf pine sandhills responded to fire alone or fire following mechanical removal or herbicide application to reduce hardwood levels. Individual treatments were compared to fire-suppressed controls and reference sites. After initial treatment, all sites were managed with prescribed fire, on an approximately two- to three-year interval, for over a decade. Nonmetric multidimensional scaling ordinations suggested that avian assemblages on sites that experienced any form of hardwood removal differed from assemblages on both fire-suppressed sites and reference sites 3-4 years after treatment (i.e., early posttreatment). After >10 years of prescribed burning on all sites (i.e., late posttreatment), only assemblages at sites treated with herbicide were indistinguishable from assemblages at reference sites. By the end of the study, individual species that were once indicators of reference sites no longer contributed to making reference sites unique. Occupancy modeling of these indicator species also demonstrated increasing similarity across treatments over time. Overall, although we documented long-term and variable assemblage-level change, our results indicate occupancy for birds considered longleaf pine specialists was similar at treatment and reference sites after over a decade of prescribed burning, regardless of initial method of hardwood removal. In other words, based on the response of species highly associated with the habitat, we found no justification for the added cost and effort of fire surrogates; fire alone was sufficient to restore these species.

Towards predictive data-driven simulations of wildfire spread - Part I: Reduced-cost Ensemble Kalman Filter based on a Polynomial Chaos surrogate model for parameter estimation

NASA Astrophysics Data System (ADS)

Rochoux, M. C.; Ricci, S.; Lucor, D.; Cuenot, B.; Trouvé, A.

2014-05-01

This paper is the first part in a series of two articles and presents a data-driven wildfire simulator for forecasting wildfire spread scenarios, at a reduced computational cost that is consistent with operational systems. The prototype simulator features the following components: a level-set-based fire propagation solver FIREFLY that adopts a regional-scale modeling viewpoint, treats wildfires as surface propagating fronts, and uses a description of the local rate of fire spread (ROS) as a function of environmental conditions based on Rothermel's model; a series of airborne-like observations of the fire front positions; and a data assimilation algorithm based on an ensemble Kalman filter (EnKF) for parameter estimation. This stochastic algorithm partly accounts for the non-linearities between the input parameters of the semi-empirical ROS model and the fire front position, and is sequentially applied to provide a spatially-uniform correction to wind and biomass fuel parameters as observations become available. A wildfire spread simulator combined with an ensemble-based data assimilation algorithm is therefore a promising approach to reduce uncertainties in the forecast position of the fire front and to introduce a paradigm-shift in the wildfire emergency response. In order to reduce the computational cost of the EnKF algorithm, a surrogate model based on a polynomial chaos (PC) expansion is used in place of the forward model FIREFLY in the resulting hybrid PC-EnKF algorithm. The performance of EnKF and PC-EnKF is assessed on synthetically-generated simple configurations of fire spread to provide valuable information and insight on the benefits of the PC-EnKF approach as well as on a controlled grassland fire experiment. The results indicate that the proposed PC-EnKF algorithm features similar performance to the standard EnKF algorithm, but at a much reduced computational cost. In particular, the re-analysis and forecast skills of data assimilation strongly relate to the spatial and temporal variability of the errors in the ROS model parameters.

Fire severity and ecosytem responses following crown fires in California shrublands

USGS Publications Warehouse

Keeley, J.E.; Brennan, T.; Pfaff, A.H.

2008-01-01

Chaparral shrublands burn in large high-intensity crown fires. Managers interested in how these wildfires affect ecosystem processes generally rely on surrogate measures of fire intensity known as fire severity metrics. In shrublands burned in the autumn of 2003, a study of 250 sites investigated factors determining fire severity and ecosystem responses.Using structural equation modeling we show that stand age, prefire shrub density, and the shortest interval of the prior fire history had significant direct effects on fire severity, explaining >50% of the variation in severity.Fire severity per se is of interest to resource managers primarily because it is presumed to be an indicator of important ecosystem processes such as vegetative regeneration, community recovery, and erosion. Fire severity contributed relatively little to explaining patterns of regeneration after fire. Two generalizations can be drawn: fire severity effects are mostly short-lived, i.e., by the second year they are greatly diminished, and fire severity may have opposite effects on different functional types.Species richness exhibited a negative relationship to fire severity in the first year, but fire severity impacts were substantially less in the second postfire year and varied by functional type. Much of this relationship was due to alien plants that are sensitive to high fire severity; at all scales from 1 to 1000 m2, the percentage of alien species in the postfire flora declined with increased fire severity. Other aspects of disturbance history are also important determinants of alien cover and richness as both increased with the number of times the site had burned and decreased with time since last fire.A substantial number of studies have shown that remote-sensing indices are correlated with field measurements of fire severity. Across our sites, absolute differenced normalized burn ratio (dNBR) was strongly correlated with field measures of fire severity and with fire history at a site but relative dNBR was not. Despite being correlated with fire severity, absolute dNBR showed little or no relationship with important ecosystem responses to wildfire such as shrub resprouting or total vegetative regeneration. These findings point to a critical need for further research on interpreting remote sensing indices as applied to postfire management of these shrublands.

Fire severity and ecosytem responses following crown fires in California shrublands.

PubMed

Keeley, Jon E; Brennan, Teresa; Pfaff, Anne H

2008-09-01

Chaparral shrublands burn in large high-intensity crown fires. Managers interested in how these wildfires affect ecosystem processes generally rely on surrogate measures of fire intensity known as fire severity metrics. In shrublands burned in the autumn of 2003, a study of 250 sites investigated factors determining fire severity and ecosystem responses. Using structural equation modeling we show that stand age, prefire shrub density, and the shortest interval of the prior fire history had significant direct effects on fire severity, explaining > 50% of the variation in severity. Fire severity per se is of interest to resource managers primarily because it is presumed to be an indicator of important ecosystem processes such as vegetative regeneration, community recovery, and erosion. Fire severity contributed relatively little to explaining patterns of regeneration after fire. Two generalizations can be drawn: fire severity effects are mostly shortlived, i.e., by the second year they are greatly diminished, and fire severity may have opposite effects on different functional types. Species richness exhibited a negative relationship to fire severity in the first year, but fire severity impacts were substantially less in the second postfire year and varied by functional type. Much of this relationship was due to alien plants that are sensitive to high fire severity; at all scales from 1 to 1000 m2, the percentage of alien species in the postfire flora declined with increased fire severity. Other aspects of disturbance history are also important determinants of alien cover and richness as both increased with the number of times the site had burned and decreased with time since last fire. A substantial number of studies have shown that remote-sensing indices are correlated with field measurements of fire severity. Across our sites, absolute differenced normalized burn ratio (dNBR) was strongly correlated with field measures of fire severity and with fire history at a site but relative dNBR was not. Despite being correlated with fire severity, absolute dNBR showed little or no relationship with important ecosystem responses to wildfire such as shrub resprouting or total vegetative regeneration. These findings point to a critical need for further research on interpreting remote sensing indices as applied to postfire management of these shrublands.

Gaseous Surrogate Hydrocarbons for a Hifire Scramjet that Mimic Opposed Jet Extinction Limits for Cracked JP Fuels

NASA Technical Reports Server (NTRS)

Pellett, Gerald L.; Vaden, Sarah N.; Wilson, Lloyd G.

2008-01-01

This paper describes, first, the top-down methodology used to define simple gaseous surrogate hydrocarbon (HC) fuel mixtures for a hypersonic scramjet combustion subtask of the HiFIRE program. It then presents new and updated Opposed Jet Burner (OJB) extinction-limit Flame Strength (FS) data obtained from laminar non-premixed HC vs. air counterflow diffusion flames at 1-atm, which follow from earlier investigations. FS represents a strain-induced extinction limit based on cross-section-average air jet velocity, U(sub air), that sustains combustion of a counter jet of gaseous fuel just before extinction. FS uniquely characterizes a kinetically limited fuel combustion rate. More generally, Applied Stress Rates (ASRs) at extinction (U(sub air) normalized by nozzle or tube diameter, D(sub n or t) can directly be compared with extinction limits determined numerically using either a 1-D or (preferably) a 2-D Navier Stokes simulation with detailed transport and finite rate chemistry. The FS results help to characterize and define three candidate surrogate HC fuel mixtures that exhibit a common FS 70% greater than for vaporized JP-7 fuel. These include a binary fuel mixture of 64% ethylene + 36% methane, which is our primary recommendation. It is intended to mimic the critical flameholding limit of a thermally- or catalytically-cracked JP-7 like fuel in HiFIRE scramjet combustion tests. Our supporting experimental results include: (1) An idealized kinetically-limited ASR reactivity scale, which represents maximum strength non-premixed flames for several gaseous and vaporized liquid HCs; (2) FS characterizations of Colket and Spadaccini s suggested ternary surrogate, of 60% ethylene + 30% methane + 10% n-heptane, which matches the ignition delay of a typical cracked JP fuel; (3) Data showing how our recommended binary surrogate, of 64% ethylene + 36% methane, has an identical FS; (4) Data that characterize an alternate surrogate of 44% ethylene + 56% ethane with identical FS and nearly equal molecular weights; this could be useful when systematically varying the fuel composition. However, the mixture liquefies at much lower pressure, which limits on-board storage of gaseous fuel; (5) Dynamic Flame Weakening results that show how oscillations in OJB input flow (and composition) can weaken (extinguish) surrogate flames up to 200 Hz, but the weakening is 2.5x smaller compared to pure methane; and finally, (6) FS limits at 1-atm that compare with three published 1-D numerical OJB extinction results using four chemical kinetic models. The methane kinetics generally agree closely at 1-atm, whereas, the various ethylene models predict extinction limits that average 45% high, which represents a significant problem for numerical simulation of surrogate-based flameholding in a scramjet cavity. Finally, we continue advocating the FS approach as more direct and fundamental for assessing idealized scramjet flameholding potentials than measurements of "unstrained" premixed laminar burning velocity or blowout in a Perfectly Stirred Reactor.

Towards predictive data-driven simulations of wildfire spread - Part I: Reduced-cost Ensemble Kalman Filter based on a Polynomial Chaos surrogate model for parameter estimation

NASA Astrophysics Data System (ADS)

Rochoux, M. C.; Ricci, S.; Lucor, D.; Cuenot, B.; Trouvé, A.

2014-11-01

This paper is the first part in a series of two articles and presents a data-driven wildfire simulator for forecasting wildfire spread scenarios, at a reduced computational cost that is consistent with operational systems. The prototype simulator features the following components: an Eulerian front propagation solver FIREFLY that adopts a regional-scale modeling viewpoint, treats wildfires as surface propagating fronts, and uses a description of the local rate of fire spread (ROS) as a function of environmental conditions based on Rothermel's model; a series of airborne-like observations of the fire front positions; and a data assimilation (DA) algorithm based on an ensemble Kalman filter (EnKF) for parameter estimation. This stochastic algorithm partly accounts for the nonlinearities between the input parameters of the semi-empirical ROS model and the fire front position, and is sequentially applied to provide a spatially uniform correction to wind and biomass fuel parameters as observations become available. A wildfire spread simulator combined with an ensemble-based DA algorithm is therefore a promising approach to reduce uncertainties in the forecast position of the fire front and to introduce a paradigm-shift in the wildfire emergency response. In order to reduce the computational cost of the EnKF algorithm, a surrogate model based on a polynomial chaos (PC) expansion is used in place of the forward model FIREFLY in the resulting hybrid PC-EnKF algorithm. The performance of EnKF and PC-EnKF is assessed on synthetically generated simple configurations of fire spread to provide valuable information and insight on the benefits of the PC-EnKF approach, as well as on a controlled grassland fire experiment. The results indicate that the proposed PC-EnKF algorithm features similar performance to the standard EnKF algorithm, but at a much reduced computational cost. In particular, the re-analysis and forecast skills of DA strongly relate to the spatial and temporal variability of the errors in the ROS model parameters.

Munitions and Explosives of Concern Survey Methodology and In-field Testing for Wind Energy Areas on the Atlantic Outer Continental Shelf

NASA Astrophysics Data System (ADS)

DuVal, C.; Carton, G.; Trembanis, A. C.; Edwards, M.; Miller, J. K.

2017-12-01

Munitions and explosives of concern (MEC) are present in U.S. waters as a result of past and ongoing live-fire testing and training, combat operations, and sea disposal. To identify MEC that may pose a risk to human safety during development of offshore wind facilities on the Atlantic Outer Continental Shelf (OCS), the Bureau of Ocean Energy Management (BOEM) is preparing to develop guidance on risk analysis and selection processes for methods and technologies to identify MEC in Wind Energy Areas (WEA). This study developed a process for selecting appropriate technologies and methodologies for MEC detection using a synthesis of historical research, physical site characterization, remote sensing technology review, and in-field trials. Personnel were tasked with seeding a portion of the Delaware WEA with munitions surrogates, while a second group of researchers not privy to the surrogate locations tested and optimized the selected methodology to find and identify the placed targets. This in-field trial, conducted in July 2016, emphasized the use of multiple sensors for MEC detection, and led to further guidance for future MEC detection efforts on the Atlantic OCS. An April 2017 follow on study determined the fate of the munitions surrogates after the Atlantic storm season had passed. Using regional hydrodynamic models and incorporating the recommendations from the 2016 field trial, the follow on study examined the fate of the MEC and compared the findings to existing research on munitions mobility, as well as models developed as part of the Office of Naval Research Mine-Burial Program. Focus was given to characterizing the influence of sediment type on surrogate munitions behavior and the influence of mophodynamics and object burial on MEC detection. Supporting Mine-Burial models, ripple bedforms were observed to impede surrogate scour and burial in coarse sediments, while surrogate burial was both predicted and observed in finer sediments. Further, incorporation of recommendations from the previous trial in the 2017 study led to fourfold improvement of MEC detection rates over the 2016 approach. The use of modeling to characterize local morphodynamics, MEC burial or mobility, and the impact of seasonal or episodic storm events are discussed in light of technology selection and timing for future MEC detection surveys.

Normalized algorithm for mapping and dating forest disturbances and regrowth for the United States

Treesearch

Liming He; Jing M. Chen; Shaoliang Zhang; Gustavo Gomez; Yude Pan; Kevin McCullough; Richard Birdsey; Jeffrey G. Masek

2011-01-01

Forest disturbances such as harvesting, wildfire and insect infestation are critical ecosystem processes affecting the carbon cycle. Because carbon dynamics are related to time since disturbance, forest stand age that can be used as a surrogate for major clear-cut/fire disturbance information has recently been recognized as an important input to forest carbon cycle...

Antelope bitterbrush and Scouler's willow response to a shelterwood harvest and prescribed burn in western Montana

Treesearch

Dayna M. Ayers; Donald J. Bedunah; Michael G. Harrington

1999-01-01

In many western Montana ponderosa pine (Pinus ponderosa) stands, fire suppression and past selective logging of large trees have resulted in conditions favoring succession to dense stands of shade-tolerant, but insect- and disease-prone Douglas-fir (Pseudotsuga menziesii). Stand thinning and understory prescribed burning have been proposed as surrogates for pre-Euro-...

Data and Summaries for Catalytic Destruction of a Surrogate Organic Hazardous Air Pollutant as a Potential Co-benefit for Coal-Fired Selective Catalytic Reduction Systems

EPA Pesticide Factsheets

Table 1 summarizes and explanis the Operating Conditions of the SCR Reactor used in the Benzene-Destruction.Table 2 summarizes and explains the Experimental Design and Test Results.Table 3 summarizes and explains the Estimates for Individual Effects and Cross Effects Obtained from the Linear Regression Models for Destruction of C6H6 and Reduction of NO.Fig. 1 shows the Down-flow SCR reactor system in detail.Fig. 2 shows the graphical summary of the Effect of the inlet C6H6 concentration to the SCR reactor on the destruction of C6H6.Fig.3 shows the summary of Carbon mass balance for C6H6 destruction promoted by the V2O5-WO3/TiO2 catalyst.This dataset is associated with the following publication:Lee , C., Y. Zhao, S. Lu, and W.R. Stevens. Catalytic Destruction of a Surrogate Organic Hazardous Air Polutant as a Potential Co-benefit for Coal-fired Selective Catalyst Reduction Systems. AMERICAN CHEMICAL SOCIETY. American Chemical Society, Washington, DC, USA, 30(3): 2240-2247, (2016).

Response of white-footed mice (Peromyscus leucopus) to fire and fire surrogate fuel reduction treatments in a southern Appalachian hardwood forest

USGS Publications Warehouse

Greenberg, C.H.; Otis, D.L.; Waldrop, T.A.

2006-01-01

An experiment conducted as part of the multidisciplinary National Fire and Fire Surrogate Study was designed to determine effects of three fuel reduction techniques on small mammals and habitat structure in the southern Appalachian mountains. Four experimental units, each >14-ha were contained within each of three replicate blocks at the Green River Game Land, Polk County, NC. Treatments were (1) prescribed burning (B); (2) mechanical felling of shrubs and small trees (M); (3) mechanical felling + burning (MB); (4) controls (C). Mechanical understory felling treatments were conducted in winter 2001-2002, and prescribed burning was conducted in March 2003. After treatment, there were fewer live trees, more snags, and greater canopy openness in MB than in other treatments. Leaf litter depth was reduced by burning in both B and MB treatments, and tall shrub cover was reduced in all fuel reduction treatments compared to C. Coarse woody debris pieces and percent cover were similar among treatments and controls. We captured 990 individuals of eight rodent species a total of 2823 times. Because white-footed mice composed >79% of all captures, we focused on this species. Populations in experimental units increased 228% on average between 2001 and 2002, but there was no evidence of an effect of the mechanical treatment. From 2002 to 2003, all units again showed an average increase in relative population size, but increases were greater in MB than in the other treatments. Age structure and male to female ratio were not affected by the fuel reduction treatment. Average adult body weight declined from 2001 to 2002, but less so in M than in units that remained C in both years. The proportion of mice captured near coarse woody debris was similar to the proportion captured in open areas for all treatments, indicating that white-footed mice did not use coarse woody debris preferentially or change their use patterns in response to fuel reduction treatments. Land managers should understand possible effects of different fuel reduction treatments on white-footed mouse populations, as they are an important component of the fauna and food chain of deciduous southern Appalachian forests.

SOLID PHASE MICROEXTRACTION SAMPLING OF FIRE DEBRIS RESIDUES IN THE PRESENCE OF RADIONUCLIDE SURROGATE METALS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duff, M; Keisha Martin, K; S Crump, S

2007-03-23

The Federal Bureau of Investigation (FBI) Laboratory currently does not have on site facilities for handling radioactive evidentiary materials and there are no established FBI methods or procedures for decontaminating highly radioactive fire debris (FD) evidence while maintaining evidentiary value. One experimental method for the isolation of FD residue from radionuclide metals involves using solid phase microextraction (SPME) fibers to remove the residues of interest. Due to their high affinity for organics, SPME fibers should have little affinity for most (radioactive) metals. The focus of this research was to develop an examination protocol that was applicable to safe work inmore » facilities where high radiation doses are shielded from the workers (as in radioactive shielded cells or ''hot cells''). We also examined the affinity of stable radionuclide surrogate metals (Co, Ir, Re, Ni, Ba, Cs, Nb, Zr and Nd) for sorption by the SPME fibers. This was done under exposure conditions that favor the uptake of FD residues under conditions that will provide little contact between the SPME and the FD material (such as charred carpet or wood that contains commonly-used accelerants). Our results from mass spectrometric analyses indicate that SPME fibers show promise for use in the room temperature head space uptake of organic FD residue (namely, diesel fuel oil, kerosene, gasoline and paint thinner) with subsequent analysis by gas chromatography (GC) with mass spectrometric (MS) detection. No inorganic forms of ignitable fluids were included in this study.« less

Seasonal Variation and Ecosystem Dependence of Emission Factors for Selected Trace Gases and PM2.5 for Southern African Savanna Fires

NASA Technical Reports Server (NTRS)

Korontzi, S.; Ward, D. E.; Susott, R. A.; Yokelson, R. J.; Justice, C. O.; Hobbs, P. V.; Smithwick, E. A. H.; Hao, W. M.

2003-01-01

In this paper we present the first early dry season (early June-early August) emission factor measurements for carbon dioxide (CO2), carbon monoxide (CO), methane (Ca), nonmethane hydrocarbons (NMHC), and particulates with a diameter less than 2.5 microns (pM2.5) for southern African grassland and woodland fires. Seasonal emission factors for grassland fires correlate linearly with the proportion of green grass, used as a surrogate for the fuel moisture content, and are higher for products of incomplete combustion in the early part of the dry season compared with later in the dry season. Models of emission factors for NMHC and PM(sub 2.5) versus modified combustion efficiency (MCE) are statistically different in grassland compared with woodland ecosystems. We compare predictions based on the integration of emissions factors from this study, from the southern African Fire-Atmosphere Research Initiative 1992 (SAFARI-92), and from SAFARI-2000 with those based on the smaller set of ecosystem-specific emission factors to estimate the effects of using regional-average rather than ecosystem-specific emission factors. We also test the validity of using the SAFARI-92 models for emission factors versus MCE to predict the early dry season emission factors measured in this study. The comparison indicates that the largest discrepancies occur at the low end (0.907) and high end (0.972) of MCE values measured in this study. Finally, we combine our models of MCE versus proportion of green grass for grassland fires with emission factors versus MCE for selected oxygenated volatile organic compounds measured in the SAFARI-2000 campaign to derive the first seasonal emission factors for these compounds. The results of this study demonstrate that seasonal variations in savanna fire emissions are important and should be considered in modeling emissions at regional to continental scales.

Development of a Surrogate STANAG 4240 Fire Exposure

DTIC Science & Technology

2012-05-01

26 Table 4. Gasoline fuel properties and calculated flame characteristics. .......................................26 Table...pool was enhanced using 3.8 L (1 gal) of gasoline , which was floated on the surface of the fuel. Applying the same calculations to the gasoline , an...additional 1 min of burn duration was added to the beginning of the test, with a slightly higher (9.5 MW vs. 9.0 MW) heat release rate. The gasoline

Changes in fire intensity have carry-over effects on plant responses after the next fire in southern California chaparral

USGS Publications Warehouse

Moreno, Jose M.; Torres, Ivan; Luna, Belen; Oechel, Walter C.; Keeley, Jon E.

2013-01-01

QuestionDo variations in fire intensity within a stand determine changes in fire intensity and plant demographics in a subsequent fire?LocationSan Diego (CA, USA); chaparral dominated by Adenostoma fasciculatum (resprouter) and Ceanothus greggii (seeder).MethodsIn 2003, a wildfire burned a young (16-yr-old) stand containing a set of experimental plots burned in 1987 with various levels of fire intensity. In 2004, all the 1987 plots were sampled for Adenostoma survival and the recruitment of both species. Similar measures were carried out in the adjacent old (75-yr) stand. Fire intensity in 2003 was estimated by a surrogate fire severity measure [minimum diameter of burned branches (branch diameter)].ResultsIn the young stand, branch diameter in 2003 was similar to the control plots in 1987, but lower than in the old stand. Fire intensity in 1987 did not significantly affect branch diameter in 2003. Survival of Adenostoma in the young stand was very low, much lower than after the 1987 burn and that in the old stand. Fire intensity in 1987 did not affect Adenostoma survival. Recruitment in Adenostoma increased, and in Ceanothus decreased, with increased fire intensity in 1987.ConclusionsWe demonstrate that there is a carry-over effect of fire intensity across a whole fire cycle on plant recruitment of the two dominant species. The 2003 fire partially reversed the relative effects on recruitment caused by elevated fire intensity in 1987. Arguably, this effect was driven by the contrasted relationships of the two species to fire intensity. Adenostoma survival in the young stand was much lower in 2003 than in 1987, despite similar branch diameter, and was also lower than in the old stand, despite higher branch diameter in this case. The causes of such mortality are unknown.

Can the physical properties associated with uncertainties in the NASA MODIS AOD retrievals in the western U.S. be determined?

NASA Astrophysics Data System (ADS)

Loria Salazar, S. M.; Holmes, H.; Panorska, A. K.; Arnott, W. P.; Barnard, J.

2016-12-01

Previous investigations have used satellite remote sensing to estimate surface air pollution concentrations. While most of these studies rely on models developed for the dark-vegetated eastern U.S., they are being used in the semi-arid western U.S without modifications. These models are not robust in the western U.S. due to: 1. Irregular topography that leads to complicated boundary layer physics, 2. Pollutant mixtures, 3. Heterogeneous vertical profile of aerosol concentrations, and 4. High surface reflectance. Here, results from Nevada and California demonstrate poor AOD correlation between AERONET MODIS retrievals. Smoke from wildfires strengthened the aerosol signal, but the MODIS versus AERONET AOD correlation did not improve significantly during fire events [r2 0.17 (non-fire), r2 0.2 (fire)]. Furthermore, aerosol from fires increased the normalized mean bias (NMB) of MODIS retrievals of AOD[NMB 82% (non-fire), NMB 146% (fire)]. Additional results of this investigation found that aerosol plumes confined with the boundary layer improves MODIS AOD retrievals. However, when this condition is not met (i.e., 70% of the time downwind of mountains regions) MODIS AOD has a poor correlation and high bias with respect to AERONET AOD. Fire injection height, complicated boundary layer mixing, and entrainment disperse smoke plumes into the free atmosphere. Therefore, smoke plumes exacerbate the complex aerosol transport typical in the western U.S. and the non-linear relationship between surface pollutant concentrations and conditions aloft. This work uses stochastic methods, including regression to investigate the influence of each of these physical behaviors on the MODIS, AERONET AOD discrepancy using surrogates for each physical phenomenon, e.g., surface albedo for surface reflectance, boundary layer height and elevation for complex mixing, aerosol optical height for vertical aerosol concentrations, and fire radiative power for smoke plume injection height.

Fire treatment effects on vegetation structure, fuels, and potential fire severity in western U.S. forests

USGS Publications Warehouse

Stephens, S.L.; Moghaddas, J.J.; Edminster, C.; Fiedler, C.E.; Haase, S.; Harrington, M.; Keeley, J.E.; Knapp, E.E.; Mciver, J.D.; Metlen, K.; Skinner, C.N.; Youngblood, A.

2009-01-01

Abstract. Forest structure and species composition in many western U.S. coniferous forests have been altered through fire exclusion, past and ongoing harvesting practices, and livestock grazing over the 20th century. The effects of these activities have been most pronounced in seasonally dry, low and mid-elevation coniferous forests that once experienced frequent, low to moderate intensity, fire regimes. In this paper, we report the effects of Fire and Fire Surrogate (FFS) forest stand treatments on fuel load profiles, potential fire behavior, and fire severity under three weather scenarios from six western U.S. FFS sites. This replicated, multisite experiment provides a framework for drawing broad generalizations about the effectiveness of prescribed fire and mechanical treatments on surface fuel loads, forest structure, and potential fire severity. Mechanical treatments without fire resulted in combined 1-, 10-, and 100-hour surface fuel loads that were significantly greater than controls at three of five FFS sites. Canopy cover was significantly lower than controls at three of five FFS sites with mechanical-only treatments and at all five FFS sites with the mechanical plus burning treatment; fire-only treatments reduced canopy cover at only one site. For the combined treatment of mechanical plus fire, all five FFS sites with this treatment had a substantially lower likelihood of passive crown fire as indicated by the very high torching indices. FFS sites that experienced significant increases in 1-, 10-, and 100-hour combined surface fuel loads utilized harvest systems that left all activity fuels within experimental units. When mechanical treatments were followed by prescribed burning or pile burning, they were the most effective treatment for reducing crown fire potential and predicted tree mortality because of low surface fuel loads and increased vertical and horizontal canopy separation. Results indicate that mechanical plus fire, fire-only, and mechanical-only treatments using whole-tree harvest systems were all effective at reducing potential fire severity under severe fire weather conditions. Retaining the largest trees within stands also increased fire resistance. ?? 2009 by the Ecological Society of America.

Pyromania and the primal scene: a psychoanalytic comment on the work of Yukio Mishima.

PubMed

Arlow, J A

1978-01-01

In the writings of the Japanese novelist, Yukio Mishima, primal scene experiences and derivative expressions of them recur persistently. The element of fire figures prominently in connection with the wish to wreak vengeance on the persons originally observed in the act of intercourse. As a destructive, attention-compelling spectacle, fire is a particularly suitable vehicle for this purpose. In Mishima's works, revenge takes the form of retaliation in kind: parental figures, or their surrogates, are put into the position of having to observe the child, or substitutes for him, in the act of sexual infidelity. These observations as well as clinical reports in the literature suggest some insights into fantasies of pyromania. They also make possible certain speculations concerning Misima's turbulent life and dramatic suicide.

Self-consistent determination of the spike-train power spectrum in a neural network with sparse connectivity.

PubMed

Dummer, Benjamin; Wieland, Stefan; Lindner, Benjamin

2014-01-01

A major source of random variability in cortical networks is the quasi-random arrival of presynaptic action potentials from many other cells. In network studies as well as in the study of the response properties of single cells embedded in a network, synaptic background input is often approximated by Poissonian spike trains. However, the output statistics of the cells is in most cases far from being Poisson. This is inconsistent with the assumption of similar spike-train statistics for pre- and postsynaptic cells in a recurrent network. Here we tackle this problem for the popular class of integrate-and-fire neurons and study a self-consistent statistics of input and output spectra of neural spike trains. Instead of actually using a large network, we use an iterative scheme, in which we simulate a single neuron over several generations. In each of these generations, the neuron is stimulated with surrogate stochastic input that has a similar statistics as the output of the previous generation. For the surrogate input, we employ two distinct approximations: (i) a superposition of renewal spike trains with the same interspike interval density as observed in the previous generation and (ii) a Gaussian current with a power spectrum proportional to that observed in the previous generation. For input parameters that correspond to balanced input in the network, both the renewal and the Gaussian iteration procedure converge quickly and yield comparable results for the self-consistent spike-train power spectrum. We compare our results to large-scale simulations of a random sparsely connected network of leaky integrate-and-fire neurons (Brunel, 2000) and show that in the asynchronous regime close to a state of balanced synaptic input from the network, our iterative schemes provide an excellent approximations to the autocorrelation of spike trains in the recurrent network.

Wotan’s Workshop: Military Experiments before World War II

DTIC Science & Technology

2013-06-27

photo: A column of mock tanks—with wood and canvas armor shapes mounted on light vehicles—participated in German military maneuvers in 1928. (Imperial...37mm antitank gun. The gunners called it a “ wood -o- meter” and claimed it could fire 400 splinters and 15 drops of turpentine per minute. Charles Gorry...ticipation in maneuvers. These surrogates, made of wood and canvas and mounted on cars or even on bicycles, were used in force-on-force maneuvers that

Development Program of Dual Mode Impact Delay Module for Artillery Fuzes.

DTIC Science & Technology

1979-12-31

analysis phase to demonstrate design confidence and reliability of performance in the artillery firing environment. See Figure I for drawing of the latest...Device P/N KF88590 as proposed by us. This analysis will be based on results of penalty test« in which the test variables will include loading and...istently and unmistakably Dextrinated lead azide was, tent surrogate. On the basis of stab s Id be predicted that any system whi r mated lead azide

An integrated simulation and optimization approach for managing human health risks of atmospheric pollutants by coal-fired power plants.

PubMed

Dai, C; Cai, X H; Cai, Y P; Guo, H C; Sun, W; Tan, Q; Huang, G H

2014-06-01

This research developed a simulation-aided nonlinear programming model (SNPM). This model incorporated the consideration of pollutant dispersion modeling, and the management of coal blending and the related human health risks within a general modeling framework In SNPM, the simulation effort (i.e., California puff [CALPUFF]) was used to forecast the fate of air pollutants for quantifying the health risk under various conditions, while the optimization studies were to identify the optimal coal blending strategies from a number of alternatives. To solve the model, a surrogate-based indirect search approach was proposed, where the support vector regression (SVR) was used to create a set of easy-to-use and rapid-response surrogates for identifying the function relationships between coal-blending operating conditions and health risks. Through replacing the CALPUFF and the corresponding hazard quotient equation with the surrogates, the computation efficiency could be improved. The developed SNPM was applied to minimize the human health risk associated with air pollutants discharged from Gaojing and Shijingshan power plants in the west of Beijing. Solution results indicated that it could be used for reducing the health risk of the public in the vicinity of the two power plants, identifying desired coal blending strategies for decision makers, and considering a proper balance between coal purchase cost and human health risk. A simulation-aided nonlinear programming model (SNPM) is developed. It integrates the advantages of CALPUFF and nonlinear programming model. To solve the model, a surrogate-based indirect search approach based on the combination of support vector regression and genetic algorithm is proposed. SNPM is applied to reduce the health risk caused by air pollutants discharged from Gaojing and Shijingshan power plants in the west of Beijing. Solution results indicate that it is useful for generating coal blending schemes, reducing the health risk of the public, reflecting the trade-offbetween coal purchase cost and health risk.

Fire suppression impacts on postfire recovery of Sierra Nevada chaparral shrublands

USGS Publications Warehouse

Keeley, J.E.; Pfaff, A.H.; Safford, H.D.

2005-01-01

A substantial portion of chaparral shrublands in the southern part of California's Sierra Nevada Mountain Range has never had a recorded fire since record keeping began in 1910. We hypothesised that such long periods without fire are outside the historical range of variability and that when such areas burn, postfire recovery is weaker than in younger stands. We predicted that long fire-free periods will result in loss of shrub species and deterioration of soil seed banks, which, coupled with higher fire intensities from the greater accumulation of dead biomass, will lead to poorer postfire regeneration. The 2002 McNally Fire burned ancient stands that were as much as 150 years old, as well as much younger (mature) stands. Based on shrub skeletons in the burned area as a surrogate for prefire density, we found that ancient stands change in structure, owing primarily to the loss of obligate seeding Ceanothus cuneatus; other species appear to have great longevity. Despite the reduction in C. cuneatus, postfire shrub-seedling recruitment remained strong in these ancient stands, although some seed bank deterioration is suggested by the three-quarters lower seedling recruitment than recorded from mature stands. Total diversity and the abundance of postfire endemic annuals are two other response variables that suggest that these ancient stands are recovering as well as mature stands. The one area of some concern is that non-native species richness and abundance increased in the ancient stands, suggesting that these are more open to alien colonisers. It is concluded that chaparral more than a century old is resilient to such long fire-free periods and fire severity impacts are indistinguishable from those in younger chaparral stands.

A high-resolution open biomass burning emission inventory based on statistical data and MODIS observations in mainland China

NASA Astrophysics Data System (ADS)

Xu, Y.; Fan, M.; Huang, Z.; Zheng, J.; Chen, L.

2017-12-01

Open biomass burning which has adverse effects on air quality and human health is an important source of gas and particulate matter (PM) in China. Current emission estimations of open biomass burning are generally based on single source (alternative to statistical data and satellite-derived data) and thus contain large uncertainty due to the limitation of data. In this study, to quantify the 2015-based amount of open biomass burning, we established a new estimation method for open biomass burning activity levels by combining the bottom-up statistical data and top-down MODIS observations. And three sub-category sources which used different activity data were considered. For open crop residue burning, the "best estimate" of activity data was obtained by averaging the statistical data from China statistical yearbooks and satellite observations from MODIS burned area product MCD64A1 weighted by their uncertainties. For the forest and grassland fires, their activity levels were represented by the combination of statistical data and MODIS active fire product MCD14ML. Using the fire radiative power (FRP) which is considered as a better indicator of active fire level as the spatial allocation surrogate, coarse gridded emissions were reallocated into 3km ×3km grids to get a high-resolution emission inventory. Our results showed that emissions of CO, NOx, SO2, NH3, VOCs, PM2.5, PM10, BC and OC in mainland China were 6607, 427, 84, 79, 1262, 1198, 1222, 159 and 686 Gg/yr, respectively. Among all provinces of China, Henan, Shandong and Heilongjiang were the top three contributors to the total emissions. In this study, the developed open biomass burning emission inventory with a high-resolution could support air quality modeling and policy-making for pollution control.

Surrogate decision making: do we have to trade off accuracy and procedural satisfaction?

PubMed

Frey, Renato; Hertwig, Ralph; Herzog, Stefan M

2014-02-01

Making surrogate decisions on behalf of incapacitated patients can raise difficult questions for relatives, physicians, and society. Previous research has focused on the accuracy of surrogate decisions (i.e., the proportion of correctly inferred preferences). Less attention has been paid to the procedural satisfaction that patients' surrogates and patients attribute to specific approaches to making surrogate decisions. The objective was to investigate hypothetical patients' and surrogates' procedural satisfaction with specific approaches to making surrogate decisions and whether implementing these preferences would lead to tradeoffs between procedural satisfaction and accuracy. Study 1 investigated procedural satisfaction by assigning participants (618 in a mixed-age but relatively young online sample and 50 in an older offline sample) to the roles of hypothetical surrogates or patients. Study 2 (involving 64 real multigenerational families with a total of 253 participants) investigated accuracy using 24 medical scenarios. Hypothetical patients and surrogates had closely aligned preferences: Procedural satisfaction was highest with a patient-designated surrogate, followed by shared surrogate decision-making approaches and legally assigned surrogates. These approaches did not differ substantially in accuracy. Limitations are that participants' preferences regarding existing and novel approaches to making surrogate decisions can only be elicited under hypothetical conditions. Next to decision making by patient-designated surrogates, shared surrogate decision making is the preferred approach among patients and surrogates alike. This approach appears to impose no tradeoff between procedural satisfaction and accuracy. Therefore, shared decision making should be further studied in representative samples of the general population, and if people's preferences prove to be robust, they deserve to be weighted more strongly in legal frameworks in addition to patient-designated surrogates.

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

PubMed

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

2018-02-23

How does the psychological well-being and prenatal bonding of Indian surrogates differ from a comparison group of mothers? Surrogates had higher levels of depression during pregnancy and post-birth, displayed lower emotional connection with the unborn baby, and greater care towards the healthy growth of the foetus, than the comparison group of mothers. Studies in the West have found that surrogates do not suffer long-term psychological harm. One study has shown that surrogates bond less with the foetus than expectant mothers. This study uses a prospective, longitudinal and cross-sectional design. Surrogates and a matched group of expectant mothers were seen twice, during 4-9 months of pregnancy and 4-6 months after the birth. Semi-structured interviews and standardized questionnaires were administered to 50 surrogates and 69 expectant mothers during pregnancy and 45 surrogates and 49 expectant mothers post-birth. All gestational surrogates were hosting pregnancies for international intended parents. Surrogates had higher levels of depression compared to the comparison group of mothers, during pregnancy and post-birth (P < 0.02). Low social support during pregnancy, hiding surrogacy and criticism from others were found to be predictive of higher depression in surrogates post-birth (P < 0.05). Regarding prenatal bonding, surrogates interacted less with and thought less about the foetus but adopted better eating habits and were more likely to avoid unhealthy practices during pregnancy, than expectant mothers (P < 0.05). No associations were found between greater prenatal bonding and greater psychological distress during pregnancy or after relinquishment. All surrogates were recruited from one clinic in Mumbai, and thus the representativeness of this sample is not known. Also, the possibility of socially desirable responding from surrogates cannot be ruled out. As this is the first study of the psychological well-being of surrogates in low-income countries, the findings have important policy implications. Providing support and counselling to surrogates, especially during pregnancy, may alleviate some of the psychological problems faced by surrogates. This study was supported by the Wellcome Trust [097857/Z/11/Z] and Nehru Trust, Cambridge. K.K. is the Medical Director of Corion Fertility Clinic. All other authors have no conflict of interest to declare.

The psychological well-being and prenatal bonding of gestational surrogates

PubMed Central

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

2018-01-01

Abstract STUDY QUESTION How does the psychological well-being and prenatal bonding of Indian surrogates differ from a comparison group of mothers? SUMMARY ANSWER Surrogates had higher levels of depression during pregnancy and post-birth, displayed lower emotional connection with the unborn baby, and greater care towards the healthy growth of the foetus, than the comparison group of mothers. WHAT IS ALREADY KNOWN Studies in the West have found that surrogates do not suffer long-term psychological harm. One study has shown that surrogates bond less with the foetus than expectant mothers. STUDY, DESIGN, SIZE, DURATION This study uses a prospective, longitudinal and cross-sectional design. Surrogates and a matched group of expectant mothers were seen twice, during 4–9 months of pregnancy and 4–6 months after the birth. PARTICIPANTS/MATERIALS, SETTING, METHODS Semi-structured interviews and standardized questionnaires were administered to 50 surrogates and 69 expectant mothers during pregnancy and 45 surrogates and 49 expectant mothers post-birth. All gestational surrogates were hosting pregnancies for international intended parents. MAIN RESULTS AND THE ROLE OF CHANCE Surrogates had higher levels of depression compared to the comparison group of mothers, during pregnancy and post-birth (P < 0.02). Low social support during pregnancy, hiding surrogacy and criticism from others were found to be predictive of higher depression in surrogates post-birth (P < 0.05). Regarding prenatal bonding, surrogates interacted less with and thought less about the foetus but adopted better eating habits and were more likely to avoid unhealthy practices during pregnancy, than expectant mothers (P < 0.05). No associations were found between greater prenatal bonding and greater psychological distress during pregnancy or after relinquishment. LIMITATIONS, REASONS FOR CAUTION All surrogates were recruited from one clinic in Mumbai, and thus the representativeness of this sample is not known. Also, the possibility of socially desirable responding from surrogates cannot be ruled out. WIDER IMPLICATIONS OF THE FINDINGS As this is the first study of the psychological well-being of surrogates in low-income countries, the findings have important policy implications. Providing support and counselling to surrogates, especially during pregnancy, may alleviate some of the psychological problems faced by surrogates. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the Wellcome Trust [097857/Z/11/Z] and Nehru Trust, Cambridge. K.K. is the Medical Director of Corion Fertility Clinic. All other authors have no conflict of interest to declare. PMID:29566176

Forest restoration treatments have subtle long-term effects on soil C and N cycling in mixed conifer forests.

PubMed

Ganzlin, Peter W; Gundale, Michael J; Becknell, Rachel E; Cleveland, Cory C

2016-07-01

Decades of fire suppression following extensive timber harvesting have left much of the forest in the intermountain western United States exceedingly dense, and forest restoration techniques (i.e., thinning and prescribed fire) are increasingly being used in an attempt to mitigate the effects of severe wildfire, to enhance tree growth and regeneration, and to stimulate soil nutrient cycling. While many of the short-term effects of forest restoration have been established, the long-term effects on soil biogeochemical and ecosystem processes are largely unknown. We assessed the effects of commonly used forest restoration treatments (thinning, burning, and thinning + burning) on nutrient cycling and other ecosystem processes 11 yr after restoration treatments were implemented in a ponderosa pine (Pinus ponderosa var. scopulorum)/Douglas fir (Pseudotsuga menziesii var. glauca) forest at the Lubrecht Fire and Fire Surrogates Study (FFS) site in western Montana, USA. Despite short-term (<3 yr) increases in soil inorganic nitrogen (N) pools and N cycling rates following prescribed fire, long-term soil N pools and N mineralization rates showed only subtle differences from untreated control plots. Similarly, despite a persistent positive correlation between fuels consumed in prescribed burns and several metrics of N cycling, variability in inorganic N pools decreased significantly since treatments were implemented, indicating a decline in N spatial heterogeneity through time. However, rates of net nitrification remain significantly higher in a thin + burn treatment relative to other treatments. Short-term declines in forest floor carbon (C) pools have persisted in the thin + burn treatment, but there were no significant long-term differences among treatments in extractable soil phosphorus (P). Finally, despite some short-term differences, long-term foliar nutrient concentrations, litter decomposition rates, and rates of free-living N fixation in the experimental plots were not different from control plots, suggesting nutrient cycles and ecosystem processes in temperate coniferous forests are resilient to disturbance following long periods of fire suppression. Overall, this study provides forest managers and policymakers valuable information showing that the effects of these commonly used restoration prescriptions on soil nutrient cycling are ephemeral and that use of repeated treatments (i.e., frequent fire) will be necessary to ensure continued restoration success. © 2016 by the Ecological Society of America.

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

PubMed

Hu, Mengyi; Gurtler, Joshua B

2017-09-01

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

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

PubMed

Wendler, David; Rid, Annette

2011-03-01

Clinical practice relies on surrogates to make or help to make treatment decisions for incapacitated adults; however, the effect of this practice on surrogates has not been evaluated. To assess the effect on surrogates of making treatment decisions for adults who cannot make their own decisions. Empirical studies published in English and listed in MEDLINE, EMBASE, CINAHL, BIOETHICSLINE, PsycINFO, or Scopus before 1 July 2010. Eligible studies provided quantitative or qualitative empirical data, by evaluating surrogates, regarding the effect on surrogates of making treatment decisions for an incapacitated adult. Information on study location, number and type of surrogates, timing of data collection, type of decisions, patient setting, methods, main findings, and limitations. 40 studies, 29 using qualitative and 11 using quantitative methods, provided data on 2854 surrogates, more than one half of whom were family members of the patient. Most surrogates were surveyed several months to years after making treatment decisions, the majority of which were end-of-life decisions. The quantitative studies found that at least one third of surrogates experienced a negative emotional burden as the result of making treatment decisions. The qualitative studies reported that many or most surrogates experienced negative emotional burden. The negative effects on surrogates were often substantial and typically lasted months or, in some cases, years. The most common negative effects cited by surrogates were stress, guilt over the decisions they made, and doubt regarding whether they had made the right decisions. Nine of the 40 studies also reported beneficial effects on a few surrogates, the most common of which were supporting the patient and feeling a sense of satisfaction. Knowing which treatment is consistent with the patient's preferences was frequently cited as reducing the negative effect on surrogates. Thirty-two of the 40 articles reported data collected in the United States. Because the study populations were relatively homogenous, it is unclear whether the findings apply to other groups. In some cases, the effect of making treatment decisions could not be isolated from that of other stressors, such as grief or prognostic uncertainty. Nine of the studies had a response rate less than 50%, and 9 did not report a response rate. Many of the studies had a substantial interval between the treatment decisions and data collection. Making treatment decisions has a negative emotional effect on at least one third of surrogates, which is often substantial and typically lasts months (or sometimes years). Future research should evaluate ways to reduce this burden, including methods to identify which treatment options are consistent with the patient's preferences. National Institutes of Health.

Bird functional diversity decreases with time since disturbance: Does patchy prescribed fire enhance ecosystem function?.

PubMed

Sitters, Holly; Di Stefano, Julian; Christie, Fiona; Swan, Matthew; York, Alan

2016-01-01

Animal species diversity is often associated with time since disturbance, but the effects of disturbances such as fire on functional diversity are unknown. Functional diversity measures the range, abundance, and distribution of trait values in a community, and links changes in species composition with the consequences for ecosystem function. Improved understanding of the relationship between time since fire (TSF) and functional diversity is critical given that the frequency of both prescribed fire and wildfire is expected to increase. To address this knowledge gap, we examined responses of avian functional diversity to TSF and two direct measures of environmental heterogeneity, plant diversity, and structural heterogeneity. We surveyed birds across a 70-year chronosequence spanning four vegetation types in southeast Australia. Six bird functional traits were used to derive four functional diversity indices (richness, evenness, divergence, and dispersion) and the effects of TSF, plant diversity and structural heterogeneity on species richness and the functional diversity indices were examined using mixed models. We used a regression tree method to identify traits associated with species more common in young vegetation. Functional richness and dispersion were negatively associated with TSF in all vegetation types, suggesting that recent prescribed fire generates heterogeneous vegetation and provides greater opportunities for resource partitioning. Species richness was not significantly associated with TSF, and is probably an unreliable surrogate for functional diversity in fire-prone systems. A positive, relationship between functional evenness and structural heterogeneity was comnon to all vegetation types, suggesting that fine-scale (tens of meters) structural variation can enhance ecosystem function. Species more common in young vegetation were primarily linked by their specialist diets, indicating that ecosystem services such as seed dispersal and insect control are enhanced in more recently burnt vegetation. We suggest that patchy prescribed fire sustains functional diversity, and that controlled use of patchy fire to break up large expanses of mature vegetation will enhance ecosystem function.

Network algorithmics and the emergence of the cortical synaptic-weight distribution

NASA Astrophysics Data System (ADS)

Nathan, Andre; Barbosa, Valmir C.

2010-02-01

When a neuron fires and the resulting action potential travels down its axon toward other neurons’ dendrites, the effect on each of those neurons is mediated by the strength of the synapse that separates it from the firing neuron. This strength, in turn, is affected by the postsynaptic neuron’s response through a mechanism that is thought to underlie important processes such as learning and memory. Although of difficult quantification, cortical synaptic strengths have been found to obey a long-tailed unimodal distribution peaking near the lowest values (approximately lognormal), thus confirming some of the predictive models built previously. Most of these models are causally local, in the sense that they refer to the situation in which a number of neurons all fire directly at the same postsynaptic neuron. Consequently, they necessarily embody assumptions regarding the generation of action potentials by the presynaptic neurons that have little biological interpretability. We introduce a network model of large groups of interconnected neurons and demonstrate, making none of the assumptions that characterize the causally local models, that its long-term behavior gives rise to a distribution of synaptic weights (the mathematical surrogates of synaptic strengths) with the same properties that were experimentally observed. In our model, the action potentials that create a neuron’s input are, ultimately, the product of network-wide causal chains relating what happens at a neuron to the firings of others. Our model is then of a causally global nature and predicates the emergence of the synaptic-weight distribution on network structure and function. As such, it has the potential to become instrumental also in the study of other emergent cortical phenomena.

Investigating conflict in ICUs - Is the clinicians’ perspective enough?

PubMed Central

Schuster, Rachel A.; Hong, Seo Yeon; Arnold, Robert M.; White, Douglas B.

2013-01-01

Objective Most studies have assessed conflict between clinicians and surrogate decision makers in ICUs from only clinicians’ perspectives. It is unknown if surrogates’ perceptions differ from clinicians’. We sought to determine the degree of agreement between physicians and surrogates about conflict, and to identify predictors of physician-surrogate conflict. Design Prospective cohort study. Setting Four ICUs of two hospitals in San Francisco, California. Patients 230 surrogate decision makers and 100 physicians of 175 critically ill patients. Measurements Questionnaires addressing participants’ perceptions of whether there was physician-surrogate conflict, as well as attitudes and preferences about clinician-surrogate communication; kappa scores to quantify physician-surrogate concordance about the presence of conflict; and hierarchical multivariate modeling to determine predictors of conflict. Main Results Either the physician or surrogate identified conflict in 63% of cases. Physicians were less likely to perceive conflict than surrogates (27.8% vs 42.3%; p=0.007). Agreement between physicians and surrogates about conflict was poor (kappa = 0.14). Multivariable analysis with surrogate-assessed conflict as the outcome revealed that higher levels of surrogates’ satisfaction with physicians’ bedside manner were associated with lower odds of conflict (OR: 0.75 per 1 point increase in satisfaction, 95% CI 0.59–0.96). Multivariable analysis with physician-assessed conflict as the outcome revealed that the surrogate having felt discriminated against in the healthcare setting was associated with higher odds of conflict (OR 17.5, 95% CI 1.6–190.1) while surrogates’ satisfaction with physicians’ bedside manner was associated with lower odds of conflict (0–10 scale, OR 0.76 per 1 point increase, 95% CI 0.58–0.99). Conclusions Conflict between physicians and surrogates is common in ICUs. There is little agreement between physicians and surrogates about whether physician-surrogate conflict has occurred. Further work is needed to develop reliable and valid methods to assess conflict. In the interim, future studies should assess conflict from the perspective of both clinicians and surrogates. PMID:24434440

Fire helps restore natural disturbance regime to benefit rare and endangered marsh birds endemic to the Colorado River.

PubMed

Conway, Courtney J; Nadeau, Christopher P; Piest, Linden

2010-10-01

Large flood events were part of the historical disturbance regime within the lower basin of most large river systems around the world. Large flood events are now rare in the lower basins of most large river systems due to flood control structures. Endemic organisms that are adapted to this historical disturbance regime have become less abundant due to these dramatic changes in the hydrology and the resultant changes in vegetation structure. The Yuma Clapper Rail is a federally endangered bird that breeds in emergent marshes within the lower Colorado River basin in the southwestern United States and northwestern Mexico. We evaluated whether prescribed fire could be used as a surrogate disturbance event to help restore historical conditions for the benefit of Yuma Clapper Rails and four sympatric marsh-dependent birds. We conducted call-broadcast surveys for marsh birds within burned and unburned (control) plots both pre- and post-burn. Fire increased the numbers of Yuma Clapper Rails and Virginia Rails, and did not affect the numbers of Black Rails, Soras, and Least Bitterns. We found no evidence that detection probability of any of the five species differed between burn and control plots. Our results suggest that prescribed fire can be used to set back succession of emergent marshlands and help mimic the natural disturbance regime in the lower Colorado River basin. Hence, prescribed fire can be used to help increase Yuma Clapper Rail populations without adversely affecting sympatric species. Implementing a coordinated long-term fire management plan within marshes of the lower Colorado River may allow regulatory agencies to remove the Yuma Clapper Rail from the endangered species list.

Fire helps restore natural disturbance regime to benefit rare and endangered marsh birds endemic to the Colorado River

USGS Publications Warehouse

Conway, C.J.; Nadeau, C.P.; Piest, L.

2010-01-01

Large flood events were part of the historical disturbance regime within the lower basin of most large river systems around the world. Large flood events are now rare in the lower basins of most large river systems due to flood control structures. Endemic organisms that are adapted to this historical disturbance regime have become less abundant due to these dramatic changes in the hydrology and the resultant changes in vegetation structure. The Yuma Clapper Rail is a federally endangered bird that breeds in emergent marshes within the lower Colorado River basin in the southwestern United States and northwestern Mexico. We evaluated whether prescribed fire could be used as a surrogate disturbance event to help restore historical conditions for the benefit of Yuma Clapper Rails and four sympatric marsh-dependent birds. We conducted call-broadcast surveys for marsh birds within burned and unburned (control) plots both pre-and post-burn. Fire increased the numbers of Yuma Clapper Rails and Virginia Rails, and did not affect the numbers of Black Rails, Soras, and Least Bitterns. We found no evidence that detection probability of any of the five species differed between burn and control plots. Our results suggest that prescribed fire can be used to set back succession of emergent marshlands and help mimic the natural disturbance regime in the lower Colorado River basin. Hence, prescribed fire can be used to help increase Yuma Clapper Rail populations without adversely affecting sympatric species. Implementing a coordinated long-term fire management plan within marshes of the lower Colorado River may allow regulatory agencies to remove the Yuma Clapper Rail from the endangered species list. ?? 2010 by the Ecological Society of America.

An Empirical Assessment and Comparison of Species-Based and Habitat-Based Surrogates: A Case Study of Forest Vertebrates and Large Old Trees

PubMed Central

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

2014-01-01

A holy grail of conservation is to find simple but reliable measures of environmental change to guide management. For example, particular species or particular habitat attributes are often used as proxies for the abundance or diversity of a subset of other taxa. However, the efficacy of such kinds of species-based surrogates and habitat-based surrogates is rarely assessed, nor are different kinds of surrogates compared in terms of their relative effectiveness. We use 30-year datasets on arboreal marsupials and vegetation structure to quantify the effectiveness of: (1) the abundance of a particular species of arboreal marsupial as a species-based surrogate for other arboreal marsupial taxa, (2) hollow-bearing tree abundance as a habitat-based surrogate for arboreal marsupial abundance, and (3) a combination of species- and habitat-based surrogates. We also quantify the robustness of species-based and habitat-based surrogates over time. We then use the same approach to model overall species richness of arboreal marsupials. We show that a species-based surrogate can appear to be a valid surrogate until a habitat-based surrogate is co-examined, after which the effectiveness of the former is lost. The addition of a species-based surrogate to a habitat-based surrogate made little difference in explaining arboreal marsupial abundance, but altered the co-occurrence relationship between species. Hence, there was limited value in simultaneously using a combination of kinds of surrogates. The habitat-based surrogate also generally performed significantly better and was easier and less costly to gather than the species-based surrogate. We found that over 30 years of study, the relationships which underpinned the habitat-based surrogate generally remained positive but variable over time. Our work highlights why it is important to compare the effectiveness of different broad classes of surrogates and identify situations when either species- or habitat-based surrogates are likely to be superior. PMID:24587050

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

PubMed

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

2014-01-01

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

Comparison between surrogate indexes of insulin sensitivity/resistance and hyperinsulinemic euglycemic clamp estimates in rats

PubMed Central

Muniyappa, Ranganath; Chen, Hui; Muzumdar, Radhika H.; Einstein, Francine H.; Yan, Xu; Yue, Lilly Q.; Barzilai, Nir

2009-01-01

Assessing insulin resistance in rodent models gives insight into mechanisms that cause type 2 diabetes and the metabolic syndrome. The hyperinsulinemic euglycemic glucose clamp, the reference standard for measuring insulin sensitivity in humans and animals, is labor intensive and technically demanding. A number of simple surrogate indexes of insulin sensitivity/resistance have been developed and validated primarily for use in large human studies. These same surrogates are also frequently used in rodent studies. However, in general, these indexes have not been rigorously evaluated in animals. In a recent validation study in mice, we demonstrated that surrogates have a weaker correlation with glucose clamp estimates of insulin sensitivity/resistance than in humans. This may be due to increased technical difficulties in mice and/or intrinsic differences between human and rodent physiology. To help distinguish among these possibilities, in the present study, using data from rats substantially larger than mice, we compared the clamp glucose infusion rate (GIR) with surrogate indexes, including QUICKI, HOMA, 1/HOMA, log (HOMA), and 1/fasting insulin. All surrogates were modestly correlated with GIR (r = 0.34–0.40). Calibration analyses of surrogates adjusted for body weight demonstrated similar predictive accuracy for GIR among all surrogates. We conclude that linear correlations of surrogate indexes with clamp estimates and predictive accuracy of surrogate indexes in rats are similar to those in mice (but not as substantial as in humans). This additional rat study (taken with the previous mouse study) suggests that application of surrogate insulin sensitivity indexes developed for humans may not be appropriate for determining primary outcomes in rodent studies due to intrinsic differences in metabolic physiology. However, use of surrogates may be appropriate in rodents, where feasibility of clamps is an obstacle and measurement of insulin sensitivity is a secondary outcome. PMID:19706785

Proceedings of the Annual Seismic Research Symposium on Monitoring a Comprehensive Test Ban Treaty (19th). Held in Orlando, Florida on 23-25 September 1997

DTIC Science & Technology

1997-09-05

explosions be used as sources of ground truth information? Can these sources be used as surrogates for single-fired explosions in regions where no such... sources exist? (Stump) 3. Is there a single regional discriminant that will work for all mining explosions or will it be necessary to apply a suite of...the Treaty be used to take advantage of mining sources as Ground Truth information? Is it possible to use such information to "finger print" mines

Challenge of surrogate endpoints.

PubMed

Furgerson, James L; Hannah, William N; Thompson, Jennifer C

2012-03-01

Surrogate endpoints are biomarkers that are intended to substitute for clinical endpoints. They have been used to find novel therapeutic targets, improve the statistical power and shorten the duration of clinical trials, and control the cost of conducting research studies. The more generalized use of surrogate endpoints in clinical decision making can be hazardous and should be undertaken with great caution. This article reviews prior work with surrogate endpoints and highlights caveats and lessons learned from studies using surrogate endpoints.

Nonspinning numerical relativity waveform surrogates: assessing the model

NASA Astrophysics Data System (ADS)

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

2015-04-01

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

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

PubMed

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

2015-06-01

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

Delayed conifer mortality after fuel reduction treatments: Interactive effects of fuel, fire intensity, and bark beetles

USGS Publications Warehouse

Youngblood, A.; Grace, J.B.; Mciver, J.D.

2009-01-01

Many low-elevation dry forests of the western United States contain more small trees and fewer large trees, more down woody debris, and less diverse and vigorous understory plant communities compared to conditions under historical fire regimes. These altered structural conditions may contribute to increased probability of unnaturally severe wildfires, susceptibility to uncharacteristic insect outbreaks, and drought-related mortality. Broad-scale fuel reduction and restoration treatments are proposed to promote stand development on trajectories toward more sustainable structures. Little research to date, however, has quantified the effects of these treatments on the ecosystem, especially delayed and latent tree mortality resulting directly or indirectly from treatments. In this paper, we explore complex hypotheses relating to the cascade of effects that influence ponderosa pine (Pinus ponderosa) and Douglas-fir (Pseudotsuga menziesii) mortality using structural equation modeling (SEM). We used annual census and plot data through six growing seasons after thinning and four growing seasons after burning from a replicated, operational-scale, completely randomized experiment conducted in northeastern Oregon, USA, as part of the national Fire and Fire Surrogate study. Treatments included thin, burn, thin followed by burn (thin+burn), and control. Burn and thin+burn treatments increased the proportion of dead trees while the proportion of dead trees declined or remained constant in thin and control units, although the density of dead trees was essentially unchanged with treatment. Most of the new mortality (96%) occurred within two years of treatment and was attributed to bark beetles. Bark beetle-caused tree mortality, while low overall, was greatest in thin + burn treatments. SEM results indicate that the probability of mortality of large-diameter ponderosa pine from bark beetles and wood borers was directly related to surface fire severity and bole charring, which in turn depended on fire intensity, which was greater in units where thinning increased large woody fuels. These results have implications when deciding among management options for restoring ecosystem health in similar ponderosa pine and Douglas-fir forests. ?? 2009 by the Ecological Society of America.

Surrogate outcomes: experiences at the Common Drug Review

PubMed Central

2013-01-01

Background Surrogate outcomes are a significant challenge in drug evaluation for health technology assessment (HTA) agencies. The research objectives were to: identify factors associated with surrogate use and acceptability in Canada’s Common Drug Review (CDR) recommendations, and compare the CDR with other HTA or regulatory agencies regarding surrogate concerns. Methods Final recommendations were identified from CDR inception (September 2003) to December 31, 2010. Recommendations were classified by type of outcome (surrogate, final, other) and acceptability of surrogates (determined by the presence/absence of statements of concern regarding surrogates). Descriptive and statistical analyses examined factors related to surrogate use and acceptability. For thirteen surrogate-based submissions, recommendations from international HTA and regulatory agencies were reviewed for statements about surrogate acceptability. Results Of 156 final recommendations, 68 (44%) involved surrogates. The overall ‘do not list’ (DNL) rate was 48%; the DNL rate for surrogates was 41% (p = 0.175). The DNL rate was 64% for non-accepted surrogates (n = 28) versus 25% for accepted surrogates (odds ratio 5.4, p = 0.002). Clinical uncertainty, use of economic evidence over price alone, and a premium price were significantly associated with non-accepted surrogates. Surrogates were used most commonly for HIV, diabetes, rare diseases, cardiovascular disease and cancer. For the subset of drugs studied, other HTA agencies did not express concerns for most recommendations, while regulatory agencies frequently stated surrogate acceptance. Conclusions The majority of surrogates were accepted at the CDR. Non-accepted surrogates were significantly associated with clinical uncertainty and a DNL recommendation. There was inconsistency of surrogate acceptability across several international agencies. Stakeholders should consider collaboratively establishing guidelines on the use, validation, and acceptability of surrogates. PMID:24341379

Surrogate outcomes are associated with low methodological quality of studies of rheumatoid arthritis treated with antitumour necrosis factor agents: a systematic review.

PubMed

Nobre, Moacyr Roberto Cuce; da Costa, Frnanda Marques

2012-02-01

Surrogate endpoints may be used as substitutes for, but often do not predict clinically relevant events. Objective To assess the methodological quality of articles that present their conclusions based on clinically relevant or surrogate outcomes in a systematic review of randomised trials and cohort studies of patients with rheumatoid arthritis treated with antitumour necrosis factor (TNF) agents. PubMed, Embase and Cochrane databases were searched. The Jadad score, the percentage of Consolidated Standards Of Reporting Trials (CONSORT) statement items adequately reported and levels-of-evidence (Center for Evidence-based Medicine, Oxford) were used in a descriptive synthesis. Among 88 articles appraised, 27 had surrogate endpoints, mainly radiographic, and 44 were duplicate publications; 74% of articles with surrogate and 39% of articles with clinical endpoints (p=0.006). Fewer articles with surrogate endpoints represented a high level of evidence (Level 1b, 33% vs 62%, p=0.037) and the mean percentage of CONSORT statement items met was also lower for articles with surrogate endpoints (62.5 vs 70.7, p=0.026). Although fewer articles with surrogate endpoints were randomised trials (63% vs 74%, p=0.307) and articles with surrogate endpoints had lower Jadad scores (3.0 vs 3.2, p=0.538), these differences were not statistically significant. Studies of anti-TNF agents that report surrogate outcomes are of lesser methodological quality. As such, inclusion of such studies in evidence syntheses may bias results.

Surrogate Agreement in Tzotzil.

ERIC Educational Resources Information Center

Aissen, Judith L.

This study investigates whether other relationships in sentence structure besides the "brother-in-law" relation sanction surrogate agreement in Zinacanteco Tzotzil (Mayan). Surrogate agreement refers to cases in which an element that lies outside the class of regular agreement controllers in a language (the surrogate) controls…

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

PubMed Central

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

2012-01-01

BACKGROUND This study aimed to prospectively examine families created using surrogacy over a 10-year period in the UK with respect to intending parents' and children's relationship with the surrogate mother, parents' decisions over disclosure and children's understanding of the nature of their conception. METHODS Semi-structured interviews were administered by trained researchers to intending mothers, intending fathers and children on four occasions over a 10-year period. Forty-two families (19 with a genetic surrogate mother) participated when the child was 1-year old and by age 10 years, 33 families remained in the study. Data were collected on the frequency of contact with the surrogate mother, relationship with the surrogate, disclosure of surrogacy to the child and the child's understanding of their surrogacy birth. RESULTS Frequency of contact between surrogacy families and their surrogate mother decreased over time, particularly for families whose surrogate was a previously unknown genetic carrier (P < 0.001) (i.e. where they had met through a third party and the surrogate mother's egg was used to conceive the child). Most families reported harmonious relationships with their surrogate mother. At age 10 years, 19 (90%) children who had been informed of the nature of their conception had a good understanding of this and 13 of the 14 children who were in contact with their surrogate reported that they liked her. CONCLUSIONS Surrogacy families maintained good relationships with the surrogate mother over time. Children felt positive about their surrogate mother and their surrogacy birth. The sample size of this study was small and further, larger investigations are needed before firm conclusions can be drawn. PMID:22814484

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

PubMed

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

2012-10-01

This study aimed to prospectively examine families created using surrogacy over a 10-year period in the UK with respect to intending parents' and children's relationship with the surrogate mother, parents' decisions over disclosure and children's understanding of the nature of their conception. Semi-structured interviews were administered by trained researchers to intending mothers, intending fathers and children on four occasions over a 10-year period. Forty-two families (19 with a genetic surrogate mother) participated when the child was 1-year old and by age 10 years, 33 families remained in the study. Data were collected on the frequency of contact with the surrogate mother, relationship with the surrogate, disclosure of surrogacy to the child and the child's understanding of their surrogacy birth. Frequency of contact between surrogacy families and their surrogate mother decreased over time, particularly for families whose surrogate was a previously unknown genetic carrier (P < 0.001) (i.e. where they had met through a third party and the surrogate mother's egg was used to conceive the child). Most families reported harmonious relationships with their surrogate mother. At age 10 years, 19 (90%) children who had been informed of the nature of their conception had a good understanding of this and 13 of the 14 children who were in contact with their surrogate reported that they liked her. Surrogacy families maintained good relationships with the surrogate mother over time. Children felt positive about their surrogate mother and their surrogacy birth. The sample size of this study was small and further, larger investigations are needed before firm conclusions can be drawn.

Assessing the potential of surrogate EPS to mimic natural biofilm mechanical properties

NASA Astrophysics Data System (ADS)

Thom, Moritz; Schimmels, Stefan

2017-04-01

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

The Trial of Ascertaining Individual Preferences for Loved Ones' Role in End-of-Life Decisions (TAILORED) Study: A Randomized Controlled Trial to Improve Surrogate Decision Making.

PubMed

Sulmasy, Daniel P; Hughes, Mark T; Yenokyan, Gayane; Kub, Joan; Terry, Peter B; Astrow, Alan B; Johnson, Julie A; Ho, Grace; Nolan, Marie T

2017-10-01

Patients with terminal illnesses often require surrogate decision makers. Prior research has demonstrated high surrogate stress, and that despite standards promoting substituted judgment, most patients do not want their surrogates to make pure substituted judgments for them. It is not known how best to help loved ones fulfill the surrogate role. To test the effectiveness of an intervention to help surrogate decision makers. One hundred sixty-six patients (41% with amyotrophic lateral sclerosis and 59% with gastrointestinal cancers) and their surrogates at two university medical centers were randomized to an intensive nurse-directed discussion of the end-of-life decision control preferences of the patient (TAILORED) or a discussion of nutrition (CONTROL); 163 completed baseline interviews and underwent the intervention. Twelve patients died during follow-up and 137 dyads completed the study. Post-intervention, using all available data, TAILORED patients and surrogates became more likely to endorse mutual surrogate decision making, that is, a balance of their own wishes and what the surrogate thinks best (adjusted odds compared with baseline for patients = 1.78, P = 0.04; adjusted odds for surrogates = 2.05, P = 0.03). CONTROL patients became 40% less likely to endorse mutual surrogate decision making (P = 0.08), and CONTROL surrogates did not change significantly from baseline (adjusted odds = 1.44, P = 0.28). Stress levels decreased for TAILORED surrogates (impact of events scale = 23.1 ± 14.6 baseline, 20.8 ± 15.3 f/u, P = 0.046), but not for CONTROL (P = 0.85), and post-intervention stress was lower for TAILORED than CONTROL (P = 0.04). Surrogates' confidence was uniformly high at baseline and did not change. Caregiver burden (Zarit) increased from 12.5 ± 6.5 to 14.7 ± 8.1 for TAILORED (P < 0.01), while not changing for CONTROL, yet satisfaction with involvement in decision making was higher at follow-up for TAILORED than for CONTROL (71% vs. 52%, P = 0.03). TAILORED patients and surrogates who completed the study adopted a more mutual decision-making style, balancing their own wishes with what the surrogate thinks would be best for them. Surrogates reported less stress and more satisfaction. Confidence was high at baseline and did not change. There was a modest increase in caregiver burden. These findings suggest that interventions like TAILORED might positively impact surrogate decision making. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Incorporating approximation error in surrogate based Bayesian inversion

NASA Astrophysics Data System (ADS)

Zhang, J.; Zeng, L.; Li, W.; Wu, L.

2015-12-01

There are increasing interests in applying surrogates for inverse Bayesian modeling to reduce repetitive evaluations of original model. In this way, the computational cost is expected to be saved. However, the approximation error of surrogate model is usually overlooked. This is partly because that it is difficult to evaluate the approximation error for many surrogates. Previous studies have shown that, the direct combination of surrogates and Bayesian methods (e.g., Markov Chain Monte Carlo, MCMC) may lead to biased estimations when the surrogate cannot emulate the highly nonlinear original system. This problem can be alleviated by implementing MCMC in a two-stage manner. However, the computational cost is still high since a relatively large number of original model simulations are required. In this study, we illustrate the importance of incorporating approximation error in inverse Bayesian modeling. Gaussian process (GP) is chosen to construct the surrogate for its convenience in approximation error evaluation. Numerical cases of Bayesian experimental design and parameter estimation for contaminant source identification are used to illustrate this idea. It is shown that, once the surrogate approximation error is well incorporated into Bayesian framework, promising results can be obtained even when the surrogate is directly used, and no further original model simulations are required.

Emerging investigator series: the effect of wildfire on streamwater mercury and organic carbon in a forested watershed in the southeastern United States.

PubMed

Jensen, Allison M; Scanlon, Todd M; Riscassi, Ami L

2017-12-13

Wildfires alter forested ecosystems, which include large stores of mercury (Hg) and organic carbon, two compounds that are closely linked in vegetation, soils, and streamwater. Studies have shown that wildfires release elevated levels of mercury to the atmosphere which can be locally redeposited and leave charred organic material (vegetation and litter) on the soil surface. Both can contribute to the elevated mobilization of Hg into lakes and streams. However, no studies have conducted a detailed examination of hydrological transport of Hg following a wildfire. This study investigates the coupled transport of mercury and carbon at Twomile Run, a headwater stream located in the forested mountains of Shenandoah National Park, in the year following a low-severity wildfire. Weekly baseflow samples and bi-hourly high-flow storm samples were analyzed for dissolved and particulate mercury (Hg D and Hg P , respectively), dissolved organic carbon (DOC), UV absorbance at 254 nm (UV 254 , surrogate for DOC quantity and character), and total suspended solids (TSS), and were compared with identical measurements taken from a nearby unburned watershed. For all flow conditions sampled at the burned site (which did not include the 2 months following the fire), streamwater Hg D and DOC concentrations, and corresponding UV 254 , were similar to the unburned system. TSS concentrations varied between sites but overall differences were relatively small in magnitude and likely attributable to site differences rather than fire effects. Notably, the Hg P per unit of TSS at the burned site was an order of magnitude higher than the unburned site (2.66 and 0.13 ng Hg P per mg TSS, respectively) for 8 months following the fire, resulting in elevated Hg P concentrations for the range of flow conditions, after which there was a rapid return to non-disturbed conditions. Streamwater total Hg fluxes roughly doubled (0.55 to 1.04 μg m -2 yr -1 ) as a consequence of the fire, indicating that in addition to changing atmospheric and terrestrial Hg cycling, fires can rapidly and significantly alter the streamwater Hg which has implication for downstream ecosystems. These findings are particularly relevant as the occurrence and severity of wildfires are expected to increase in the mid-latitudes in response to climate change.

Evaluating measurements of carbon dioxide emissions using a precision source--A natural gas burner.

PubMed

Bryant, Rodney; Bundy, Matthew; Zong, Ruowen

2015-07-01

A natural gas burner has been used as a precise and accurate source for generating large quantities of carbon dioxide (CO2) to evaluate emissions measurements at near-industrial scale. Two methods for determining carbon dioxide emissions from stationary sources are considered here: predicting emissions based on fuel consumption measurements-predicted emissions measurements, and direct measurement of emissions quantities in the flue gas-direct emissions measurements. Uncertainty for the predicted emissions measurement was estimated at less than 1%. Uncertainty estimates for the direct emissions measurement of carbon dioxide were on the order of ±4%. The relative difference between the direct emissions measurements and the predicted emissions measurements was within the range of the measurement uncertainty, therefore demonstrating good agreement. The study demonstrates how independent methods are used to validate source emissions measurements, while also demonstrating how a fire research facility can be used as a precision test-bed to evaluate and improve carbon dioxide emissions measurements from stationary sources. Fossil-fuel-consuming stationary sources such as electric power plants and industrial facilities account for more than half of the CO2 emissions in the United States. Therefore, accurate emissions measurements from these sources are critical for evaluating efforts to reduce greenhouse gas emissions. This study demonstrates how a surrogate for a stationary source, a fire research facility, can be used to evaluate the accuracy of measurements of CO2 emissions.

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

NASA Astrophysics Data System (ADS)

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

2017-12-01

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

A longitudinal pre-pregnancy to post-delivery comparison of genetic and gestational surrogate and intended mothers: confidence and genealogy.

PubMed

Van Den Akker, Olga B A

2005-12-01

For women opting to use surrogacy to overcome subfertility, a choice can be made to have a genetically related or unrelated baby. Similarly, women opting to become surrogate mothers also have to choose to gestate and relinquish a genetically related or unrelated baby. This study explored the cognitions behind the initial choices made and determined the strength of those cognitions six months post-delivery of the surrogate baby. Surrogate and Intended mothers (N=81) undergoing Artificial Insemination (AI, genetic) or Embryo Transfer (ET, gestational) were studied separately (four groups) at the start of their surrogate arrangement and those with a positive outcome (n=34) were re-interviewed at six months post-relinquishment. There were significant differences between surrogate and intended mothers in their confidence about the arrangement. Beliefs about the importance of a genetic link were predictors of ET arrangements. Responses were consistent over a one and a half-year study period. The ethical and clinical implications of the results are discussed in relation to appropriate self-selection and confidence with the surrogate process and the importance of genetic offspring.

Emotional experiences in surrogate mothers: A qualitative study

PubMed Central

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

2014-01-01

Background: Surrogacy is one of the new techniques of assisted reproduction technology in which a woman carries and bears a child for another woman. In Iran, many Shia clerics and jurists considered it permissible so there is no religious prohibition for it. In addition to the risk of physical complications for complete surrogate mothers, the possibility of psychological complications resulted from emotional attachment to a living creature in the surrogate mother as another injury requires counseling and assessment prior to acceptance by infertile couples and complete surrogate mothers. Objective: The purpose of this study was to assess the emotional experiences of surrogate mothers. Materials and Methods: This was a qualitative, phenomenological study. We selected eight complete surrogate mothers in Isfahan. We used convenient sampling method and in-depth interview to collect the information. The data analysis was fulfilled via Colaizzi’s seven-stage method. Reliability and validity study of the roots in the four-axis was done. Results: The findings of these interviews were classified into two main themes and four sub themes: acquired experiences in pregnancy (feelings toward pregnancy, relationship with family, relatives and commissioning couple) and consequences of surrogacy (complications of pregnancy, religious and financial problems of surrogacy). Conclusion: Surrogacy pregnancy should be considered as high-risk emotional experience because many of surrogate mothers may face negative experiences. Therefore, it is recommended that surrogates should receive professional counseling prior to, during and following pregnancy. PMID:25114669

Emotional experiences in surrogate mothers: A qualitative study.

PubMed

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

2014-07-01

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

Surrogate endpoints in oncology: when are they acceptable for regulatory and clinical decisions, and are they currently overused?

PubMed

Kemp, Robert; Prasad, Vinay

2017-07-21

Surrogate outcomes are not intrinsically beneficial to patients, but are designed to be easier and faster to measure than clinically meaningful outcomes. The use of surrogates as an endpoint in clinical trials and basis for regulatory approval is common, and frequently exceeds the guidance given by regulatory bodies. In this article, we demonstrate that the use of surrogates in oncology is widespread and increasing. At the same time, the strength of association between the surrogates used and clinically meaningful outcomes is often unknown or weak. Attempts to validate surrogates are rarely undertaken. When this is done, validation relies on only a fraction of available data, and often concludes that the surrogate is poor. Post-marketing studies, designed to ensure drugs have meaningful benefits, are often not performed. Alternatively, if a drug fails to improve quality of life or overall survival, market authorization is rarely revoked. We suggest this reliance on surrogates, and the imprecision surrounding their acceptable use, means that numerous drugs are now approved based on small yet statistically significant increases in surrogates of questionable reliability. In turn, this means the benefits of many approved drugs are uncertain. This is an unacceptable situation for patients and professionals, as prior experience has shown that such uncertainty can be associated with significant harm. The use of surrogate outcomes should be limited to situations where a surrogate has demonstrated robust ability to predict meaningful benefits, or where cases are dire, rare or with few treatment options. In both cases, surrogates must be used only when continuing studies examining hard endpoints have been fully recruited.

Two Decades of Cardiovascular Trials With Primary Surrogate Endpoints: 1990-2011.

PubMed

Bikdeli, Behnood; Punnanithinont, Natdanai; Akram, Yasir; Lee, Ike; Desai, Nihar R; Ross, Joseph S; Krumholz, Harlan M

2017-03-21

Surrogate endpoint trials test strategies more efficiently but are accompanied by uncertainty about the relationship between changes in surrogate markers and clinical outcomes. We identified cardiovascular trials with primary surrogate endpoints published in the New England Journal of Medicine , Lancet , and JAMA: Journal of the American Medical Association from 1990 to 2011 and determined the trends in publication of surrogate endpoint trials and the success of the trials in meeting their primary endpoints. We tracked for publication of clinical outcome trials on the interventions tested in surrogate trials. We screened 3016 articles and identified 220 surrogate endpoint trials. From the total of 220 surrogate trials, 157 (71.4%) were positive for their primary endpoint. Only 59 (26.8%) surrogate trials had a subsequent clinical outcomes trial. Among these 59 trials, 24 outcomes trial results validated the positive surrogates, whereas 20 subsequent outcome trials were negative following positive results on a surrogate. We identified only 3 examples in which the surrogate trial was negative but a subsequent outcomes trial was conducted and showed benefit. Findings were consistent in a sample cohort of 383 screened articles inclusive of 37 surrogate endpoint trials from 6 other high-impact journals. Although cardiovascular surrogate outcomes trials frequently show superiority of the tested intervention, they are infrequently followed by a prominent outcomes trial. When there was a high-profile clinical outcomes study, nearly half of the positive surrogate trials were not validated. Cardiovascular surrogate outcome trials may be more appropriate for excluding benefit from the patient perspective than for identifying it. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

A VARI-Based Relative Greenness from MODIS Data for Computing the Fire Potential Index

NASA Technical Reports Server (NTRS)

Schneider, P.; Roberts, D. A.; Kyriakidis, P. C.

2008-01-01

The Fire Potential Index (FPI) relies on relative greenness (RG) estimates from remote sensing data. The Normalized Difference Vegetation index (NDVI), derived from NOAA Advanced Very High Resolution Radiometer (AVHRR) imagery is currently used to calculate RG operationally. Here we evaluated an alternate measure of RG using the Visible Atmospheric Resistant Index (VARI) derived from Moderate Resolution Imaging Spectrometer (MODIS) data. VARI was chosen because it has previously been shown to have the strongest relationship with Live Fuel Moisture (LFM) out of a wide selection of MODIS-derived indices in southern California shrublands. To compare MODIS-based NDVI-FPI and VARI-FPI, RG was calculated from a 6-year time series of MODIS composites and validated against in-situ observations of LFM as a surrogate for vegetation greenness. RG from both indices was then compared in terms of its performance for computing the FPI using historical wildfire data. Computed RG values were regressed against ground-sampled LFM at 14 sites within Los Angeles County. The results indicate the VARI-based RG consistently shows a stronger relationship with observed LFM than NDVI-based RG. With an average R2 of 0.727 compared to a value of only 0.622 for NDVI-RG, VARI-RG showed stronger relationships at 13 out of 14 sites. Based on these results, daily FPI maps were computed for the years 2001 through 2005 using both NDVI-RG and VARI-RG. These were then validated against 12,490 fire detections from the MODIS active fire product using logistic regression. Deviance of the logistic regression model was 408.8 for NDVI-FPI and 176.2 for VARI-FPI. The c-index was found to be 0.69 and 0.78, respectively. The results show that VARI-FP outperforms NDVI-FPI in distinguishing between fire and no-fire events for historical wildfire data in southern California for the given time period.

Toward a Psychology of Surrogate Decision Making.

PubMed

Tunney, Richard J; Ziegler, Fenja V

2015-11-01

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

Surrogate endpoints in randomized cardiovascular clinical trials.

PubMed

Domanski, Michael; Pocock, Stuart; Bernaud, Corine; Borer, Jeffrey; Geller, Nancy; Revkin, James; Zannad, Faiez

2011-08-01

Surrogate endpoints predict the occurrence and timing of a clinical endpoint of interest (CEI). Substitution of a surrogate endpoint for a CEI can dramatically reduce the time and cost necessary to complete a Phase III clinical trial. However, assurance that use of a surrogate endpoint will result in a correct conclusion regarding treatment effect on a CEI requires prior rigorous validation of the surrogate. Surrogate endpoints can also be of substantial use in Phase I and II studies to assess whether the intended therapeutic pathway is operative, thus providing assurance regarding the reasonableness of proceeding to a Phase III trial. This paper discusses the uses and validation of surrogate endpoints. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.

Surviving Surrogate Decision-Making: What Helps and Hampers the Experience of Making Medical Decisions for Others

PubMed Central

Starks, Helene; Taylor, Janelle S.; Hopley, Elizabeth K.; Fryer-Edwards, Kelly

2007-01-01

BACKGROUND A majority of end-of-life medical decisions are made by surrogate decision-makers who have varying degrees of preparation and comfort with their role. Having a seriously ill family member is stressful for surrogates. Moreover, most clinicians have had little training in working effectively with surrogates. OBJECTIVES To better understand the challenges of decision-making from the surrogate’s perspective. DESIGN Semistructured telephone interview study of the experience of surrogate decision-making. PARTICIPANTS Fifty designated surrogates with previous decision-making experience. APPROACH We asked surrogates to describe and reflect on their experience of making medical decisions for others. After coding transcripts, we conducted a content analysis to identify and categorize factors that made decision-making more or less difficult for surrogates. RESULTS Surrogates identified four types of factors: (1) surrogate characteristics and life circumstances (such as coping strategies and competing responsibilities), (2) surrogates’ social networks (such as intrafamily discord about the “right” decision), (3) surrogate–patient relationships and communication (such as difficulties with honoring known preferences), and (4) surrogate–clinician communication and relationship (such as interacting with a single physician whom the surrogate recognizes as the clinical spokesperson vs. many clinicians). CONCLUSIONS These data provide insights into the challenges that surrogates encounter when making decisions for loved ones and indicate areas where clinicians could intervene to facilitate the process of surrogate decision-making. Clinicians may want to include surrogates in advance care planning prior to decision-making, identify and address surrogate stressors during decision-making, and designate one person to communicate information about the patient’s condition, prognosis, and treatment options. PMID:17619223

Selection, validation and utility of pathogen surrogate bacteria used in food safety challenge studies: A Review

USDA-ARS?s Scientific Manuscript database

Non-pathogenic surrogate bacteria are prevalently used in a variety of food challenge studies in place of foodborne pathogens such as Listeria monocytogenes, Salmonella, Escherichia coli O157:H7, and Clostridium botulinum, due to safety and sanitary concerns. Surrogate bacteria should demonstrate si...

Effectiveness of Biodiversity Surrogates for Conservation Planning: Different Measures of Effectiveness Generate a Kaleidoscope of Variation

PubMed Central

Grantham, Hedley S.; Pressey, Robert L.; Wells, Jessie A.; Beattie, Andrew J.

2010-01-01

Conservation planners represent many aspects of biodiversity by using surrogates with spatial distributions readily observed or quantified, but tests of their effectiveness have produced varied and conflicting results. We identified four factors likely to have a strong influence on the apparent effectiveness of surrogates: (1) the choice of surrogate; (2) differences among study regions, which might be large and unquantified (3) the test method, that is, how effectiveness is quantified, and (4) the test features that the surrogates are intended to represent. Analysis of an unusually rich dataset enabled us, for the first time, to disentangle these factors and to compare their individual and interacting influences. Using two data-rich regions, we estimated effectiveness using five alternative methods: two forms of incidental representation, two forms of species accumulation index and irreplaceability correlation, to assess the performance of ‘forest ecosystems’ and ‘environmental units’ as surrogates for six groups of threatened species—the test features—mammals, birds, reptiles, frogs, plants and all of these combined. Four methods tested the effectiveness of the surrogates by selecting areas for conservation of the surrogates then estimating how effective those areas were at representing test features. One method measured the spatial match between conservation priorities for surrogates and test features. For methods that selected conservation areas, we measured effectiveness using two analytical approaches: (1) when representation targets for the surrogates were achieved (incidental representation), or (2) progressively as areas were selected (species accumulation index). We estimated the spatial correlation of conservation priorities using an index known as summed irreplaceability. In general, the effectiveness of surrogates for our taxa (mostly threatened species) was low, although environmental units tended to be more effective than forest ecosystems. The surrogates were most effective for plants and mammals and least effective for frogs and reptiles. The five testing methods differed in their rankings of effectiveness of the two surrogates in relation to different groups of test features. There were differences between study areas in terms of the effectiveness of surrogates for different test feature groups. Overall, the effectiveness of the surrogates was sensitive to all four factors. This indicates the need for caution in generalizing surrogacy tests. PMID:20644726

Towards predictive simulations of soot formation: from surrogate to turbulence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blanquart, Guillaume

The combustion of transportation fuels leads to the formation of several kinds of pollutants, among which are soot particles. These particles, also formed during coal combustion and in fires, are the source of several health problems and environmental issues. Unfortunately, our current understanding of the chemical and physical phenomena leading to the formation of soot particles remains incomplete, and as a result, the predictive capability of our numerical tools is lacking. The objective of the work was to reduce the gap in the present understanding and modeling of soot formation both in laminar and turbulent flames. The effort spanned severalmore » length scales from the molecular level to large scale turbulent transport.« less

Surrogate mothers 10 years on: a longitudinal study of psychological well-being and relationships with the parents and child.

PubMed

Jadva, V; Imrie, S; Golombok, S

2015-02-01

How do the psychological health and experiences of surrogate mothers change from 1 year to 10 years following the birth of the surrogacy child? The psychological well-being of surrogate mothers did not change 10 years following the birth, with all remaining positive about the surrogacy arrangement and the majority continuing to report good mental health. Studies have found that surrogates may find the weeks following the birth difficult, but do not experience psychological problems 6 months or 1 year later. Research has also shown that surrogates can form close relationships with the intended parents during the pregnancy which may continue after the birth. This study used a prospective longitudinal design, in which 20 surrogates were seen at two time points: 1 year following the birth of the surrogacy child and 10 years later. The 20 surrogates (representing 59% of the original sample) participated in a semi-structured interview and completed self-report questionnaires. Eleven surrogates were gestational carriers and nine surrogates had used their own oocyte (genetic surrogacy). Four were previously known to the intended parents and 16 were previously not known. Ten years following the birth of the surrogacy child, surrogate mothers scored within the normal range for self-esteem and did not show signs of depression as measured by the Beck Depression Inventory. Marital quality remained positive over time. All surrogates reported that their expectations of their relationship with the intended parents had been either met or exceeded and most reported positive feelings towards the child. In terms of expectations for the future, most surrogates reported that they would like to maintain contact or would be available to the child if the child wished to contact them. None expressed regrets about their involvement in surrogacy. The sample size of this study was small and the women may not be representative of all surrogates. Therefore the extent to which these findings can be generalized is not known. Contrary to concerns about the potentially negative long-term effect of surrogacy, the findings suggest that surrogacy can be a positive experience for some women at least. These findings are important for policy and practice of surrogacy around the world. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

PubMed

Jadva, V; Imrie, S

2014-01-01

What impact does surrogacy have on the surrogates' own children? The children of surrogate mothers do not experience any negative consequences as a result of their mother's decision to be a surrogate, irrespective of whether or not the surrogate uses her own egg. Participants were recruited as part of a study of the long-term effects of surrogacy for surrogates and their family members. Data were collected from 36 children of surrogates at a single time point. Participants whose mother had been a surrogate 5-15 years prior to interview and who were aged over 12 years were eligible to take part. Thirty-six participants (14 male and 22 female) aged 12-25 years were interviewed (response rate = 52%). Questionnaires assessing psychological health and family functioning were administered. Forty-four per cent (15) of participants' mothers had undergone gestational surrogacy, 39% (14) had used their own egg (genetic surrogacy) and 19% (7) had completed both types of surrogacy. Most surrogates' children (86%, 31) had a positive view of their mother's surrogacy. Forty-seven per cent (17) of children were in contact with the surrogacy child and all reported good relationships with him/her. Forty per cent (14) of children referred to the child as a sibling or half-sibling and this did not differ between genetic and gestational surrogacy. Most children (89%, 32), reported a positive view of family life, with all enjoying spending time with their mother. Mean scores on the questionnaire assessments of psychological health and self-esteem were within the normal range and did not differ by surrogacy type. The sample size for this study was relatively small and not all children chose to take part, therefore their views cannot be known. Nevertheless, this is the first study to assess the experiences of surrogacy from the perspective of the surrogates' own children. There may be some bias from the inclusion of siblings from the same family. Findings of this study show that family relationships within the surrogate's own family are good and that the children are not negatively affected as a result of their mother's decision to be a surrogate. These results are of importance to counsellors and support groups offering advice to surrogates and intended parents. This work was supported by the Economic and Social Research Council (grant number ES/I009221/1). None of the authors has any conflict of interest to declare.

Surrogacy: the experiences of surrogate mothers.

PubMed

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

2003-10-01

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

Exposure assessment in investigations of waterborne illness: a quantitative estimate of measurement error

PubMed Central

Jones, Andria Q; Dewey, Catherine E; Doré, Kathryn; Majowicz, Shannon E; McEwen, Scott A; Waltner-Toews, David

2006-01-01

Background Exposure assessment is typically the greatest weakness of epidemiologic studies of disinfection by-products (DBPs) in drinking water, which largely stems from the difficulty in obtaining accurate data on individual-level water consumption patterns and activity. Thus, surrogate measures for such waterborne exposures are commonly used. Little attention however, has been directed towards formal validation of these measures. Methods We conducted a study in the City of Hamilton, Ontario (Canada) in 2001–2002, to assess the accuracy of two surrogate measures of home water source: (a) urban/rural status as assigned using residential postal codes, and (b) mapping of residential postal codes to municipal water systems within a Geographic Information System (GIS). We then assessed the accuracy of a commonly-used surrogate measure of an individual's actual drinking water source, namely, their home water source. Results The surrogates for home water source provided good classification of residents served by municipal water systems (approximately 98% predictive value), but did not perform well in classifying those served by private water systems (average: 63.5% predictive value). More importantly, we found that home water source was a poor surrogate measure of the individuals' actual drinking water source(s), being associated with high misclassification errors. Conclusion This study demonstrated substantial misclassification errors associated with a surrogate measure commonly used in studies of drinking water disinfection byproducts. Further, the limited accuracy of two surrogate measures of an individual's home water source heeds caution in their use in exposure classification methodology. While these surrogates are inexpensive and convenient, they should not be substituted for direct collection of accurate data pertaining to the subjects' waterborne disease exposure. In instances where such surrogates must be used, estimation of the misclassification and its subsequent effects are recommended for the interpretation and communication of results. Our results also lend support for further investigation into the quantification of the exposure misclassification associated with these surrogate measures, which would provide useful estimates for consideration in interpretation of waterborne disease studies. PMID:16729887

Diesel surrogate fuels for engine testing and chemical-kinetic modeling: Compositions and properties

DOE PAGES

Mueller, Charles J.; Cannella, William J.; Bays, J. Timothy; ...

2016-01-07

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

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

PubMed Central

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

2016-01-01

The primary objectives of this work were to formulate, blend, and characterize a set of four ultralow-sulfur diesel surrogate fuels in quantities sufficient to enable their study in single-cylinder-engine and combustion-vessel experiments. The surrogate fuels feature increasing levels of compositional accuracy (i.e., increasing exactness in matching hydrocarbon structural characteristics) relative to the single target diesel fuel upon which the surrogate fuels are based. This approach was taken to assist in determining the minimum level of surrogate-fuel compositional accuracy that is required to adequately emulate the performance characteristics of the target fuel under different combustion modes. For each of the four surrogate fuels, an approximately 30 L batch was blended, and a number of the physical and chemical properties were measured. This work documents the surrogate-fuel creation process and the results of the property measurements. PMID:27330248

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

PubMed

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

2012-04-01

To describe how critical care physicians manage conflicts with surrogates about withdrawing or withholding patients' life support. Qualitative analysis of key informant interviews with critical care physicians during 2010. We transcribed interviews verbatim and used grounded theory to code and revise a taxonomy of themes and to identify illustrative quotes. Three academic medical centers, one academic-affiliated medical center, and four private practice groups or private hospitals in a large Midwestern city Fourteen critical care physicians. None. Physicians reported tailoring their approach to address specific reasons for disagreement with surrogates. Five common approaches were identified: 1) building trust; 2) educating and informing; 3) providing surrogates more time; 4) adjusting surrogate and physician roles; and 5) highlighting specific values. When mistrust was an issue, physicians endeavored to build a more trusting relationship with the surrogate before readdressing decision making. Physicians also reported correcting misunderstandings by providing targeted education, and some reported highlighting specific patient, surrogate, or physician values that they hoped would guide surrogates to agree with them. When surrogates struggled with decisionmaking roles, physicians attempted to reinforce the concept of substituted judgment. Physicians noted that some surrogates needed time to "come to terms" with the patent's illness before agreeing with physicians. Many physicians had witnessed colleagues negotiate in ways they found objectionable such as providing misleading information, injecting their own values into the negotiation or behaving unprofessionally toward surrogates. Although some physicians viewed their efforts to encourage surrogates' agreement as persuasive, others strongly denied persuading surrogates and described their actions as "guiding" or "negotiating." Physicians reported using a tailored approach to resolve decisional conflicts about life support and attempted to change surrogates' decisions in accordance with what the physician thought was in the patients' best interests. Although physicians acknowledged their efforts to change surrogates' decisions, many physicians did not perceive these efforts as persuasive.

Bayesian meta-analytical methods to incorporate multiple surrogate endpoints in drug development process.

PubMed

Bujkiewicz, Sylwia; Thompson, John R; Riley, Richard D; Abrams, Keith R

2016-03-30

A number of meta-analytical methods have been proposed that aim to evaluate surrogate endpoints. Bivariate meta-analytical methods can be used to predict the treatment effect for the final outcome from the treatment effect estimate measured on the surrogate endpoint while taking into account the uncertainty around the effect estimate for the surrogate endpoint. In this paper, extensions to multivariate models are developed aiming to include multiple surrogate endpoints with the potential benefit of reducing the uncertainty when making predictions. In this Bayesian multivariate meta-analytic framework, the between-study variability is modelled in a formulation of a product of normal univariate distributions. This formulation is particularly convenient for including multiple surrogate endpoints and flexible for modelling the outcomes which can be surrogate endpoints to the final outcome and potentially to one another. Two models are proposed, first, using an unstructured between-study covariance matrix by assuming the treatment effects on all outcomes are correlated and second, using a structured between-study covariance matrix by assuming treatment effects on some of the outcomes are conditionally independent. While the two models are developed for the summary data on a study level, the individual-level association is taken into account by the use of the Prentice's criteria (obtained from individual patient data) to inform the within study correlations in the models. The modelling techniques are investigated using an example in relapsing remitting multiple sclerosis where the disability worsening is the final outcome, while relapse rate and MRI lesions are potential surrogates to the disability progression. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Ethical Concerns and Procedural Pathways for Patients Who are Incapacitated and Alone: Implications from a Qualitative Study for Advancing Ethical Practice

PubMed Central

Catlin, Casey; Kwak, Jennifer; Wood, Erica; Teaster, Pamela B.

2017-01-01

Adults who are incapacitated and alone, having no surrogates, may be known as “unbefriended.” Decision-making for these particularly vulnerable patients is a common and vexing concern for healthcare providers and hospital ethics committees. When all other avenues for resolving the need for surrogate decision-making fail, patients who are incapacitated and alone may be referred for “public guardianship” or guardianship of last resort. While an appropriate mechanism in theory, these programs are often under-staffed and under-funded, laying the consequences of inadequacies on the healthcare system and the patient him or herself. We describe a qualitative study of professionals spanning clinical, court, and agency settings about the mechanisms for resolving surrogate consent for these patients and problems therein within the state of Massachusetts. Interviews found that all participants encountered adults who are incapacitated and without surrogates. Four approaches for addressing surrogate needs were: (1) work to restore capacity; (2) find previously unknown surrogates; (3) work with agencies to obtain surrogates; and (4) access the guardianship system. The use of guardianship was associated with procedural challenges and ethical concerns including delays in care, short term gains for long term costs, inabilities to meet a patient’s values and preferences, conflicts of interest, and ethical discomfort among interviewees. Findings are discussed in the context of resources to restore capacity, identify previously unknown surrogates, and establish improved surrogate mechanisms for this vulnerable population. PMID:28084575

Ethical Concerns and Procedural Pathways for Patients Who are Incapacitated and Alone: Implications from a Qualitative Study for Advancing Ethical Practice.

PubMed

Moye, Jennifer; Catlin, Casey; Kwak, Jennifer; Wood, Erica; Teaster, Pamela B

2017-06-01

Adults who are incapacitated and alone, having no surrogates, may be known as "unbefriended." Decision-making for these particularly vulnerable patients is a common and vexing concern for healthcare providers and hospital ethics committees. When all other avenues for resolving the need for surrogate decision-making fail, patients who are incapacitated and alone may be referred for "public guardianship" or guardianship of last resort. While an appropriate mechanism in theory, these programs are often under-staffed and under-funded, laying the consequences of inadequacies on the healthcare system and the patient him or herself. We describe a qualitative study of professionals spanning clinical, court, and agency settings about the mechanisms for resolving surrogate consent for these patients and problems therein within the state of Massachusetts. Interviews found that all participants encountered adults who are incapacitated and without surrogates. Four approaches for addressing surrogate needs were: (1) work to restore capacity; (2) find previously unknown surrogates; (3) work with agencies to obtain surrogates; and (4) access the guardianship system. The use of guardianship was associated with procedural challenges and ethical concerns including delays in care, short term gains for long term costs, inabilities to meet a patient's values and preferences, conflicts of interest, and ethical discomfort among interviewees. Findings are discussed in the context of resources to restore capacity, identify previously unknown surrogates, and establish improved surrogate mechanisms for this vulnerable population.

Voices of African American, Caucasian, and Hispanic surrogates on the burdens of end-of-life decision making.

PubMed

Braun, Ursula K; Beyth, Rebecca J; Ford, Marvella E; McCullough, Laurence B

2008-03-01

End-of-life decisions are frequently made by patients' surrogates. Race and ethnicity may affect such decision making. Few studies have described how different racial/ethnic groups experience end-of-life surrogate decision making. To describe the self-reported experience the self-reported experience of African-American, Caucasian, and Hispanic surrogate decision makers of seriously ill patients and to examine the relationship of race, ethnicity, and culture to that experience. Purposive sample to include racial/ethnic minorities in a qualitative study using focus group interviews. The participants of the study were 44 experienced, mostly female, surrogate decision makers for older veterans. Transcripts were qualitatively analyzed to identify major themes, with particular attention to themes that might be unique to each of the three groups. The experience of burden of end-of-life decision making was similar in all three groups. This burden in its medical, personal, and familial dimensions is compounded by uncertainty about prognosis and the patient's preferences. Racial/ethnic variations of responses to this burden concerned the physician-family relationship, religion and faith, and past experiences with race/ethnicity concordant versus non-concordant physicians. Regardless of race/ethnicity, surrogates for seriously ill patients appeared to experience increased significant, multidimensional burdens of decision making under conditions of uncertainty about a patient's preferences. This aspect of the burden of surrogate decision making may not be fully appreciated by physicians. Physicians should identify and be especially attentive to strategies used by surrogates, which may vary by race/ethnicity, to reduce the uncertainty about a patient's preferences and thus the burden of surrogate decision making to assist them in this difficult process.

Production of cloned NIBS (Nippon Institute for Biological Science) and α-1, 3-galactosyltransferase knockout MGH miniature pigs by somatic cell nuclear transfer using the NIBS breed as surrogates.

PubMed

Shimatsu, Yoshiki; Yamada, Kazuhiko; Horii, Wataru; Hirakata, Atsushi; Sakamoto, Yuji; Waki, Shiori; Sano, Junichi; Saitoh, Toshiki; Sahara, Hisashi; Shimizu, Akira; Yazawa, Hajime; Sachs, David H; Nunoya, Tetsuo

2013-01-01

Nuclear transfer (NT) technologies offer a means for producing the genetically modified pigs necessary to develop swine models for mechanistic studies of disease processes as well as to serve as organ donors for xenotransplantation. Most previous studies have used commercial pigs as surrogates. In this study, we established a cloning technique for miniature pigs by somatic cell nuclear transfer (SCNT) using Nippon Institute for Biological Science (NIBS) miniature pigs as surrogates. Moreover, utilizing this technique, we have successfully produced an α-1, 3-galactosyltransferase knockout (GalT-KO) miniature swine. Fibroblasts procured from a NIBS miniature pig fetus were injected into 1312 enucleated oocytes. The cloned embryos were transferred to 11 surrogates of which five successfully delivered 13 cloned offspring; the production efficiency was 1.0% (13/1312). In a second experiment, lung fibroblasts obtained from neonatal GalT-KO MGH miniature swine were used as donor cells and 1953 cloned embryos were transferred to 12 surrogates. Six cloned offspring were born from five surrogates, a production efficiency of 0.3% (6/1953). These results demonstrate successful establishment of a miniature pig cloning technique by SCNT using NIBS miniature pigs as surrogates. To our knowledge, this is the first demonstration of successful production of GalT-KO miniature swine using miniature swine surrogates. This technique could help to ensure a stable supply of the cloned pigs through the use of miniature pig surrogates and could expand production in countries with limited space or in facilities with special regulations such as specific pathogen-free or good laboratory practice. © 2013 John Wiley & Sons A/S.

Production of cloned NIBS (Nippon Institute for Biological Science) and α-1, 3-galactosyltransferase knockout MGH miniature pigs by somatic cell nuclear transfer using the NIBS breed as surrogates

PubMed Central

Shimatsu, Yoshiki; Yamada, Kazuhiko; Horii, Wataru; Hirakata, Atsushi; Sakamoto, Yuji; Waki, Shiori; Sano, Junichi; Saitoh, Toshiki; Sahara, Hisashi; Shimizu, Akira; Yazawa, Hajime; Sachs, David H.; Nunoya, Tetsuo

2013-01-01

Background Nuclear transfer (NT) technologies offer a means for producing the genetically modified pigs necessary to develop swine models for mechanistic studies of disease processes as well as to serve as organ donors for xenotransplantation. Most previous studies have used commercial pigs as surrogates. Method and Results In this study, we established a cloning technique for miniature pigs by somatic cell nuclear transfer (SCNT) using Nippon Institute for Biological Science (NIBS) miniature pigs as surrogates. Moreover, utilizing this technique, we have successfully produced an α-1, 3-galactosyltransferase knockout (GalT-KO) miniature swine. Fibroblasts procured from a NIBS miniature pig fetus were injected into 1312 enucleated oocytes. The cloned embryos were transferred to 11 surrogates of which five successfully delivered 13 cloned offspring; the production efficiency was 1.0% (13/1312). In a second experiment, lung fibroblasts obtained from neonatal GalT-KO MGH miniature swine were used as donor cells and 1953 cloned embryos were transferred to 12 surrogates. Six cloned offspring were born from five surrogates, a production efficiency of 0.3% (6/1953). Conclusions These results demonstrate successful establishment of a miniature pig cloning technique by SCNT using NIBS miniature pigs as surrogates. To our knowledge, this is the first demonstration of successful production of GalT-KO miniature swine using miniature swine surrogates. This technique could help to ensure a stable supply of the cloned pigs through the use of miniature pig surrogates and could expand production in countries with limited space or in facilities with special regulations such as specific pathogen-free or good laboratory practice. PMID:23581451

Psychosocial aspects of surrogate motherhood.

PubMed

van den Akker, Olga B A

2007-01-01

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

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

PubMed

Richards, Gary P

2012-03-01

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

TOXICITY OF PENTACHLOROPHENOL TO ENDANGERED AND SURROGATE FISH SPECIES

EPA Science Inventory

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

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

PubMed

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

2016-11-01

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

Adaptive surrogate model based multiobjective optimization for coastal aquifer management

NASA Astrophysics Data System (ADS)

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

2018-06-01

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

Statistical characteristics of surrogate data based on geophysical measurements

NASA Astrophysics Data System (ADS)

Venema, V.; Bachner, S.; Rust, H. W.; Simmer, C.

2006-09-01

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

Best Practicable Aggregation of Species: a step forward for species surrogacy in environmental assessment and monitoring

PubMed Central

Bevilacqua, Stanislao; Claudet, Joachim; Terlizzi, Antonio

2013-01-01

The available taxonomic expertise and knowledge of species is still inadequate to cope with the urgent need for cost-effective methods to quantifying community response to natural and anthropogenic drivers of change. So far, the mainstream approach to overcome these impediments has focused on using higher taxa as surrogates for species. However, the use of such taxonomic surrogates often limits inferences about the causality of community patterns, which in turn is essential for effective environmental management strategies. Here, we propose an alternative approach to species surrogacy, the “Best Practicable Aggregation of Species” (BestAgg), in which surrogates exulate from fixed taxonomic schemes. The approach uses null models from random aggregations of species to minimizing the number of surrogates without causing significant losses of information on community patterns. Surrogate types are then selected in order to maximize ecological information. We applied the approach to real case studies on natural and human-driven gradients from marine benthic communities. Outcomes from BestAgg were also compared with those obtained using classic taxonomic surrogates. Results showed that BestAgg surrogates are effective in detecting community changes. In contrast to classic taxonomic surrogates, BestAgg surrogates allow retaining significantly higher information on species-level community patterns than what is expected to occur by chance and a potential time saving during sample processing up to 25% higher. Our findings showed that BestAgg surrogates from a pilot study could be used successfully in similar environmental investigations in the same area, or for subsequent long-term monitoring programs. BestAgg is virtually applicable to any environmental context, allowing exploiting multiple surrogacy schemes beyond stagnant perspectives strictly relying on taxonomic relatedness among species. This prerogative is crucial to extend the concept of species surrogacy to ecological traits of species, thus leading to ecologically meaningful surrogates that, while cost effective in reflecting community patterns, may also contribute to unveil underlying processes. A specific R code for BestAgg is provided. PMID:24198939

A perfect correlate does not a surrogate make

PubMed Central

Baker, Stuart G; Kramer, Barnett S

2003-01-01

Background There is common belief among some medical researchers that if a potential surrogate endpoint is highly correlated with a true endpoint, then a positive (or negative) difference in potential surrogate endpoints between randomization groups would imply a positive (or negative) difference in unobserved true endpoints between randomization groups. We investigate this belief when the potential surrogate and unobserved true endpoints are perfectly correlated within each randomization group. Methods We use a graphical approach. The vertical axis is the unobserved true endpoint and the horizontal axis is the potential surrogate endpoint. Perfect correlation within each randomization group implies that, for each randomization group, potential surrogate and true endpoints are related by a straight line. In this scenario the investigator does not know the slopes or intercepts. We consider a plausible example where the slope of the line is higher for the experimental group than for the control group. Results In our example with unknown lines, a decrease in mean potential surrogate endpoints from control to experimental groups corresponds to an increase in mean true endpoint from control to experimental groups. Thus the potential surrogate endpoints give the wrong inference. Similar results hold for binary potential surrogate and true outcomes (although the notion of correlation does not apply). The potential surrogate endpointwould give the correct inference if either (i) the unknown lines for the two group coincided, which means that the distribution of true endpoint conditional on potential surrogate endpoint does not depend on treatment group, which is called the Prentice Criterion or (ii) if one could accurately predict the lines based on data from prior studies. Conclusion Perfect correlation between potential surrogate and unobserved true outcomes within randomized groups does not guarantee correct inference based on a potential surrogate endpoint. Even in early phase trials, investigators should not base conclusions on potential surrogate endpoints in which the only validation is high correlation with the true endpoint within a group. PMID:12962545

Surrogate endpoints and competing risk of death in cardiac arrest research.

PubMed

McCredie, Victoria A; Scales, Damon C

2016-06-29

We urgently need new therapies to improve outcomes after cardiac arrest. Initial studies typically target surrogate endpoints, and these studies help to inform subsequent larger trials that are powered to measure more patient-orientated clinical outcomes such as survival. The competing risk of death and premature assessment of neurological prognosis pose significant challenges to measuring these surrogate endpoints after cardiac arrest.

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

PubMed

Imrie, Susan; Jadva, Vasanti

2014-10-01

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

I don't want to be the one saying 'we should just let him die': intrapersonal tensions experienced by surrogate decision makers in the ICU.

PubMed

Schenker, Yael; Crowley-Matoka, Megan; Dohan, Daniel; Tiver, Greer A; Arnold, Robert M; White, Douglas B

2012-12-01

Although numerous studies have addressed external factors associated with difficulty in surrogate decision making, intrapersonal sources of tension are an important element of decision making that have received little attention. To characterize key intrapersonal tensions experienced by surrogate decision makers in the intensive care unit (ICU), and explore associated coping strategies. Qualitative interview study. Thirty surrogates from five ICUs at two hospitals in Pittsburgh, Pennsylvania, who were actively involved in making life-sustaining treatment decisions for a critically ill loved one. We conducted in-depth, semi-structured interviews with surrogates, focused on intrapersonal tensions, role challenges, and coping strategies. We analyzed transcripts using constant comparative methods. Surrogates experience significant emotional conflict between the desire to act in accordance with their loved one's values and 1) not wanting to feel responsible for a loved one's death, 2) a desire to pursue any chance of recovery, and 3) the need to preserve family well-being. Associated coping strategies included 1) recalling previous discussions with a loved one, 2) sharing decisions with family members, 3) delaying or deferring decision making, 4) spiritual/religious practices, and 5) story-telling. Surrogates' struggle to reconcile personal and family emotional needs with their loved ones' wishes, and utilize common coping strategies to combat intrapersonal tensions. These data suggest reasons surrogates may struggle to follow a strict substituted judgment standard. They also suggest ways clinicians may improve decision making, including attending to surrogates' emotions, facilitating family decision making, and eliciting potential emotional conflicts and spiritual needs.

A review of selection-based tests of abiotic surrogates for species representation.

PubMed

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

2015-06-01

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

Identifying experimental surrogates for Bacillus anthracis spores: a review

PubMed Central

2010-01-01

Bacillus anthracis, the causative agent of anthrax, is a proven biological weapon. In order to study this threat, a number of experimental surrogates have been used over the past 70 years. However, not all surrogates are appropriate for B. anthracis, especially when investigating transport, fate and survival. Although B. atrophaeus has been widely used as a B. anthracis surrogate, the two species do not always behave identically in transport and survival models. Therefore, we devised a scheme to identify a more appropriate surrogate for B. anthracis. Our selection criteria included risk of use (pathogenicity), phylogenetic relationship, morphology and comparative survivability when challenged with biocides. Although our knowledge of certain parameters remains incomplete, especially with regards to comparisons of spore longevity under natural conditions, we found that B. thuringiensis provided the best overall fit as a non-pathogenic surrogate for B. anthracis. Thus, we suggest focusing on this surrogate in future experiments of spore fate and transport modelling. PMID:21092338

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

PubMed

Fuchs, Erika L; Berenson, Abbey B

2018-05-01

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

Dynamic response due to behind helmet blunt trauma measured with a human head surrogate.

PubMed

Freitas, Christopher J; Mathis, James T; Scott, Nikki; Bigger, Rory P; Mackiewicz, James

2014-01-01

A Human Head Surrogate has been developed for use in behind helmet blunt trauma experiments. This human head surrogate fills the void between Post-Mortem Human Subject testing (with biofidelity but handling restrictions) and commercial ballistic head forms (with no biofidelity but ease of use). This unique human head surrogate is based on refreshed human craniums and surrogate materials representing human head soft tissues such as the skin, dura, and brain. A methodology for refreshing the craniums is developed and verified through material testing. A test methodology utilizing these unique human head surrogates is also developed and then demonstrated in a series of experiments in which non-perforating ballistic impact of combat helmets is performed with and without supplemental ceramic appliques for protecting against larger caliber threats. Sensors embedded in the human head surrogates allow for direct measurement of intracranial pressure, cranial strain, and head and helmet acceleration. Over seventy (70) fully instrumented experiments have been executed using this unique surrogate. Examples of the data collected are presented. Based on these series of tests, the Southwest Research Institute (SwRI) Human Head Surrogate has demonstrated great potential for providing insights in to injury mechanics resulting from non-perforating ballistic impact on combat helmets, and directly supports behind helmet blunt trauma studies.

Dynamic Response Due to Behind Helmet Blunt Trauma Measured with a Human Head Surrogate

PubMed Central

Freitas, Christopher J.; Mathis, James T.; Scott, Nikki; Bigger, Rory P.; MacKiewicz, James

2014-01-01

A Human Head Surrogate has been developed for use in behind helmet blunt trauma experiments. This human head surrogate fills the void between Post-Mortem Human Subject testing (with biofidelity but handling restrictions) and commercial ballistic head forms (with no biofidelity but ease of use). This unique human head surrogate is based on refreshed human craniums and surrogate materials representing human head soft tissues such as the skin, dura, and brain. A methodology for refreshing the craniums is developed and verified through material testing. A test methodology utilizing these unique human head surrogates is also developed and then demonstrated in a series of experiments in which non-perforating ballistic impact of combat helmets is performed with and without supplemental ceramic appliques for protecting against larger caliber threats. Sensors embedded in the human head surrogates allow for direct measurement of intracranial pressure, cranial strain, and head and helmet acceleration. Over seventy (70) fully instrumented experiments have been executed using this unique surrogate. Examples of the data collected are presented. Based on these series of tests, the Southwest Research Institute (SwRI) Human Head Surrogate has demonstrated great potential for providing insights in to injury mechanics resulting from non-perforating ballistic impact on combat helmets, and directly supports behind helmet blunt trauma studies. PMID:24688303

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mueller, Charles J.; Cannella, William J.; Bays, J. Timothy

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

Application of 2-Aminothiazoline-4-carboxylic Acid as a Forensic Marker of Cyanide Exposure.

PubMed

Rużycka, Monika; Giebułtowicz, Joanna; Fudalej, Marcin; Krajewski, Paweł; Wroczyński, Piotr

2017-02-20

Cyanides are infamous for their highly poisonous properties. Accidental cyanide poisoning occurs frequently, but occasionally, intentional poisonings also occur. Inhalation of fumes generated by fire may also cause cyanide poisoning. There are many limitations in direct analysis of cyanide. 2-Aminothiazoline-4-carboxylic acid (ATCA), a cyanide metabolite, seems to be the only surrogate that is being used in the detection of cyanide because of its stability and its cyanide-dependent quality in a biological matrix. Unfortunately, toxicokinetic studies on diverse animal models suggest significant interspecies differences; therefore, the attempt to extrapolate animal models to human models may be unsuccessful. The aim of the present study was to evaluate the use of ATCA as a forensic marker of cyanide exposure. For this purpose, post-mortem materials (blood and organs) from fire victims (n = 32) and cyanide-poisoned persons (n = 3) were collected. The distribution of ATCA in organs and its thermal stability were evaluated. The variability of cyanides in a putrid sample and in the context of their long-term and higher temperature stability was established. The presence of ATCA was detected by using an LC-MS/MS method and that of cyanide was detected spectrofluorimetrically. This is the first report on the endogenous ATCA concentrations and the determination of ATCA distribution in tissues of fire victims and cyanide-poisoned persons. It was found that blood and heart had the highest ATCA concentrations. ATCA was observed to be thermally stable even at 90 °C. Even though the cyanide concentration was not elevated in putrid samples, it was unstable during long-term storage and at higher temperature, as expected. The relationship between ATCA and cyanides was also observed. Higher ATCA concentrations were related to increased levels of cyanide in blood and organs (less prominent). ATCA seems to be a reliable forensic marker of exposure to lethal doses of cyanide.

Inactivation of Tulane virus, a novel surrogate for human norovirus

USDA-ARS?s Scientific Manuscript database

Human noroviruses (HuNoVs) are the major cause of non-bacterial epidemics of gastroenteritis. Due to the inability to cultivate HuNoVs and the lack of an efficient small animal model, surrogates are used to study HuNoV biology. Two such surrogates, the feline calicivirus (FCV) and the murine norovir...

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

USDA-ARS?s Scientific Manuscript database

The inability to propagate human norovirus (NoV) or to clearly differentiate infectious from noninfectious virus particles have led to the use of surrogate viruses, like feline calicivirus (FCV) and murine norovirus-1 (MNV), which are propagatable in cell culture. The use of surrogates is predicate...

Altruistic surrogacy: the necessary objectification of surrogate mothers.

PubMed

Tieu, M M

2009-03-01

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

Review of meta-analyses evaluating surrogate endpoints for overall survival in oncology.

PubMed

Sherrill, Beth; Kaye, James A; Sandin, Rickard; Cappelleri, Joseph C; Chen, Connie

2012-01-01

Overall survival (OS) is the gold standard in measuring the treatment effect of new drug therapies for cancer. However, practical factors may preclude the collection of unconfounded OS data, and surrogate endpoints are often used instead. Meta-analyses have been widely used for the validation of surrogate endpoints, specifically in oncology. This research reviewed published meta-analyses on the types of surrogate measures used in oncology studies and examined the extent of correlation between surrogate endpoints and OS for different cancer types. A search was conducted in October 2010 to compile available published evidence in the English language for the validation of disease progression-related endpoints as surrogates of OS, based on meta-analyses. We summarize published meta-analyses that quantified the correlation between progression-based endpoints and OS for multiple advanced solid-tumor types. We also discuss issues that affect the interpretation of these findings. Progression-free survival is the most commonly used surrogate measure in studies of advanced solid tumors, and correlation with OS is reported for a limited number of cancer types. Given the increased use of crossover in trials and the availability of second-/third-line treatment options available to patients after progression, it will become increasingly more difficult to establish correlation between effects on progression-free survival and OS in additional tumor types.

A Conceptual Model of the Role of Communication in Surrogate Decision Making for Hospitalized Adults

PubMed Central

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

2011-01-01

Objective To build a conceptual model of the role of communication in decision making, based on literature from medicine, communication studies and medical ethics. Methods We propose a model and describe each construct in detail. We review what is known about interpersonal and patient-physician communication, describe literature about surrogate-clinician communication, and discuss implications for our developing model. Results The communication literature proposes two major elements of interpersonal communication: information processing and relationship building. These elements are composed of constructs such as information disclosure and emotional support that are likely to be relevant to decision making. We propose these elements of communication impact decision making, which in turn affects outcomes for both patients and surrogates. Decision making quality may also mediate the relationship between communication and outcomes. Conclusion Although many elements of the model have been studied in relation to patient-clinician communication, there is limited data about surrogate decision making. There is evidence of high surrogate distress associated with decision making that may be alleviated by communication–focused interventions. More research is needed to test the relationships proposed in the model. Practice Implications Good communication with surrogates may improve both the quality of medical decisions and outcomes for the patient and surrogate. PMID:21889865

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

PubMed

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

2012-04-01

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

Defining Surrogate Endpoints for Clinical Trials in Severe Falciparum Malaria

PubMed Central

Plewes, Katherine; Maude, Richard J.; Hanson, Josh; Herdman, M. Trent; Leopold, Stije J.; Ngernseng, Thatsanun; Charunwatthana, Prakaykaew; Phu, Nguyen Hoan; Ghose, Aniruddha; Hasan, M. Mahtab Uddin; Fanello, Caterina I.; Faiz, Md Abul; Hien, Tran Tinh; Day, Nicholas P. J.; White, Nicholas J.; Dondorp, Arjen M.

2017-01-01

Background Clinical trials in severe falciparum malaria require a large sample size to detect clinically meaningful differences in mortality. This means few interventions can be evaluated at any time. Using a validated surrogate endpoint for mortality would provide a useful alternative allowing a smaller sample size. Here we evaluate changes in coma score and plasma lactate as surrogate endpoints for mortality in severe falciparum malaria. Methods Three datasets of clinical studies in severe malaria were re-evaluated: studies from Chittagong, Bangladesh (adults), the African ‘AQUAMAT’ trial comparing artesunate and quinine (children), and the Vietnamese ‘AQ’ study (adults) comparing artemether with quinine. The absolute change, relative change, slope of the normalization over time, and time to normalization were derived from sequential measurements of plasma lactate and coma score, and validated for their use as surrogate endpoint, including the proportion of treatment effect on mortality explained (PTE) by these surrogate measures. Results Improvements in lactate concentration or coma scores over the first 24 hours of admission, were strongly prognostic for survival in all datasets. In hyperlactataemic patients in the AQ study (n = 173), lower mortality with artemether compared to quinine closely correlated with faster reduction in plasma lactate concentration, with a high PTE of the relative change in plasma lactate at 8 and 12 hours of 0.81 and 0.75, respectively. In paediatric patients enrolled in the ‘AQUAMAT’ study with cerebral malaria (n = 785), mortality was lower with artesunate compared to quinine, but this was not associated with faster coma recovery. Conclusions The relative changes in plasma lactate concentration assessed at 8 or 12 hours after admission are valid surrogate endpoints for severe malaria studies on antimalarial drugs or adjuvant treatments aiming at improving the microcirculation. Measures of coma recovery are not valid surrogate endpoints for mortality. PMID:28052109

Defining Surrogate Endpoints for Clinical Trials in Severe Falciparum Malaria.

PubMed

Jeeyapant, Atthanee; Kingston, Hugh W; Plewes, Katherine; Maude, Richard J; Hanson, Josh; Herdman, M Trent; Leopold, Stije J; Ngernseng, Thatsanun; Charunwatthana, Prakaykaew; Phu, Nguyen Hoan; Ghose, Aniruddha; Hasan, M Mahtab Uddin; Fanello, Caterina I; Faiz, Md Abul; Hien, Tran Tinh; Day, Nicholas P J; White, Nicholas J; Dondorp, Arjen M

2017-01-01

Clinical trials in severe falciparum malaria require a large sample size to detect clinically meaningful differences in mortality. This means few interventions can be evaluated at any time. Using a validated surrogate endpoint for mortality would provide a useful alternative allowing a smaller sample size. Here we evaluate changes in coma score and plasma lactate as surrogate endpoints for mortality in severe falciparum malaria. Three datasets of clinical studies in severe malaria were re-evaluated: studies from Chittagong, Bangladesh (adults), the African 'AQUAMAT' trial comparing artesunate and quinine (children), and the Vietnamese 'AQ' study (adults) comparing artemether with quinine. The absolute change, relative change, slope of the normalization over time, and time to normalization were derived from sequential measurements of plasma lactate and coma score, and validated for their use as surrogate endpoint, including the proportion of treatment effect on mortality explained (PTE) by these surrogate measures. Improvements in lactate concentration or coma scores over the first 24 hours of admission, were strongly prognostic for survival in all datasets. In hyperlactataemic patients in the AQ study (n = 173), lower mortality with artemether compared to quinine closely correlated with faster reduction in plasma lactate concentration, with a high PTE of the relative change in plasma lactate at 8 and 12 hours of 0.81 and 0.75, respectively. In paediatric patients enrolled in the 'AQUAMAT' study with cerebral malaria (n = 785), mortality was lower with artesunate compared to quinine, but this was not associated with faster coma recovery. The relative changes in plasma lactate concentration assessed at 8 or 12 hours after admission are valid surrogate endpoints for severe malaria studies on antimalarial drugs or adjuvant treatments aiming at improving the microcirculation. Measures of coma recovery are not valid surrogate endpoints for mortality.

NURSE-LED INTERVENTION TO IMPROVE SURROGATE DECISION MAKING FOR PATIENTS WITH ADVANCED CRITICAL ILLNESS

PubMed Central

White, Douglas B.; Cua, Sarah Martin; Walk, Roberta; Pollice, Laura; Weissfeld, Lisa; Hong, Seoyeon; Landefeld, C. Seth; Arnold, Robert M.

2013-01-01

Background Problems persist with surrogate decision making in intensive care units, leading to distress for surrogates and treatment that may not reflect patients’ values. Objectives To assess the feasibility, acceptability, and perceived effectiveness of a multifaceted, nurse-led intervention to improve surrogate decision making in intensive care units. Study Design A single-center, single-arm, interventional study in which 35 surrogates and 15 physicians received the Four Supports Intervention, which involved incorporating a family support specialist into the intensive care team. That specialist maintained a longitudinal relationship with surrogates and provided emotional support, communication support, decision support, and anticipatory grief support. A mixed-methods approach was used to evaluate the intervention. Results The intervention was implemented successfully in all 15 patients, with a high level of completion of each component of the intervention. The family support specialist devoted a mean of 48 (SD 36) minutes per day to each clinician-patient-family triad. All participants reported that they would recommend the intervention to others. At least 90% of physicians and surrogates reported that the intervention (1) improved the quality and timeliness of communication, (2) facilitated discussion of the patient’s values and treatment preferences, and (3) improved the patient-centeredness of care. Conclusions The Four Supports Intervention is feasible, acceptable, and was perceived by physicians and surrogates to improve the quality of decision making and the patient-centeredness of care. A randomized trial is warranted to determine whether the intervention improves patient, family, and health system outcomes. PMID:23117903

Bioaccessibility of metals in alloys: Evaluation of three surrogate biofluids

PubMed Central

Hillwalker, Wendy E.; Anderson, Kim A.

2014-01-01

Bioaccessibility in vitro tests measure the solubility of materials in surrogate biofluids. However, the lack of uniform methods and the effects of variable test parameters on material solubility limit interpretation. One aim of this study was to measure and compare bioaccessibility of selected economically important alloys and metals in surrogate physiologically based biofluids representing oral, inhalation and dermal exposures. A second aim was to experimentally test different biofluid formulations and residence times in vitro. A third aim was evaluation of dissolution behavior of alloys with in vitro lung and dermal biofluid surrogates. This study evaluated the bioaccessibility of sixteen elements in six alloys and 3 elemental/metal powders. We found that the alloys/metals, the chemical properties of the surrogate fluid, and residence time all had major impacts on metal solubility. The large variability of bioaccessibility indicates the relevancy of assessing alloys as toxicologically distinct relative to individual metals. PMID:24212234

Opposing Responses of Bird Functional Diversity to Vegetation Structural Diversity in Wet and Dry Forest.

PubMed

Sitters, Holly; York, Alan; Swan, Matthew; Christie, Fiona; Di Stefano, Julian

2016-01-01

Disturbance regimes are changing worldwide, and the consequences for ecosystem function and resilience are largely unknown. Functional diversity (FD) provides a surrogate measure of ecosystem function by capturing the range, abundance and distribution of trait values in a community. Enhanced understanding of the responses of FD to measures of vegetation structure at landscape scales is needed to guide conservation management. To address this knowledge gap, we used a whole-of-landscape sampling approach to examine relationships between bird FD, vegetation diversity and time since fire. We surveyed birds and measured vegetation at 36 landscape sampling units in dry and wet forest in southeast Australia during 2010 and 2011. Four uncorrelated indices of bird FD (richness, evenness, divergence and dispersion) were derived from six bird traits, and we investigated responses of these indices and species richness to both vertical and horizontal vegetation diversity using linear mixed models. We also considered the extent to which the mean and diversity of time since fire were related to vegetation diversity. Results showed opposing responses of FD to vegetation diversity in dry and wet forest. In dry forest, where fire is frequent, species richness and two FD indices (richness and dispersion) were positively related to vertical vegetation diversity, consistent with theory relating to environmental variation and coexistence. However, in wet forest subject to infrequent fire, the same three response variables were negatively associated with vertical diversity. We suggest that competitive dominance by species results in lower FD as vegetation diversity increases in wet forest. The responses of functional evenness were opposite to those of species richness, functional richness and dispersion in both forest types, highlighting the value of examining multiple FD metrics at management-relevant scales. The mean and diversity of time since fire were uncorrelated with vegetation diversity in wet forest, but positively correlated with vegetation diversity in dry forest. We therefore suggest that protection of older vegetation is important, but controlled application of low-severity fire in dry forest may sustain ecosystem function by enhancing different elements of FD.

Opposing Responses of Bird Functional Diversity to Vegetation Structural Diversity in Wet and Dry Forest

PubMed Central

York, Alan; Swan, Matthew; Christie, Fiona; Di Stefano, Julian

2016-01-01

Disturbance regimes are changing worldwide, and the consequences for ecosystem function and resilience are largely unknown. Functional diversity (FD) provides a surrogate measure of ecosystem function by capturing the range, abundance and distribution of trait values in a community. Enhanced understanding of the responses of FD to measures of vegetation structure at landscape scales is needed to guide conservation management. To address this knowledge gap, we used a whole-of-landscape sampling approach to examine relationships between bird FD, vegetation diversity and time since fire. We surveyed birds and measured vegetation at 36 landscape sampling units in dry and wet forest in southeast Australia during 2010 and 2011. Four uncorrelated indices of bird FD (richness, evenness, divergence and dispersion) were derived from six bird traits, and we investigated responses of these indices and species richness to both vertical and horizontal vegetation diversity using linear mixed models. We also considered the extent to which the mean and diversity of time since fire were related to vegetation diversity. Results showed opposing responses of FD to vegetation diversity in dry and wet forest. In dry forest, where fire is frequent, species richness and two FD indices (richness and dispersion) were positively related to vertical vegetation diversity, consistent with theory relating to environmental variation and coexistence. However, in wet forest subject to infrequent fire, the same three response variables were negatively associated with vertical diversity. We suggest that competitive dominance by species results in lower FD as vegetation diversity increases in wet forest. The responses of functional evenness were opposite to those of species richness, functional richness and dispersion in both forest types, highlighting the value of examining multiple FD metrics at management-relevant scales. The mean and diversity of time since fire were uncorrelated with vegetation diversity in wet forest, but positively correlated with vegetation diversity in dry forest. We therefore suggest that protection of older vegetation is important, but controlled application of low-severity fire in dry forest may sustain ecosystem function by enhancing different elements of FD. PMID:27741290

Surrogate endpoints for clinical trials in primary sclerosing cholangitis: Review and results from an International PSC Study Group consensus process.

PubMed

Ponsioen, Cyriel Y; Chapman, Roger W; Chazouillères, Olivier; Hirschfield, Gideon M; Karlsen, Tom H; Lohse, Ansgar W; Pinzani, Massimo; Schrumpf, Erik; Trauner, Michael; Gores, Gregory J

2016-04-01

Primary sclerosing cholangitis (PSC) is a rare, but serious, cholestatic disease for which, to date, no effective therapy exists to halt disease progression toward end-stage liver disease. Clinical trial design to study drugs that improve prognosis is hampered by the relatively low event rate of clinically relevant endpoints. To overcome this shortcoming, there is an urgent need to identify appropriate surrogate endpoints. At present, there are no established surrogate endpoints. This article provides a critical review and describes the results of a consensus process initiated by the International PSC Study Group to delineate appropriate candidate surrogate endpoints at present for clinical trials in this frequently dismal disease. The consensus process resulted in a shortlist of five candidates as surrogate endpoints for measuring disease progression: alkaline phosphatase (ALP); transient elastography (TE); histology; combination of ALP+histology; and bilirubin. Of these, histology, ALP, and TE came out as the most promising. However, the expert panel concluded that no biomarker currently exceeds level 3 validation. Combining multiple endpoints is advisable. At present, there are insufficient data to support level 2 validation for any surrogate endpoint in PSC. Concerted efforts by all stakeholders are highly needed. Novel, promising noninvasive biomarkers are under study and should be incorporated as exploratory endpoints in clinical trials. © 2015 by the American Association for the Study of Liver Diseases.

Intensivist-reported Facilitators and Barriers to Discussing Post-Discharge Outcomes with Intensive Care Unit Surrogates. A Qualitative Study

PubMed Central

Davis, Wesley E.; Needham, Dale M.; White, Douglas B.; Eakin, Michelle N.

2016-01-01

Rationale: Intensive care unit (ICU) patients’ expected post-discharge outcomes are rarely discussed in family meetings despite this information being centrally important to patients and their families. Objectives: To characterize intensivist-identified barriers and facilitators to discussing post-discharge outcomes with surrogates of ICU patients. Methods: Qualitative study conducted via one-on-one, semistructured telephone interviews with 23 intensivists from 20 hospitals with accreditation council for graduate medical education–accredited critical care medicine programs in 16 states. A limited application of grounded theory methods was used to code transcribed interviews and identify themes and illustrative quotes. Measurements and Main Results: Intensivists reported tension between their professional responsibility to discuss likely functional outcomes versus uncertainty about their ability to predict those outcomes for an individual patient. They cited three main barriers as limiting their ability to conduct conversations about post-discharge outcomes with ICU surrogates: (1) incorrectly optimistic expectations for recovery among ICU surrogates, (2) having little or no contact with their patients after ICU discharge, and (3) minimal confidence applying existing outcomes research to individual patients. Despite these barriers, experience talking to ICU surrogates, seeing ICU survivors in the outpatient setting, and trusted research on functional outcomes were identified as important facilitators to discussing likely patient outcomes with surrogates. Intensivists generally welcomed questions from surrogates about post-discharge outcomes as opportunities to initiate conversations about prognosis and patient values. Conclusions: In this sample of intensivists from 20 academic hospitals, experience conducting conversations with surrogates and interactions with ICU survivors as outpatients were identified as facilitating discussion of expected post-discharge outcomes while optimistic surrogate expectations and prognostic uncertainty were barriers. There was tension between self-perceived ability to prognosticate and belief in a professional obligation to discuss patient outcomes. PMID:27294981

A Dyadic Perspective on Engagement in Advance Care Planning.

PubMed

Fried, Terri; Zenoni, Maria; Iannone, Lynne

2017-01-01

To understand the perspectives of both patients and the person who would make medical decisions for them if they were unable (surrogates) on their participation in advance care planning (ACP). Qualitative cross-sectional study. Community. Thirty-one veterans age 55 years and older and their surrogates. In interviews conducted with both the veteran and surrogate, they were asked to discuss their participation in four ACP activities: communication about life-sustaining treatment, communication about views on quality of life, completion of a living will, and appointment of a healthcare proxy. They were asked about barriers to and facilitators of ACP engagement. When they did not agree about engagement, they each provided their perspective on what they believed had or had not occurred. Many of the same barriers to and facilitators of engagement were discussed by both patients and surrogates. These included difficulty thinking about dying, differences in values, and experiences with others that demonstrated the ability of ACP to decrease burden or avoid conflict. Reasons for disagreements in perceptions about whether communication had occurred included surrogates' need for more detailed information, surrogates' lack of readiness to hear what the patient was saying, and surrogates' reliance on what they know about the patient. For some dyads, participation in the study prompted additional communication, resulting in a better shared understanding of ACP engagement. Surrogates can both impede and facilitate engagement in ACP, and they can hold different perceptions from patients regarding this engagement. Efforts to promote ACP may be most successful if they assess and address both patients' and surrogates' attitudes and help to facilitate clear communication between them. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Weighted Iterative Bayesian Compressive Sensing (WIBCS) for High Dimensional Polynomial Surrogate Construction

NASA Astrophysics Data System (ADS)

Sargsyan, K.; Ricciuto, D. M.; Safta, C.; Debusschere, B.; Najm, H. N.; Thornton, P. E.

2016-12-01

Surrogate construction has become a routine procedure when facing computationally intensive studies requiring multiple evaluations of complex models. In particular, surrogate models, otherwise called emulators or response surfaces, replace complex models in uncertainty quantification (UQ) studies, including uncertainty propagation (forward UQ) and parameter estimation (inverse UQ). Further, surrogates based on Polynomial Chaos (PC) expansions are especially convenient for forward UQ and global sensitivity analysis, also known as variance-based decomposition. However, the PC surrogate construction strongly suffers from the curse of dimensionality. With a large number of input parameters, the number of model simulations required for accurate surrogate construction is prohibitively large. Relatedly, non-adaptive PC expansions typically include infeasibly large number of basis terms far exceeding the number of available model evaluations. We develop Weighted Iterative Bayesian Compressive Sensing (WIBCS) algorithm for adaptive basis growth and PC surrogate construction leading to a sparse, high-dimensional PC surrogate with a very few model evaluations. The surrogate is then readily employed for global sensitivity analysis leading to further dimensionality reduction. Besides numerical tests, we demonstrate the construction on the example of Accelerated Climate Model for Energy (ACME) Land Model for several output QoIs at nearly 100 FLUXNET sites covering multiple plant functional types and climates, varying 65 input parameters over broad ranges of possible values. This work is supported by the U.S. Department of Energy, Office of Science, Biological and Environmental Research, Accelerated Climate Modeling for Energy (ACME) project. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Intensivist-reported Facilitators and Barriers to Discussing Post-Discharge Outcomes with Intensive Care Unit Surrogates. A Qualitative Study.

PubMed

Turnbull, Alison E; Davis, Wesley E; Needham, Dale M; White, Douglas B; Eakin, Michelle N

2016-09-01

Intensive care unit (ICU) patients' expected post-discharge outcomes are rarely discussed in family meetings despite this information being centrally important to patients and their families. To characterize intensivist-identified barriers and facilitators to discussing post-discharge outcomes with surrogates of ICU patients. Qualitative study conducted via one-on-one, semistructured telephone interviews with 23 intensivists from 20 hospitals with accreditation council for graduate medical education-accredited critical care medicine programs in 16 states. A limited application of grounded theory methods was used to code transcribed interviews and identify themes and illustrative quotes. Intensivists reported tension between their professional responsibility to discuss likely functional outcomes versus uncertainty about their ability to predict those outcomes for an individual patient. They cited three main barriers as limiting their ability to conduct conversations about post-discharge outcomes with ICU surrogates: (1) incorrectly optimistic expectations for recovery among ICU surrogates, (2) having little or no contact with their patients after ICU discharge, and (3) minimal confidence applying existing outcomes research to individual patients. Despite these barriers, experience talking to ICU surrogates, seeing ICU survivors in the outpatient setting, and trusted research on functional outcomes were identified as important facilitators to discussing likely patient outcomes with surrogates. Intensivists generally welcomed questions from surrogates about post-discharge outcomes as opportunities to initiate conversations about prognosis and patient values. In this sample of intensivists from 20 academic hospitals, experience conducting conversations with surrogates and interactions with ICU survivors as outpatients were identified as facilitating discussion of expected post-discharge outcomes while optimistic surrogate expectations and prognostic uncertainty were barriers. There was tension between self-perceived ability to prognosticate and belief in a professional obligation to discuss patient outcomes.

Perinatal outcomes after natural conception versus in vitro fertilization (IVF) in gestational surrogates: a model to evaluate IVF treatment versus maternal effects.

PubMed

Woo, Irene; Hindoyan, Rita; Landay, Melanie; Ho, Jacqueline; Ingles, Sue Ann; McGinnis, Lynda K; Paulson, Richard J; Chung, Karine

2017-12-01

To study the perinatal outcomes between singleton live births achieved with the use of commissioned versus spontaneously conceived embryos carried by the same gestational surrogate. Retrospective cohort study. Academic in vitro fertilization center. Gestational surrogate. None. Pregnancy outcome, gestational age at birth, birth weight, perinatal complications. We identified 124 gestational surrogates who achieved a total of 494 pregnancies. Pregnancy outcomes for surrogate and spontaneous pregnancies were significantly different (P<.001), with surrogate pregnancies more likely to result in twin pregnancies: 33% vs. 1%. Miscarriage and ectopic rates were similar. Of these pregnancies, there were 352 singleton live births: 103 achieved from commissioned embryos and 249 conceived spontaneously. Surrogate births had lower mean gestational age at delivery (38.8 ± 2.1 vs. 39.7 ± 1.4), higher rates of preterm birth (10.7% vs. 3.1%), and higher rates of low birth weight (7.8% vs. 2.4%). Neonates from surrogacy had birth weights that were, on average, 105 g lower. Surrogate births had significantly higher obstetrical complications, including gestational diabetes, hypertension, use of amniocentesis, placenta previa, antibiotic requirement during labor, and cesarean section. Neonates born from commissioned embryos and carried by gestational surrogates have increased adverse perinatal outcomes, including preterm birth, low birth weight, hypertension, maternal gestational diabetes, and placenta previa, compared with singletons conceived spontaneously and carried by the same woman. Our data suggest that assisted reproductive procedures may potentially affect embryo quality and that its negative impact can not be overcome even with a proven healthy uterine environment. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Robust estimation of the proportion of treatment effect explained by surrogate marker information.

PubMed

Parast, Layla; McDermott, Mary M; Tian, Lu

2016-05-10

In randomized treatment studies where the primary outcome requires long follow-up of patients and/or expensive or invasive obtainment procedures, the availability of a surrogate marker that could be used to estimate the treatment effect and could potentially be observed earlier than the primary outcome would allow researchers to make conclusions regarding the treatment effect with less required follow-up time and resources. The Prentice criterion for a valid surrogate marker requires that a test for treatment effect on the surrogate marker also be a valid test for treatment effect on the primary outcome of interest. Based on this criterion, methods have been developed to define and estimate the proportion of treatment effect on the primary outcome that is explained by the treatment effect on the surrogate marker. These methods aim to identify useful statistical surrogates that capture a large proportion of the treatment effect. However, current methods to estimate this proportion usually require restrictive model assumptions that may not hold in practice and thus may lead to biased estimates of this quantity. In this paper, we propose a nonparametric procedure to estimate the proportion of treatment effect on the primary outcome that is explained by the treatment effect on a potential surrogate marker and extend this procedure to a setting with multiple surrogate markers. We compare our approach with previously proposed model-based approaches and propose a variance estimation procedure based on a perturbation-resampling method. Simulation studies demonstrate that the procedure performs well in finite samples and outperforms model-based procedures when the specified models are not correct. We illustrate our proposed procedure using a data set from a randomized study investigating a group-mediated cognitive behavioral intervention for peripheral artery disease participants. Copyright © 2015 John Wiley & Sons, Ltd.

Augmenting communication and decision making in the intensive care unit with a cardiopulmonary resuscitation video decision support tool: a temporal intervention study.

PubMed

McCannon, Jessica B; O'Donnell, Walter J; Thompson, B Taylor; El-Jawahri, Areej; Chang, Yuchiao; Ananian, Lillian; Bajwa, Ednan K; Currier, Paul F; Parikh, Mihir; Temel, Jennifer S; Cooper, Zara; Wiener, Renda Soylemez; Volandes, Angelo E

2012-12-01

Effective communication between intensive care unit (ICU) providers and families is crucial given the complexity of decisions made regarding goals of therapy. Using video images to supplement medical discussions is an innovative process to standardize and improve communication. In this six-month, quasi-experimental, pre-post intervention study we investigated the impact of a cardiopulmonary resuscitation (CPR) video decision support tool upon knowledge about CPR among surrogate decision makers for critically ill adults. We interviewed surrogate decision makers for patients aged 50 and over, using a structured questionnaire that included a four-question CPR knowledge assessment similar to those used in previous studies. Surrogates in the post-intervention arm viewed a three-minute video decision support tool about CPR before completing the knowledge assessment and completed questions about perceived value of the video. We recruited 23 surrogates during the first three months (pre-intervention arm) and 27 surrogates during the latter three months of the study (post-intervention arm). Surrogates viewing the video had more knowledge about CPR (p=0.008); average scores were 2.0 (SD 1.1) and 2.9 (SD 1.2) (out of a total of 4) in pre-intervention and post-intervention arms. Surrogates who viewed the video were comfortable with its content (81% very) and 81% would recommend the video. CPR preferences for patients at the time of ICU discharge/death were distributed as follows: pre-intervention: full code 78%, DNR 22%; post-intervention: full code 59%, DNR 41% (p=0.23).

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

PubMed

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

2016-01-01

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

Communicating with Clinicians: The Experiences of Surrogate Decision Makers for Hospitalized Older Adults

PubMed Central

Torke, Alexia M.; Petronio, Sandra; Purnell, Christianna E.; Sachs, Greg A.; Helft, Paul R.; Callahan, Christopher M.

2012-01-01

Background/Objectives When hospitalized older adults have impaired cognition, family members or other surrogates must communicate with clinicians to provide information and make medical decisions for the patient. The present study describes communication experiences of surrogates who recently made a major medical decision for a hospitalized older adult. Design Semi-structured interviews about a recent hospitalization. Setting Two hospitals both affiliated with 1 large medical school: an urban, public hospital; and a university-affiliated tertiary referral hospital. Participants Surrogates were eligible if they had recently made a major medical decision for a hospitalized patient aged 65 or older and were available for an interview within 1 month (2-5 months if the patient died). Measurements Interviews were audio-recorded, transcribed, and analyzed using methods of grounded theory. Results We interviewed 35 surrogates. They were 80% female, 44% white and 56% African American. Three primary themes emerged. We found the Nature of Surrogate/Clinician Relationships was best characterized as a relationship with a “team” of clinicians rather than individual clinicians due to frequent staff changes and multiple clinicians. Surrogates reported their Communication Needs, including frequent communication, information, and emotional support. Surrogates valued communication from any member of the clinical team, including nurses, social workers, and physicians. Third, surrogates described Trust and Mistrust, which were formed largely through surrogates’ communication experiences. Conclusion In the hospital, surrogates form relationships with a “team” of clinicians rather than with individuals. Yet effective communication and expressions of emotional support frequently occur and are highly valued by surrogates. Future interventions should focus on meeting surrogates’ needs for frequent communication, high levels of information and emotional support. PMID:22881864

Surrogate measures and consistent surrogates

PubMed Central

VanderWeele, Tyler J.

2014-01-01

Summary Surrogates which allow one to predict the effect of the treatment on the outcome of interest from the effect of the treatment on the surrogate are of importance when it is difficult or expensive to measure the primary outcome. Unfortunately, the use of such surrogates can give rise to paradoxical situations in which the effect of the treatment on the surrogate is positive, the surrogate and outcome are strongly positively correlated, but the effect of the treatment on the outcome is negative, a phenomenon sometimes referred to as the "surrogate paradox." New results are given for consistent surrogates that extend the existing literature on sufficient conditions that ensure the surrogate paradox is not manifest. Specifically, it is shown that for the surrogate paradox to beman.est it must be the case that either there is (i) a direct effect of treatment on the outcome not through the surrogate and in the opposite direction as that through the surrogate or (ii) confounding for the effect of the surrogate on the outcome, or (iii) a lack of transitivity so that treatment does not positively affect the surrogate for all the same individuals for which the surrogate positively affects the outcome. The conditions for consistent surrogates and the results of the paper are important because they allow investigators to predict the direction of the effect of the treatment on the outcome simply from the direction of the effect of the treatment on the surrogate. These results on consistent surrogates are then related to the four approaches to surrogate outcomes described by Joffe and Greene (2009, Biometrics 65, 530–538) to assess whether the standard criterion used by these approaches to assess whether a surrogate is "good" suffices to avoid the surrogate paradox. PMID:24073861

Using Video Images to Improve the Accuracy of Surrogate Decision-Making: A Randomized Controlled Trial

PubMed Central

Volandes, Angelo E.; Mitchell, Susan L.; Gillick, Muriel R.; Chang, Yuchiao; Paasche-Orlow, Michael K.

2009-01-01

Introduction When patients are unable to make important end-of-life decisions, doctors ask surrogate decision makers to provide insight into patients’ preferences. Unfortunately, multiple studies have shown that surrogates’ knowledge of patient preferences is poor. We hypothesized that a video decision tool would improve concordance between patients and their surrogates for end-of-life preferences. Objective To compare the concordance of preferences among elderly patients and their surrogates listening to only a verbal description of advanced dementia or viewing a video decision support tool of the disease after hearing the verbal description. Methods This was a randomized controlled trial of a convenience sample of community-dwelling elderly subjects (≥65 years) and their surrogates, and was conducted at 2 geriatric clinics affiliated with 2 academic medical centers in Boston. The study was conducted between September 1, 2007, and May 30, 2008. Random assignment of patient and surrogate dyads was to either a verbal narrative or a video decision support tool after the verbal narrative. End points were goals of care chosen by the patient and predicted goals of care by the surrogate. Goals of care included life-prolonging care (CPR, mechanical ventilation), limited care (hospitalization, antibiotics, but not CPR), and comfort care (only treatment to relieve symptoms). The primary outcome measure was the concordance rate of preferences between patients and their surrogates. Results A total of 14 pairs of patients and their surrogates were randomized to verbal narrative (n = 6) or video after verbal narrative (n = 8). Among the 6 patients receiving only the verbal narrative, 3 (50%) preferred comfort care, 1 (17%) chose limited care, and 2 (33%) desired life-prolonging care. Among the surrogates for these patients, only 2 correctly chose what their loved one would want if in a state of advanced dementia, yielding a concordance rate of 33%. Among the 8 patients receiving the video decision support tool, all 8 chose comfort care. Among the surrogates for these patients, all 8 correctly chose what their loved one would want if in a state of advanced dementia, yielding a concordance rate of 100%. Conclusion Patients and surrogates viewing a video decision support tool for advanced dementia are more likely to concur about the patient’s end-of-life preferences than when solely listening to a verbal description of the disease. PMID:19808156

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

PubMed

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

2012-03-01

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

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

PubMed Central

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

2013-01-01

Objective To describe how critical care physicians manage conflicts with surrogates about withdrawing or withholding patients’ life support. Design Qualitative analysis of key informant interviews with critical care physicians during 2010. We transcribed interviews verbatim and used grounded theory to code and revise a taxonomy of themes and to identify illustrative quotes. Setting 3 academic medical centers, 1 academic-affiliated medical center and 4 private practice groups or private hospitals in a large Midwestern city Subjects 14 critical care physicians Measurements and main results Physicians reported tailoring their approach to address specific reasons for disagreement with surrogates. Five common approaches were identified: (1) building trust, (2) educating and informing, (3) providing surrogates more time, (4) adjusting surrogate and physician roles, and (5) highlighting specific values. When mistrust was an issue, physicians endeavored to build a more trusting relationship with the surrogate before re-addressing decision making. Physicians also reported correcting misunderstandings by providing targeted education, and some reported highlighting specific patient, surrogate, or physician values that they hoped would guide surrogates to agree with them. When surrogates struggled with decision making roles, physicians attempted to reinforce the concept of substituted judgment. Physicians noted that some surrogates needed time to “come to terms” with the patent’s illness before agreeing with physicians. Many physicians had witnessed colleagues negotiate in ways they found objectionable, such as providing misleading information, injecting their own values into the negotiation, or behaving unprofessionally towards surrogates. While some physicians viewed their efforts to encourage surrogates’ agreement as persuasive, others strongly denied persuading surrogates and described their actions as “guiding” or “negotiating.” Conclusions Physicians reported using a tailored approach to resolve decisional conflicts about life support; and attempted to change surrogates’ decisions in accordance with what the physician thought was in the patients’ best interests. While physicians acknowledged their efforts to change surrogate’s decisions, many physicians did not perceive these as persuasive. PMID:22080645

Use of surrogate outcomes in US FDA drug approvals, 2003-2012: a survey.

PubMed

Yu, Tsung; Hsu, Yea-Jen; Fain, Kevin M; Boyd, Cynthia M; Holbrook, Janet T; Puhan, Milo A

2015-11-27

To evaluate, across a spectrum of diseases, how often surrogate outcomes are used as a basis for drug approvals by the US Food and Drug Administration (FDA), and whether and how the rationale for using treatment effects on surrogates as predictors of treatment effects on patient-centred outcomes is discussed. We used the Drugs@FDA website to identify drug approvals produced from 2003 to 2012 by the FDA. We focused on four diseases (chronic obstructive pulmonary disease (COPD), type 1 or 2 diabetes, glaucoma and osteoporosis) for which surrogates are commonly used in trials. We reviewed the drug labels and medical reviews to provide empirical evidence on how surrogate outcomes are handled by the FDA. Of 1043 approvals screened, 58 (6%) were for the four diseases of interest. Most drugs for COPD (7/9, 78%), diabetes (26/26, 100%) and glaucoma (9/9, 100%) were approved based on surrogates while for osteoporosis, most drugs (10/14, 71%) were also approved for patient-centred outcomes (fractures). The rationale for using surrogates was discussed in 11 of the 43 (26%) drug approvals based on surrogates. In these drug approvals, we found drug approvals for diabetes are more likely than the other examined conditions to contain a discussion of trial evidence demonstrating that treatment effects on surrogate outcomes predict treatment effects on patient-centred outcomes. Our results suggest that the FDA did not use a consistent approach to address surrogates in assessing the benefits and harms of drugs for COPD, type 1 or 2 diabetes, glaucoma and osteoporosis. For evaluating new drugs, patient-centred outcomes should be chosen whenever possible. If the use of surrogate outcomes is necessary, then a consistent approach is important to review the evidence for surrogacy and consider surrogate's usage in the treatment and population under study. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Doubt and belief in physicians' ability to prognosticate during critical illness: The perspective of surrogate decision makers

PubMed Central

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

2009-01-01

Objectives: Although discussing a prognosis is a duty of physicians caring for critically ill patients, little is known about surrogate decision-makers' beliefs about physicians' ability to prognosticate. We sought to determine: 1) surrogates' beliefs about whether physicians can accurately prognosticate for critically ill patients; and 2) how individuals use prognostic information in their role as surrogate decision-makers. Design, Setting, and Patients: Multicenter study in intensive care units of a public hospital, a tertiary care hospital, and a veterans' hospital. We conducted semistructured interviews with 50 surrogate decision-makers of critically ill patients. We analyzed the interview transcripts using grounded theory methods to inductively develop a framework to describe surrogates' beliefs about physicians' ability to prognosticate. Validation methods included triangulation by multidisciplinary analysis and member checking. Measurements and Main Results: Overall, 88% (44 of 50) of surrogates expressed doubt about physicians' ability to prognosticate for critically ill patients. Four distinct themes emerged that explained surrogates' doubts about prognostic accuracy: a belief that God could alter the course of the illness, a belief that predicting the future is inherently uncertain, prior experiences where physicians' prognostications were inaccurate, and experiences with prognostication during the patient's intensive care unit stay. Participants also identified several factors that led to belief in physicians' prognostications, such as receiving similar prognostic estimates from multiple physicians and prior experiences with accurate prognostication. Surrogates' doubts about prognostic accuracy did not prevent them from wanting prognostic information. Instead, most surrogate decision-makers view physicians' prognostications as rough estimates that are valuable in informing decisions, but are not determinative. Surrogates identified the act of prognostic disclosure as a key step in preparing emotionally and practically for the possibility that a patient may not survive. Conclusions: Although many surrogate decision-makers harbor some doubt about the accuracy of physicians' prognostications, they highly value discussions about prognosis and use the information for multiple purposes. (Crit Care Med 2008; 36: 2341–2347) PMID:18596630

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

PubMed

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

2007-03-01

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

An Open-Source Toolbox for Surrogate Modeling of Joint Contact Mechanics

PubMed Central

Eskinazi, Ilan

2016-01-01

Goal Incorporation of elastic joint contact models into simulations of human movement could facilitate studying the interactions between muscles, ligaments, and bones. Unfortunately, elastic joint contact models are often too expensive computationally to be used within iterative simulation frameworks. This limitation can be overcome by using fast and accurate surrogate contact models that fit or interpolate input-output data sampled from existing elastic contact models. However, construction of surrogate contact models remains an arduous task. The aim of this paper is to introduce an open-source program called Surrogate Contact Modeling Toolbox (SCMT) that facilitates surrogate contact model creation, evaluation, and use. Methods SCMT interacts with the third party software FEBio to perform elastic contact analyses of finite element models and uses Matlab to train neural networks that fit the input-output contact data. SCMT features sample point generation for multiple domains, automated sampling, sample point filtering, and surrogate model training and testing. Results An overview of the software is presented along with two example applications. The first example demonstrates creation of surrogate contact models of artificial tibiofemoral and patellofemoral joints and evaluates their computational speed and accuracy, while the second demonstrates the use of surrogate contact models in a forward dynamic simulation of an open-chain leg extension-flexion motion. Conclusion SCMT facilitates the creation of computationally fast and accurate surrogate contact models. Additionally, it serves as a bridge between FEBio and OpenSim musculoskeletal modeling software. Significance Researchers may now create and deploy surrogate models of elastic joint contact with minimal effort. PMID:26186761

Pull out strength calculator for pedicle screws using a surrogate ensemble approach.

PubMed

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

2016-12-01

Pedicle screw instrumentation is widely used in the treatment of spinal disorders and deformities. Currently, the surgeon decides the holding power of instrumentation based on the perioperative feeling which is subjective in nature. The objective of the paper is to develop a surrogate model which will predict the pullout strength of pedicle screw based on density, insertion angle, insertion depth and reinsertion. A Taguchi's orthogonal array was used to design an experiment to find the factors effecting pullout strength of pedicle screw. The pullout studies were carried using polyaxial pedicle screw on rigid polyurethane foam block according to American society for testing of materials (ASTM F543). Analysis of variance (ANOVA) and Tukey's honestly significant difference multiple comparison tests were done to find factor effect. Based on the experimental results, surrogate models based on Krigging, polynomial response surface and radial basis function were developed for predicting the pullout strength for different combination of factors. An ensemble of these surrogates based on weighted average surrogate model was also evaluated for prediction. Density, insertion depth, insertion angle and reinsertion have a significant effect (p <0.05) on pullout strength of pedicle screw. Weighted average surrogate performed the best in predicting the pull out strength amongst the surrogate models considered in this study and acted as insurance against bad prediction. A predictive model for pullout strength of pedicle screw was developed using experimental values and surrogate models. This can be used in pre-surgical planning and decision support system for spine surgeon. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Review of meta-analyses evaluating surrogate endpoints for overall survival in oncology

PubMed Central

Sherrill, Beth; Kaye, James A; Sandin, Rickard; Cappelleri, Joseph C; Chen, Connie

2012-01-01

Overall survival (OS) is the gold standard in measuring the treatment effect of new drug therapies for cancer. However, practical factors may preclude the collection of unconfounded OS data, and surrogate endpoints are often used instead. Meta-analyses have been widely used for the validation of surrogate endpoints, specifically in oncology. This research reviewed published meta-analyses on the types of surrogate measures used in oncology studies and examined the extent of correlation between surrogate endpoints and OS for different cancer types. A search was conducted in October 2010 to compile available published evidence in the English language for the validation of disease progression-related endpoints as surrogates of OS, based on meta-analyses. We summarize published meta-analyses that quantified the correlation between progression-based endpoints and OS for multiple advanced solid-tumor types. We also discuss issues that affect the interpretation of these findings. Progression-free survival is the most commonly used surrogate measure in studies of advanced solid tumors, and correlation with OS is reported for a limited number of cancer types. Given the increased use of crossover in trials and the availability of second-/third-line treatment options available to patients after progression, it will become increasingly more difficult to establish correlation between effects on progression-free survival and OS in additional tumor types. PMID:23109809

Minimum energy control for in vitro neurons.

PubMed

Nabi, Ali; Stigen, Tyler; Moehlis, Jeff; Netoff, Theoden

2013-06-01

To demonstrate the applicability of optimal control theory for designing minimum energy charge-balanced input waveforms for single periodically-firing in vitro neurons from brain slices of Long-Evans rats. The method of control uses the phase model of a neuron and does not require prior knowledge of the neuron's biological details. The phase model of a neuron is a one-dimensional model that is characterized by the neuron's phase response curve (PRC), a sensitivity measure of the neuron to a stimulus applied at different points in its firing cycle. The PRC for each neuron is experimentally obtained by measuring the shift in phase due to a short-duration pulse injected into the periodically-firing neuron at various phase values. Based on the measured PRC, continuous-time, charge-balanced, minimum energy control waveforms have been designed to regulate the next firing time of the neuron upon application at the onset of an action potential. The designed waveforms can achieve the inter-spike-interval regulation for in vitro neurons with energy levels that are lower than those of conventional monophasic pulsatile inputs of past studies by at least an order of magnitude. They also provide the advantage of being charge-balanced. The energy efficiency of these waveforms is also shown by performing several supporting simulations that compare the performance of the designed waveforms against that of phase shuffled surrogate inputs, variants of the minimum energy waveforms obtained from suboptimal PRCs, as well as pulsatile stimuli that are applied at the point of maximum PRC. It was found that the minimum energy waveforms perform better than all other stimuli both in terms of control and in the amount of energy used. Specifically, it was seen that these charge-balanced waveforms use at least an order of magnitude less energy than conventional monophasic pulsatile stimuli. The significance of this work is that it uses concepts from the theory of optimal control and introduces a novel approach in designing minimum energy charge-balanced input waveforms for neurons that are robust to noise and implementable in electrophysiological experiments.

Minimum energy control for in vitro neurons

NASA Astrophysics Data System (ADS)

Nabi, Ali; Stigen, Tyler; Moehlis, Jeff; Netoff, Theoden

2013-06-01

Objective. To demonstrate the applicability of optimal control theory for designing minimum energy charge-balanced input waveforms for single periodically-firing in vitro neurons from brain slices of Long-Evans rats. Approach. The method of control uses the phase model of a neuron and does not require prior knowledge of the neuron’s biological details. The phase model of a neuron is a one-dimensional model that is characterized by the neuron’s phase response curve (PRC), a sensitivity measure of the neuron to a stimulus applied at different points in its firing cycle. The PRC for each neuron is experimentally obtained by measuring the shift in phase due to a short-duration pulse injected into the periodically-firing neuron at various phase values. Based on the measured PRC, continuous-time, charge-balanced, minimum energy control waveforms have been designed to regulate the next firing time of the neuron upon application at the onset of an action potential. Main result. The designed waveforms can achieve the inter-spike-interval regulation for in vitro neurons with energy levels that are lower than those of conventional monophasic pulsatile inputs of past studies by at least an order of magnitude. They also provide the advantage of being charge-balanced. The energy efficiency of these waveforms is also shown by performing several supporting simulations that compare the performance of the designed waveforms against that of phase shuffled surrogate inputs, variants of the minimum energy waveforms obtained from suboptimal PRCs, as well as pulsatile stimuli that are applied at the point of maximum PRC. It was found that the minimum energy waveforms perform better than all other stimuli both in terms of control and in the amount of energy used. Specifically, it was seen that these charge-balanced waveforms use at least an order of magnitude less energy than conventional monophasic pulsatile stimuli. Significance. The significance of this work is that it uses concepts from the theory of optimal control and introduces a novel approach in designing minimum energy charge-balanced input waveforms for neurons that are robust to noise and implementable in electrophysiological experiments.

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

USDA-ARS?s Scientific Manuscript database

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

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

ERIC Educational Resources Information Center

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

2012-01-01

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

Strategies for Countering Terrorist Safe Havens

DTIC Science & Technology

2014-02-20

within safe havens, tactical containment, pseudo operations, and surrogate security forces. The thesis draws from four historical case studies to...leadership targeting within safe havens, tactical containment, pseudo operations, and surrogate security forces. The thesis draws from four historical case ...surrogate forces and pseudo operations—provide viable potential options for USSOF to counter the complex problem of safe havens. Overall, the case

Considerations for development of surrogate endpoints for antifracture efficacy of new treatments in osteoporosis: a perspective.

PubMed

Bouxsein, Mary L; Delmas, Pierre D

2008-08-01

Because of the broad availability of efficacious osteoporosis therapies, conduct of placebo-controlled trials in subjects at high risk for fracture is becoming increasing difficult. Alternative trial designs include placebo-controlled trials in patients at low risk for fracture or active comparator studies, both of which would require enormous sample sizes and associated financial resources. Another more attractive alternative is to develop and validate surrogate endpoints for fracture. In this perspective, we review the concept of surrogate endpoints as it has been developed in other fields of medicine and discuss how it could be applied in clinical trials of osteoporosis. We outline a stepwise approach and possible study designs to qualify a biomarker as a surrogate endpoint in osteoporosis and review the existing data for several potential surrogate endpoints to assess their success in meeting the proposed criteria. Finally, we suggest a research agenda needed to advance the development of biomarkers as surrogate endpoints for fracture in osteoporosis trials. To ensure optimal development and best use of biomarkers to accelerate drug development, continuous dialog among the health professionals, industry, and regulators is of paramount importance.

Biodegradation of naphthenic acid surrogates by axenic cultures.

PubMed

Yue, Siqing; Ramsay, Bruce A; Ramsay, Juliana A

2015-07-01

This is the first study to report that bacteria from the genera Ochrobactrum, Brevundimonas and Bacillus can be isolated by growth on naphthenic acids (NAs) extracted from oil sands process water (OSPW). These pure cultures were screened for their ability to use a range of aliphatic, cyclic and aromatic NA surrogates in 96-well microtiter plates using water-soluble tetrazolium redox dyes (Biolog Redox Dye H) as the indicator of metabolic activity. Of the three cultures, Ochrobactrum showed most metabolic activity on the widest range of NA surrogates. Brevundomonas and especially Ochrobactrum had higher metabolic activity on polycyclic aromatic compounds than other classes of NA surrogates. Bacillus also oxidized a wide range of NA surrogates but not as well as Ochrobactrum. Using this method to characterize NA utilisation, one can identify which NAs or NA classes in OSPW are more readily degraded. Since aromatic NAs have been shown to have an estrogenic effect and polycyclic monoaromatic compounds have been suggested to pose the greatest environmental threat among the NAs, these bacterial genera may play an important role in detoxification of OSPW. Furthermore, this study demonstrates that bacteria belonging to the genera Ochrobactrum and Bacillus can also degrade surrogates of tricyclic NAs.

Limited predictive ability of surrogate indices of insulin sensitivity/resistance in Asian-Indian men.

PubMed

Muniyappa, Ranganath; Irving, Brian A; Unni, Uma S; Briggs, William M; Nair, K Sreekumaran; Quon, Michael J; Kurpad, Anura V

2010-12-01

Insulin resistance is highly prevalent in Asian Indians and contributes to worldwide public health problems, including diabetes and related disorders. Surrogate measurements of insulin sensitivity/resistance are used frequently to study Asian Indians, but these are not formally validated in this population. In this study, we compared the ability of simple surrogate indices to accurately predict insulin sensitivity as determined by the reference glucose clamp method. In this cross-sectional study of Asian-Indian men (n = 70), we used a calibration model to assess the ability of simple surrogate indices for insulin sensitivity [quantitative insulin sensitivity check index (QUICKI), homeostasis model assessment (HOMA2-IR), fasting insulin-to-glucose ratio (FIGR), and fasting insulin (FI)] to predict an insulin sensitivity index derived from the reference glucose clamp method (SI(Clamp)). Predictive accuracy was assessed by both root mean squared error (RMSE) of prediction as well as leave-one-out cross-validation-type RMSE of prediction (CVPE). QUICKI, FIGR, and FI, but not HOMA2-IR, had modest linear correlations with SI(Clamp) (QUICKI: r = 0.36; FIGR: r = -0.36; FI: r = -0.27; P < 0.05). No significant differences were noted among CVPE or RMSE from any of the surrogate indices when compared with QUICKI. Surrogate measurements of insulin sensitivity/resistance such as QUICKI, FIGR, and FI are easily obtainable in large clinical studies, but these may only be useful as secondary outcome measurements in assessing insulin sensitivity/resistance in clinical studies of Asian Indians.

Is prostate-specific antigen a valid surrogate end point for survival in hormonally treated patients with metastatic prostate cancer? Joint research of the European Organisation for Research and Treatment of Cancer, the Limburgs Universitair Centrum, and AstraZeneca Pharmaceuticals.

PubMed

Collette, Laurence; Burzykowski, Tomasz; Carroll, Kevin J; Newling, Don; Morris, Tom; Schröder, Fritz H

2005-09-01

The long duration of phase III clinical trials of overall survival (OS) slows down the treatment-development process. It could be shortened by using surrogate end points. Prostate-specific antigen (PSA) is the most studied biomarker in prostate cancer (PCa). This study attempts to validate PSA end points as surrogates for OS in advanced PCa. Individual data from 2,161 advanced PCa patients treated in studies comparing bicalutamide to castration were used in a meta-analytic approach to surrogate end-point validation. PSA response, PSA normalization, time to PSA progression, and longitudinal PSA measurements were considered. The known association between PSA and OS at the individual patient level was confirmed. The association between the effect of intervention on any PSA end point and on OS was generally low (determination coefficient, < 0.69). It is a common misconception that high correlation between biomarkers and true end point justify the use of the former as surrogates. To statistically validate surrogate end points, a high correlation between the treatment effects on the surrogate and true end point needs to be established across groups of patients treated with two alternative interventions. The levels of association observed in this study indicate that the effect of hormonal treatment on OS cannot be predicted with a high degree of precision from observed treatment effects on PSA end points, and thus statistical validity is unproven. In practice, non-null treatment effects on OS can be predicted only from precisely estimated large effects on time to PSA progression (TTPP; hazard ratio, < 0.50).

Bending testing and characterization of surrogate nuclear fuel rods made of Zircaloy-4 cladding and aluminum oxide pellets

NASA Astrophysics Data System (ADS)

Wang, Hong; Wang, Jy-An John

2016-10-01

Behavior of surrogate nuclear fuel rods made of Zircaloy-4 (Zry-4) cladding with alumina pellets under reversed cyclic bending was studied. Tests were performed under load or moment control at 5 Hz. The surrogate rods fractured under moment amplitudes greater than 10.16 Nm with fatigue lives between 2.4 × 103 and 2.2 × 106 cycles. Fatigue response of Zry-4 cladding was characterized by using flexural rigidity. Degradation of flexural rigidity was shown to depend on the moment and the prefatigue condition of specimens. Pellet-to-pellet interface (PPI), pellet-to-cladding interface (PCI), and pellet condition affect surrogate rod failure. Both debonding of PPI/PCI and pellet fracturing contribute to surrogate rod bending fatigue. The effect of sensor spacing on curvature measurement using three-point deflections was studied; the method based on effective gauge length is effective in sensor spacing correction. The database developed and the understanding gained in this study can serve as input to analysis of SNF (spent nuclear fuel) vibration integrity.

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

NASA Astrophysics Data System (ADS)

Hou, Zeyu; Lu, Wenxi

2018-05-01

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

Ceramic media amended with metal oxide for the capture of viruses in drinking water.

PubMed

Brown, J; Sobsey, M D

2009-04-01

Ceramic materials that can adsorb and/or inactivate viruses in water may find widespread application in low-tech drinking-water treatment technologies in developing countries, where porous ceramic filters and ceramic granular media filters are increasingly promoted for that purpose. We examined the adsorption and subsequent inactivation of bacteriophages MS2 and (phiX-174 on five ceramic media in batch adsorption studies to determine media suitability for use in a ceramic water filter application. The media examined were a kaolinitic ceramic medium and four kaolinitic ceramic media amended with iron or aluminium oxides that had been incorporated into the kaolinitic clays before firing. Batch adsorption tests indicate increased sorption and inactivation of surrogate viruses by media amended with Fe and Al oxide, with FeOOH-amended ceramic inactivating all bacteriophages up to 8 log10. Unmodified ceramic was a poor adsorbent of bacteriophages at less than 1 log10 adsorption-inactivation and high recovery of sorbed phages. These studies suggest that contact with ceramic media, modified with electropositive Fe or Al oxides, can reduce bacteriophages in waters to a greater extent than unmodified ceramic.

Urinary metal and polycyclic aromatic hydrocarbon biomarkers in boilermakers exposed to metal fume and residual oil fly ash.

PubMed

Mukherjee, Sutapa; Rodrigues, Ema; Aeschliman, David B; Houk, R S; Palmer, Lyle J; Woodin, Mark A; Weker, Robert; Christiani, David C

2005-06-01

Boilermakers are occupationally exposed to known carcinogens. The association of urinary 1-hydroxy-pyrene (1-OHP), a biomarker of polycyclic aromatic hydrocarbon (PAH) exposure, with biomarkers of metal exposure (vanadium, chromium, manganese, nickel, copper, and lead) in boilermakers exposed to metal fume from welding and dust particulates from residual oil fly ash (ROFA) was examined. A repeated measures cohort study was conducted during the overhaul of an oil-fired boiler. Twice-daily urine samples were obtained for 5 days and analyzed for cotinine, 1-OHP, and metals. Generalized estimating equations (GEE) were used to model the multivariate relationship of 1-OHP to the explanatory variables. Metal and 1-OHP levels were determined for 165 urine samples from 20 boilermakers and these levels increased during the workweek. However, the 1-OHP level was not significantly associated with any individual metal level at any time point. This suggests that boilermakers were occupationally exposed to PAH and metals, but 1-OHP as a PAH biomarker was unable to serve as a surrogate marker of metal exposure for the metals measured in this study.

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

NASA Astrophysics Data System (ADS)

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

2017-08-01

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

Beyond multi-fractals: surrogate time series and fields

NASA Astrophysics Data System (ADS)

Venema, V.; Simmer, C.

2007-12-01

Most natural complex are characterised by variability on a large range of temporal and spatial scales. The two main methodologies to generate such structures are Fourier/FARIMA based algorithms and multifractal methods. The former is restricted to Gaussian data, whereas the latter requires the structure to be self-similar. This work will present so-called surrogate data as an alternative that works with any (empirical) distribution and power spectrum. The best-known surrogate algorithm is the iterative amplitude adjusted Fourier transform (IAAFT) algorithm. We have studied six different geophysical time series (two clouds, runoff of a small and a large river, temperature and rain) and their surrogates. The power spectra and consequently the 2nd order structure functions were replicated accurately. Even the fourth order structure function was more accurately reproduced by the surrogates as would be possible by a fractal method, because the measured structure deviated too strong from fractal scaling. Only in case of the daily rain sums a fractal method could have been more accurate. Just as Fourier and multifractal methods, the current surrogates are not able to model the asymmetric increment distributions observed for runoff, i.e., they cannot reproduce nonlinear dynamical processes that are asymmetric in time. Furthermore, we have found differences for the structure functions on small scales. Surrogate methods are especially valuable for empirical studies, because the time series and fields that are generated are able to mimic measured variables accurately. Our main application is radiative transfer through structured clouds. Like many geophysical fields, clouds can only be sampled sparsely, e.g. with in-situ airborne instruments. However, for radiative transfer calculations we need full 3-dimensional cloud fields. A first study relating the measured properties of the cloud droplets and the radiative properties of the cloud field by generating surrogate cloud fields yielded good results within the measurement error. A further test of the suitability of the surrogate clouds for radiative transfer is evaluated by comparing the radiative properties of model cloud fields of sparse cumulus and stratocumulus with their surrogate fields. The bias and root mean square error in various radiative properties is small and the deviations in the radiances and irradiances are not statistically significant, i.e. these deviations can be attributed to the Monte Carlo noise of the radiative transfer calculations. We compared these results with optical properties of synthetic clouds that have either the correct distribution (but no spatial correlations) or the correct power spectrum (but a Gaussian distribution). These clouds did show statistical significant deviations. For more information see: http://www.meteo.uni-bonn.de/venema/themes/surrogates/

Surrogate Decision Makers and Proxy Ownership: Challenges of Privacy Management in Health Care Decision Making

PubMed Central

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

2016-01-01

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

Comparison between Surrogate Indexes of Insulin Sensitivity/Resistance and Hyperinsulinemic Euglycemic Glucose Clamps in Rhesus Monkeys

PubMed Central

Lee, Ho-Won; Muniyappa, Ranganath; Yan, Xu; Yue, Lilly Q.; Linden, Ellen H.; Chen, Hui; Hansen, Barbara C.

2011-01-01

The euglycemic glucose clamp is the reference method for assessing insulin sensitivity in humans and animals. However, clamps are ill-suited for large studies because of extensive requirements for cost, time, labor, and technical expertise. Simple surrogate indexes of insulin sensitivity/resistance including quantitative insulin-sensitivity check index (QUICKI) and homeostasis model assessment (HOMA) have been developed and validated in humans. However, validation studies of QUICKI and HOMA in both rats and mice suggest that differences in metabolic physiology between rodents and humans limit their value in rodents. Rhesus monkeys are a species more similar to humans than rodents. Therefore, in the present study, we evaluated data from 199 glucose clamp studies obtained from a large cohort of 86 monkeys with a broad range of insulin sensitivity. Data were used to evaluate simple surrogate indexes of insulin sensitivity/resistance (QUICKI, HOMA, Log HOMA, 1/HOMA, and 1/Fasting insulin) with respect to linear regression, predictive accuracy using a calibration model, and diagnostic performance using receiver operating characteristic. Most surrogates had modest linear correlations with SIClamp (r ≈ 0.4–0.64) with comparable correlation coefficients. Predictive accuracy determined by calibration model analysis demonstrated better predictive accuracy of QUICKI than HOMA and Log HOMA. Receiver operating characteristic analysis showed equivalent sensitivity and specificity of most surrogate indexes to detect insulin resistance. Thus, unlike in rodents but similar to humans, surrogate indexes of insulin sensitivity/resistance including QUICKI and log HOMA may be reasonable to use in large studies of rhesus monkeys where it may be impractical to conduct glucose clamp studies. PMID:21209021

The impact of the High Park Wildfire on stream water quality and implications for drinking water treatment

NASA Astrophysics Data System (ADS)

Rosario-Ortiz, F.

2014-12-01

The Cache La Poudre (CLP) watershed in Northern Colorado was impacted by the High Park fire, which burned from June 9th through July 1st of 2012. The CLP watershed serves as a source of drinking water for three water districts in Northern Colorado, including the City of Fort Collins. Sampling was conducted during four different storm events immediately after the fire was extinguished. The sampling was expanded through spring and summer 2013 in order to capture the flush of debris from the wildfire into the CLP River. Samples were also collected from an unburned control site for comparison. Surface water samples were analyzed for parameters including nutrients, dissolved organic carbon (DOC) concentration and dissolved organic matter (DOM) characterization. In addition, bench scale treatment analyses were conducted to better understand the impacts of the wildfire on treatment processes for drinking water utilities. Lastly, leaching of stream bank sediments was conducted to determine the potential longer term inputs of burned material to the stream water. The overarching goals of the sampling campaign were to: 1) Evaluate the impact that wildfires have on the properties of DOM, specifically with respect to DBP formation and speciation (TTHM, HAA5, HAN, NDMA); 2) Establish the condition under which the source water could be effectively treated (using coagulation) to remove DBP precursors; 3) Evaluate the use of fluorescence spectroscopy as a surrogate for the concentration and reactivity of DOM in the CLP watershed; and 4) Assess the quantity and quality of DOM leached from streambed sediments. Preliminary results showed elevated DOC levels during the storm events and at wildfire impacted sites compared to the unburned site following the fire. DBP yields were higher for the four storm events following the fire when compared to yields for the control site located upstream of the burn area, and also when compared to data from a previous DBP study conducted on similar Colorado source waters in 2010. Fluorescence spectroscopy shows promise as a tool for discerning differences in DOM quality between burned and unburned areas of the CLP watershed. Ultimately, the results of this study will offer insight for recovering this watershed as a sustainable water source and will prepare utilities for future wildfires.

Surrogate versus couple therapy in vaginismus.

PubMed

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

2007-05-01

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

Magnetic resonance imaging as a surrogate outcome for multiple sclerosis relapses

PubMed Central

Petkau, J; Reingold, SC; Held, U; Cutter, GR; Fleming, TR; Hughes, MD; Miller, DH; McFarland, HF; Wolinsky, JS

2009-01-01

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. PMID:18535021

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

PubMed

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

2015-11-01

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

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

PubMed

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

2011-06-01

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

The Role of Surrogate Endpoints in the Evaluation of Efficacy and Safety of Therapeutic Interventions in Diabetes Mellitus

PubMed Central

Wieczorek, Aleksandra; Rys, Przemyslaw; Skrzekowska-Baran, Iwona; Malecki, Maciej

2008-01-01

In this paper, we examine the concept of surrogate endpoints (i.e. substitute outcome measures) and review their use in clinical trials involving therapies for diabetes mellitus using the example of metformin. Trials such as DCCT and UKPDS, in which patient-important endpoints were evaluated, are relatively rare in diabetology. Clinical decisions, therefore, are often based on evidence obtained using surrogate outcomes, usually fasting or postprandial glycemia or glycated hemoglobin level. In contrast to patient-important endpoints, surrogates do not describe direct clinical benefit to the patient. However, a proven association between a surrogate and patient-important endpoint is essential to draw appropriate therapeutic conclusions. In the process of new drug development, the duration of follow-up, sample size and methodology of the studies initially available are often inadequate to demonstrate the effect of the intervention on patient-important endpoints. Evidence concerning the effect of an intervention on surrogate outcomes usually comes first, followed only later by reports describing its influence on patient-important endpoints. Metformin may serve as an example in several ways. The first publications reported beneficial effects on glycemic control and body weight. Outcomes from the subsequent UKPDS study suggested the patient-important efficacy of metformin measured as a reduction in mortality and a decrease in the incidence of diabetic complications, including myocardial infarction. This reasoning process worked for some but not all strategies. It is particularly questionable whether a change in surrogate endpoint was associated with a potential deterioration in patient-important outcomes. Defining the general relationship between surrogates widely used as measures of metabolic control and patient-important endpoints remains an important challenge in contemporary diabetology. PMID:19099084

The role of surrogate endpoints in the evaluation of efficacy and safety of therapeutic interventions in diabetes mellitus.

PubMed

Wieczorek, Aleksandra; Rys, Przemyslaw; Skrzekowska-Baran, Iwona; Malecki, Maciej

2008-01-01

In this paper, we examine the concept of surrogate endpoints (i.e. substitute outcome measures) and review their use in clinical trials involving therapies for diabetes mellitus using the example of metformin. Trials such as DCCT and UKPDS, in which patient-important endpoints were evaluated, are relatively rare in diabetology. Clinical decisions, therefore, are often based on evidence obtained using surrogate outcomes, usually fasting or postprandial glycemia or glycated hemoglobin level. In contrast to patient-important endpoints, surrogates do not describe direct clinical benefit to the patient. However, a proven association between a surrogate and patient-important endpoint is essential to draw appropriate therapeutic conclusions. In the process of new drug development, the duration of follow-up, sample size and methodology of the studies initially available are often inadequate to demonstrate the effect of the intervention on patient-important endpoints. Evidence concerning the effect of an intervention on surrogate outcomes usually comes first, followed only later by reports describing its influence on patient-important endpoints. Metformin may serve as an example in several ways. The first publications reported beneficial effects on glycemic control and body weight. Outcomes from the subsequent UKPDS study suggested the patient-important efficacy of metformin measured as a reduction in mortality and a decrease in the incidence of diabetic complications, including myocardial infarction. This reasoning process worked for some but not all strategies. It is particularly questionable whether a change in surrogate endpoint was associated with a potential deterioration in patient-important outcomes. Defining the general relationship between surrogates widely used as measures of metabolic control and patient-important endpoints remains an important challenge in contemporary diabetology.

Ensemble of surrogates-based optimization for identifying an optimal surfactant-enhanced aquifer remediation strategy at heterogeneous DNAPL-contaminated sites

NASA Astrophysics Data System (ADS)

Jiang, Xue; Lu, Wenxi; Hou, Zeyu; Zhao, Haiqing; Na, Jin

2015-11-01

The purpose of this study was to identify an optimal surfactant-enhanced aquifer remediation (SEAR) strategy for aquifers contaminated by dense non-aqueous phase liquid (DNAPL) based on an ensemble of surrogates-based optimization technique. A saturated heterogeneous medium contaminated by nitrobenzene was selected as case study. A new kind of surrogate-based SEAR optimization employing an ensemble surrogate (ES) model together with a genetic algorithm (GA) is presented. Four methods, namely radial basis function artificial neural network (RBFANN), kriging (KRG), support vector regression (SVR), and kernel extreme learning machines (KELM), were used to create four individual surrogate models, which were then compared. The comparison enabled us to select the two most accurate models (KELM and KRG) to establish an ES model of the SEAR simulation model, and the developed ES model as well as these four stand-alone surrogate models was compared. The results showed that the average relative error of the average nitrobenzene removal rates between the ES model and the simulation model for 20 test samples was 0.8%, which is a high approximation accuracy, and which indicates that the ES model provides more accurate predictions than the stand-alone surrogate models. Then, a nonlinear optimization model was formulated for the minimum cost, and the developed ES model was embedded into this optimization model as a constrained condition. Besides, GA was used to solve the optimization model to provide the optimal SEAR strategy. The developed ensemble surrogate-optimization approach was effective in seeking a cost-effective SEAR strategy for heterogeneous DNAPL-contaminated sites. This research is expected to enrich and develop the theoretical and technical implications for the analysis of remediation strategy optimization of DNAPL-contaminated aquifers.

Ensemble of Surrogates-based Optimization for Identifying an Optimal Surfactant-enhanced Aquifer Remediation Strategy at Heterogeneous DNAPL-contaminated Sites

NASA Astrophysics Data System (ADS)

Lu, W., Sr.; Xin, X.; Luo, J.; Jiang, X.; Zhang, Y.; Zhao, Y.; Chen, M.; Hou, Z.; Ouyang, Q.

2015-12-01

The purpose of this study was to identify an optimal surfactant-enhanced aquifer remediation (SEAR) strategy for aquifers contaminated by dense non-aqueous phase liquid (DNAPL) based on an ensemble of surrogates-based optimization technique. A saturated heterogeneous medium contaminated by nitrobenzene was selected as case study. A new kind of surrogate-based SEAR optimization employing an ensemble surrogate (ES) model together with a genetic algorithm (GA) is presented. Four methods, namely radial basis function artificial neural network (RBFANN), kriging (KRG), support vector regression (SVR), and kernel extreme learning machines (KELM), were used to create four individual surrogate models, which were then compared. The comparison enabled us to select the two most accurate models (KELM and KRG) to establish an ES model of the SEAR simulation model, and the developed ES model as well as these four stand-alone surrogate models was compared. The results showed that the average relative error of the average nitrobenzene removal rates between the ES model and the simulation model for 20 test samples was 0.8%, which is a high approximation accuracy, and which indicates that the ES model provides more accurate predictions than the stand-alone surrogate models. Then, a nonlinear optimization model was formulated for the minimum cost, and the developed ES model was embedded into this optimization model as a constrained condition. Besides, GA was used to solve the optimization model to provide the optimal SEAR strategy. The developed ensemble surrogate-optimization approach was effective in seeking a cost-effective SEAR strategy for heterogeneous DNAPL-contaminated sites. This research is expected to enrich and develop the theoretical and technical implications for the analysis of remediation strategy optimization of DNAPL-contaminated aquifers.

Comparison of treatment effect sizes from pivotal and postapproval trials of novel therapeutics approved by the FDA based on surrogate markers of disease: a meta-epidemiological study.

PubMed

Wallach, Joshua D; Ciani, Oriana; Pease, Alison M; Gonsalves, Gregg S; Krumholz, Harlan M; Taylor, Rod S; Ross, Joseph S

2018-03-21

The U.S. Food and Drug Administration (FDA) often approves new drugs based on trials that use surrogate markers for endpoints, which involve certain trade-offs and may risk making erroneous inferences about the medical product's actual clinical effect. This study aims to compare the treatment effects among pivotal trials supporting FDA approval of novel therapeutics based on surrogate markers of disease with those observed among postapproval trials for the same indication. We searched Drugs@FDA and PubMed to identify published randomized superiority design pivotal trials for all novel drugs initially approved by the FDA between 2005 and 2012 based on surrogate markers as primary endpoints and published postapproval trials using the same surrogate markers or patient-relevant outcomes as endpoints. Summary ratio of odds ratios (RORs) and difference between standardized mean differences (dSMDs) were used to quantify the average difference in treatment effects between pivotal and matched postapproval trials. Between 2005 and 2012, the FDA approved 88 novel drugs for 90 indications based on one or multiple pivotal trials using surrogate markers of disease. Of these, 27 novel drugs for 27 indications were approved based on pivotal trials using surrogate markers as primary endpoints that could be matched to at least one postapproval trial, for a total of 43 matches. For nine (75.0%) of the 12 matches using the same non-continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than postapproval trials. On average, treatment effects were 50% higher (more beneficial) in the pivotal than the postapproval trials (ROR 1.5; 95% confidence interval CI 1.01-2.23). For 17 (54.8%) of the 31 matches using the same continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than the postapproval trials. On average, there was no difference in treatment effects between pivotal and postapproval trials (dSMDs 0.01; 95% CI -0.15-0.16). Many postapproval drug trials are not directly comparable to previously published pivotal trials, particularly with respect to endpoint selection. Although treatment effects from pivotal trials supporting FDA approval of novel therapeutics based on non-continuous surrogate markers of disease are often larger than those observed among postapproval trials using surrogate markers as trial endpoints, there is no evidence of difference between pivotal and postapproval trials using continuous surrogate markers.

Effect of acute stretch injury on action potential and network activity of rat neocortical neurons in culture.

PubMed

Magou, George C; Pfister, Bryan J; Berlin, Joshua R

2015-10-22

The basis for acute seizures following traumatic brain injury (TBI) remains unclear. Animal models of TBI have revealed acute hyperexcitablility in cortical neurons that could underlie seizure activity, but studying initiating events causing hyperexcitability is difficult in these models. In vitro models of stretch injury with cultured cortical neurons, a surrogate for TBI, allow facile investigation of cellular changes after injury but they have only demonstrated post-injury hypoexcitability. The goal of this study was to determine if neuronal hyperexcitability could be triggered by in vitro stretch injury. Controlled uniaxial stretch injury was delivered to a spatially delimited region of a spontaneously active network of cultured rat cortical neurons, yielding a region of stretch-injured neurons and adjacent regions of non-stretched neurons that did not directly experience stretch injury. Spontaneous electrical activity was measured in non-stretched and stretch-injured neurons, and in control neuronal networks not subjected to stretch injury. Non-stretched neurons in stretch-injured cultures displayed a three-fold increase in action potential firing rate and bursting activity 30-60 min post-injury. Stretch-injured neurons, however, displayed dramatically lower rates of action potential firing and bursting. These results demonstrate that acute hyperexcitability can be observed in non-stretched neurons located in regions adjacent to the site of stretch injury, consistent with reports that seizure activity can arise from regions surrounding the site of localized brain injury. Thus, this in vitro procedure for localized neuronal stretch injury may provide a model to study the earliest cellular changes in neuronal function associated with acute post-traumatic seizures. Copyright © 2015. Published by Elsevier B.V.

Predictors of advance directives among nursing home residents with dementia.

PubMed

Huang, Hsiu-Li; Shyu, Yea-Ing Lotus; Weng, Li-Chueh; Chen, Kang-Hua; Hsu, Wen-Chuin

2018-03-01

ABSTRACTBackground:Advance directives are important for nursing home residents with dementia; for those with advanced dementia, surrogates determine medical decisions. However, in Taiwan, little is known about what influences the completion of these advance directives. The purpose of this study was to identify factors, which influence the presence of advance directives for nursing home residents with dementia in Taiwan. Our cross-sectional study analyzed a convenience sample of 143 nursing home dyads comprised of residents with dementia and family surrogates. Documentation of residents' advance directives, physical and cognitive status was obtained from medical charts. Surrogates completed the stress of end-of-life care decision scale and a questionnaire regarding their demographic characteristics. Nursing home characteristics were obtained from each chief administrator. Less than half of the nursing home residents (39.2%) had advance directives and most (96.4%) had been completed by family surrogates. The following were predictors of an advance directive: surrogates had previously signed a do-not-resuscitate as a proxy and had been informed of advance directives by a healthcare provider; nursing homes had policies for advance directives and a religious affiliation. Advance directives were uncommon for nursing home residents with dementia. Presence of an advance directive was associated with surrogate characteristics and the nursing home facilities; there was no association with characteristics of the nursing home resident. Our findings emphasize the need to develop policies and strategies, which ensure that all residents of nursing homes and their surrogates are aware of their right to an advance directive.

Dimensions and Role-Specific Mediators of Surrogate Trust in the ICU.

PubMed

Hutchison, Paul J; McLaughlin, Katie; Corbridge, Tom; Michelson, Kelly N; Emanuel, Linda; Sporn, Peter H S; Crowley-Matoka, Megan

2016-12-01

In the ICU, discussions between clinicians and surrogate decision makers are often accompanied by conflict about a patient's prognosis or care plan. Trust plays a role in limiting conflict, but little is known about the determinants of trust in the ICU. We sought to identify the dimensions of trust and clinician behaviors conducive to trust formation in the ICU. Prospective qualitative study. Medical ICU of a major urban university hospital. Surrogate decision makers of intubated, mechanically ventilated patients in the medical ICU. Semistructured interviews focused on surrogates' general experiences in the ICU and on their trust in the clinicians caring for the patient. Interviews were audio-recorded, transcribed verbatim, and coded by two reviewers. Constant comparison was used to identify themes pertaining to trust. Thirty surrogate interviews revealed five dimensions of trust in ICU clinicians: technical competence, communication, honesty, benevolence, and interpersonal skills. Most surrogates emphasized the role of nurses in trust formation, frequently citing their technical competence. Trust in physicians was most commonly related to honesty and the quality of their communication with surrogates. Interventions to improve trust in the ICU should be role-specific, since surrogate expectations are different for physicians and nurses with regard to behaviors relevant to trust. Further research is needed to confirm our findings and explore the impact of trust modification on clinician-family conflict.

A traits-based approach for prioritizing species for monitoring and surrogacy selection

DOE PAGES

Pracheil, Brenda M.; McManamay, Ryan A.; Bevelhimer, Mark S.; ...

2016-11-28

The bar for justifying the use of vertebrate animals for study is being increasingly raised, thus requiring increased rigor for species selection and study design. Although we have power analyses to provide quantitative backing for the numbers of organisms used, quantitative backing for selection of study species is not frequently employed. This can be especially important when measuring the impacts of ecosystem alteration, when study species must be chosen that are both sensitive to the alteration and of sufficient abundance for study. Just as important is providing justification for designation of surrogate species for study, especially when the species ofmore » interest is rare or of conservation concern and selection of an appropriate surrogate can have legal implications. In this study, we use a combination of GIS, a fish traits database and multivariate statistical analyses to quantitatively prioritize species for study and to determine potential study surrogate species. We provide two case studies to illustrate our quantitative, traits-based approach for designating study species and surrogate species. In the first case study, we select broadly representative fish species to understand the effects of turbine passage on adult fishes based on traits that suggest sensitivity to turbine passage. In our second case study, we present a framework for selecting a surrogate species for an endangered species. Lastly, we suggest that our traits-based framework can provide quantitative backing and added justification to selection of study species while expanding the inference space of study results.« less

A traits-based approach for prioritizing species for monitoring and surrogacy selection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pracheil, Brenda M.; McManamay, Ryan A.; Bevelhimer, Mark S.

The bar for justifying the use of vertebrate animals for study is being increasingly raised, thus requiring increased rigor for species selection and study design. Although we have power analyses to provide quantitative backing for the numbers of organisms used, quantitative backing for selection of study species is not frequently employed. This can be especially important when measuring the impacts of ecosystem alteration, when study species must be chosen that are both sensitive to the alteration and of sufficient abundance for study. Just as important is providing justification for designation of surrogate species for study, especially when the species ofmore » interest is rare or of conservation concern and selection of an appropriate surrogate can have legal implications. In this study, we use a combination of GIS, a fish traits database and multivariate statistical analyses to quantitatively prioritize species for study and to determine potential study surrogate species. We provide two case studies to illustrate our quantitative, traits-based approach for designating study species and surrogate species. In the first case study, we select broadly representative fish species to understand the effects of turbine passage on adult fishes based on traits that suggest sensitivity to turbine passage. In our second case study, we present a framework for selecting a surrogate species for an endangered species. Lastly, we suggest that our traits-based framework can provide quantitative backing and added justification to selection of study species while expanding the inference space of study results.« less

Surrogates for numerical simulations; optimization of eddy-promoter heat exchangers

NASA Technical Reports Server (NTRS)

Patera, Anthony T.; Patera, Anthony

1993-01-01

Although the advent of fast and inexpensive parallel computers has rendered numerous previously intractable calculations feasible, many numerical simulations remain too resource-intensive to be directly inserted in engineering optimization efforts. An attractive alternative to direct insertion considers models for computational systems: the expensive simulation is evoked only to construct and validate a simplified, input-output model; this simplified input-output model then serves as a simulation surrogate in subsequent engineering optimization studies. A simple 'Bayesian-validated' statistical framework for the construction, validation, and purposive application of static computer simulation surrogates is presented. As an example, dissipation-transport optimization of laminar-flow eddy-promoter heat exchangers are considered: parallel spectral element Navier-Stokes calculations serve to construct and validate surrogates for the flowrate and Nusselt number; these surrogates then represent the originating Navier-Stokes equations in the ensuing design process.

Evaluation of Escherichia coli biotype 1 as a surrogate for Escherichia coli O157:H7 for cooking, fermentation, freezing, and refrigerated storage in meat processes.

PubMed

Keeling, Carisa; Niebuhr, Steven E; Acuff, Gary R; Dickson, James S

2009-04-01

Five Escherichia coli biotype I isolates were compared with E. coli O157:H7 under four common meat processing conditions. The processes that were evaluated were freezing, refrigerating, fermentation, and thermal inactivation. For each study, at least one surrogate organism was not statistically different when compared with E. coli O157:H7. However, the four studies did not consistently show the same isolate as having this agreement. The three studies that involved temperature as a method of controlling or reducing the E. coli population all had at least one possible surrogate in common. In the fermentation study, only one isolate (BAA-1429) showed no statistical difference when compared with E. coli O157:H7. However, the population reductions that were observed indicated the isolates BAA-1427 and BAA-1431 would overestimate the surviving E. coli O157:H7 population in a fermented summer sausage. When all of the data from all of the surrogates were examined, it was found that isolates BAA-1427, BAA-1429, and BAA-1430 would be good surrogates for all four of the processes that were examined in this study. There was no statistical difference noted between these three isolates and E. coli O157:H7 in the refrigeration study. These isolates resulted in smaller population reductions than did E. coli O157:H7 in the frozen, fermentation, and thermal inactivation studies. This would indicate that these isolates would overpredict the E. coli O157:H7 population in these three instances. This overprediction results in an additional margin of safety when using E. coli biotype 1 as a surrogate.

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

PubMed

Carone, Nicola; Baiocco, Roberto; Lingiardi, Vittorio

2017-02-01

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

Surrogate Model Application to the Identification of Optimal Groundwater Exploitation Scheme Based on Regression Kriging Method—A Case Study of Western Jilin Province

PubMed Central

An, Yongkai; Lu, Wenxi; Cheng, Weiguo

2015-01-01

This paper introduces a surrogate model to identify an optimal exploitation scheme, while the western Jilin province was selected as the study area. A numerical simulation model of groundwater flow was established first, and four exploitation wells were set in the Tongyu county and Qian Gorlos county respectively so as to supply water to Daan county. Second, the Latin Hypercube Sampling (LHS) method was used to collect data in the feasible region for input variables. A surrogate model of the numerical simulation model of groundwater flow was developed using the regression kriging method. An optimization model was established to search an optimal groundwater exploitation scheme using the minimum average drawdown of groundwater table and the minimum cost of groundwater exploitation as multi-objective functions. Finally, the surrogate model was invoked by the optimization model in the process of solving the optimization problem. Results show that the relative error and root mean square error of the groundwater table drawdown between the simulation model and the surrogate model for 10 validation samples are both lower than 5%, which is a high approximation accuracy. The contrast between the surrogate-based simulation optimization model and the conventional simulation optimization model for solving the same optimization problem, shows the former only needs 5.5 hours, and the latter needs 25 days. The above results indicate that the surrogate model developed in this study could not only considerably reduce the computational burden of the simulation optimization process, but also maintain high computational accuracy. This can thus provide an effective method for identifying an optimal groundwater exploitation scheme quickly and accurately. PMID:26264008

Choice of surrogate tissue influences neonatal EWAS findings.

PubMed

Lin, Xinyi; Teh, Ai Ling; Chen, Li; Lim, Ives Yubin; Tan, Pei Fang; MacIsaac, Julia L; Morin, Alexander M; Yap, Fabian; Tan, Kok Hian; Saw, Seang Mei; Lee, Yung Seng; Holbrook, Joanna D; Godfrey, Keith M; Meaney, Michael J; Kobor, Michael S; Chong, Yap Seng; Gluckman, Peter D; Karnani, Neerja

2017-12-05

Epigenomes are tissue specific and thus the choice of surrogate tissue can play a critical role in interpreting neonatal epigenome-wide association studies (EWAS) and in their extrapolation to target tissue. To develop a better understanding of the link between tissue specificity and neonatal EWAS, and the contributions of genotype and prenatal factors, we compared genome-wide DNA methylation of cord tissue and cord blood, two of the most accessible surrogate tissues at birth. In 295 neonates, DNA methylation was profiled using Infinium HumanMethylation450 beadchip arrays. Sites of inter-individual variability in DNA methylation were mapped and compared across the two surrogate tissues at birth, i.e., cord tissue and cord blood. To ascertain the similarity to target tissues, DNA methylation profiles of surrogate tissues were compared to 25 primary tissues/cell types mapped under the Epigenome Roadmap project. Tissue-specific influences of genotype on the variable CpGs were also analyzed. Finally, to interrogate the impact of the in utero environment, EWAS on 45 prenatal factors were performed and compared across the surrogate tissues. Neonatal EWAS results were tissue specific. In comparison to cord blood, cord tissue showed higher inter-individual variability in the epigenome, with a lower proportion of CpGs influenced by genotype. Both neonatal tissues were good surrogates for target tissues of mesodermal origin. They also showed distinct phenotypic associations, with effect sizes of the overlapping CpGs being in the same order of magnitude. The inter-relationship between genetics, prenatal factors and epigenetics is tissue specific, and requires careful consideration in designing and interpreting future neonatal EWAS. This birth cohort is a prospective observational study, designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875 .

On the relationship between the causal-inference and meta-analytic paradigms for the validation of surrogate endpoints.

PubMed

Alonso, Ariel; Van der Elst, Wim; Molenberghs, Geert; Buyse, Marc; Burzykowski, Tomasz

2015-03-01

The increasing cost of drug development has raised the demand for surrogate endpoints when evaluating new drugs in clinical trials. However, over the years, it has become clear that surrogate endpoints need to be statistically evaluated and deemed valid, before they can be used as substitutes of "true" endpoints in clinical studies. Nowadays, two paradigms, based on causal-inference and meta-analysis, dominate the scene. Nonetheless, although the literature emanating from these paradigms is wide, till now the relationship between them has largely been left unexplored. In the present work, we discuss the conceptual framework underlying both approaches and study the relationship between them using theoretical elements and the analysis of a real case study. Furthermore, we show that the meta-analytic approach can be embedded within a causal-inference framework on the one hand and that it can be heuristically justified why surrogate endpoints successfully evaluated using this approach will often be appealing from a causal-inference perspective as well, on the other. A newly developed and user friendly R package Surrogate is provided to carry out the evaluation exercise. © 2014, The International Biometric Society.

A unified framework for the evaluation of surrogate endpoints in mental-health clinical trials.

PubMed

Molenberghs, Geert; Burzykowski, Tomasz; Alonso, Ariel; Assam, Pryseley; Tilahun, Abel; Buyse, Marc

2010-06-01

For a number of reasons, surrogate endpoints are considered instead of the so-called true endpoint in clinical studies, especially when such endpoints can be measured earlier, and/or with less burden for patient and experimenter. Surrogate endpoints may occur more frequently than their standard counterparts. For these reasons, it is not surprising that the use of surrogate endpoints in clinical practice is increasing. Building on the seminal work of Prentice(1) and Freedman et al.,(2) Buyse et al. (3) framed the evaluation exercise within a meta-analytic setting, in an effort to overcome difficulties that necessarily surround evaluation efforts based on a single trial. In this article, we review the meta-analytic approach for continuous outcomes, discuss extensions to non-normal and longitudinal settings, as well as proposals to unify the somewhat disparate collection of validation measures currently on the market. Implications for design and for predicting the effect of treatment in a new trial, based on the surrogate, are discussed. A case study in schizophrenia is analysed.

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

PubMed

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

2014-04-01

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

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

PubMed Central

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

2014-01-01

In clinical trials, a surrogate outcome variable (S) can be measured before the outcome of interest (T) and may provide early information regarding the treatment (Z) effect on T. Using the principal surrogacy framework introduced by Frangakis and Rubin (2002. Principal stratification in causal inference. Biometrics 58, 21–29), we consider an approach that has a causal interpretation and develop a Bayesian estimation strategy for surrogate validation when the joint distribution of potential surrogate and outcome measures is multivariate normal. From the joint conditional distribution of the potential outcomes of T, given the potential outcomes of S, we propose surrogacy validation measures from this model. As the model is not fully identifiable from the data, we propose some reasonable prior distributions and assumptions that can be placed on weakly identified parameters to aid in estimation. We explore the relationship between our surrogacy measures and the surrogacy measures proposed by Prentice (1989. Surrogate endpoints in clinical trials: definition and operational criteria. Statistics in Medicine 8, 431–440). The method is applied to data from a macular degeneration study and an ovarian cancer study. PMID:24285772

Do-not-resuscitate orders in an extended-care study group.

PubMed

Meyers, R M; Lurie, N; Breitenbucher, R B; Waring, C J

1990-09-01

We examined the charts of 911 nursing home patients in Hennepin County, Minnesota, to determine the prevalence of written do-not-resuscitate (DNR) orders. Information regarding demographic characteristics, and whether a surrogate decisionmaker was available and participated in the decision, was also collected. Twenty-seven percent of patients had DNR orders. Ninety percent of all patients had potentially available surrogate decisionmakers. However, for 31% of patients with DNR orders, there was no documentation of patient or surrogate participation in the DNR decision. Univariate analysis identified female sex; increased age, level of care (skilled versus intermediate), presence of a potential surrogate decisionmaker, and increasing length of time since nursing home admission as factors associated with presence of DNR orders. When a logistic regression model was used, increased age, increased length of time since nursing home admission, skilled versus intermediate level of care, and presence of a surrogate decisionmaker were independently associated with presence of DNR status. Several variables are independently associated with written DNR orders; their relationship to the factors physicians use in decision making requires further study.

Spot Sampling and Exposure Surrogate Selection as Sources of Bias in Environmental Epidemiology Studies

EPA Science Inventory

Spot measurements of chemical biomarkers are often used as quantitative exposure surrogates in environmental epidemiology studies. These measures can be expressed a number of different ways – for example, urinary biomarkers can be expressed in units of concentration (&micr...

Surrogate-based Analysis and Optimization

NASA Technical Reports Server (NTRS)

Queipo, Nestor V.; Haftka, Raphael T.; Shyy, Wei; Goel, Tushar; Vaidyanathan, Raj; Tucker, P. Kevin

2005-01-01

A major challenge to the successful full-scale development of modem aerospace systems is to address competing objectives such as improved performance, reduced costs, and enhanced safety. Accurate, high-fidelity models are typically time consuming and computationally expensive. Furthermore, informed decisions should be made with an understanding of the impact (global sensitivity) of the design variables on the different objectives. In this context, the so-called surrogate-based approach for analysis and optimization can play a very valuable role. The surrogates are constructed using data drawn from high-fidelity models, and provide fast approximations of the objectives and constraints at new design points, thereby making sensitivity and optimization studies feasible. This paper provides a comprehensive discussion of the fundamental issues that arise in surrogate-based analysis and optimization (SBAO), highlighting concepts, methods, techniques, as well as practical implications. The issues addressed include the selection of the loss function and regularization criteria for constructing the surrogates, design of experiments, surrogate selection and construction, sensitivity analysis, convergence, and optimization. The multi-objective optimal design of a liquid rocket injector is presented to highlight the state of the art and to help guide future efforts.

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

PubMed

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

2007-01-01

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

A Taylor Expansion-Based Adaptive Design Strategy for Global Surrogate Modeling With Applications in Groundwater Modeling

NASA Astrophysics Data System (ADS)

Mo, Shaoxing; Lu, Dan; Shi, Xiaoqing; Zhang, Guannan; Ye, Ming; Wu, Jianfeng; Wu, Jichun

2017-12-01

Global sensitivity analysis (GSA) and uncertainty quantification (UQ) for groundwater modeling are challenging because of the model complexity and significant computational requirements. To reduce the massive computational cost, a cheap-to-evaluate surrogate model is usually constructed to approximate and replace the expensive groundwater models in the GSA and UQ. Constructing an accurate surrogate requires actual model simulations on a number of parameter samples. Thus, a robust experimental design strategy is desired to locate informative samples so as to reduce the computational cost in surrogate construction and consequently to improve the efficiency in the GSA and UQ. In this study, we develop a Taylor expansion-based adaptive design (TEAD) that aims to build an accurate global surrogate model with a small training sample size. TEAD defines a novel hybrid score function to search informative samples, and a robust stopping criterion to terminate the sample search that guarantees the resulted approximation errors satisfy the desired accuracy. The good performance of TEAD in building global surrogate models is demonstrated in seven analytical functions with different dimensionality and complexity in comparison to two widely used experimental design methods. The application of the TEAD-based surrogate method in two groundwater models shows that the TEAD design can effectively improve the computational efficiency of GSA and UQ for groundwater modeling.

Developing the role of the social worker as coordinator of services at the surrogate parenting center.

PubMed

Gagin, Roni; Cohen, Miri; Greenblatt, Lee; Solomon, Hanah; Itskovitz-Eldor, Joseph

2004-01-01

A law permitting couples to conceive biological children through surrogacy was legislated in Israel in March 1996. The Rambam Medical Center has established the only nonprofit Surrogate Parenting Center at a public hospital in Israel. The multidisciplinary teamwork at the Center is case managed by a social worker. An important role of the social work intervention is consultation and support for the couple and the surrogate at all stages of the process. The case study presented in the article illustrates the need for sensitive and professional intervention due to the complexity of the surrogacy process and the crisis it involves for both the surrogate and the couple. In light of the growing parenting surrogacy cases in the United States, Europe, and Israel, a structured social work intervention model is described, which may be implemented at public or private surrogate parenting centers.

Biomarkers and Surrogate Endpoints: Lessons Learned From Glaucoma

PubMed Central

Medeiros, Felipe A.

2017-01-01

With the recent progress in imaging technologies for assessment of structural damage in glaucoma, a debate has emerged on whether these measurements can be used as valid surrogate endpoints in clinical trials evaluating new therapies for the disease. A discussion of surrogates should be grounded on knowledge acquired from their use in other areas of medicine as well as regulatory requirements. This article reviews the conditions for valid surrogacy in the context of glaucoma clinical trials and critically evaluates the role of biomarkers such as IOP and imaging measurements as potential surrogates for clinically relevant outcomes. Valid surrogate endpoints must be able to predict a clinically relevant endpoint, such as loss of vision or decrease in quality of life. In addition, the effect of a proposed treatment on the surrogate must capture the effect of the treatment on the clinically relevant endpoint. Despite its widespread use in clinical trials, no proper validation of IOP as a surrogate endpoint has yet been conducted for any class of IOP-lowering treatments. Although strong evidence has accumulated about imaging measurements as predictors of relevant functional outcomes in glaucoma, there is still insufficient evidence to support their use as valid surrogate endpoints. However, imaging biomarkers could potentially be used as part of composite endpoints in glaucoma trials, overcoming weaknesses of the use of structural or functional endpoints in isolation. Efforts should be taken to properly design and conduct studies that can provide proper validation of potential biomarkers in glaucoma clinical trials. PMID:28475699

Biomarkers and Surrogate Endpoints: Lessons Learned From Glaucoma.

PubMed

Medeiros, Felipe A

2017-05-01

With the recent progress in imaging technologies for assessment of structural damage in glaucoma, a debate has emerged on whether these measurements can be used as valid surrogate endpoints in clinical trials evaluating new therapies for the disease. A discussion of surrogates should be grounded on knowledge acquired from their use in other areas of medicine as well as regulatory requirements. This article reviews the conditions for valid surrogacy in the context of glaucoma clinical trials and critically evaluates the role of biomarkers such as IOP and imaging measurements as potential surrogates for clinically relevant outcomes. Valid surrogate endpoints must be able to predict a clinically relevant endpoint, such as loss of vision or decrease in quality of life. In addition, the effect of a proposed treatment on the surrogate must capture the effect of the treatment on the clinically relevant endpoint. Despite its widespread use in clinical trials, no proper validation of IOP as a surrogate endpoint has yet been conducted for any class of IOP-lowering treatments. Although strong evidence has accumulated about imaging measurements as predictors of relevant functional outcomes in glaucoma, there is still insufficient evidence to support their use as valid surrogate endpoints. However, imaging biomarkers could potentially be used as part of composite endpoints in glaucoma trials, overcoming weaknesses of the use of structural or functional endpoints in isolation. Efforts should be taken to properly design and conduct studies that can provide proper validation of potential biomarkers in glaucoma clinical trials.

An optical method for characterizing carbon content in ceramic pot filters.

PubMed

Goodwin, J Y; Elmore, A C; Salvinelli, C; Reidmeyer, Mary R

2017-08-01

Ceramic pot filter (CPF) technology is a relatively common means of household water treatment in developing areas, and performance characteristics of CPFs have been characterized using production CPFs, experimental CPFs fabricated in research laboratories, and ceramic disks intended to be CPF surrogates. There is evidence that CPF manufacturers do not always fire their products according to best practices and the result is incomplete combustion of the pore forming material and the creation of a carbon core in the final CPFs. Researchers seldom acknowledge the existence of potential existence of carbon cores, and at least one CPF producer has postulated that the carbon may be beneficial in terms of final water quality because of the presence of activated carbon in consumer filters marketed in the Western world. An initial step in characterizing the presence and impact of carbon cores is the characterization of those cores. An optical method which may be more viable to producers relative to off-site laboratory analysis of carbon content has been developed and verified. The use of the optical method is demonstrated via preliminary disinfection and flowrate studies, and the results of these studies indicate that the method may be of use in studying production kiln operation.

Internet health information seeking is a team sport: analysis of the Pew Internet Survey.

PubMed

Sadasivam, Rajani S; Kinney, Rebecca L; Lemon, Stephenie C; Shimada, Stephanie L; Allison, Jeroan J; Houston, Thomas K

2013-03-01

Previous studies examining characteristics of Internet health information seekers do not distinguish between those who only seek for themselves, and surrogate seekers who look for health information for family or friends. Identifying the unique characteristics of surrogate seekers would help in developing Internet interventions that better support these information seekers. To assess differences between self seekers versus those that act also as surrogate seekers. We analyzed data from the cross-sectional Pew Internet and American Life Project November/December 2008 health survey. Our dependent variable was self-report of type of health information seeking (surrogate versus self seeking). Independent variables included demographics, health status, and caregiving. After bivariate comparisons, we then developed multivariable models using logistic regression to assess characteristics associated with surrogate seeking. Out of 1250 respondents who reported seeking health information online, 56% (N=705) reported being surrogate seekers. In multivariable models, compared with those who sought information for themselves only, surrogate seekers were more likely both married and a parent (OR=1.57, CI=1.08, 2.28), having good (OR=2.05, CI=1.34, 3.12) or excellent (OR=2.72, CI=1.70, 4.33) health status, being caregiver of an adult relative (OR=1.76, CI=1.34, 2.30), having someone close with a serious medical condition (OR=1.62, CI=1.21, 2.17) and having someone close to them facing a chronic illness (OR=1.55, CI=1.17, 2.04). Our findings provide evidence that information needs of surrogate seekers are not being met, specifically of caregivers. Additional research is needed to develop new functions that support surrogate seekers. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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

2017-08-01

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

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

PubMed

Methy, Nicolas; Bedenne, Laurent; Bonnetain, Franck

2010-06-10

Overall survival (OS) is the gold standard for the demonstration of a clinical benefit in cancer trials. Replacement of OS by a surrogate endpoint allows to reduce trial duration. To date, few surrogate endpoints have been validated in digestive oncology. The aim of this study was to draw up an ordered list of potential surrogate endpoints for OS in digestive cancer trials, by way of a survey among clinicians and methodologists. Secondary objective was to obtain their opinion on surrogacy and quality of life (QoL). In 2007 and 2008, self administered sequential questionnaires were sent to a panel of French clinicians and methodologists involved in the conduct of cancer clinical trials. In the first questionnaire, panellists were asked to choose the most important characteristics defining a surrogate among six proposals, to give advantages and drawbacks of the surrogates, and to answer questions about their validation and use. Then they had to suggest potential surrogate endpoints for OS in each of the following tumour sites: oesophagus, stomach, liver, pancreas, biliary tract, lymphoma, colon, rectum, and anus. They finally gave their opinion on QoL as surrogate endpoint. In the second questionnaire, they had to classify the previously proposed candidate surrogates from the most (position #1) to the least relevant in their opinion.Frequency at which the endpoints were chosen as first, second or third most relevant surrogates was calculated and served as final ranking. Response rate was 30% (24/80) in the first round and 20% (16/80) in the second one. Participants highlighted key points concerning surrogacy. In particular, they reminded that a surrogate endpoint is expected to predict clinical benefit in a well-defined therapeutic situation. Half of them thought it was not relevant to study QoL as surrogate for OS.DFS, in the neoadjuvant settings or early stages, and PFS, in the non operable or metastatic settings, were ranked first, with a frequency of more than 69% in 20 out of 22 settings. PFS was proposed in association with QoL in metastatic primary liver and stomach cancers (both 81%). This composite endpoint was ranked second in metastatic oesophageal (69%), colorectal (56%) and anal (56%) cancers, whereas QoL alone was also suggested in most metastatic situations.Other endpoints frequently suggested were R0 resection in the neoadjuvant settings (oesophagus (69%), stomach (56%), pancreas (75%) and biliary tract (63%)) and response. An unexpected endpoint was metastatic PFS in non operable oesophageal (31%) and pancreatic (44%) cancers. Quality and results of surgical procedures like sphincter preservation were also cited as eligible surrogate endpoints in rectal (19%) and anal (50% in case of localized disease) cancers. Except for alpha-FP kinetic in hepatocellular carcinoma (13%) and CA19-9 decline (6%) in pancreas, few endpoints based on biological or tumour markers were proposed. The overall results should help prioritise the endpoints to be statistically evaluated as surrogate for OS, so that trialists and clinicians can rely on endpoints that ensure relevant clinical benefit to the patient.

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

PubMed Central

2010-01-01

Background Overall survival (OS) is the gold standard for the demonstration of a clinical benefit in cancer trials. Replacement of OS by a surrogate endpoint allows to reduce trial duration. To date, few surrogate endpoints have been validated in digestive oncology. The aim of this study was to draw up an ordered list of potential surrogate endpoints for OS in digestive cancer trials, by way of a survey among clinicians and methodologists. Secondary objective was to obtain their opinion on surrogacy and quality of life (QoL). Methods In 2007 and 2008, self administered sequential questionnaires were sent to a panel of French clinicians and methodologists involved in the conduct of cancer clinical trials. In the first questionnaire, panellists were asked to choose the most important characteristics defining a surrogate among six proposals, to give advantages and drawbacks of the surrogates, and to answer questions about their validation and use. Then they had to suggest potential surrogate endpoints for OS in each of the following tumour sites: oesophagus, stomach, liver, pancreas, biliary tract, lymphoma, colon, rectum, and anus. They finally gave their opinion on QoL as surrogate endpoint. In the second questionnaire, they had to classify the previously proposed candidate surrogates from the most (position #1) to the least relevant in their opinion. Frequency at which the endpoints were chosen as first, second or third most relevant surrogates was calculated and served as final ranking. Results Response rate was 30% (24/80) in the first round and 20% (16/80) in the second one. Participants highlighted key points concerning surrogacy. In particular, they reminded that a surrogate endpoint is expected to predict clinical benefit in a well-defined therapeutic situation. Half of them thought it was not relevant to study QoL as surrogate for OS. DFS, in the neoadjuvant settings or early stages, and PFS, in the non operable or metastatic settings, were ranked first, with a frequency of more than 69% in 20 out of 22 settings. PFS was proposed in association with QoL in metastatic primary liver and stomach cancers (both 81%). This composite endpoint was ranked second in metastatic oesophageal (69%), colorectal (56%) and anal (56%) cancers, whereas QoL alone was also suggested in most metastatic situations. Other endpoints frequently suggested were R0 resection in the neoadjuvant settings (oesophagus (69%), stomach (56%), pancreas (75%) and biliary tract (63%)) and response. An unexpected endpoint was metastatic PFS in non operable oesophageal (31%) and pancreatic (44%) cancers. Quality and results of surgical procedures like sphincter preservation were also cited as eligible surrogate endpoints in rectal (19%) and anal (50% in case of localized disease) cancers. Except for alpha-FP kinetic in hepatocellular carcinoma (13%) and CA19-9 decline (6%) in pancreas, few endpoints based on biological or tumour markers were proposed. Conclusion The overall results should help prioritise the endpoints to be statistically evaluated as surrogate for OS, so that trialists and clinicians can rely on endpoints that ensure relevant clinical benefit to the patient. PMID:20537166

Design Mining Interacting Wind Turbines.

PubMed

Preen, Richard J; Bull, Larry

2016-01-01

An initial study has recently been presented of surrogate-assisted evolutionary algorithms used to design vertical-axis wind turbines wherein candidate prototypes are evaluated under fan-generated wind conditions after being physically instantiated by a 3D printer. Unlike other approaches, such as computational fluid dynamics simulations, no mathematical formulations were used and no model assumptions were made. This paper extends that work by exploring alternative surrogate modelling and evolutionary techniques. The accuracy of various modelling algorithms used to estimate the fitness of evaluated individuals from the initial experiments is compared. The effect of temporally windowing surrogate model training samples is explored. A surrogate-assisted approach based on an enhanced local search is introduced; and alternative coevolution collaboration schemes are examined.

Air Pollution Exposure Modeling for Epidemiology Studies and Public Health

EPA Science Inventory

Air pollution epidemiology studies of ambient fine particulate matter (PM2.5) often use outdoor concentrations as exposure surrogates. These surrogates can induce exposure error since they do not account for (1) time spent indoors with ambient PM2.5 levels attenuated from outdoor...

Shape Optimization by Bayesian-Validated Computer-Simulation Surrogates

NASA Technical Reports Server (NTRS)

Patera, Anthony T.

1997-01-01

A nonparametric-validated, surrogate approach to optimization has been applied to the computational optimization of eddy-promoter heat exchangers and to the experimental optimization of a multielement airfoil. In addition to the baseline surrogate framework, a surrogate-Pareto framework has been applied to the two-criteria, eddy-promoter design problem. The Pareto analysis improves the predictability of the surrogate results, preserves generality, and provides a means to rapidly determine design trade-offs. Significant contributions have been made in the geometric description used for the eddy-promoter inclusions as well as to the surrogate framework itself. A level-set based, geometric description has been developed to define the shape of the eddy-promoter inclusions. The level-set technique allows for topology changes (from single-body,eddy-promoter configurations to two-body configurations) without requiring any additional logic. The continuity of the output responses for input variations that cross the boundary between topologies has been demonstrated. Input-output continuity is required for the straightforward application of surrogate techniques in which simplified, interpolative models are fitted through a construction set of data. The surrogate framework developed previously has been extended in a number of ways. First, the formulation for a general, two-output, two-performance metric problem is presented. Surrogates are constructed and validated for the outputs. The performance metrics can be functions of both outputs, as well as explicitly of the inputs, and serve to characterize the design preferences. By segregating the outputs and the performance metrics, an additional level of flexibility is provided to the designer. The validated outputs can be used in future design studies and the error estimates provided by the output validation step still apply, and require no additional appeals to the expensive analysis. Second, a candidate-based a posteriori error analysis capability has been developed which provides probabilistic error estimates on the true performance for a design randomly selected near the surrogate-predicted optimal design.

Ultrasound and radiology surrogate endpoints in pharmacological studies.

PubMed

Agewall, S; DeGroot, E; Marcos-Alberca, P; Zamorano, J L; Barrero, A A; Badano, L P; Perrone-Filardi, P

2012-09-01

Cardiovascular studies investigating therapeutic intervention with clinical endpoints are costly due to the need for considerable duration and large number of patients, or both. Therefore, for evaluation of novel cardiovascular drug efficacy, surrogate endpoints are used. Cardiovascular imaging endpoints have proven their worth. Sometimes the relevance of imaging is questioned and other methods are suggested instead. There is also some confusion about the strengths of imaging endpoints. The aim of the present paper is to review ultrasound and radiology imaging techniques as surrogate endpoints in pharmacological trials. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Identifying family members who may struggle in the role of surrogate decision maker.

PubMed

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

2012-08-01

Although acting as a surrogate decision maker can be highly distressing for some family members of intensive care unit patients, little is known about whether there are modifiable risk factors for the occurrence of such difficulties. To identify: 1) factors associated with lower levels of confidence among family members to function as surrogates and 2) whether the quality of clinician-family communication is associated with the timing of decisions to forego life support. We conducted a prospective study of 230 surrogate decision makers for incapacitated, mechanically ventilated patients at high risk of death in four intensive care units at University of California San Francisco Medical Center from 2006 to 2007. Surrogates completed a questionnaire addressing their perceived ability to act as a surrogate and the quality of their communication with physicians. We used clustered multivariate logistic regression to identify predictors of low levels of perceived ability to act as a surrogate and a Cox proportional hazard model to determine whether quality of communication was associated with the timing of decisions to withdraw life support. There was substantial variability in family members' confidence to act as surrogate decision makers, with 27% rating their perceived ability as 7 or lower on a 10-point scale. Independent predictors of lower role confidence were the lack of prior experience as a surrogate (odds ratio 2.2, 95% confidence interval [1.04-4.46], p=.04), no prior discussions with the patient about treatment preferences (odds ratio 3.7, 95% confidence interval [1.79-7.76], p<.001), and poor quality of communication with the ICU physician (odds ratio 1.2, 95% confidence interval [1.09-1.35] p<.001). Higher quality physician-family communication was associated with a significantly shorter duration of life-sustaining treatment among patients who died (β=0.11, p=.001). Family members without prior experience as a surrogate and those who had not engaged in advanced discussions with the patient about treatment preferences were at higher risk to report less confidence in carrying out the surrogate role. Better-quality clinician-family communication was associated with both more confidence among family members to act as surrogates and a shorter duration of use of life support among patients who died.

Communication Quality Predicts Psychological Well-Being and Satisfaction in Family Surrogates of Hospitalized Older Adults: An Observational Study.

PubMed

Torke, Alexia M; Callahan, Christopher M; Sachs, Greg A; Wocial, Lucia D; Helft, Paul R; Monahan, Patrick O; Slaven, James E; Montz, Kianna; Burke, Emily S; Inger, Lev

2018-03-01

Many hospitalized older adults require family surrogates to make decisions, but surrogates may perceive that the quality of medical decisions is low and may have poor psychological outcomes after the patient's hospitalization. To determine the relationship between communication quality and high-quality medical decisions, psychological well-being, and satisfaction for surrogates of hospitalized older adults. Observational study at three hospitals in a Midwest metropolitan area. Hospitalized older adults (65+ years) admitted to medicine and medical intensive care units who were unable to make medical decisions, and their family surrogates. Among 799 eligible dyads, 364 (45.6%) completed the study. Communication was assessed during hospitalization using the information and emotional support subscales of the Family Inpatient Communication Survey. Decision quality was assessed with the Decisional Conflict Scale. Outcomes assessed at baseline and 4-6 weeks post-discharge included anxiety (Generalized Anxiety Disorder-7), depression (Patient Health Questionnaire-9), post-traumatic stress (Impact of Event Scale-Revised), and satisfaction (Hospital Consumer Assessment of Healthcare Providers and Systems). The mean patient age was 81.9 years (SD 8.32); 62% were women, and 28% African American. Among surrogates, 67% were adult children. Six to eight weeks post-discharge, 22.6% of surrogates reported anxiety (11.3% moderate-severe anxiety); 29% reported depression, (14.0% moderate-severe), and 14.6% had high levels of post-traumatic stress. Emotional support was associated with lower odds of anxiety (adjusted odds ratio [AOR] = 0.65, 95% CI 0.50, 0.85) and depression (AOR = 0.80, 95% CI 0.65, 0.99) at follow-up. In multivariable linear regression, emotional support was associated with lower post-traumatic stress (β = -0.30, p = 0.003) and higher decision quality (β = -0.44, p < 0.0001). Information was associated with higher post-traumatic stress (β = 0.23, p = 0.022) but also higher satisfaction (β = 0.61, p < 0.001). Emotional support of hospital surrogates is consistently associated with better psychological outcomes and decision quality, suggesting an opportunity to improve decision making and well-being.

Exploring the relationship between the causal-inference and meta-analytic paradigms for the evaluation of surrogate endpoints.

PubMed

Van der Elst, Wim; Molenberghs, Geert; Alonso, Ariel

2016-04-15

Nowadays, two main frameworks for the evaluation of surrogate endpoints, based on causal-inference and meta-analysis, dominate the scene. Earlier work showed that the metrics of surrogacy introduced in both paradigms are related, although in a complex way that is difficult to study analytically. In the present work, this relationship is further examined using simulations and the analysis of a case study. The results indicate that the extent to which both paradigms lead to similar conclusions regarding the validity of the surrogate, depends on a complex interplay between multiple factors like the ratio of the between and within trial variability and the unidentifiable correlations between the potential outcomes. All the analyses were carried out using the newly developed R package Surrogate, which is freely available via CRAN. Copyright © 2015 John Wiley & Sons, Ltd.

Comparison of Alcian blue and total carbohydrate assays for quantitation of transparent exopolymer particles (TEP) in biofouling studies.

PubMed

Li, Xu; Skillman, Lucy; Li, Dan; Ela, Wendell P

2018-04-15

Transparent exopolymer particles (TEP) and their precursors are gel-like acidic polysaccharide particles. Both TEP precursors and TEP have been identified as causal factors in fouling of desalination and water treatment systems. For comparison between studies, it is important to accurately measure the amount and fouling capacity of both components. However, the accuracy and recovery of the currently used Alcian blue based TEP measurement of different surrogates and different size fractions are not well understood. In this study, we compared Alcian blue based TEP measurements with a total carbohydrate assay method. Three surrogates; xanthan gum, pectin and alginic acid; were evaluated at different salinities. Total carbohydrate concentrations of particulates (>0.4 μm) and their precursors (<0.4 μm, >10 kDa) varied depending on water salinity and method of recovery. As xanthan gum is the most frequently used surrogate in fouling studies, TEP concentration is expressed as xanthan gum equivalents (mg XG eq /L) in this study. At a salinity of 35 mg/L sea salt, total carbohydrate assays showed a much higher particulate TEP fraction for alginic acid (38%) compared to xanthan gum (9%) and pectin (12%). The concentrations of particulate TEP therefore may only represent ∼10% of the total mass; while precursor TEP represents ∼80% of the total TEP. This highlights the importance of reporting both particulate and precursor TEP for membrane biofouling studies. The calculated concentrations of TEP and their precursors in seawater samples are also highly dependent on type of surrogate and resulting calibration factor. A linear correlation between TEP recovery and calibration factor was demonstrated in this study for all three surrogates. The relative importance and accuracy of measurement method, particulate size, surrogate type, and recovery are described in detail in this study. Copyright © 2017. Published by Elsevier Ltd.

Dynamic Load Measurement of Ballistic Gelatin Impact Using an Instrumented Tube

NASA Technical Reports Server (NTRS)

Seidt, J. D.; Periira, J. M.; Hammer, J. T.; Gilat, A.; Ruggeri, C. R.

2012-01-01

Bird strikes are a common problem for the aerospace industry and can cause serious damage to an aircraft. Ballistic gelatin is frequently used as a surrogate for actual bird carcasses in bird strike tests. Numerical simulations of these tests are used to supplement experimental data, therefore it is necessary to use numerical modeling techniques that can accurately capture the dynamic response of ballistic gelatin. An experimental technique is introduced to validate these modeling techniques. A ballistic gelatin projectile is fired into a strike plate attached to a 36 in. long sensor tube. Dynamic load is measured at two locations relative to the strike plate using strain gages configured in a full Wheatstone bridge. Data from these experiments are used to validate a gelatin constitutive model. Simulations of the apparatus are analyzed to investigate its performance.

The oral disposition index is a strong predictor of incident diabetes in Asian Indian prediabetic men.

PubMed

Ram, Jagannathan; Snehalatha, Chamukuttan; Selvam, Sundaram; Nanditha, Arun; Shetty, Ananth Samith; Godsland, Ian F; Johnston, Desmond G; Ramachandran, Ambady

2015-08-01

In this analysis, we sought to examine the prospective association of the disposition index (DIo) derived from oral glucose tolerance test with incident diabetes in Asian Indian men with impaired glucose tolerance (IGT). These post hoc analyses used data from a 2-year prospective study in primary prevention of diabetes using lifestyle intervention among 517 men with IGT. All the participants received standard lifestyle advice at baseline. The surrogate insulin sensitivity and insulin secretion measures were tested for their hyperbolic relationship. Predictive associations of various surrogate measures with incident diabetes were determined using receiver operating characteristic curves. The combination of total area under the curve of insulin-to-glucose ratio (AUCinsulin/glucose) and Matsuda's insulin sensitivity index was the best equation to depict DIo [β: -0.954 (95 % CI -1.015 to -0.893)] compared to other measures tested in this cohort. There was an inverse association between change in DIo at the final follow-up and development of incident diabetes. Among the surrogate insulin measures studied, DIo [AUC (0.717 (95 % CI 0.675-0.756))] as a composite measure was superior than other surrogate indices. Among the surrogate indices studied, DIo was the best measure associated with incident diabetes.

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

PubMed

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

2017-08-01

Difficult conversations in medical care often occur between physicians and patients' surrogates, individuals entrusted with medical decisions for patients who lack the capacity to make them. Poor communication between patients' surrogates and physicians may exacerbate anxiety and guilt for surrogates, and may contribute to physician stress and burnout. This pilot study assesses the effectiveness of an experiential learning workshop that was conducted in a clinical setting, and aimed at improving resident physician communication skills with a focus on surrogate decision-making. From April through June 2016, we assessed internal medicine residents' baseline communication skills through an objective structured clinical examination (OSCE) with actors representing standardized surrogates. After an intensive, 6-hour communication skills workshop, residents were reassessed via an OSCE on the same day. A faculty facilitator and the surrogate evaluated participants' communication skills via the expanded Gap Kalamazoo Consensus Statement Assessment Form. Wilcoxon signed rank tests (α of .05) compared mean pre- and postworkshop scores. Of 44 residents, 33 (75%) participated. Participants' average preworkshop OSCE scores ( M  = 3.3, SD = 0.9) were significantly lower than postworkshop scores ( M  = 4.3; SD = 0.8; Z  = 4.193; P  < .001; effect size r  = 0.52). After the workshop, the majority of participants self-reported feeling "more confident." 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.

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

PubMed

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

2008-05-01

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

A Taylor Expansion-Based Adaptive Design Strategy for Global Surrogate Modeling With Applications in Groundwater Modeling

DOE PAGES

Mo, Shaoxing; Lu, Dan; Shi, Xiaoqing; ...

2017-12-27

Global sensitivity analysis (GSA) and uncertainty quantification (UQ) for groundwater modeling are challenging because of the model complexity and significant computational requirements. To reduce the massive computational cost, a cheap-to-evaluate surrogate model is usually constructed to approximate and replace the expensive groundwater models in the GSA and UQ. Constructing an accurate surrogate requires actual model simulations on a number of parameter samples. Thus, a robust experimental design strategy is desired to locate informative samples so as to reduce the computational cost in surrogate construction and consequently to improve the efficiency in the GSA and UQ. In this study, we developmore » a Taylor expansion-based adaptive design (TEAD) that aims to build an accurate global surrogate model with a small training sample size. TEAD defines a novel hybrid score function to search informative samples, and a robust stopping criterion to terminate the sample search that guarantees the resulted approximation errors satisfy the desired accuracy. The good performance of TEAD in building global surrogate models is demonstrated in seven analytical functions with different dimensionality and complexity in comparison to two widely used experimental design methods. The application of the TEAD-based surrogate method in two groundwater models shows that the TEAD design can effectively improve the computational efficiency of GSA and UQ for groundwater modeling.« less

The Family Navigator: A Pilot Intervention to Support Intensive Care Unit Family Surrogates.

PubMed

Torke, Alexia M; Wocial, Lucia D; Johns, Shelley A; Sachs, Greg A; Callahan, Christopher M; Bosslet, Gabriel T; Slaven, James E; Perkins, Susan M; Hickman, Susan E; Montz, Kianna; Burke, Emily S

2016-11-01

Communication problems between family surrogates and intensive care unit (ICU) clinicians have been documented, but few interventions are effective. Nurses have the potential to play an expanded role in ICU communication and decision making. To conduct a pilot randomized controlled trial of the family navigator (FN), a distinct nursing role to address family members' unmet communication needs early in an ICU stay. An interprofessional team developed the FN protocol. A randomized controlled pilot intervention trial of the FN was performed in a tertiary referral hospital's ICU to test the feasibility and acceptability of the intervention. The intervention addressed informational and emotional communication needs through daily contact by using structured clinical updates, emotional and informational support modules, family meeting support, and follow-up phone calls. Twenty-six surrogate/patient pairs (13 per study arm) were enrolled. Surrogates randomized to the intervention had contact with the FN on 90% or more of eligible patient days. All surrogates agreed that they would recom mend the FN to other families. Open-ended comments from both surrogates and clinicians were uniformly positive. Having a fully integrated nurse empowered to facilitate decision making is a feasible intervention in an ICU and is well-received by ICU families and staff. A larger randomized controlled trial is needed to demonstrate impact on important outcomes, such as surrogates' well-being and decision quality. ©2016 American Association of Critical-Care Nurses.

A Taylor Expansion-Based Adaptive Design Strategy for Global Surrogate Modeling With Applications in Groundwater Modeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mo, Shaoxing; Lu, Dan; Shi, Xiaoqing

Global sensitivity analysis (GSA) and uncertainty quantification (UQ) for groundwater modeling are challenging because of the model complexity and significant computational requirements. To reduce the massive computational cost, a cheap-to-evaluate surrogate model is usually constructed to approximate and replace the expensive groundwater models in the GSA and UQ. Constructing an accurate surrogate requires actual model simulations on a number of parameter samples. Thus, a robust experimental design strategy is desired to locate informative samples so as to reduce the computational cost in surrogate construction and consequently to improve the efficiency in the GSA and UQ. In this study, we developmore » a Taylor expansion-based adaptive design (TEAD) that aims to build an accurate global surrogate model with a small training sample size. TEAD defines a novel hybrid score function to search informative samples, and a robust stopping criterion to terminate the sample search that guarantees the resulted approximation errors satisfy the desired accuracy. The good performance of TEAD in building global surrogate models is demonstrated in seven analytical functions with different dimensionality and complexity in comparison to two widely used experimental design methods. The application of the TEAD-based surrogate method in two groundwater models shows that the TEAD design can effectively improve the computational efficiency of GSA and UQ for groundwater modeling.« less

Dimensions and Role-Specific Mediators of Surrogate Trust in the ICU

PubMed Central

Hutchison, Paul J.; McLaughlin, Katie; Corbridge, Tom; Michelson, Kelly N.; Emanuel, Linda; Sporn, Peter H. S.; Crowley-Matoka, Megan

2016-01-01

Objective In the ICU, discussions between clinicians and surrogate decision makers are often accompanied by conflict about a patient’s prognosis or care plan. Trust plays a role in limiting conflict, but little is known about the determinants of trust in the ICU. We sought to identify the dimensions of trust and clinician behaviors conducive to trust formation in the ICU. Design Prospective qualitative study. Setting Medical ICU of a major urban university hospital. Subjects Surrogate decision makers of intubated, mechanically ventilated patients in the medical ICU. Measurements and Main Results Semistructured interviews focused on surrogates’ general experiences in the ICU and on their trust in the clinicians caring for the patient. Interviews were audio-recorded, transcribed verbatim, and coded by two reviewers. Constant comparison was used to identify themes pertaining to trust. Thirty surrogate interviews revealed five dimensions of trust in ICU clinicians: technical competence, communication, honesty, benevolence, and interpersonal skills. Most surrogates emphasized the role of nurses in trust formation, frequently citing their technical competence. Trust in physicians was most commonly related to honesty and the quality of their communication with surrogates. Conclusions Interventions to improve trust in the ICU should be role-specific, since surrogate expectations are different for physicians and nurses with regard to behaviors relevant to trust. Further research is needed to confirm our findings and explore the impact of trust modification on clinician-family conflict. PMID:27513360

Evaluating the Efficacy of Three U.S. Department of Agriculture-Approved Antimicrobial Sprays for Reducing Shiga Toxin-Producing Escherichia coli Surrogate Populations on Bob Veal Carcasses.

PubMed

2016-06-01

Effective antimicrobial intervention strategies to reduce Shiga toxin-producing Escherichia coli (STEC) risks associated with veal are needed. This study evaluated the efficacy of lactic acid (4.5%, pH 2.0), Citrilow (pH 1.2), and Beefxide (2.25%, pH 2.3) for reducing STEC surrogates on prerigor and chilled bob veal carcasses and monitored the effects of these interventions on chilled carcass color. Dehided bob veal carcasses were inoculated with a five-strain cocktail of rifampin-resistant, surrogate E. coli bacteria.E. coli surrogates were enumerated after inoculation, after water wash, after prechill carcass antimicrobial spray application, after chilling for 24 h, and after postchill carcass antimicrobial spray application; carcass color was measured throughout the process. A standard carcass water wash (∼50°C) reduced the STEC surrogate population by 0.9 log CFU/cm(2) (P ≤ 0.05). All three antimicrobial sprays applied to prerigor carcasses delivered an additional ∼0.5-log reduction (P ≤ 0.05) of the surrogates. Chilling of carcasses for 24 h reduced (P ≤ 0.05) the surrogate population by an additional ∼0.4 log cycles. The postchill application of the antimicrobial sprays provided no further reductions. Carcass L*, a*, and b* color values were not different (P > 0.05) among carcass treatments. Generally, the types and concentrations of the antimicrobial sprays evaluated herein did not negatively impact visual or instrumental color of chilled veal carcasses. This study demonstrates that warm water washing, followed by a prechill spray treatment with a low-pH chemical intervention, can effectively reduce STEC risks associated with veal carcasses; this provides processors a validated control point in slaughter operations.

Social surrogacy and adjustment: exploring the correlates of having a "social helper" for shy and non-shy young adolescents.

PubMed

Markovic, Andrea; Bowker, Julie C

2015-01-01

A social surrogate is an individual who offers help and comfort in social situations or makes social events more exciting. In this study of 157 young adolescents (55% female; Mage = 13.84 years, SD = 0.75 years), the authors examined whether the linear and curvilinear associations between self-reported social surrogate use and adjustment outcomes (social problems, loneliness, anxiety symptoms, depressive symptoms) varied as a function of shyness and gender, after accounting for the effects of positive friendship quality. Regression analyses revealed that low and high levels of social surrogate use were related to greater social problems for all adolescents. In addition, shyness emerged as a moderator for several curvilinear effects. Specifically, results indicated that (a) high levels of social surrogate use were associated with greater anxiety for adolescents high in shyness; and (b) low levels of social surrogate use were associated with greater depressive symptoms for adolescents low in shyness. Findings highlight the developmental importance of specific types of relationship experiences during early adolescence and point to different implications of social surrogate use for shy and non-shy young adolescents.

Combining endangered plants and animals as surrogates to identify priority conservation areas in Yunnan, China

NASA Astrophysics Data System (ADS)

Yang, Feiling; Hu, Jinming; Wu, Ruidong

2016-08-01

Suitable surrogates are critical for identifying optimal priority conservation areas (PCAs) to protect regional biodiversity. This study explored the efficiency of using endangered plants and animals as surrogates for identifying PCAs at the county level in Yunnan, southwest China. We ran the Dobson algorithm under three surrogate scenarios at 75% and 100% conservation levels and identified four types of PCAs. Assessment of the protection efficiencies of the four types of PCAs showed that endangered plants had higher surrogacy values than endangered animals but that the two were not substitutable; coupled endangered plants and animals as surrogates yielded a higher surrogacy value than endangered plants or animals as surrogates; the plant-animal priority areas (PAPAs) was the optimal among the four types of PCAs for conserving both endangered plants and animals in Yunnan. PAPAs could well represent overall species diversity distribution patterns and overlap with critical biogeographical regions in Yunnan. Fourteen priority units in PAPAs should be urgently considered as optimizing Yunnan’s protected area system. The spatial pattern of PAPAs at the 100% conservation level could be conceptualized into three connected conservation belts, providing a valuable reference for optimizing the layout of the in situ protected area system in Yunnan.

Patient Preferences and Surrogate Decision Making in Neuroscience Intensive Care Units

PubMed Central

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

2016-01-01

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

An entropy-based nonparametric test for the validation of surrogate endpoints.

PubMed

Miao, Xiaopeng; Wang, Yong-Cheng; Gangopadhyay, Ashis

2012-06-30

We present a nonparametric test to validate surrogate endpoints based on measure of divergence and random permutation. This test is a proposal to directly verify the Prentice statistical definition of surrogacy. The test does not impose distributional assumptions on the endpoints, and it is robust to model misspecification. Our simulation study shows that the proposed nonparametric test outperforms the practical test of the Prentice criterion in terms of both robustness of size and power. We also evaluate the performance of three leading methods that attempt to quantify the effect of surrogate endpoints. The proposed method is applied to validate magnetic resonance imaging lesions as the surrogate endpoint for clinical relapses in a multiple sclerosis trial. Copyright © 2012 John Wiley & Sons, Ltd.

Development of a surrogate biomodel for the investigation of clubfoot bracing.

PubMed

Dimeo, Andrew J; Lalush, David S; Grant, Edward; Morcuende, Jose A

2012-01-01

Congenital talipes equinovarus (clubfoot) is a complex deformity of the lower extremity and foot occurring in 1/1000 live births. Regardless of treatment, whether conservative or surgical, clubfoot has a stubborn tendency to relapse, thus requiring postcorrection bracing. However, to date, there are no investigations specifically focused on clubfoot bracing from a bioengineering perspective. This study applied engineering principles to clubfoot bracing through construction of a surrogate biomodel. The surrogate was developed to represent an average 5-year-old human subject capable of biomechanical characteristics including joint articulation and kinematics. The components include skeleton, articulating joints, muscle-tendon systems, and ligaments. A protocol was developed to measure muscle-tendon tension in resting and braced positions of the surrogate. Measurement error ranged from 1% to 6% and was considered variance due to brace and investigator. In conclusion, this study shows that surrogate biomodeling is an accurate and repeatable method to investigate clubfoot bracing. The methodology is an effective means to evaluate wide ranging brace options and can be used to assist in future brace development and the tuning of brace parameters. Such patient-specific brace tuning may also lead to advanced braces that increase compliance.

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

PubMed

Nixon, Richard M; Duffy, Stephen W; Fender, Guy R K

2003-09-24

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

A Surrogate Approach to the Experimental Optimization of Multielement Airfoils

NASA Technical Reports Server (NTRS)

Otto, John C.; Landman, Drew; Patera, Anthony T.

1996-01-01

The incorporation of experimental test data into the optimization process is accomplished through the use of Bayesian-validated surrogates. In the surrogate approach, a surrogate for the experiment (e.g., a response surface) serves in the optimization process. The validation step of the framework provides a qualitative assessment of the surrogate quality, and bounds the surrogate-for-experiment error on designs "near" surrogate-predicted optimal designs. The utility of the framework is demonstrated through its application to the experimental selection of the trailing edge ap position to achieve a design lift coefficient for a three-element airfoil.

When life imitates art: surrogate decision making at the end of life.

PubMed

Shapiro, Susan P

2007-01-01

The privileging of the substituted judgment standard as the gold standard for surrogate decision making in law and bioethics has constrained the research agenda in end-of-life decision making. The empirical literature is inundated with a plethora of "Newlywed Game" designs, in which potential patients and potential surrogates respond to hypothetical scenarios to see how often they "get it right." The preoccupation with determining the capacity of surrogates to accurately reproduce the judgments of another makes a number of assumptions that blind scholars to the variables central to understanding how surrogates actually make medical decisions on behalf of another. These assumptions include that patient preferences are knowable, surrogates have adequate and accurate information, time stands still, patients get the surrogates they want, patients want and surrogates utilize substituted judgment criteria, and surrogates are disinterested. This article examines these assumptions and considers the challenges of designing research that makes them problematic.

The variability in iron speciation in size fractionated residual oil fly ash particulate matter (ROFA PM).

PubMed

Pattanaik, Sidhartha; Huggins, Frank E; Huffman, Gerald P

2016-08-15

Ambient particulate matter (PM) containing iron can catalyze Fenton reaction leading to the production of reactive oxygen species in cells. It can also catalyze atmospheric redox reaction. These reactions are governed by the physicochemical characteristics of iron in ambient PM. As a surrogate for ambient PM, we prepared residual oil fly ash PM (ROFA PM) in a practical fire tube boiler firing residual oils with varying sulfur and ash contents. The ROFA particles were resolved into fine PM or PM2.5 (aerodynamic diameter (AD)<2.5μm) and coarse PM or PM2.5+ (AD between 2.5μm and 50μm). The iron speciation in PM2.5+ was ascertained using X-ray absorption spectroscopy and leaching method while that in PM2.5 was reported earlier. The results of both studies are compared to get an insight into the variability in the iron speciation in different size fractions. The results show the predominance of ferric sulfate, with a minor spinal ferrite in both PM (i.e. ZnxNi1-xFe2O4 in PM2.5, ZnFe2O4 in PM2.5+). The iron solubility in ROFA PM depends on its speciation, mode of incorporation of iron into particle's carbonaceous matrix, the grade and composition of oils, and pH of the medium. The soluble fraction of iron in PM is critical in assessing its interaction with the biological systems and its toxic potential. Copyright © 2016 Elsevier B.V. All rights reserved.

On assessing surrogacy in a single trial setting using a semi-competing risks paradigm

PubMed Central

Ghosh, Debashis

2009-01-01

Summary There has been a recent emphasis on the identification of biomarkers and other biologic measures that may be potentially used as surrogate endpoints in clinical trials. We focus on the setting of data from a single clinical trial. In this paper, we consider a framework in which the surrogate must occur before the true endpoint. This suggests viewing the surrogate and true endpoints as semi-competing risks data; this approach is new to the literature on surrogate endpoints and leads to an asymmetrical treatment of the surrogate and true endpoints. However, such a data structure also conceptually complicates many of the previously considered measures of surrogacy in the literature. We propose novel estimation and inferential procedures for the relative effect and adjusted association quantities proposed by Buyse and Molenberghs (1998, Biometrics, 1014 – 1029). The proposed methodology is illustrated with application to simulated data, as well as to data from a leukemia study. PMID:18759839

Endospore surface properties of commonly used Bacillus anthracis surrogates vary in aqueous solution

EPA Science Inventory

The hydrophobic character and electrophoretic mobility of microorganisms are vital aspects of understanding their interactions with the environment. These properties are fundamental in fate-and-transport, physiological, and virulence studies, and thus integral in surrogate select...

Mimicking Retention and Transport of Rotavirus and Adenovirus in Sand Media Using DNA-labeled, Protein-coated Silica Nanoparticles

NASA Astrophysics Data System (ADS)

Pang, Liping; Farkas, Kata; Bennett, Grant; Varsani, Arvind; Easingwood, Richard; Tilley, Richard; Nowostawska, Urszula; Lin, Susan

2014-05-01

Rotavirus (RoV) and adenovirus (AdV) are important viral pathogens for the risk analysis of drinking water. Despite this, little is known about their retention and transport behaviors in porous media (e.g. sand filtered used for water treatment and groundwater aquifers due to a lack of representative surrogates. In this study, we developed RoV and AdV surrogates by covalently coating 70-nm sized silica nanoparticles with specific proteins and a DNA marker for sensitive detection. Filtration experiments using beach sand columns demonstrated the similarity of the surrogates' concentrations, attachment, and filtration efficiencies to the target viruses. The surrogates showed the same magnitude of concentration reduction as the viruses. Conversely, MS2 phage (a traditional virus model) over predicted concentrations of AdV and RoV by 1- and 2-orders of magnitude, respectively. The surrogates remained stable in size, surface charge and DNA concentration for at least one year. They can be easily and rapidly detected at concentrations down to one particle per PCR reaction and are readily detectable in natural waters and even in effluent. With up-scaling validation in pilot trials, the surrogates can be a useful cost-effective new tool for studying virus retention and transport in porous media, e.g. for assessing filter efficiency in water and wastewater treatment, tracking virus migration in groundwater after effluent land disposal, and establishing safe setback distances for groundwater protection.

Applicability of UV resistant Bacillus pumilus endospores as a human adenovirus surrogate for evaluating the effectiveness of virus inactivation in low-pressure UV treatment systems

EPA Science Inventory

Recent studies have demonstrated the potential to use Bacillus pumilus endospores as a surrogate of human adenovirus (HAdV) in UV disinfection studies. The use of endospores has been limited by observations of batch-to-batch variation in UV sensitivity. This study reports on a pr...

Strategies for Countering Terrorist Safe Havens

DTIC Science & Technology

2013-12-01

tactical containment, pseudo operations, and surrogate security forces. The thesis draws from four historical case studies to examine these strategies...safe havens, tactical containment, pseudo operations, and surrogate security forces. The thesis draws from four historical case studies to examine...pseudo operations—provide viable potential options for USSOF to counter the complex problem of safe havens. Overall, the case studies will demonstrate

A rank test for bivariate time-to-event outcomes when one event is a surrogate

PubMed Central

Shaw, Pamela A.; Fay, Michael P.

2016-01-01

In many clinical settings, improving patient survival is of interest but a practical surrogate, such as time to disease progression, is instead used as a clinical trial’s primary endpoint. A time-to-first endpoint (e.g. death or disease progression) is commonly analyzed but may not be adequate to summarize patient outcomes if a subsequent event contains important additional information. We consider a surrogate outcome very generally, as one correlated with the true endpoint of interest. Settings of interest include those where the surrogate indicates a beneficial outcome so that the usual time-to-first endpoint of death or surrogate event is nonsensical. We present a new two-sample test for bivariate, interval-censored time-to-event data, where one endpoint is a surrogate for the second, less frequently observed endpoint of true interest. This test examines whether patient groups have equal clinical severity. If the true endpoint rarely occurs, the proposed test acts like a weighted logrank test on the surrogate; if it occurs for most individuals, then our test acts like a weighted logrank test on the true endpoint. If the surrogate is a useful statistical surrogate, our test can have better power than tests based on the surrogate that naively handle the true endpoint. In settings where the surrogate is not valid (treatment affects the surrogate but not the true endpoint), our test incorporates the information regarding the lack of treatment effect from the observed true endpoints and hence is expected to have a dampened treatment effect compared to tests based on the surrogate alone. PMID:27059817

Surrogate outcomes in health technology assessment: an international comparison.

PubMed

Velasco Garrido, Marcial; Mangiapane, Sandra

2009-07-01

Our aim was to review the recommendations given by health technology assessment (HTA) institutions in their methodological guidelines concerning the use of surrogate outcomes in their assessments. In a second step, we aimed at quantifying the role surrogate parameters take in assessment reports. We analyzed methodological papers and guidelines from HTA agencies with International Network of Agencies for Health Technology Assessment membership as well as from institutions related to pharmaceutical regulation (i.e., reimbursement, pricing). We analyzed the use of surrogate outcomes in a sample of HTA reports randomly drawn from the HTA database. We checked methods, results (including evidence tables), and conclusions sections and extracted the outcomes reported. We report descriptive statistics on the presence of surrogate outcomes in the reports. We identified thirty-four methodological guidelines, twenty of them addressing the issue of outcome parameter choice and the problematic of surrogate outcomes. Overall HTA agencies call on caution regarding the reliance on surrogate outcomes. None of the agencies has provided a list or catalog of acceptable and validated surrogate outcomes. We extracted the outcome parameter of 140 HTA reports. Only around half of the reports determined the outcomes for the assessment prospectively. Surrogate outcomes had been used in 62 percent of the reports. However, only 3.6 percent were based upon surrogate outcomes exclusively. All of them assessed diagnostic or screening technologies and the surrogate outcomes were predominantly test characteristics. HTA institutions seem to agree on a cautious approach to the use of surrogate outcomes in technology assessment. Thorough assessment of health technologies should not rely exclusively on surrogate outcomes.

Advanced topics in evidence-based urologic oncology: surrogate endpoints.

PubMed

Lavallée, Luke T; Montori, Victor M; Canfield, Stephen E; Breau, Rodney H

2011-01-01

Clinical trials often report surrogate endpoint data. A surrogate endpoint is a biological marker or clinical sign that can be substituted for a patient-important outcome. Using surrogate endpoints correctly may facilitate and expedite clinical trials and may improve medical decisions. However, rigorous criteria must be met for an endpoint to be considered a valid surrogate. The purpose of this article is to review the topic of surrogate endpoints in the context of a urologic encounter. Copyright © 2011 Elsevier Inc. All rights reserved.

Impact of a Decision Aid on Surrogate Decision-makers’ Perceptions of Feeding Options for Patients with Dementia

PubMed Central

Snyder, E. Amanda; Caprio, Anthony J.; Wessell, Kathryn; Lin, Feng Chang; Hanson, Laura C.

2012-01-01

Objective In advanced dementia, feeding problems are nearly universal, and families face difficult decisions about feeding options. Initial interviews for a randomized trial were used to describe surrogates’ perceptions feeding options, and to determine if a decision aid on feeding options in advanced dementia would improve knowledge, reduce expectation of benefit from tube feeding, and reduce conflict over treatment choices for persons with advanced dementia. Design Semi-structured interview with pre-post study design for surrogates in the intervention group. Setting Twenty-four skilled nursing facilities across North Carolina participating in a cluster randomized trial. Participants Two hundred fifty-five surrogate decision-makers for nursing home residents with advanced dementia and feeding problems, in control (n=129) and intervention (n=126) groups. Intervention For intervention surrogates only, an audiovisual-print decision aid provided information on dementia, feeding problems in dementia, advantages and disadvantages of feeding tubes or assisted oral feeding options and the role of surrogates in making these decisions. Measurements The interview included open-ended items asking surrogates to report advantages and disadvantages of tube feeding and assisted oral feeding. Knowledge of feeding options was measured with 19 true-false items, and items measuring expectation of benefit from tube feeding. Surrogates reported which of these two feeding options they preferred for the person with dementia, and how confident they were in this choice; their level of conflict about the choice was measured using the Decisional Conflict Scale. Results Prior to the decision aid, surrogates described advantages and disadvantages of assisted oral feeding and tube feeding in practical, ethical and medical terms. After review of the decision aid, intervention surrogates had improved knowledge scores (15.5 vs. 16.8; p<0.001), decreased expectation of benefits from tube feeding (2.73 vs. 2.32; p = 0.001) and reduced decisional conflict (2.24 vs. 1.91, p<0.001). Surrogates preferred assisted oral feeding initially, and reported more certainty about this choice after the decision aid. Conclusion A structured decision aid can be used to improve decision-making about feeding options in dementia care. PMID:23273855

Improvements to surrogate data methods for nonstationary time series.

PubMed

Lucio, J H; Valdés, R; Rodríguez, L R

2012-05-01

The method of surrogate data has been extensively applied to hypothesis testing of system linearity, when only one realization of the system, a time series, is known. Normally, surrogate data should preserve the linear stochastic structure and the amplitude distribution of the original series. Classical surrogate data methods (such as random permutation, amplitude adjusted Fourier transform, or iterative amplitude adjusted Fourier transform) are successful at preserving one or both of these features in stationary cases. However, they always produce stationary surrogates, hence existing nonstationarity could be interpreted as dynamic nonlinearity. Certain modifications have been proposed that additionally preserve some nonstationarity, at the expense of reproducing a great deal of nonlinearity. However, even those methods generally fail to preserve the trend (i.e., global nonstationarity in the mean) of the original series. This is the case of time series with unit roots in their autoregressive structure. Additionally, those methods, based on Fourier transform, either need first and last values in the original series to match, or they need to select a piece of the original series with matching ends. These conditions are often inapplicable and the resulting surrogates are adversely affected by the well-known artefact problem. In this study, we propose a simple technique that, applied within existing Fourier-transform-based methods, generates surrogate data that jointly preserve the aforementioned characteristics of the original series, including (even strong) trends. Moreover, our technique avoids the negative effects of end mismatch. Several artificial and real, stationary and nonstationary, linear and nonlinear time series are examined, in order to demonstrate the advantages of the methods. Corresponding surrogate data are produced with the classical and with the proposed methods, and the results are compared.

Surrogate Mobility and Orientation Affect the Early Neurobehavioral Development of Infant Rhesus Macaques (Macaca mulatta)

PubMed Central

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

2008-01-01

A biological mother’s movement appears necessary for optimal development in infant monkeys. However, nursery-reared monkeys are typically provided with inanimate surrogate mothers that move very little. The purpose of this study was to evaluate the effects of a novel, highly mobile surrogate mother on motor development, exploration, and reactions to novelty. Six infant rhesus macaques (Macaca mulatta) were reared on mobile hanging surrogates (MS) and compared to six infants reared on standard stationary rocking surrogates (RS) and to 9-15 infants reared with their biological mothers (MR) for early developmental outcome. We predicted that MS infants would develop more similarly to MR infants than RS infants. In neonatal assessments conducted at day 30, both MS and MR infants showed more highly developed motor activity than RS infants on measures of grasping (p=.009), coordination (p=.038), spontaneous crawl (p=.009), and balance (p=.003). At 2-3 months of age, both MS and MR infants displayed higher levels of exploration in the home cage than RS infants (p=.016). In a novel situation in which only MS and RS infants were tested, MS infants showed less of a stress response, spending less time near their surrogates in the first five minutes of the test session than RS infants (p=.05) and exhibiting a significantly lower rise in salivary cortisol after the test than RS infants (p=.018). Collectively, these results suggest that when nursery-rearing of infant monkeys is necessary, a mobile hanging surrogate may encourage more normative development of gross motor skills and exploratory behavior and may serve as a useful alternative to stationary or rocking surrogates. PMID:19810188

Evaluation of lung tumor motion management in radiation therapy with dynamic MRI

NASA Astrophysics Data System (ADS)

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

2017-03-01

Surrogate-based tumor motion estimation and tracing methods are commonly used in radiotherapy despite the lack of continuous real time 3D tumor and surrogate data. In this study, we propose a method to simultaneously track the tumor and external surrogates with dynamic MRI, which allows us to evaluate their reproducible correlation. Four MRIcompatible fiducials are placed on the patient's chest and upper abdomen, and multi-slice 2D cine MRIs are acquired to capture the lung and whole tumor, followed by two-slice 2D cine MRIs to simultaneously track the tumor and fiducials, all in sagittal orientation. A phase-binned 4D-MRI is first reconstructed from multi-slice MR images using body area as a respiratory surrogate and group-wise registration. The 4D-MRI provides 3D template volumes for different breathing phases. 3D tumor position is calculated by 3D-2D template matching in which 3D tumor templates in 4D-MRI reconstruction and the 2D cine MRIs from the two-slice tracking dataset are registered. 3D trajectories of the external surrogates are derived via matching a 3D geometrical model to the fiducial segmentations on the 2D cine MRIs. We tested our method on five lung cancer patients. Internal target volume from 4D-CT showed average sensitivity of 86.5% compared to the actual tumor motion for 5 min. 3D tumor motion correlated with the external surrogate signal, but showed a noticeable phase mismatch. The 3D tumor trajectory showed significant cycle-to-cycle variation, while the external surrogate was not sensitive enough to capture such variations. Additionally, there was significant phase mismatch between surrogate signals obtained from fiducials at different locations.

Arm span and ulnar length are reliable and accurate estimates of recumbent length and height in a multiethnic population of infants and children under 6 years of age.

PubMed

Forman, Michele R; Zhu, Yeyi; Hernandez, Ladia M; Himes, John H; Dong, Yongquan; Danish, Robert K; James, Kyla E; Caulfield, Laura E; Kerver, Jean M; Arab, Lenore; Voss, Paula; Hale, Daniel E; Kanafani, Nadim; Hirschfeld, Steven

2014-09-01

Surrogate measures are needed when recumbent length or height is unobtainable or unreliable. Arm span has been used as a surrogate but is not feasible in children with shoulder or arm contractures. Ulnar length is not usually impaired by joint deformities, yet its utility as a surrogate has not been adequately studied. In this cross-sectional study, we aimed to examine the accuracy and reliability of ulnar length measured by different tools as a surrogate measure of recumbent length and height. Anthropometrics [recumbent length, height, arm span, and ulnar length by caliper (ULC), ruler (ULR), and grid (ULG)] were measured in 1479 healthy infants and children aged <6 y across 8 study centers in the United States. Multivariate mixed-effects linear regression models for recumbent length and height were developed by using ulnar length and arm span as surrogate measures. The agreement between the measured length or height and the predicted values by ULC, ULR, ULG, and arm span were examined by Bland-Altman plots. All 3 measures of ulnar length and arm span were highly correlated with length and height. The degree of precision of prediction equations for length by ULC, ULR, and ULG (R(2) = 0.95, 0.95, and 0.92, respectively) was comparable with that by arm span (R(2) = 0.97) using age, sex, and ethnicity as covariates; however, height prediction by ULC (R(2) = 0.87), ULR (R(2) = 0.85), and ULG (R(2) = 0.88) was less comparable with arm span (R(2) = 0.94). Our study demonstrates that arm span and ULC, ULR, or ULG can serve as accurate and reliable surrogate measures of recumbent length and height in healthy children; however, ULC, ULR, and ULG tend to slightly overestimate length and height in young infants and children. Further testing of ulnar length as a surrogate is warranted in physically impaired or nonambulatory children. © 2014 American Society for Nutrition.

Air pollution exposure modeling of individuals

EPA Science Inventory

Air pollution epidemiology studies of ambient fine particulate matter (PM2.5) often use outdoor concentrations as exposure surrogates. These surrogates can induce exposure error since they do not account for (1) time spent indoors with ambient PM2.5 levels attenuated from outdoor...

The inhibition, reactivation and mechanism of VX-, sarin-, fluoro-VX and fluoro-sarin surrogates following their interaction with HuAChE and HuBuChE.

PubMed

Chao, Chih-Kai; Balasubramanian, Narayanaganesh; Gerdes, John M; Thompson, Charles M

2018-06-16

In this study, the mechanisms of HuAChE and HuBChE inhibition by Me-P(O) (OPNP) (OR) [PNP = p-nitrophenyl; R = CH 2 CH 3 , CH 2 CH 2 F, OCH(CH 3 ) 2 , OCH(CH 3 ) (CH 2 F)] representing surrogates and fluoro-surrogates of VX and sarin were studied by in vitro kinetics and mass spectrometry. The in vitro measures showed that the VX- and fluoro-VX surrogates were relatively strong inhibitors of HuAChE and HuBChE (k i  ∼ 10 5 -10 6  M -1 min -1 ) and underwent spontaneous and 2-PAM-mediated reactivation within 30 min. The sarin surrogates were weaker inhibitors of HuAChE and HuBChE (k i  ∼ 10 4 -10 5  M -1 min -1 ), and in general did not undergo spontaneous reactivation, although HuAChE adducts were partially reactivatable at 18 h using 2-PAM. The mechanism of HuAChE and HuBChE inhibition by the surrogates was determined by Q-TOF and MALDI-TOF mass spectral analyses. The surrogate-adducted proteins were trypsin digested and the active site-containing peptide bearing the OP-modified serine identified by Q-TOF as triply- and quadruply-charged ions representing the respective increase in mass of the attached OP moiety. Correspondingly, monoisotopic ions of the tryptic peptides representing the mass increase of the OP-adducted peptide was identified by MALDI-TOF. The mass spectrometry analyses validated the identity of the OP moiety attached to HuAChE or HuBChE as MeP(O) (OR)-O-serine peptides (loss of the PNP leaving group) via mechanisms consistent with those found with chemical warfare agents. MALDI-TOF MS analyses of the VX-modified peptides versus time showed a steady reduction in adduct versus parent peptide (reactivation), whereas the sarin-surrogate-modified peptides remained largely intact over the course of the experiment (24 h). Overall, the presence of a fluorine atom on the surrogate modestly altered the rate constants of inhibition and reactivation, however, the mechanism of inhibition (ejection of PNP group) did not change. Copyright © 2018. Published by Elsevier B.V.

Surrogate endpoints and emerging surrogate endpoints for risk reduction of cardiovascular disease.

PubMed

Rasnake, Crystal M; Trumbo, Paula R; Heinonen, Therese M

2008-02-01

This article reviews surrogate endpoints and emerging biomarkers that were discussed at the annual "Cardiovascular Biomarkers and Surrogate Endpoints" symposium cosponsored by the US Food and Drug Administration (FDA) and the Montreal Heart Institute. The FDA's Center for Food Safety and Applied Nutrition (CFSAN) uses surrogate endpoints in its scientific review of a substance/disease relationship for a health claim. CFSAN currently recognizes three validated surrogate endpoints: blood pressure, blood total cholesterol, and blood low-density lipoprotein (LDL) concentration in its review of a health claim for cardiovascular disease (CVD). Numerous potential surrogate endpoints of CVD are being evaluated as the pathophysiology of heart disease is becoming better understood. However, these emerging biomarkers need to be validated as surrogate endpoints before they are used by CFSAN in the evaluation of a CVD health claim.

Surrogate matrix and surrogate analyte approaches for definitive quantitation of endogenous biomolecules.

PubMed

Jones, Barry R; Schultz, Gary A; Eckstein, James A; Ackermann, Bradley L

2012-10-01

Quantitation of biomarkers by LC-MS/MS is complicated by the presence of endogenous analytes. This challenge is most commonly overcome by calibration using an authentic standard spiked into a surrogate matrix devoid of the target analyte. A second approach involves use of a stable-isotope-labeled standard as a surrogate analyte to allow calibration in the actual biological matrix. For both methods, parallelism between calibration standards and the target analyte in biological matrix must be demonstrated in order to ensure accurate quantitation. In this communication, the surrogate matrix and surrogate analyte approaches are compared for the analysis of five amino acids in human plasma: alanine, valine, methionine, leucine and isoleucine. In addition, methodology based on standard addition is introduced, which enables a robust examination of parallelism in both surrogate analyte and surrogate matrix methods prior to formal validation. Results from additional assays are presented to introduce the standard-addition methodology and to highlight the strengths and weaknesses of each approach. For the analysis of amino acids in human plasma, comparable precision and accuracy were obtained by the surrogate matrix and surrogate analyte methods. Both assays were well within tolerances prescribed by regulatory guidance for validation of xenobiotic assays. When stable-isotope-labeled standards are readily available, the surrogate analyte approach allows for facile method development. By comparison, the surrogate matrix method requires greater up-front method development; however, this deficit is offset by the long-term advantage of simplified sample analysis.

Surrogate end points in clinical research: hazardous to your health.

PubMed

Grimes, David A; Schulz, Kenneth F

2005-05-01

Surrogate end points in clinical research pose real danger. A surrogate end point is an outcome measure, commonly a laboratory test, that substitutes for a clinical event of true importance. Resistance to activated protein C, for example, has been used as a surrogate for venous thrombosis in women using oral contraceptives. Other examples of inappropriate surrogate end points in contraception include the postcoital test instead of pregnancy to evaluate new spermicides, breakage and slippage instead of pregnancy to evaluate condoms, and bone mineral density instead of fracture to assess the safety of depo-medroxyprogesterone acetate. None of these markers captures the effect of the treatment on the true outcome. A valid surrogate end point must both correlate with and accurately predict the outcome of interest. Although many surrogate markers correlate with an outcome, few have been shown to capture the effect of a treatment (for example, oral contraceptives) on the outcome (venous thrombosis). As a result, thousands of useless and misleading reports on surrogate end points litter the medical literature. New drugs have been shown to benefit a surrogate marker, but, paradoxically, triple the risk of death. Thousands of patients have died needlessly because of reliance on invalid surrogate markers. Researchers should avoid surrogate end points unless they have been validated; that requires at least one well done trial using both the surrogate and true outcome. The clinical maxim that "a difference to be a difference must make a difference" applies to research as well. Clinical research should focus on outcomes that matter.

Business Administration Students as Surrogates for IT Professionals: Summary of a Study

ERIC Educational Resources Information Center

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

2015-01-01

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

Evaluation of two new surrogate indices including parameters not using insulin to assess insulin sensitivity/resistance in non-diabetic postmenopausal women: a MONET group study.

PubMed

Bastard, J-P; Lavoie, M-E; Messier, V; Prud'homme, D; Rabasa-Lhoret, R

2012-06-01

The study evaluated and compared, with other surrogate indices of insulin sensitivity/resistance (IS/R), the relevance of the TyG index, a product of fasting glucose and triglyceride (TG) levels, and the EGIR index, which includes TG, high-density lipoprotein cholesterol (HDL-c) and waist circumference in its formula to estimate IS/R, in non-diabetic postmenopausal women. A secondary analysis was performed using the baseline data for 163 non-diabetic postmenopausal women from the Montreal-Ottawa New Emerging Team (MONET) population database. The subjects participated in hyperinsulinaemic-euglycaemic (HIEG) clamp and oral glucose tolerance (OGTT) tests. Correlations and comparisons between surrogate indices were performed in addition to inter-rater agreement tests. The optimal value of surrogate indices for diagnosis of IS/R was established on a receiver operating characteristic (ROC) scatter plot. A significant correlation was found between the HIEG clamp and all IS/R surrogate indices tested [r=-0.370 (TyG index) to 0.608 (SIisOGTT index); P<0.001]. On ROC curve analysis, a higher AUROC was found for SIisOGTT (0.791) than for TyG and EGIR (0.706 and 0.675, respectively; P=0.07 and P<0.05, respectively). The TyG and EGIR IS/R indices were only relatively modestly related to the HIEG clamp. In contrast, both fasting- and OGTT-derived IS/R surrogate indices, which include insulin values in their formulae, appeared to be more accurate in estimating IS/R in our study population. Thus, the TyG and EGIR IS/R indices need to be tested and validated more extensively in different populations before being put to large-scale clinical use. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

An investigation into the two-stage meta-analytic copula modelling approach for evaluating time-to-event surrogate endpoints which comprise of one or more events of interest.

PubMed

Dimier, Natalie; Todd, Susan

2017-09-01

Clinical trials of experimental treatments must be designed with primary endpoints that directly measure clinical benefit for patients. In many disease areas, the recognised gold standard primary endpoint can take many years to mature, leading to challenges in the conduct and quality of clinical studies. There is increasing interest in using shorter-term surrogate endpoints as substitutes for costly long-term clinical trial endpoints; such surrogates need to be selected according to biological plausibility, as well as the ability to reliably predict the unobserved treatment effect on the long-term endpoint. A number of statistical methods to evaluate this prediction have been proposed; this paper uses a simulation study to explore one such method in the context of time-to-event surrogates for a time-to-event true endpoint. This two-stage meta-analytic copula method has been extensively studied for time-to-event surrogate endpoints with one event of interest, but thus far has not been explored for the assessment of surrogates which have multiple events of interest, such as those incorporating information directly from the true clinical endpoint. We assess the sensitivity of the method to various factors including strength of association between endpoints, the quantity of data available, and the effect of censoring. In particular, we consider scenarios where there exist very little data on which to assess surrogacy. Results show that the two-stage meta-analytic copula method performs well under certain circumstances and could be considered useful in practice, but demonstrates limitations that may prevent universal use. Copyright © 2017 John Wiley & Sons, Ltd.

Robust best linear estimator for Cox regression with instrumental variables in whole cohort and surrogates with additive measurement error in calibration sample

PubMed Central

Wang, Ching-Yun; Song, Xiao

2017-01-01

SUMMARY Biomedical researchers are often interested in estimating the effect of an environmental exposure in relation to a chronic disease endpoint. However, the exposure variable of interest may be measured with errors. In a subset of the whole cohort, a surrogate variable is available for the true unobserved exposure variable. The surrogate variable satisfies an additive measurement error model, but it may not have repeated measurements. The subset in which the surrogate variables are available is called a calibration sample. In addition to the surrogate variables that are available among the subjects in the calibration sample, we consider the situation when there is an instrumental variable available for all study subjects. An instrumental variable is correlated with the unobserved true exposure variable, and hence can be useful in the estimation of the regression coefficients. In this paper, we propose a nonparametric method for Cox regression using the observed data from the whole cohort. The nonparametric estimator is the best linear combination of a nonparametric correction estimator from the calibration sample and the difference of the naive estimators from the calibration sample and the whole cohort. The asymptotic distribution is derived, and the finite sample performance of the proposed estimator is examined via intensive simulation studies. The methods are applied to the Nutritional Biomarkers Study of the Women’s Health Initiative. PMID:27546625

Validated surrogate endpoints needed for peri-implantitis.

PubMed

Lee, Dong Won

2011-01-01

Pubmed, Cochrane and Lilac databases, Google, Google Scholar, hand searching of websites of major dental journals. The reference list of five recently published systematic reviews on peri-implantitis treatment were also screened for potential studies. Randomised controlled trials and non-randomised studies in English, German, French, Spanish and Italian on peri-implantitis treatment in humans were included. Case series, case reports and cross sectional or non-therapy studies were excluded from the assessment of endpoints. No minimum follow up time was set for studies that were included. Data were extracted in duplicate by two reviewers and disagreements were resolved by consensus. True endpoints for peri-implantitis treatment were considered only if they provided evidence of tangible benefit to the patient. The outcome variables regarded as true endpoints were implant failure, aesthetic assessment and variables related to quality of life, but these were only considered if they were clearly identified as an objective of the research, not as an outcome of treatment. Surrogate endpoints were considered as those measurements of clinical outcomes such as probing pocket depth and clinical attachment level. Fourteen studies were included in this review with data on implant failure presented solely as consequence of peri-implantitis therapy. No true endpoint was described for any study on peri-implantitis. Mean pocket probing depth, clinical attachment level and bleeding on probing were the three surrogate endpoints cited most often in the literature. All endpoints used in the trials reviewed are surrogates of clinical events, such as implant failure. Clinical surrogate endpoints should be validated to assess the real effect of these measures on true endpoints.

A multi-damages identification method for cantilever beam based on mode shape curvatures and Kriging surrogate model

NASA Astrophysics Data System (ADS)

Xie, Fengle; Jiang, Zhansi; Jiang, Hui

2018-05-01

This paper presents a multi-damages identification method for Cantilever Beam. First, the damage location is identified by using the mode shape curvatures. Second, samples of varying damage severities at the damage location and their corresponding natural frequencies are used to construct the initial Kriging surrogate model. Then a particle swarm optimization (PSO) algorithm is employed to identify the damage severities based on Kriging surrogate model. The simulation study of a double-damaged cantilever beam demonstrated that the proposed method is effective.

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

PubMed

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

2009-12-01

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

Effects of Exposure Measurement Error in the Analysis of Health Effects from Traffic-Related Air Pollution

EPA Science Inventory

In large epidemiological studies, many researchers use surrogates of air pollution exposure such as geographic information system (GIS)-based characterizations of traffic or simple housing characteristics. It is important to validate these surrogates against measured pollutant co...

Salmonella surrogate reduction using industrial peanut dry roasting parameters

USDA-ARS?s Scientific Manuscript database

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

Combining endangered plants and animals as surrogates to identify priority conservation areas in Yunnan, China

PubMed Central

Yang, Feiling; Hu, Jinming; Wu, Ruidong

2016-01-01

Suitable surrogates are critical for identifying optimal priority conservation areas (PCAs) to protect regional biodiversity. This study explored the efficiency of using endangered plants and animals as surrogates for identifying PCAs at the county level in Yunnan, southwest China. We ran the Dobson algorithm under three surrogate scenarios at 75% and 100% conservation levels and identified four types of PCAs. Assessment of the protection efficiencies of the four types of PCAs showed that endangered plants had higher surrogacy values than endangered animals but that the two were not substitutable; coupled endangered plants and animals as surrogates yielded a higher surrogacy value than endangered plants or animals as surrogates; the plant-animal priority areas (PAPAs) was the optimal among the four types of PCAs for conserving both endangered plants and animals in Yunnan. PAPAs could well represent overall species diversity distribution patterns and overlap with critical biogeographical regions in Yunnan. Fourteen priority units in PAPAs should be urgently considered as optimizing Yunnan’s protected area system. The spatial pattern of PAPAs at the 100% conservation level could be conceptualized into three connected conservation belts, providing a valuable reference for optimizing the layout of the in situ protected area system in Yunnan. PMID:27538537

Hard, harder, hardest: principal stratification, statistical identifiability, and the inherent difficulty of finding surrogate endpoints.

PubMed

Wolfson, Julian; Henn, Lisa

2014-01-01

In many areas of clinical investigation there is great interest in identifying and validating surrogate endpoints, biomarkers that can be measured a relatively short time after a treatment has been administered and that can reliably predict the effect of treatment on the clinical outcome of interest. However, despite dramatic advances in the ability to measure biomarkers, the recent history of clinical research is littered with failed surrogates. In this paper, we present a statistical perspective on why identifying surrogate endpoints is so difficult. We view the problem from the framework of causal inference, with a particular focus on the technique of principal stratification (PS), an approach which is appealing because the resulting estimands are not biased by unmeasured confounding. In many settings, PS estimands are not statistically identifiable and their degree of non-identifiability can be thought of as representing the statistical difficulty of assessing the surrogate value of a biomarker. In this work, we examine the identifiability issue and present key simplifying assumptions and enhanced study designs that enable the partial or full identification of PS estimands. We also present example situations where these assumptions and designs may or may not be feasible, providing insight into the problem characteristics which make the statistical evaluation of surrogate endpoints so challenging.

Hard, harder, hardest: principal stratification, statistical identifiability, and the inherent difficulty of finding surrogate endpoints

PubMed Central

2014-01-01

In many areas of clinical investigation there is great interest in identifying and validating surrogate endpoints, biomarkers that can be measured a relatively short time after a treatment has been administered and that can reliably predict the effect of treatment on the clinical outcome of interest. However, despite dramatic advances in the ability to measure biomarkers, the recent history of clinical research is littered with failed surrogates. In this paper, we present a statistical perspective on why identifying surrogate endpoints is so difficult. We view the problem from the framework of causal inference, with a particular focus on the technique of principal stratification (PS), an approach which is appealing because the resulting estimands are not biased by unmeasured confounding. In many settings, PS estimands are not statistically identifiable and their degree of non-identifiability can be thought of as representing the statistical difficulty of assessing the surrogate value of a biomarker. In this work, we examine the identifiability issue and present key simplifying assumptions and enhanced study designs that enable the partial or full identification of PS estimands. We also present example situations where these assumptions and designs may or may not be feasible, providing insight into the problem characteristics which make the statistical evaluation of surrogate endpoints so challenging. PMID:25342953

Surrogate data--a secure way to share corporate data.

PubMed

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

2005-01-01

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

Progression-free survival as surrogate and as true end point: insights from the breast and colorectal cancer literature.

PubMed

Saad, E D; Katz, A; Hoff, P M; Buyse, M

2010-01-01

Significant achievements in the systemic treatment of both advanced breast cancer and advanced colorectal cancer over the past 10 years have led to a growing number of drugs, combinations, and sequences to be tested. The choice of surrogate and true end points has become a critical issue and one that is currently the subject of much debate. Many recent randomized trials in solid tumor oncology have used progression-free survival (PFS) as the primary end point. PFS is an attractive end point because it is available earlier than overall survival (OS) and is not influenced by second-line treatments. PFS is now undergoing validation as a surrogate end point in various disease settings. The question of whether PFS can be considered an acceptable surrogate end point depends not only on formal validation studies but also on a standardized definition and unbiased ascertainment of disease progression in clinical trials. In advanced breast cancer, formal validation of PFS as a surrogate for OS has so far been unsuccessful. In advanced colorectal cancer, in contrast, current evidence indicates that PFS is a valid surrogate for OS after first-line treatment with chemotherapy. The other question is whether PFS sufficiently reflects clinical benefit to be considered a true end point in and of itself.

An information-theoretic approach for the evaluation of surrogate endpoints based on causal inference.

PubMed

Alonso, Ariel; Van der Elst, Wim; Molenberghs, Geert; Buyse, Marc; Burzykowski, Tomasz

2016-09-01

In this work a new metric of surrogacy, the so-called individual causal association (ICA), is introduced using information-theoretic concepts and a causal inference model for a binary surrogate and true endpoint. The ICA has a simple and appealing interpretation in terms of uncertainty reduction and, in some scenarios, it seems to provide a more coherent assessment of the validity of a surrogate than existing measures. The identifiability issues are tackled using a two-step procedure. In the first step, the region of the parametric space of the distribution of the potential outcomes, compatible with the data at hand, is geometrically characterized. Further, in a second step, a Monte Carlo approach is proposed to study the behavior of the ICA on the previous region. The method is illustrated using data from the Collaborative Initial Glaucoma Treatment Study. A newly developed and user-friendly R package Surrogate is provided to carry out the evaluation exercise. © 2016, The International Biometric Society.

Sediment transport and evaluation of sediment surrogate ratings in the Kootenai River near Bonners Ferry, Idaho, Water Years 2011–14

USGS Publications Warehouse

Wood, Molly S.; Fosness, Ryan L.; Etheridge, Alexandra B.

2015-12-14

Acoustic surrogate ratings were developed between backscatter data collected using acoustic Doppler velocity meters (ADVMs) and results of suspended-sediment samples. Ratings were successfully fit to various sediment size classes (total, fines, and sands) using ADVMs of different frequencies (1.5 and 3 megahertz). Surrogate ratings also were developed using variations of streamflow and seasonal explanatory variables. The streamflow surrogate ratings produced average annual sediment load estimates that were 8–32 percent higher, depending on site and sediment type, than estimates produced using the acoustic surrogate ratings. The streamflow surrogate ratings tended to overestimate suspended-sediment concentrations and loads during periods of elevated releases from Libby Dam as well as on the falling limb of the streamflow hydrograph. Estimates from the acoustic surrogate ratings more closely matched suspended-sediment sample results than did estimates from the streamflow surrogate ratings during these periods as well as for rating validation samples collected in water year 2014. Acoustic surrogate technologies are an effective means to obtain continuous, accurate estimates of suspended-sediment concentrations and loads for general monitoring and sediment-transport modeling. In the Kootenai River, continued operation of the acoustic surrogate sites and use of the acoustic surrogate ratings to calculate continuous suspended-sediment concentrations and loads will allow for tracking changes in sediment transport over time.

Comparison of surrogate indices for insulin sensitivity with parameters of the intravenous glucose tolerance test in early lactation dairy cattle.

PubMed

Alves-Nores, V; Castillo, C; Hernandez, J; Abuelo, A

2017-10-01

The aim of this study was to investigate the correlation between different surrogate indices and parameters of the intravenous glucose tolerance test (IVGTT) in dairy cows at the start of their lactation. Ten dairy cows underwent IVGTT on Days 3 to 7 after calving. Areas under the curve during the 90 min after infusion, peak and nadir concentrations, elimination rates, and times to reach half-maximal and basal concentrations for glucose, insulin, nonesterified fatty acids, and β-hydroxybutyrate were calculated. Surrogate indices were computed using the average of the IVGTT basal samples, and their correlation with the IVGTT parameters studied through the Spearman's rank test. No statistically significant or strong correlation coefficients (P > 0.05; |ρ| < 0.50) were observed between the insulin sensitivity measures derived from the IVGTT and any of the surrogate indices. Therefore, these results support that the assessment of insulin sensitivity in early lactation cattle cannot rely on the calculation of surrogate indices in just a blood sample, and the more laborious tests (ie, hyperinsulinemic euglycemic clamp test or IVGTT) should be employed to predict the sensitivity of the peripheral tissues to insulin accurately. Copyright © 2017 Elsevier Inc. All rights reserved.

An evaluation of surrogate chemical exposure measures and autism prevalence in Texas.

PubMed

Lewandowski, T A; Bartell, S M; Yager, J W; Levin, L

2009-01-01

There is currently considerable discussion in the scientific community as well as within the general public concerning the role mercury (Hg) exposures may play in the apparent increased incidence of neurodevelopmental disorders (particularly autism) in children. Although the primary focus of this debate has focused on ethylmercury from vaccinations, linkage to other sources of Hg has been proposed. An ecologic association between 2001 Toxic Release Inventory (TRI; www.epa.gov/tri) data for Hg and 2000-2001 school district autism prevalence was previously reported in Texas. Evaluations using industrial release data as surrogate exposure measures may be problematic, particularly for chemicals like Hg that have complex environmental fates. To explore the robustness of TRI-based analyses of the Hg-autism hypothesis in Texas, a detailed analysis was undertaken examining the extent of the ecological relationship during multiple years and examining whether surrogate exposure measures would yield similar conclusions. Using multilevel Poisson regression analysis and data obtained from a number of publicly available databases, it was found that air Hg release data were significantly associated with autism prevalence in Texas school districts when considering data for 2001 and 2002 (2001: RR = 4.45, 95% CI = 1.60-12.36, 2002: RR = 2.70, 95% CI = 1.17-6.15). Significant associations were not found using data from 2003 to 2005. A significant association was not observed when considering air Hg data for 2000 or 2001 and school district autism prevalence data for 2005-2006 or 2006-2007, an analysis allowing for a 5-yr time period between presumed exposure and entry into the public school system (2000: RR = 1.03, 95% CI = 0.59-1.83, 2001: RR = 0.94, 95% CI = 0.59-1.47). Significant associations were not observed for any year nor for the time lagged analyses when censored autism counts were replaced by threes instead of zeros. An evaluation of TRI air emissions data for several other pollutants did not find significant associations except for nickel (RR = 1.71, 1.12-2.60), which has no history of being associated with neurodevelopmental disorders. An evaluation using downwind location from coal-fired power plants as the exposure surrogate variable also did not yield statistically significant results. The analysis suggests Hg emissions are not consistently associated with autism prevalence in Texas school districts. The lack of consistency across time may be the result of the influence of a more significant factor which remains unidentified. Alternatively, it may be that the significant association observed in 2001 and 2002 does not represent a true causal association.

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

PubMed

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

2015-02-10

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

Do women who choose to become surrogate mothers have different psychological profiles compared to a normative female sample?

PubMed

Pizitz, Todd D; McCullaugh, Joseph; Rabin, Alexa

2013-03-01

Surrogate mothers are routinely assessed for their suitability to function in the role of surrogacy. Such assessments often include psychological testing including the Minnesota multiphasic personality inventory-revised (MMPI-2). There has been a paucity of research detailing the personality structures of these women, especially with the MMPI-2. The current study examined the validity and clinical profiles of surrogate mothers (N=43) compared to a non-patient, normative reference sample of women (N=40) using their MMPI-2 results. This study examined between group differences among the 68 scales of the MMPI-2. Independent-sample t-tests were conducted for each of the scales, with those violating homogeneity of variance assessed with a non-parametric, Mann-Whitney U test. The findings demonstrated that surrogate mothers produce profiles with lower values than normative samples across several MMPI-2 scales. For this unique group, elevations were observed on scales that assess profile validity, views on traditional gender roles, repression, ego strength, social obligation and duties, and contained hostility, relative to the normative group. The findings provide an initial examination of the profiles of surrogate mothers on the MMPI-2. The findings revealed that the psychological suitability of surrogate mother candidates appear to be a composite of being both tough-minded and sensitive, sufficiently resilient to manage the role of surrogacy, and aware of the importance of emotional boundary-setting related to pre-natal attachment. Copyright © 2012 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Informed consent in medical decision-making in commercial gestational surrogacy: a mixed methods study in New Delhi, India.

PubMed

Tanderup, Malene; Reddy, Sunita; Patel, Tulsi; Nielsen, Birgitte Bruun

2015-05-01

To investigate ethical issues in informed consent for decisions regarding embryo transfer and fetal reduction in commercial gestational surrogacy. Mixed methods study employing observations, an interview-guide and semi-structured interviews. Fertility clinics and agencies in Delhi, India, between December 2011 and December 2012. Doctors providing conceptive technologies to commissioning couples and carrying out surrogacy procedures; surrogate mothers; agents functioning as links for surrogacy. Interviews using semi-structured interview guides were carried out among 20 doctors in 18 fertility clinics, five agents from four agencies and 14 surrogate mothers. Surrogate mothers were interviewed both individually and in the presence of doctors and agents. Data on socio-economic context and experiences among and between various actors in the surrogacy process were coded to identify categories of ethical concern. Numerical and grounded theory-oriented analyses were used. Informed consent, number of embryos transferred, fetal reduction, conflict of interest among the involved parties. None of the 14 surrogate mothers were able to explain the risks involved in embryo transfer and fetal reduction. The majority of the doctors took unilateral decisions about embryo transfer and fetal reduction. The commissioning parents were usually only indirectly involved. In the qualitative analysis, difficulties in explaining procedures, autonomy, self-payment of fertility treatment and conflicts of interest were the main themes. Clinical procedural decisions were primarily made by the doctors. Surrogate mothers were not adequately informed. There is a need for regulation on decision-making procedures to safeguard the interests of surrogate mothers. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

Refined ambient PM2.5 exposure surrogates and the risk of myocardial infarction

EPA Science Inventory

Using a case-crossover study design and conditional logistic regression, we compared the relative odds of transmural (full-wall) myocardial infarction (MI) calculated using exposure surrogates that account for human activity patterns and the indoor transport of ambient PM_2....

Biomarkers and Surrogate Endpoints in Drug Development: A European Regulatory View.

PubMed

Wickström, Kerstin; Moseley, Jane

2017-05-01

To give a European regulatory overview of the requirements on and the use of biomarkers or surrogate endpoints in the development of drugs for ocular disease. Definitions, methods to validate new markers, and circumstances where surrogate endpoints can be appropriate are summarized. The key endpoints that have been used in registration studies so far are based on visual acuity, signs, and symptoms, or on surrogate endpoints. In some ocular conditions, established outcome measures such as those based on visual acuity or visual field are not feasible (as with slowly progressing diseases), or lack relevance (e.g., when central visual acuity may be preserved even though the patient is legally blind owing to a severely restricted visual field, or vice versa). There are several ocular conditions for which there is an unmet medical need. In some of these conditions, surrogate endpoints as well as new clinical endpoints are needed to help speed up patient access to new medicines. Interaction with European regulators through the pathway specific for the development of biomarkers or novel methods is encouraged.

Methodology for Formulating Diesel Surrogate Fuels with Accurate Compositional, Ignition-Quality, and Volatility Characteristics

DOE PAGES

Mueller, Charles J.; Cannella, William J.; Bruno, Thomas J.; ...

2012-05-22

In this study, a novel approach was developed to formulate surrogate fuels having characteristics that are representative of diesel fuels produced from real-world refinery streams. Because diesel fuels typically consist of hundreds of compounds, it is difficult to conclusively determine the effects of fuel composition on combustion properties. Surrogate fuels, being simpler representations of these practical fuels, are of interest because they can provide a better understanding of fundamental fuel-composition and property effects on combustion and emissions-formation processes in internal-combustion engines. In addition, the application of surrogate fuels in numerical simulations with accurate vaporization, mixing, and combustion models could revolutionizemore » future engine designs by enabling computational optimization for evolving real fuels. Dependable computational design would not only improve engine function, it would do so at significant cost savings relative to current optimization strategies that rely on physical testing of hardware prototypes. The approach in this study utilized the state-of-the-art techniques of 13C and 1H nuclear magnetic resonance spectroscopy and the advanced distillation curve to characterize fuel composition and volatility, respectively. The ignition quality was quantified by the derived cetane number. Two well-characterized, ultra-low-sulfur #2 diesel reference fuels produced from refinery streams were used as target fuels: a 2007 emissions certification fuel and a Coordinating Research Council (CRC) Fuels for Advanced Combustion Engines (FACE) diesel fuel. A surrogate was created for each target fuel by blending eight pure compounds. The known carbon bond types within the pure compounds, as well as models for the ignition qualities and volatilities of their mixtures, were used in a multiproperty regression algorithm to determine optimal surrogate formulations. The predicted and measured surrogate-fuel properties were quantitatively compared to the measured target-fuel properties, and good agreement was found.« less

Conversations About Goals and Values Are Feasible and Acceptable in Long-Term Acute Care Hospitals: A Pilot Study.

PubMed

Lamas, Daniela J; Owens, Robert L; Nace, R Nicholas; Massaro, Anthony F; Pertsch, Nathan J; Moore, Susan T; Bernacki, Rachelle E; Block, Susan D

2017-07-01

The chronically critically ill have survived acute critical illness but require prolonged mechanical ventilation. These patients are frequently transferred from acute care to long-term acute care hospitals (LTACHs) for prolonged recovery, yet many suffer setbacks requiring readmission to acute care. The patient's relatively improved condition while at the LTACH might be an opportunity for communication regarding care goals; however, there have been no prior studies of the feasibility of such conversations in the LTACH. To determine the feasibility, acceptability, and potential usefulness of conversations about serious illness with chronic critical illness patients or their surrogate decision makers after LTACH admission. We adapted an existing conversation guide for use in chronically critically ill (defined by tracheotomy for prolonged ventilation) LTACH patients or their surrogates to explore views about quality of life, understanding of medical conditions, expectations, and planning for setbacks. These conversations were conducted by one interviewer and summarized for the patients' clinicians. We surveyed patients, surrogates, and clinicians to assess acceptability. A total of 70 subjects were approached and 50 (71%) were enrolled, including 30 patients and 20 surrogates. The median duration of the conversation was 14 minutes 45 seconds [IQR 12:46, 19]. The presence of ongoing mechanical ventilation did not lead to longer conversations; in fact, conversations with patients were shorter than those with surrogates. The majority of subjects (81%) described the conversation as worthwhile. The majority of clinicians (73%) reported that the conversation offered a new and significant understanding of the patient's preferences if a setback were to occur. Conversations about serious illness care goals can be accomplished in a relatively short period of time, are acceptable to chronically critically ill patients and their surrogate decision makers in the LTACH, and are perceived as worthwhile by patients, surrogates, and clinicians.

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

PubMed

Lassere, Marissa N

2008-06-01

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

Opening the Door: The Experience of Chronic Critical Illness in a Long-Term Acute Care Hospital.

PubMed

Lamas, Daniela J; Owens, Robert L; Nace, R Nicholas; Massaro, Anthony F; Pertsch, Nathan J; Gass, Jonathon; Bernacki, Rachelle E; Block, Susan D

2017-04-01

Chronically critically ill patients have recurrent infections, organ dysfunction, and at least half die within 1 year. They are frequently cared for in long-term acute care hospitals, yet little is known about their experience in this setting. Our objective was to explore the understanding and expectations and goals of these patients and surrogates. We conducted semi-structured interviews with chronically critically ill long-term acute care hospital patients or surrogates. Conversations were recorded, transcribed, and analyzed. One long-term acute care hospital. Chronically critically ill patients, defined by tracheotomy for prolonged mechanical ventilation, or surrogates. Semi-structured conversation about quality of life, expectations, and planning for setbacks. A total of 50 subjects (30 patients and 20 surrogates) were enrolled. Thematic analyses demonstrated: 1) poor quality of life for patients; 2) surrogate stress and anxiety; 3) optimistic health expectations; 4) poor planning for medical setbacks; and 5) disruptive care transitions. Nearly 80% of patient and their surrogate decision makers identified going home as a goal; 38% were at home at 1 year. Our study describes the experience of chronically critically ill patients and surrogates in an long-term acute care hospital and the feasibility of patient-focused research in this setting. Our findings indicate overly optimistic expectations about return home and unmet palliative care needs, suggesting the need for integration of palliative care within the long-term acute care hospital. Further research is also needed to more fully understand the challenges of this growing population of ICU survivors.

Storytelling in the Early Bereavement Period to Reduce Emotional Distress Among Surrogates Involved in a Decision to Limit Life Support in the ICU: A Pilot Feasibility Trial.

PubMed

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

2017-01-01

Surrogate decision makers involved in decisions to limit life support for an incapacitated patient in the ICU have high rates of adverse emotional health outcomes distinct from normal processes of grief and bereavement. Narrative self-disclosure (storytelling) reduces emotional distress after other traumatic experiences. We sought to assess the feasibility, acceptability, and tolerability of storytelling among bereaved surrogates involved in a decision to limit life support in the ICU. Pilot single-blind trial. Five ICUs across three hospitals within a single health system between June 2013 and November 2014. Bereaved surrogates of ICU patients. Storytelling and control conditions involved printed bereavement materials and follow-up assessments. Storytelling involved a single 1- to 2-hour home or telephone visit by a trained interventionist who elicited the surrogate's story. The primary outcomes were feasibility (rates of enrollment, intervention receipt, 3- and 6-mo follow-up), acceptability (closed and open-ended end-of-study feedback at 6 mo), and tolerability (acute mental health services referral). Of 53 eligible surrogates, 32 (60%) consented to treatment allocation. Surrogates' mean age was 55.5 (SD, 11.8), and they were making decisions for their parent (47%), spouse (28%), sibling (13%), child (3%), or other relation (8%). We allocated 14 to control and 18 to storytelling, 17 of 18 (94%) received storytelling, 14 of 14 (100%) and 13 of 14 (94%) control subjects and 16 of 18 (89%) and 17 of 18 (94%) storytelling subjects completed their 3- and 6-month telephone assessments. At 6 months, nine of 13 control participants (69%) and 16 of 17 storytelling subjects (94%) reported feeling "better" or "much better," and none felt "much worse." One control subject (8%) and one storytelling subject (6%) said that the study was burdensome, and one control subject (8%) wished they had not participated. No subjects required acute mental health services referral. A clinical trial of storytelling in this study population is feasible, acceptable, and tolerable.

Is a Frog a Fish with Lungs? A Case Study of the Fungicide Trifloxystrobin

EPA Science Inventory

Current risk assessment practice is to use fish as a surrogate for larval stage amphibian species in determining chemical sensitivity when data for amphibians is not available. While evidence exists that fish are a sufficiently sensitive surrogate for amphibians for a wide range...

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

NASA Astrophysics Data System (ADS)

Janardhanan, S.; Datta, B.

2011-12-01

Surrogate models are widely used to develop computationally efficient simulation-optimization models to solve complex groundwater management problems. Artificial intelligence based models are most often used for this purpose where they are trained using predictor-predictand data obtained from a numerical simulation model. Most often this is implemented with the assumption that the parameters and boundary conditions used in the numerical simulation model are perfectly known. However, in most practical situations these values are uncertain. Under these circumstances the application of such approximation surrogates becomes limited. In our study we develop a surrogate model based coupled simulation optimization methodology for determining optimal pumping strategies for coastal aquifers considering parameter uncertainty. An ensemble surrogate modeling approach is used along with multiple realization optimization. The methodology is used to solve a multi-objective coastal aquifer management problem considering two conflicting objectives. Hydraulic conductivity and the aquifer recharge are considered as uncertain values. Three dimensional coupled flow and transport simulation model FEMWATER is used to simulate the aquifer responses for a number of scenarios corresponding to Latin hypercube samples of pumping and uncertain parameters to generate input-output patterns for training the surrogate models. Non-parametric bootstrap sampling of this original data set is used to generate multiple data sets which belong to different regions in the multi-dimensional decision and parameter space. These data sets are used to train and test multiple surrogate models based on genetic programming. The ensemble of surrogate models is then linked to a multi-objective genetic algorithm to solve the pumping optimization problem. Two conflicting objectives, viz, maximizing total pumping from beneficial wells and minimizing the total pumping from barrier wells for hydraulic control of saltwater intrusion are considered. The salinity levels resulting at strategic locations due to these pumping are predicted using the ensemble surrogates and are constrained to be within pre-specified levels. Different realizations of the concentration values are obtained from the ensemble predictions corresponding to each candidate solution of pumping. Reliability concept is incorporated as the percent of the total number of surrogate models which satisfy the imposed constraints. The methodology was applied to a realistic coastal aquifer system in Burdekin delta area in Australia. It was found that all optimal solutions corresponding to a reliability level of 0.99 satisfy all the constraints and as reducing reliability level decreases the constraint violation increases. Thus ensemble surrogate model based simulation-optimization was found to be useful in deriving multi-objective optimal pumping strategies for coastal aquifers under parameter uncertainty.

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

PubMed

Mitra, Sayani; Schicktanz, Silke

2016-09-19

During a commercial surrogacy arrangement, the event of embryo transfer can be seen as the formal starting point of the arrangement. However, it is common for surrogates to undergo a failed attempt at pregnancy conception or missed conception after an embryo transfer. This paper attempts to argue that such failed attempts can be understood as a loss. It aims to reconstruct the experiences of loss and grief of the surrogates and the intended parents as a consequence of their collective failure to conceive a surrogate pregnancy. Drawing on a qualitative study conducted over a period of eight months between 2014 and 2015 at two fertility clinics in Delhi and two in Kolkata, India, this paper examines the experiences of the surrogates and the intended parents when faced with missed conceptions or failed conceptions during a surrogacy arrangement. We argue that while the surrogate grieves the non-arrival of a 'good news' as an uncertain loss, the intended parents experience yet another, failure in addition to the losses they might have incurred during their previous fertility treatments. The body of the surrogate becomes a site of 'a lost opportunity'. The surrogate embodies a loss in her quest to achieve social mobility and the intended parents experience a disembodied pregnancy loss. This very emotional experience stands in stark contrast to the conceptualisation of such failed attempts as non-events within the discourse of the surrogacy industry. The experience of loss of the intended parents is recognised but their grief is given no space. We argue that such ambiguity around the nature of losses resulting out of a missed or failed conception during surrogacy is an outcome of lack of interpersonal relationship between the surrogate and the intended parents. Since commercial surrogacy is a relational process, the only way in which the experiences of losses and failures of the actors at the preconception stage can be better addressed is through developing close sharing and understanding between each other through an ethics of care. Therefore, to nurture caring relationships, surrogacy needs to be understood as a moral commitment by -the surrogates and intended parents. To enable such a commitment, there is a need to reconsider the pre-defined and legally regulated professional duty of the doctors, agents and agencies. It cannot be a one-sided commitment, but has to have elements of mutuality.

Physical and chemical analysis of lithium-ion battery cell-to-cell failure events inside custom fire chamber

NASA Astrophysics Data System (ADS)

Spinner, Neil S.; Field, Christopher R.; Hammond, Mark H.; Williams, Bradley A.; Myers, Kristina M.; Lubrano, Adam L.; Rose-Pehrsson, Susan L.; Tuttle, Steven G.

2015-04-01

A 5-cubic meter decompression chamber was re-purposed as a fire test chamber to conduct failure and abuse experiments on lithium-ion batteries. Various modifications were performed to enable remote control and monitoring of chamber functions, along with collection of data from instrumentation during tests including high speed and infrared cameras, a Fourier transform infrared spectrometer, real-time gas analyzers, and compact reconfigurable input and output devices. Single- and multi-cell packages of LiCoO2 chemistry 18650 lithium-ion batteries were constructed and data was obtained and analyzed for abuse and failure tests. Surrogate 18650 cells were designed and fabricated for multi-cell packages that mimicked the thermal behavior of real cells without using any active components, enabling internal temperature monitoring of cells adjacent to the active cell undergoing failure. Heat propagation and video recordings before, during, and after energetic failure events revealed a high degree of heterogeneity; some batteries exhibited short burst of sparks while others experienced a longer, sustained flame during failure. Carbon monoxide, carbon dioxide, methane, dimethyl carbonate, and ethylene carbonate were detected via gas analysis, and the presence of these species was consistent throughout all failure events. These results highlight the inherent danger in large format lithium-ion battery packs with regards to cell-to-cell failure, and illustrate the need for effective safety features.

A general framework to learn surrogate relevance criterion for atlas based image segmentation

NASA Astrophysics Data System (ADS)

Zhao, Tingting; Ruan, Dan

2016-09-01

Multi-atlas based image segmentation sees great opportunities in the big data era but also faces unprecedented challenges in identifying positive contributors from extensive heterogeneous data. To assess data relevance, image similarity criteria based on various image features widely serve as surrogates for the inaccessible geometric agreement criteria. This paper proposes a general framework to learn image based surrogate relevance criteria to better mimic the behaviors of segmentation based oracle geometric relevance. The validity of its general rationale is verified in the specific context of fusion set selection for image segmentation. More specifically, we first present a unified formulation for surrogate relevance criteria and model the neighborhood relationship among atlases based on the oracle relevance knowledge. Surrogates are then trained to be small for geometrically relevant neighbors and large for irrelevant remotes to the given targets. The proposed surrogate learning framework is verified in corpus callosum segmentation. The learned surrogates demonstrate superiority in inferring the underlying oracle value and selecting relevant fusion set, compared to benchmark surrogates.

The role of imperfect surrogate endpoint information in drug approval and reimbursement decisions.

PubMed

Bognar, Katalin; Romley, John A; Bae, Jay P; Murray, James; Chou, Jacquelyn W; Lakdawalla, Darius N

2017-01-01

Approval of new drugs is increasingly reliant on "surrogate endpoints," which correlate with but imperfectly predict clinical benefits. Proponents argue surrogate endpoints allow for faster approval, but critics charge they provide inadequate evidence. We develop an economic framework that addresses the value of improvement in the predictive power, or "quality," of surrogate endpoints, and clarifies how quality can influence decisions by regulators, payers, and manufacturers. For example, the framework shows how lower-quality surrogates lead to greater misalignment of incentives between payers and regulators, resulting in more drugs that are approved for use but not covered by payers. Efficient price-negotiation in the marketplace can help align payer incentives for granting access based on surrogates. Higher-quality surrogates increase manufacturer profits and social surplus from early access to new drugs. Since the return on better quality is shared between manufacturers and payers, private incentives to invest in higher-quality surrogates are inefficiently low. Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.

Mass diffusion coefficient measurement for vitreous humor using FEM and MRI

NASA Astrophysics Data System (ADS)

Rattanakijsuntorn, Komsan; Penkova, Anita; Sadha, Satwindar S.

2018-01-01

In early studies, the ‘contour method’ for determining the diffusion coefficient of the vitreous humor was developed. This technique relied on careful injection of an MRI contrast agent (surrogate drug) into the vitreous humor of fresh bovine eyes, and tracking the contours of the contrast agent in time. In addition, an analytical solution was developed for the theoretical contours built on point source model for the injected surrogate drug. The match between theoretical and experimental contours as a least square fit, while floating the diffusion coefficient, led to the value of the diffusion coefficient. This method had its limitation that the initial injection of the surrogate had to be spherical or ellipsoidal because of the analytical result based on the point-source model. With a new finite element model for the analysis in this study, the technique is much less restrictive and handles irregular shapes of the initial bolus. The fresh bovine eyes were used for drug diffusion study in the vitreous and three contrast agents of different molecular masses: gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA, 938 Da), non-ionic gadoteridol (Prohance, 559 Da), and bovine albumin conjugated with gadolinium (Galbumin, 74 kDa) were used as drug surrogates to visualize the diffusion process by MRI. The 3D finite element model was developed to determine the diffusion coefficients of these surrogates with the images from MRI. This method can be used for other types of bioporous media provided the concentration profile can be visualized (by methods such as MRI or fluorescence).

Safety surrogate histograms (SSH): A novel real-time safety assessment of dilemma zone related conflicts at signalized intersections.

PubMed

Ghanipoor Machiani, Sahar; Abbas, Montasir

2016-11-01

Drivers' indecisiveness in dilemma zones (DZ) could result in crash-prone situations at signalized intersections. DZ is to the area ahead of an intersection in which drivers encounter a dilemma regarding whether to stop or proceed through the intersection when the signal turns yellow. An improper decision to stop by the leading driver, combined with the following driver deciding to go, can result in a rear-end collision, unless the following driver recognizes a collision is imminent and adjusts his or her behavior at or shortly after the onset of yellow. Considering the significance of DZ-related crashes, a comprehensive safety measure is needed to characterize the level of safety at signalized intersections. In this study, a novel safety surrogate measure was developed utilizing real-time radar field data. This new measure, called safety surrogate histogram (SSH), captures the degree and frequency of DZ-related conflicts at each intersection approach. SSH includes detailed information regarding the possibility of crashes, because it is calculated based on the vehicles conflicts. An example illustrating the application of the new methodology at two study sites in Virginia is presented and discussed, and a comparison is provided between SSH and other DZ-related safety surrogate measures mentioned in the literature. The results of the study reveal the efficacy of the SSH as complementary to existing surrogate measures. Copyright © 2015 Elsevier Ltd. All rights reserved.

Robust best linear estimator for Cox regression with instrumental variables in whole cohort and surrogates with additive measurement error in calibration sample.

PubMed

Wang, Ching-Yun; Song, Xiao

2016-11-01

Biomedical researchers are often interested in estimating the effect of an environmental exposure in relation to a chronic disease endpoint. However, the exposure variable of interest may be measured with errors. In a subset of the whole cohort, a surrogate variable is available for the true unobserved exposure variable. The surrogate variable satisfies an additive measurement error model, but it may not have repeated measurements. The subset in which the surrogate variables are available is called a calibration sample. In addition to the surrogate variables that are available among the subjects in the calibration sample, we consider the situation when there is an instrumental variable available for all study subjects. An instrumental variable is correlated with the unobserved true exposure variable, and hence can be useful in the estimation of the regression coefficients. In this paper, we propose a nonparametric method for Cox regression using the observed data from the whole cohort. The nonparametric estimator is the best linear combination of a nonparametric correction estimator from the calibration sample and the difference of the naive estimators from the calibration sample and the whole cohort. The asymptotic distribution is derived, and the finite sample performance of the proposed estimator is examined via intensive simulation studies. The methods are applied to the Nutritional Biomarkers Study of the Women's Health Initiative. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

SVAw - a web-based application tool for automated surrogate variable analysis of gene expression studies

PubMed Central

2013-01-01

Background Surrogate variable analysis (SVA) is a powerful method to identify, estimate, and utilize the components of gene expression heterogeneity due to unknown and/or unmeasured technical, genetic, environmental, or demographic factors. These sources of heterogeneity are common in gene expression studies, and failing to incorporate them into the analysis can obscure results. Using SVA increases the biological accuracy and reproducibility of gene expression studies by identifying these sources of heterogeneity and correctly accounting for them in the analysis. Results Here we have developed a web application called SVAw (Surrogate variable analysis Web app) that provides a user friendly interface for SVA analyses of genome-wide expression studies. The software has been developed based on open source bioconductor SVA package. In our software, we have extended the SVA program functionality in three aspects: (i) the SVAw performs a fully automated and user friendly analysis workflow; (ii) It calculates probe/gene Statistics for both pre and post SVA analysis and provides a table of results for the regression of gene expression on the primary variable of interest before and after correcting for surrogate variables; and (iii) it generates a comprehensive report file, including graphical comparison of the outcome for the user. Conclusions SVAw is a web server freely accessible solution for the surrogate variant analysis of high-throughput datasets and facilitates removing all unwanted and unknown sources of variation. It is freely available for use at http://psychiatry.igm.jhmi.edu/sva. The executable packages for both web and standalone application and the instruction for installation can be downloaded from our web site. PMID:23497726

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

PubMed

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

2016-01-01

Surrogacy is a highly debated method mainly used for treating women with infertility caused by uterine factors. This systematic review summarizes current levels of knowledge of the obstetric, medical and psychological outcomes for the surrogate mothers, the intended parents and children born as a result of surrogacy. PubMed, Cochrane and Embase databases up to February 2015 were searched. Cohort studies and case series were included. Original studies published in English and the Scandinavian languages were included. In case of double publications, the latest study was included. Abstracts only and case reports were excluded. Studies with a control group and case series (more than three cases) were included. Cohort studies, but not case series, were assessed for methodological quality, in terms of risk of bias. We examined a variety of main outcomes for the surrogate mothers, children and intended mothers, including obstetric outcome, relationship between surrogate mother and intended couple, surrogate's experiences after relinquishing the child, preterm birth, low birthweight, birth defects, perinatal mortality, child psychological development, parent-child relationship, and disclosure to the child. The search returned 1795 articles of which 55 met the inclusion criteria. The medical outcome for the children was satisfactory and comparable to previous results for children conceived after fresh IVF and oocyte donation. The rate of multiple pregnancies was 2.6-75.0%. Preterm birth rate in singletons varied between 0 and 11.5% and low birthweight occurred in between 0 and 11.1% of cases. At the age of 10 years there were no major psychological differences between children born after surrogacy and children born after other types of assisted reproductive technology (ART) or after natural conception. The obstetric outcomes for the surrogate mothers were mainly reported from case series. Hypertensive disorders in pregnancy were reported in between 3.2 and 10% of cases and placenta praevia/placental abruption in 4.9%. Cases with hysterectomies have also been reported. Most surrogate mothers scored within the normal range on personality tests. Most psychosocial variables were satisfactory, although difficulties related to handing over the child did occur. The psychological well-being of children whose mother had been a surrogate mother between 5 and 15 years earlier was found to be good. No major differences in psychological state were found between intended mothers, mothers who conceived after other types of ART and mothers whose pregnancies were the result of natural conception. Most studies reporting on surrogacy have serious methodological limitations. According to these studies, most surrogacy arrangements are successfully implemented and most surrogate mothers are well-motivated and have little difficulty separating from the children born as a result of the arrangement. The perinatal outcome of the children is comparable to standard IVF and oocyte donation and there is no evidence of harm to the children born as a result of surrogacy. However, these conclusions should be interpreted with caution. To date, there are no studies on children born after cross-border surrogacy or growing up with gay fathers. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Does the decision in a validation process of a surrogate endpoint change with level of significance of treatment effect? A proposal on validation of surrogate endpoints.

PubMed

Sertdemir, Y; Burgut, R

2009-01-01

In recent years the use of surrogate end points (S) has become an interesting issue. In clinical trials, it is important to get treatment outcomes as early as possible. For this reason there is a need for surrogate endpoints (S) which are measured earlier than the true endpoint (T). However, before a surrogate endpoint can be used it must be validated. For a candidate surrogate endpoint, for example time to recurrence, the validation result may change dramatically between clinical trials. The aim of this study is to show how the validation criterion (R(2)(trial)) proposed by Buyse et al. are influenced by the magnitude of treatment effect with an application using real data. The criterion R(2)(trial) proposed by Buyse et al. (2000) is applied to the four data sets from colon cancer clinical trials (C-01, C-02, C-03 and C-04). Each clinical trial is analyzed separately for treatment effect on survival (true endpoint) and recurrence free survival (surrogate endpoint) and this analysis is done also for each center in each trial. Results are used for standard validation analysis. The centers were grouped by the Wald statistic in 3 equal groups. Validation criteria R(2)(trial) were 0.641 95% CI (0.432-0.782), 0.223 95% CI (0.008-0.503), 0.761 95% CI (0.550-0.872) and 0.560 95% CI (0.404-0.687) for C-01, C-02, C-03 and C-04 respectively. The R(2)(trial) criteria changed by the Wald statistics observed for the centers used in the validation process. Higher the Wald statistic groups are higher the R(2)(trial) values observed. The recurrence free survival is not a good surrogate for overall survival in clinical trials with non significant treatment effects and moderate for significant treatment effects. This shows that the level of significance of treatment effect should be taken into account in validation process of surrogate endpoints.

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

PubMed

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

2016-04-01

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

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

PubMed

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

2015-09-01

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

Surrogate Endpoint Evaluation: Principal Stratification Criteria and the Prentice Definition

PubMed Central

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

2015-01-01

A common problem of interest within a randomized clinical trial is the evaluation of an inexpensive response endpoint as a valid surrogate endpoint for a clinical endpoint, where a chief purpose of a valid surrogate is to provide a way to make correct inferences on clinical treatment effects in future studies without needing to collect the clinical endpoint data. Within the principal stratification framework for addressing this problem based on data from a single randomized clinical efficacy trial, a variety of definitions and criteria for a good surrogate endpoint have been proposed, all based on or closely related to the “principal effects” or “causal effect predictiveness (CEP)” surface. We discuss CEP-based criteria for a useful surrogate endpoint, including (1) the meaning and relative importance of proposed criteria including average causal necessity (ACN), average causal sufficiency (ACS), and large clinical effect modification; (2) the relationship between these criteria and the Prentice definition of a valid surrogate endpoint; and (3) the relationship between these criteria and the consistency criterion (i.e., assurance against the “surrogate paradox”). This includes the result that ACN plus a strong version of ACS generally do not imply the Prentice definition nor the consistency criterion, but they do have these implications in special cases. Moreover, the converse does not hold except in a special case with a binary candidate surrogate. The results highlight that assumptions about the treatment effect on the clinical endpoint before the candidate surrogate is measured are influential for the ability to draw conclusions about the Prentice definition or consistency. In addition, we emphasize that in some scenarios that occur commonly in practice, the principal strata sub-populations for inference are identifiable from the observable data, in which cases the principal stratification framework has relatively high utility for the purpose of effect modification analysis, and is closely connected to the treatment marker selection problem. The results are illustrated with application to a vaccine efficacy trial, where ACN and ACS for an antibody marker are found to be consistent with the data and hence support the Prentice definition and consistency. PMID:26722639

Thermal degradation events as health hazards: Particle vs gas phase effects, mechanistic studies with particles

NASA Astrophysics Data System (ADS)

Oberdörster, G.; Ferin, J.; Finkelstein, J.; Soderholm, S.

Exposure to thermal degradation products arising from fire or smoke could be a major concern for manned space missions. Severe acute lung damage has been reported in people after accidental exposure to fumes from plastic materials, and animal studies revealed the extremely high toxicity of freshly generated fumes whereas a decrease in toxicity of aged fumes has been found. This and the fact that toxicity of the freshly generated fumes can be prevented with filters raises the question whether the toxicity may be due to the particulate rather than the gas phase components of the thermodegradation products. Indeed, results from recent studies implicate ultrafine particles (particle diameter in the nm range) as potential severe pulmonary toxicants. We have conducted a number of in vivo (inhalation and instillation studies in rats) and in vitro studies to test the hypothesis that ultrafine particles possess an increased potential to injure the lung compared to larger-sized particles. We used as surrogate particles ultrafine TiO 2 particles (12 and 20 nm diameter). Results in exposed rats showed that the ultrafine TiO 2 particles not only induce a greater acute inflammatory reaction in the lung than larger-sized TiO 2 particles, but can also lead to persistent chronic effects, as indicated by an adverse effect on alveolar macrophage mediated clearance function of particles. Release of mediators from alveolar macrophages during phagocytosis of the ultrafine particles and an increased access of the ultrafine particles to the pulmonary interstitium are likely factors contributing to their pulmonary toxicity. In vitro studies with lung cells (alveolar macrophages) showed, in addition, that ultrafine TiO 2 particles have a greater potential to induce cytokines than larger-sized particles. We conclude from our present studies that ultrafine particles have a significant potential to injure the lung and that their occurrence in thermal degradation events can play a major role in the highly acute toxicity of fumes. Future studies will include adsorption of typical gas phase components (HCl, HF) on surrogate particles to differentiate between gas and particle phase effects and to perform mechanistic studies aimed at introducing therapeutic/preventive measures. These studies will be complemented by a comparison with actual thermal degradation products.

Global Parameter Optimization of CLM4.5 Using Sparse-Grid Based Surrogates

NASA Astrophysics Data System (ADS)

Lu, D.; Ricciuto, D. M.; Gu, L.

2016-12-01

Calibration of the Community Land Model (CLM) is challenging because of its model complexity, large parameter sets, and significant computational requirements. Therefore, only a limited number of simulations can be allowed in any attempt to find a near-optimal solution within an affordable time. The goal of this study is to calibrate some of the CLM parameters in order to improve model projection of carbon fluxes. To this end, we propose a computationally efficient global optimization procedure using sparse-grid based surrogates. We first use advanced sparse grid (SG) interpolation to construct a surrogate system of the actual CLM model, and then we calibrate the surrogate model in the optimization process. As the surrogate model is a polynomial whose evaluation is fast, it can be efficiently evaluated with sufficiently large number of times in the optimization, which facilitates the global search. We calibrate five parameters against 12 months of GPP, NEP, and TLAI data from the U.S. Missouri Ozark (US-MOz) tower. The results indicate that an accurate surrogate model can be created for the CLM4.5 with a relatively small number of SG points (i.e., CLM4.5 simulations), and the application of the optimized parameters leads to a higher predictive capacity than the default parameter values in the CLM4.5 for the US-MOz site.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Jiangjiang; Li, Weixuan; Lin, Guang

In decision-making for groundwater management and contamination remediation, it is important to accurately evaluate the probability of the occurrence of a failure event. For small failure probability analysis, a large number of model evaluations are needed in the Monte Carlo (MC) simulation, which is impractical for CPU-demanding models. One approach to alleviate the computational cost caused by the model evaluations is to construct a computationally inexpensive surrogate model instead. However, using a surrogate approximation can cause an extra error in the failure probability analysis. Moreover, constructing accurate surrogates is challenging for high-dimensional models, i.e., models containing many uncertain input parameters.more » To address these issues, we propose an efficient two-stage MC approach for small failure probability analysis in high-dimensional groundwater contaminant transport modeling. In the first stage, a low-dimensional representation of the original high-dimensional model is sought with Karhunen–Loève expansion and sliced inverse regression jointly, which allows for the easy construction of a surrogate with polynomial chaos expansion. Then a surrogate-based MC simulation is implemented. In the second stage, the small number of samples that are close to the failure boundary are re-evaluated with the original model, which corrects the bias introduced by the surrogate approximation. The proposed approach is tested with a numerical case study and is shown to be 100 times faster than the traditional MC approach in achieving the same level of estimation accuracy.« less

Maintaining tumor targeting accuracy in real-time motion compensation systems for respiration-induced tumor motion.

PubMed

Malinowski, Kathleen; McAvoy, Thomas J; George, Rohini; Dieterich, Sonja; D'Souza, Warren D

2013-07-01

To determine how best to time respiratory surrogate-based tumor motion model updates by comparing a novel technique based on external measurements alone to three direct measurement methods. Concurrently measured tumor and respiratory surrogate positions from 166 treatment fractions for lung or pancreas lesions were analyzed. Partial-least-squares regression models of tumor position from marker motion were created from the first six measurements in each dataset. Successive tumor localizations were obtained at a rate of once per minute on average. Model updates were timed according to four methods: never, respiratory surrogate-based (when metrics based on respiratory surrogate measurements exceeded confidence limits), error-based (when localization error ≥ 3 mm), and always (approximately once per minute). Radial tumor displacement prediction errors (mean ± standard deviation) for the four schema described above were 2.4 ± 1.2, 1.9 ± 0.9, 1.9 ± 0.8, and 1.7 ± 0.8 mm, respectively. The never-update error was significantly larger than errors of the other methods. Mean update counts over 20 min were 0, 4, 9, and 24, respectively. The same improvement in tumor localization accuracy could be achieved through any of the three update methods, but significantly fewer updates were required when the respiratory surrogate method was utilized. This study establishes the feasibility of timing image acquisitions for updating respiratory surrogate models without direct tumor localization.

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

PubMed

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

2016-04-01

To explore the effect of emotion priming and physician communication behaviors on optimism bias. We conducted a 5 × 2 between-subject randomized factorial experiment using a Web-based interactive video designed to simulate a family meeting for a critically ill spouse/parent. Eligibility included age at least 35 years and self-identifying as the surrogate for a spouse/parent. The primary outcome was the surrogate's election of code status. We defined optimism bias as the surrogate's estimate of prognosis with cardiopulmonary resuscitation (CPR) > their recollection of the physician's estimate. Of 373 respondents, 256 (69%) logged in and were randomized and 220 (86%) had nonmissing data for prognosis. Sixty-seven (30%) of 220 overall and 56 of (32%) 173 with an accurate recollection of the physician's estimate had optimism bias. Optimism bias correlated with choosing CPR (P < .001). Emotion priming (P = .397), physician attention to emotion (P = .537), and framing of CPR as the social norm (P = .884) did not affect optimism bias. Framing the decision as the patient's vs the surrogate's (25% vs 36%, P = .066) and describing the alternative to CPR as "allow natural death" instead of "do not resuscitate" (25% vs 37%, P = .035) decreased optimism bias. Framing of CPR choice during code status conversations may influence surrogates' optimism bias. Copyright © 2015 Elsevier Inc. All rights reserved.

Statistical evaluation of surrogate endpoints with examples from cancer clinical trials.

PubMed

Buyse, Marc; Molenberghs, Geert; Paoletti, Xavier; Oba, Koji; Alonso, Ariel; Van der Elst, Wim; Burzykowski, Tomasz

2016-01-01

A surrogate endpoint is intended to replace a clinical endpoint for the evaluation of new treatments when it can be measured more cheaply, more conveniently, more frequently, or earlier than that clinical endpoint. A surrogate endpoint is expected to predict clinical benefit, harm, or lack of these. Besides the biological plausibility of a surrogate, a quantitative assessment of the strength of evidence for surrogacy requires the demonstration of the prognostic value of the surrogate for the clinical outcome, and evidence that treatment effects on the surrogate reliably predict treatment effects on the clinical outcome. We focus on these two conditions, and outline the statistical approaches that have been proposed to assess the extent to which these conditions are fulfilled. When data are available from a single trial, one can assess the "individual level association" between the surrogate and the true endpoint. When data are available from several trials, one can additionally assess the "trial level association" between the treatment effect on the surrogate and the treatment effect on the true endpoint. In the latter case, the "surrogate threshold effect" can be estimated as the minimum effect on the surrogate endpoint that predicts a statistically significant effect on the clinical endpoint. All these concepts are discussed in the context of randomized clinical trials in oncology, and illustrated with two meta-analyses in gastric cancer. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Occupant kinematics of the Hybrid III, THOR-M, and postmortem human surrogates under various restraint conditions in full-scale frontal sled tests.

PubMed

Albert, Devon L; Beeman, Stephanie M; Kemper, Andrew R

2018-02-28

The objective of this research was to compare the occupant kinematics of the Hybrid III (HIII), THOR-M, and postmortem human surrogates (PMHS) during full-scale frontal sled tests under 3 safety restraint conditions: knee bolster (KB), knee bolster and steering wheel airbag (KB/SWAB), and knee bolster airbag and steering wheel airbag (KBAB/SWAB). A total of 20 frontal sled tests were performed with at least 2 tests performed per restraint condition per surrogate. The tests were designed to match the 2012 Toyota Camry New Car Assessment Program (NCAP) full-scale crash test. Rigid polyurethane foam surrogates with compressive strength ratings of 65 and 19 psi were used to simulate the KB and KBAB, respectively. The excursions of the head, shoulders, hips, knees, and ankles were collected using motion capture. Linear acceleration and angular velocity data were also collected from the head, thorax, and pelvis of each surrogate. Time histories were compared between surrogates and restraint conditions using ISO/TS 18571. All surrogates showed some degree of sensitivity to changes in restraint condition. For example, the use of a KBAB decreased the pelvis accelerations and the forward excursions of the knees and hips for all surrogates. However, these trends were not observed for the thorax, shoulders, and head, which showed more sensitivity to the presence of a SWAB. The average scores computed using ISO/TS 18571 for the HIII/PMHS and THOR-M/PMHS comparisons were 0.527 and 0.518, respectively. The HIII had slightly higher scores than the THOR-M for the excursions (HIII average = 0.574; THOR average = 0.520). However, the THOR-M had slightly higher scores for the accelerations and angular rates (HIII average = 0.471; THOR average = 0.516). The data from the current study showed that both KBABs and SWABs affected the kinematics of all surrogates during frontal sled tests. The results of the objective rating analysis indicated that the HIII and THOR-M had comparable overall biofidelity scores. The THOR-M slightly outperformed the HIII for the acceleration and angular velocity data. However, the HIII scored slightly better than the THOR-M for the excursion data. The most notable difference in biofidelity was for the knee excursions, where the HIII had a much higher average ISO score. Only the biofidelity of the HIII and THOR-M with regard to occupant kinematics was evaluated in this study; therefore, future work will evaluate the biofidelity of the ATDs in terms of lower extremity loading, thoracic response, and neck loading.

The Limits of Surrogates' Moral Authority and Physician Professionalism: Can the Paradigm of Palliative Sedation Be Instructive?

PubMed

Berger, Jeffrey T

2017-01-01

With narrow exception, physicians' treatment of incapacitated patients requires the consent of health surrogates. Although the decision-making authority of surrogates is appropriately broad, their moral authority is not without limits. Discerning these bounds is particularly germane to ethically complex treatments and has important implications for the welfare of patients, for the professional integrity of clinicians, and, in fact, for the welfare of surrogates. Palliative sedation is one such complex treatment; as such, it provides a valuable model for analyzing the scope of surrogates' moral authority. Guidelines for palliative sedation that present it as a "last-resort" treatment for severe and intractable suffering yet require surrogate consent in order to offer it are ethically untenable, precisely because the moral limits of surrogate authority have not been considered. © 2017 The Hastings Center.

Bayesian Adaptive Trial Design for a Newly Validated Surrogate Endpoint

PubMed Central

Renfro, Lindsay A.; Carlin, Bradley P.; Sargent, Daniel J.

2011-01-01

Summary The evaluation of surrogate endpoints for primary use in future clinical trials is an increasingly important research area, due to demands for more efficient trials coupled with recent regulatory acceptance of some surrogates as ‘valid.’ However, little consideration has been given to how a trial which utilizes a newly-validated surrogate endpoint as its primary endpoint might be appropriately designed. We propose a novel Bayesian adaptive trial design that allows the new surrogate endpoint to play a dominant role in assessing the effect of an intervention, while remaining realistically cautious about its use. By incorporating multi-trial historical information on the validated relationship between the surrogate and clinical endpoints, then subsequently evaluating accumulating data against this relationship as the new trial progresses, we adaptively guard against an erroneous assessment of treatment based upon a truly invalid surrogate. When the joint outcomes in the new trial seem plausible given similar historical trials, we proceed with the surrogate endpoint as the primary endpoint, and do so adaptively–perhaps stopping the trial for early success or inferiority of the experimental treatment, or for futility. Otherwise, we discard the surrogate and switch adaptive determinations to the original primary endpoint. We use simulation to test the operating characteristics of this new design compared to a standard O’Brien-Fleming approach, as well as the ability of our design to discriminate trustworthy from untrustworthy surrogates in hypothetical future trials. Furthermore, we investigate possible benefits using patient-level data from 18 adjuvant therapy trials in colon cancer, where disease-free survival is considered a newly-validated surrogate endpoint for overall survival. PMID:21838811

Methodology for Formulating Diesel Surrogate Fuels with Accurate Compositional, Ignition-Quality, and Volatility Characteristics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mueller, Charles J.; Cannella, William J.; Bruno, Thomas J.

In this study, a novel approach was developed to formulate surrogate fuels having characteristics that are representative of diesel fuels produced from real-world refinery streams. Because diesel fuels typically consist of hundreds of compounds, it is difficult to conclusively determine the effects of fuel composition on combustion properties. Surrogate fuels, being simpler representations of these practical fuels, are of interest because they can provide a better understanding of fundamental fuel-composition and property effects on combustion and emissions-formation processes in internal-combustion engines. In addition, the application of surrogate fuels in numerical simulations with accurate vaporization, mixing, and combustion models could revolutionizemore » future engine designs by enabling computational optimization for evolving real fuels. Dependable computational design would not only improve engine function, it would do so at significant cost savings relative to current optimization strategies that rely on physical testing of hardware prototypes. The approach in this study utilized the stateof- the-art techniques of 13C and 1H nuclear magnetic resonance spectroscopy and the advanced distillation curve to characterize fuel composition and volatility, respectively. The ignition quality was quantified by the derived cetane number. Two wellcharacterized, ultra-low-sulfur #2 diesel reference fuels produced from refinery streams were used as target fuels: a 2007 emissions certification fuel and a Coordinating Research Council (CRC) Fuels for Advanced Combustion Engines (FACE) diesel fuel. A surrogate was created for each target fuel by blending eight pure compounds. The known carbon bond types within the pure compounds, as well as models for the ignition qualities and volatilities of their mixtures, were used in a multiproperty regression algorithm to determine optimal surrogate formulations. The predicted and measured surrogate-fuel properties were quantitatively compared to the measured target-fuel properties, and good agreement was found. This paper is dedicated to the memory of our friend and colleague Jim Franz. Funding for this research was provided by the U.S. Department of Energy (U.S. DOE) Office of Vehicle Technologies, and by the Coordinating Research Council (CRC) and the companies that employ the CRC members. The study was conducted under the auspices of CRC. The authors thank U.S. DOE program manager Kevin Stork for supporting the participation of the U.S. national laboratories in this study.« less

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

PubMed

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

2015-01-01

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

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

PubMed Central

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

2015-01-01

Somatic cell nuclear transfer (SCNT) is an assisted reproductive technique that can produce multiple copies of excellent livestock. However, low cloning efficiency limits the application of SCNT. In this study, we systematically investigated the major influencing factors related to the overall cloning efficiency in pigs. Here, 13620 cloned embryos derived from excellent pigs were transferred into 79 surrogate gilts, and 119 live cloned piglets were eventually generated. During cloning, group of cloned embryos derived from excellent Landrace or Large white pigs presented no significant differences of cleavage and blastocyst rates, blastocyst cell numbers, surrogate pregnancy and delivery rates, average numbers of piglets born and alive and cloning efficiencies, and group of 101–150, 151–200 or 201–250 cloned embryos transferred per surrogate also displayed a similar developmental efficiency. When estrus stage of surrogate gilts was compared, group of embryo transfer on Day 2 of estrus showed significantly higher pregnancy rate, delivery rate, average number of piglets born, average alive piglet number or cloning efficiency than group on Day 1, Day 3, Day 4 or Day 5, respectively (P<0.05). And, in comparison with the preovulation and postovulation groups, group of surrogate gilts during periovulation displayed a significantly higher overall cloning efficiency (P<0.05). Further investigation of surrogate estrus stage and ovulation status displayed that ovulation status was the real factor underlying estrus stage to determine the overall cloning efficiency. And more, follicle puncture for preovulation, not transfer position shallowed for preovulation or deepened for postovulation, significantly improved the average number of piglets alive and cloning efficiency (P<0.05). In conclusion, our results demonstrated that ovulation status of surrogate gilts was the fundamental factor determining the overall cloning efficiency of excellent pigs, and follicle puncture, not transfer position change, improved cloning efficiency. This work would have important implications in preserving and breeding excellent livestock and improving the overall cloning efficiency. PMID:26565717

An Evaluation of Culture Results during Treatment for Tuberculosis as Surrogate Endpoints for Treatment Failure and Relapse

PubMed Central

Phillips, Patrick P. J.; Fielding, Katherine; Nunn, Andrew J.

2013-01-01

It is widely acknowledged that new regimens are urgently needed for the treatment of tuberculosis. The primary endpoint in the Phase III trials is a composite outcome of failure at the end of treatment or relapse after stopping treatment. Such trials are usually both long and expensive. Valid surrogate endpoints measured during or at the end of treatment could dramatically reduce both the time and cost of assessing the effectiveness of new regimens. The objective of this study was to evaluate sputum culture results on solid media during treatment as surrogate endpoints for poor outcome. Data were obtained from twelve randomised controlled trials conducted by the British Medical Research Council in the 1970s and 80s in East Africa and East Asia, consisting of 6974 participants and 49 different treatment regimens. The month two culture result was shown to be a poor surrogate in East Africa but a good surrogate in Hong Kong. In contrast, the month three culture was a good surrogate in trials conducted in East Africa but not in Hong Kong. As well as differences in location, ethnicity and probable strain of Mycobacteria tuberculosis, Hong Kong trials more often evaluated regimens with rifampicin throughout and intermittent regimens, and patients in East African trials more often presented with extensive cavitation and were slower to convert to culture negative during treatment. An endpoint that is a summary measure of the longitudinal profile of culture results over time or that is able to detect the presence of M. tuberculosis later in treatment is more likely to be a better endpoint for a phase II trial than a culture result at a single time point and may prove to be an acceptable surrogate. More data are needed before any endpoint can be used as a surrogate in a confirmatory phase III trial. PMID:23667677

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

PubMed

Phillips, Patrick P J; Fielding, Katherine; Nunn, Andrew J

2013-01-01

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

Dependence of subject-specific parameters for a fast helical CT respiratory motion model on breathing rate: an animal study

NASA Astrophysics Data System (ADS)

O'Connell, Dylan; Thomas, David H.; Lamb, James M.; Lewis, John H.; Dou, Tai; Sieren, Jered P.; Saylor, Melissa; Hofmann, Christian; Hoffman, Eric A.; Lee, Percy P.; Low, Daniel A.

2018-02-01

To determine if the parameters relating lung tissue displacement to a breathing surrogate signal in a previously published respiratory motion model vary with the rate of breathing during image acquisition. An anesthetized pig was imaged using multiple fast helical scans to sample the breathing cycle with simultaneous surrogate monitoring. Three datasets were collected while the animal was mechanically ventilated with different respiratory rates: 12 bpm (breaths per minute), 17 bpm, and 24 bpm. Three sets of motion model parameters describing the correspondences between surrogate signals and tissue displacements were determined. The model error was calculated individually for each dataset, as well asfor pairs of parameters and surrogate signals from different experiments. The values of one model parameter, a vector field denoted α which related tissue displacement to surrogate amplitude, determined for each experiment were compared. The mean model error of the three datasets was 1.00  ±  0.36 mm with a 95th percentile value of 1.69 mm. The mean error computed from all combinations of parameters and surrogate signals from different datasets was 1.14  ±  0.42 mm with a 95th percentile of 1.95 mm. The mean difference in α over all pairs of experiments was 4.7%  ±  5.4%, and the 95th percentile was 16.8%. The mean angle between pairs of α was 5.0  ±  4.0 degrees, with a 95th percentile of 13.2 mm. The motion model parameters were largely unaffected by changes in the breathing rate during image acquisition. The mean error associated with mismatched sets of parameters and surrogate signals was 0.14 mm greater than the error achieved when using parameters and surrogate signals acquired with the same breathing rate, while maximum respiratory motion was 23.23 mm on average.

Surrogate Plant Data Base : Volume 1. Introduction, Appendix A : The Development of Surrogate Plant Data ; Appendix B : Application of the Surrogate .

DOT National Transportation Integrated Search

1983-03-01

This four volume report consists of a data base describing "surrogate" automobile and truck manufacturing plants developed as part of a methodology for evaluating capital investment requirements in new manufacturing facilities to build new fleets of ...

26 CFR 1.7874-2T - Surrogate foreign corporation (temporary).

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 13 2012-04-01 2012-04-01 false Surrogate foreign corporation (temporary). 1... Surrogate foreign corporation (temporary). (a) Scope. This section provides rules for determining whether a foreign corporation shall be treated as a surrogate foreign corporation under section 7874(a)(2)(B...

26 CFR 1.7874-2T - Surrogate foreign corporation (temporary).

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 13 2011-04-01 2011-04-01 false Surrogate foreign corporation (temporary). 1... Surrogate foreign corporation (temporary). (a) Scope. This section provides rules for determining whether a foreign corporation shall be treated as a surrogate foreign corporation under section 7874(a)(2)(B...

34 CFR 300.519 - Surrogate parents.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) Surrogate parent responsibilities. The surrogate parent may represent the child in all matters relating to... DISABILITIES Procedural Safeguards Due Process Procedures for Parents and Children § 300.519 Surrogate parents..., cannot locate a parent; (3) The child is a ward of the State under the laws of that State; or (4) The...

34 CFR 300.519 - Surrogate parents.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) Surrogate parent responsibilities. The surrogate parent may represent the child in all matters relating to... DISABILITIES Procedural Safeguards Due Process Procedures for Parents and Children § 300.519 Surrogate parents..., cannot locate a parent; (3) The child is a ward of the State under the laws of that State; or (4) The...

34 CFR 300.519 - Surrogate parents.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) Surrogate parent responsibilities. The surrogate parent may represent the child in all matters relating to... DISABILITIES Procedural Safeguards Due Process Procedures for Parents and Children § 300.519 Surrogate parents..., cannot locate a parent; (3) The child is a ward of the State under the laws of that State; or (4) The...

34 CFR 300.519 - Surrogate parents.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Surrogate parent responsibilities. The surrogate parent may represent the child in all matters relating to... DISABILITIES Procedural Safeguards Due Process Procedures for Parents and Children § 300.519 Surrogate parents..., cannot locate a parent; (3) The child is a ward of the State under the laws of that State; or (4) The...

34 CFR 300.519 - Surrogate parents.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) Surrogate parent responsibilities. The surrogate parent may represent the child in all matters relating to... DISABILITIES Procedural Safeguards Due Process Procedures for Parents and Children § 300.519 Surrogate parents..., cannot locate a parent; (3) The child is a ward of the State under the laws of that State; or (4) The...

Surrogate marker evaluation from an information theory perspective.

PubMed

Alonso, Ariel; Molenberghs, Geert

2007-03-01

The last 20 years have seen lots of work in the area of surrogate marker validation, partly devoted to frame the evaluation in a multitrial framework, leading to definitions in terms of the quality of trial- and individual-level association between a potential surrogate and a true endpoint (Buyse et al., 2000, Biostatistics 1, 49-67). A drawback is that different settings have led to different measures at the individual level. Here, we use information theory to create a unified framework, leading to a definition of surrogacy with an intuitive interpretation, offering interpretational advantages, and applicable in a wide range of situations. Our method provides a better insight into the chances of finding a good surrogate endpoint in a given situation. We further show that some of the previous proposals follow as special cases of our method. We illustrate our methodology using data from a clinical study in psychiatry.

Enhanced CRISPR/Cas9-mediated biallelic genome targeting with dual surrogate reporter-integrated donors.

PubMed

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

2017-03-01

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

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

PubMed

Omonzejele, Peter F

2011-01-01

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

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

PubMed

van den Akker, Olga B A

2007-08-01

Personality differences between surrogate mothers (SMs) who gestate and relinquish and intended mothers (IMs) who commission a genetically related or unrelated baby have been unexplored in the UK. Furthermore, the psychological effects of the arrangement have not been determined in a prospective longitudinal study, making this the first quantitative report of psychological functioning in SMs and IMs. SMs and IMs (n = 81: 61 surrogate, 20 intended) undergoing genetic or gestational surrogacy (4 groups) were assessed by postal questionnaire during the first, second and third trimesters of pregnancy. Those with a positive outcome were assessed again in the first week, at 6 weeks and 6 months post-delivery of the surrogate baby. There were no significant differences between or within SM and IM groups on personality characteristics. Social support, marital harmony and state anxiety differed significantly (to P < 0.01) between SMs and IMs at different stages of the arrangement. Differences in attitudes towards the pregnancy and the baby were also observed between groups during pregnancy (to P < 0.001), but there was no evidence of post-natal depression amongst the groups studied. These results are important because they demonstrate psychological effects of the surrogate arrangement are notable and occur over an extended period of time. It also shows that psychological screening and support prior to, during and following surrogacy is indicated.

Assessing Exposure to Household Air Pollution: A Systematic Review and Pooled Analysis of Carbon Monoxide as a Surrogate Measure of Particulate Matter.

PubMed

Carter, Ellison; Norris, Christina; Dionisio, Kathie L; Balakrishnan, Kalpana; Checkley, William; Clark, Maggie L; Ghosh, Santu; Jack, Darby W; Kinney, Patrick L; Marshall, Julian D; Naeher, Luke P; Peel, Jennifer L; Sambandam, Sankar; Schauer, James J; Smith, Kirk R; Wylie, Blair J; Baumgartner, Jill

2017-07-28

Household air pollution from solid fuel burning is a leading contributor to disease burden globally. Fine particulate matter (PM 2.5 ) is thought to be responsible for many of these health impacts. A co-pollutant, carbon monoxide (CO) has been widely used as a surrogate measure of PM 2.5 in studies of household air pollution. The goal was to evaluate the validity of exposure to CO as a surrogate of exposure to PM 2.5 in studies of household air pollution and the consistency of the PM 2.5 -CO relationship across different study settings and conditions. We conducted a systematic review of studies with exposure and/or cooking area PM 2.5 and CO measurements and assembled 2,048 PM 2.5 and CO measurements from a subset of studies (18 cooking area studies and 9 personal exposure studies) retained in the systematic review. We conducted pooled multivariate analyses of PM 2.5 -CO associations, evaluating fuels, urbanicity, season, study, and CO methods as covariates and effect modifiers. We retained 61 of 70 studies for review, representing 27 countries. Reported PM 2.5 -CO correlations ( r ) were lower for personal exposure (range: 0.22-0.97; median=0.57) than for cooking areas (range: 0.10-0.96; median=0.71). In the pooled analyses of personal exposure and cooking area concentrations, the variation in ln(CO) explained 13% and 48% of the variation in ln(PM 2.5 ), respectively. Our results suggest that exposure to CO is not a consistently valid surrogate measure of exposure to PM 2.5 . Studies measuring CO exposure as a surrogate measure of PM exposure should conduct local validation studies for different stove/fuel types and seasons. https://doi.org/10.1289/EHP767.

Assessing Exposure to Household Air Pollution: A Systematic Review and Pooled Analysis of Carbon Monoxide as a Surrogate Measure of Particulate Matter

PubMed Central

Carter, Ellison; Norris, Christina; Dionisio, Kathie L.; Balakrishnan, Kalpana; Checkley, William; Clark, Maggie L.; Ghosh, Santu; Jack, Darby W.; Kinney, Patrick L.; Marshall, Julian D.; Naeher, Luke P.; Peel, Jennifer L.; Sambandam, Sankar; Schauer, James J.; Smith, Kirk R.; Wylie, Blair J.

2017-01-01

Background: Household air pollution from solid fuel burning is a leading contributor to disease burden globally. Fine particulate matter (PM2.5) is thought to be responsible for many of these health impacts. A co-pollutant, carbon monoxide (CO) has been widely used as a surrogate measure of PM2.5 in studies of household air pollution. Objective: The goal was to evaluate the validity of exposure to CO as a surrogate of exposure to PM2.5 in studies of household air pollution and the consistency of the PM2.5–CO relationship across different study settings and conditions. Methods: We conducted a systematic review of studies with exposure and/or cooking area PM2.5 and CO measurements and assembled 2,048 PM2.5 and CO measurements from a subset of studies (18 cooking area studies and 9 personal exposure studies) retained in the systematic review. We conducted pooled multivariate analyses of PM2.5–CO associations, evaluating fuels, urbanicity, season, study, and CO methods as covariates and effect modifiers. Results: We retained 61 of 70 studies for review, representing 27 countries. Reported PM2.5–CO correlations (r) were lower for personal exposure (range: 0.22–0.97; median=0.57) than for cooking areas (range: 0.10–0.96; median=0.71). In the pooled analyses of personal exposure and cooking area concentrations, the variation in ln(CO) explained 13% and 48% of the variation in ln(PM2.5), respectively. Conclusions: Our results suggest that exposure to CO is not a consistently valid surrogate measure of exposure to PM2.5. Studies measuring CO exposure as a surrogate measure of PM exposure should conduct local validation studies for different stove/fuel types and seasons. https://doi.org/10.1289/EHP767 PMID:28886596

Surrogate mother - praiseworthy or stigmatized: a qualitative study on perceptions of surrogacy in Assam, India.

PubMed

Arvidsson, Anna; Vauquline, Polly; Johnsdotter, Sara; Essén, Birgitta

2017-01-01

Surrogacy is a reproductive practice that has been strongly marketed in India as a solution for childless couples. As a result, the number of surrogacy clinics is increasing. Meanwhile, a global discourse on surrogacy, originating from a Western perspective, has characterized surrogacy as being exploitative of women in low-income settings, where poverty drives them to become surrogate mothers. This study explored perspectives on surrogacy from men and women in Assam, an Indian state known to be a low-income setting. Surrogacy arrangements in Assam are still uncommon. It can be expected that the dominant global discourses on surrogacy will be unfamiliar to the general population, and the objective was also to position the results within the divergent global discourses of surrogacy.  In order to explore local views on surrogacy, we conducted individual interviews and focus group discussions with people from various socioeconomic groups in Assam. Our findings reveal that people in Assam perceive surrogacy as a good option for a childless couple, as it would result in a child who is a 'blood' relation - something highly desirable for sociocultural reasons. However, the part played by the surrogate mother complicates local views on surrogacy. Most people consider payment to the surrogate mother contrary to societal norms. A surrogate mother is also often judged in a moral light, either as a 'bad mother' for selling her child, or as a 'noble woman' who has helped a childless couple and deserves payment for her services. In order to decrease the stigmatization of women, a regulatory policy is needed that will take into account the complex understandings of surrogacy and perceptions of surrogate mothers in Indian society. In policy, the possible effect of the dominant exploitation discourse needs to be modulated by local understandings of this reproduction method.

Four-dimensional MRI using an internal respiratory surrogate derived by dimensionality reduction

NASA Astrophysics Data System (ADS)

Uh, Jinsoo; Ayaz Khan, M.; Hua, Chiaho

2016-11-01

This study aimed to develop a practical and accurate 4-dimensional (4D) magnetic resonance imaging (MRI) method using a non-navigator, image-based internal respiratory surrogate derived by dimensionality reduction (DR). The use of DR has been previously suggested but not implemented for reconstructing 4D MRI, despite its practical advantages. We compared multiple image-acquisition schemes and refined a retrospective-sorting process to optimally implement a DR-derived surrogate. The comparison included an unconventional scheme that acquires paired slices alternately to mitigate the internal surrogate’s dependency on a specific slice location. We introduced ‘target-oriented sorting’, as opposed to conventional binning, to quantify the coherence in retrospectively sorted images, thereby determining the minimal scan time needed for sufficient coherence. This study focused on evaluating the proposed method using digital phantoms which provided unequivocal gold standard. The evaluation indicated that the DR-based respiratory surrogate is highly accurate: the error in amplitude percentile of the surrogate signal was less than 5% with the optimal scheme. Acquiring alternating paired slices was superior to the conventional scheme of acquiring individual slices; the advantage of the unconventional scheme was more pronounced when a substantial phase shift occurred across slice locations. The analysis of coherence across sorted images confirmed the advantage of higher sampling efficiencies in non-navigator respiratory surrogates. We determined that a scan time of 20 s per imaging slice was sufficient to achieve a mean coherence error of less than 1% for the tested respiratory patterns. The clinical applicability of the proposed 4D MRI has been demonstrated with volunteers and patients. The diaphragm motion in 4D MRI was consistent with that in dynamic 2D imaging which was regarded as the gold standard (difference within 1.8 mm on average).

A model for studying the energetics of sustained high frequency firing

PubMed Central

Morris, Catherine E.

2018-01-01

Regulating membrane potential and synaptic function contributes significantly to the energetic costs of brain signaling, but the relative costs of action potentials (APs) and synaptic transmission during high-frequency firing are unknown. The continuous high-frequency (200-600Hz) electric organ discharge (EOD) of Eigenmannia, a weakly electric fish, underlies its electrosensing and communication. EODs reflect APs fired by the muscle-derived electrocytes of the electric organ (EO). Cholinergic synapses at the excitable posterior membranes of the elongated electrocytes control AP frequency. Based on whole-fish O2 consumption, ATP demand per EOD-linked AP increases exponentially with AP frequency. Continual EOD-AP generation implies first, that ion homeostatic processes reliably counteract any dissipation of posterior membrane ENa and EK and second that high frequency synaptic activation is reliably supported. Both of these processes require energy. To facilitate an exploration of the expected energy demands of each, we modify a previous excitability model and include synaptic currents able to drive APs at frequencies as high as 600 Hz. Synaptic stimuli are modeled as pulsatile cation conductance changes, with or without a small (sustained) background conductance. Over the full species range of EOD frequencies (200–600 Hz) we calculate frequency-dependent “Na+-entry budgets” for an electrocyte AP as a surrogate for required 3Na+/2K+-ATPase activity. We find that the cost per AP of maintaining constant-amplitude APs increases nonlinearly with frequency, whereas the cost per AP for synaptic input current is essentially constant. This predicts that Na+ channel density should correlate positively with EOD frequency, whereas AChR density should be the same across fish. Importantly, calculated costs (inferred from Na+-entry through Nav and ACh channels) for electrocyte APs as frequencies rise are much less than expected from published whole-fish EOD-linked O2 consumption. For APs at increasingly high frequencies, we suggest that EOD-related costs external to electrocytes (including packaging of synaptic transmitter) substantially exceed the direct cost of electrocyte ion homeostasis. PMID:29708986

Grassland bird productivity in warm season grass fields in southwest Wisconsin

USGS Publications Warehouse

Byers, Carolyn M.; Ribic, Christine; Sample, David W.; Dadisman, John D.; Guttery, Michael

2017-01-01

Surrogate grasslands established through federal set-aside programs, such as U.S. Department of Agriculture's Conservation Reserve Program (CRP), provide important habitat for grassland birds. Warm season grass CRP fields as a group have the potential for providing a continuum of habitat structure for breeding birds, depending on how the fields are managed and their floristic composition. We studied the nesting activity of four obligate grassland bird species, Bobolink (Dolichonyx oryzivorus), Eastern Meadowlark (Sturnella magna), Grasshopper Sparrow (Ammodramus savannarum), and Henslow's Sparrow (A. henslowii), in relation to vegetative composition and fire management in warm season CRP fields in southwest Wisconsin during 2009–2011. Intraspecific variation in apparent nest density was related to the number of years since the field was burned. Apparent Grasshopper Sparrow nest density was highest in the breeding season immediately following spring burns, apparent Henslow's Sparrow nest density was highest 1 y post burn, and apparent Bobolink and Eastern Meadowlark nest densities were higher in post fire years one to three. Grasshopper Sparrow nest density was highest on sites with more diverse vegetation, specifically prairie forbs, and on sites with shorter less dense vegetation. Bobolink, Eastern Meadowlark, and Henslow's Sparrow apparent nest densities were higher on sites with deeper litter; litter was the vegetative component that was most affected by spring burns. Overall nest success was 0.487 for Bobolink (22 d nesting period), 0.478 for Eastern Meadowlark (25 d nesting period), 0.507 for Grasshopper Sparrow (22 d nesting period), and 0.151 for Henslow's Sparrow (21 d nesting period). The major nest predators were grassland-associated species: thirteen-lined ground squirrel (Ictidomys tridecemlineatus), striped skunk (Mephitis mephitis), milk snake (Lampropeltis triangulum), American badger (Taxidea taxus), and western fox snake (Elaphe vulpina). Overall depredation rate was not affected by the number of years since the site had been burned. The diversity of vegetation on warm season CRP fields created by management using fire provides a continuum of structure for obligate grassland birds to use for breeding and habitat for a diversity of nest predators.

RARE Grant- Atmospheric Dry Deposition: Quantification of Mercury and Nutrients using Novel Surrogate Surface Collector Techniques

EPA Science Inventory

This study will quantify the daily surrogate surface dry deposition of mercury and nutrient species, and evaluate its relative importance to wet deposition at two sites in Florida over a two-year period. It will identify the major sources contributing to the observed mercury and...

Analysis of safety impacts of access management alternatives using the surrogate safety assessment model : final report.

DOT National Transportation Integrated Search

2017-06-01

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

76 FR 1620 - Trials to Verify and Describe Clinical Benefit of Midodrine Hydrochloride; Establishment of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-11

... a surrogate endpoint that is reasonably likely to predict clinical benefit or based on a clinical endpoint other than survival or irreversible morbidity. Approval of PROAMATINE was based on trials... surrogate endpoints are ``subject to the requirement that the applicant study the drug further to verify and...

Is Suicide Ideation a Surrogate Endpoint for Geriatric Suicide?

ERIC Educational Resources Information Center

Links, Paul S.; Heisel, Marnin J.; Quastel, Adam

2005-01-01

The present study explored the validity of treating suicide ideation as a surrogate endpoint that can serve as a proxy for suicide in clinical intervention research with suicidal seniors. Two criteria; that suicide ideation is modulated by the proposed intervention and that modulation of suicide ideation leads to a quantitative reduction in…

A surrogate model for thermal characteristics of stratospheric airship

NASA Astrophysics Data System (ADS)

Zhao, Da; Liu, Dongxu; Zhu, Ming

2018-06-01

A simple and accurate surrogate model is extremely needed to reduce the analysis complexity of thermal characteristics for a stratospheric airship. In this paper, a surrogate model based on the Least Squares Support Vector Regression (LSSVR) is proposed. The Gravitational Search Algorithm (GSA) is used to optimize hyper parameters. A novel framework consisting of a preprocessing classifier and two regression models is designed to train the surrogate model. Various temperature datasets of the airship envelope and the internal gas are obtained by a three-dimensional transient model for thermal characteristics. Using these thermal datasets, two-factor and multi-factor surrogate models are trained and several comparison simulations are conducted. Results illustrate that the surrogate models based on LSSVR-GSA have good fitting and generalization abilities. The pre-treated classification strategy proposed in this paper plays a significant role in improving the accuracy of the surrogate model.

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

DOE PAGES

Xi, Maolong; Lu, Dan; Gui, Dongwei; ...

2016-11-27

Robust calibration of an agricultural-hydrological model is critical for simulating crop yield and water quality and making reasonable agricultural management. However, calibration of the agricultural-hydrological system models is challenging because of model complexity, the existence of strong parameter correlation, and significant computational requirements. Therefore, only a limited number of simulations can be allowed in any attempt to find a near-optimal solution within an affordable time, which greatly restricts the successful application of the model. The goal of this study is to locate the optimal solution of the Root Zone Water Quality Model (RZWQM2) given a limited simulation time, so asmore » to improve the model simulation and help make rational and effective agricultural-hydrological decisions. To this end, we propose a computationally efficient global optimization procedure using sparse-grid based surrogates. We first used advanced sparse grid (SG) interpolation to construct a surrogate system of the actual RZWQM2, and then we calibrate the surrogate model using the global optimization algorithm, Quantum-behaved Particle Swarm Optimization (QPSO). As the surrogate model is a polynomial with fast evaluation, it can be efficiently evaluated with a sufficiently large number of times during the optimization, which facilitates the global search. We calibrate seven model parameters against five years of yield, drain flow, and NO 3-N loss data from a subsurface-drained corn-soybean field in Iowa. Results indicate that an accurate surrogate model can be created for the RZWQM2 with a relatively small number of SG points (i.e., RZWQM2 runs). Compared to the conventional QPSO algorithm, our surrogate-based optimization method can achieve a smaller objective function value and better calibration performance using a fewer number of expensive RZWQM2 executions, which greatly improves computational efficiency.« less

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

NASA Astrophysics Data System (ADS)

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

2017-01-01

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

Validation of surrogate endpoints in advanced solid tumors: systematic review of statistical methods, results, and implications for policy makers.

PubMed

Ciani, Oriana; Davis, Sarah; Tappenden, Paul; Garside, Ruth; Stein, Ken; Cantrell, Anna; Saad, Everardo D; Buyse, Marc; Taylor, Rod S

2014-07-01

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. 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). 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. 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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xi, Maolong; Lu, Dan; Gui, Dongwei

Robust calibration of an agricultural-hydrological model is critical for simulating crop yield and water quality and making reasonable agricultural management. However, calibration of the agricultural-hydrological system models is challenging because of model complexity, the existence of strong parameter correlation, and significant computational requirements. Therefore, only a limited number of simulations can be allowed in any attempt to find a near-optimal solution within an affordable time, which greatly restricts the successful application of the model. The goal of this study is to locate the optimal solution of the Root Zone Water Quality Model (RZWQM2) given a limited simulation time, so asmore » to improve the model simulation and help make rational and effective agricultural-hydrological decisions. To this end, we propose a computationally efficient global optimization procedure using sparse-grid based surrogates. We first used advanced sparse grid (SG) interpolation to construct a surrogate system of the actual RZWQM2, and then we calibrate the surrogate model using the global optimization algorithm, Quantum-behaved Particle Swarm Optimization (QPSO). As the surrogate model is a polynomial with fast evaluation, it can be efficiently evaluated with a sufficiently large number of times during the optimization, which facilitates the global search. We calibrate seven model parameters against five years of yield, drain flow, and NO 3-N loss data from a subsurface-drained corn-soybean field in Iowa. Results indicate that an accurate surrogate model can be created for the RZWQM2 with a relatively small number of SG points (i.e., RZWQM2 runs). Compared to the conventional QPSO algorithm, our surrogate-based optimization method can achieve a smaller objective function value and better calibration performance using a fewer number of expensive RZWQM2 executions, which greatly improves computational efficiency.« less

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

PubMed

Su, Szu-Huei; Wu, Li-Min

2018-04-01

The severity of diseases and high mortality rates that typify the intensive care unit often make it difficult for surrogate decision makers to make decisions for critically ill patients regarding whether to continue medical treatments or to accept palliative care. To explore the behavioral intentions that underlie the medical decisions of surrogate decision makers of critically ill patients and the related factors. A cross-sectional, correlation study design was used. A total of 193 surrogate decision makers from six ICUs in a medical center in southern Taiwan were enrolled as participants. Three structured questionnaires were used, including a demographic datasheet, the Family Relationship Scale, and the Behavioral Intention of Medical Decisions Scale. Significantly positive correlations were found between the behavioral intentions underlying medical decisions and the following variables: the relationship of the participant to the patient (Eta = .343, p = .020), the age of the patient (r = .295, p < .01), and whether the patient had signed a currently valid advance healthcare directive (Eta = .223, p = .002). Furthermore, a significantly negative correlation was found between these intentions and length of stay in the ICU (r = -.263, p < .01). Patient age, whether the patient had signed a currently valid advance healthcare directive, and length of stay in the ICU were all predictive factors for the behavioral intentions underlying the medical decisions of the surrogate decision makers, explaining 13.9% of the total variance. In assessing the behavioral intentions underlying the medical decisions of surrogate decision makers, health providers should consider the relationship between critical patients and their surrogate decision makers, patient age, the length of ICU stay, and whether the patient has a pre-signed advance healthcare directive in order to maximize the effectiveness of medical care provided to critically ill patients.

Abiotic Stress and Phyllosphere Bacteria Influence the Survival of Human Norovirus and Its Surrogates on Preharvest Leafy Greens

PubMed Central

Esseili, Malak A.; Gao, Xiang; Tegtmeier, Sarah; Saif, Linda J.

2015-01-01

Foodborne outbreaks of human noroviruses (HuNoVs) are frequently associated with leafy greens. Because there is no effective method to eliminate HuNoV from postharvest leafy greens, understanding virus survival under preharvest conditions is crucial. The objective of this study was to evaluate the survival of HuNoV and its surrogate viruses, murine norovirus (MNV), porcine sapovirus (SaV), and Tulane virus (TV), on preharvest lettuce and spinach that were subjected to abiotic stress (physical damage, heat, or flood). We also examined the bacteria culturable from the phyllosphere in response to abiotic stress and in relation to viral persistence. Mature plants were subjected to stressors 2 days prior to inoculation of the viruses on leaves. We quantified the viral RNA, determined the infectivity of the surrogates, and performed bacterial counts on postinoculation days (PIDs) 0, 1, 7, and 14. For both plant types, time exerted significant effects on HuNoV, MNV, SaV, and TV RNA titers, with greater effects being seen for the surrogates. Infectious surrogate viruses were undetectable on PID 14. Only physical damage on PID 14 significantly enhanced HuNoV RNA persistence on lettuce, while the three stressors differentially enhanced the persistence of MNV and TV RNA. Bacterial counts were significantly affected by time and plant type but not by the stressors. However, bacterial counts correlated significantly with HuNoV RNA titers on spinach and with the presence of surrogate viruses on both plant types under various conditions. In conclusion, abiotic stressors and phyllosphere bacterial density may differentially influence the survival of HuNoV and its surrogates on lettuce and spinach, emphasizing the need for the use of preventive measures at the preharvest stage. PMID:26497461

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

PubMed Central

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

2013-01-01

Objective Shared decision making is inadequate in intensive care units (ICUs). Decision aids can improve decision making quality, though their role in an ICU setting is unclear. We aimed to develop and pilot test a decision aid for shared decision makers of patients undergoing prolonged mechanical ventilation. Setting ICUs at three medical centers. Subjects 53 surrogate decision makers and 58 physicians. Design and interventions We developed the decision aid using defined methodological guidelines. After an iterative revision process, formative cognitive testing was performed among surrogate-physician dyads. Next, we compared the decision aid to usual care control in a prospective, before/after design study. Measurements and main results Primary outcomes were physician-surrogate discordance for expected patient survival, comprehension of relevant medical information, and the quality of communication. Compared to control, the intervention group had lower surrogate-physician discordance (7 [10] vs 43 [21]), greater comprehension (11.4 [0.7] vs 6.1 [3.7]), and improved quality of communication (8.7 [1.3] vs 8.4 [1.3]) (all p<0.05) post-intervention. Hospital costs were lower in the intervention group ($110,609 vs $178,618; p=0.044); mortality did not differ by group (38% vs 50%, p=0.95). 94% of surrogates and 100% of physicians reported that the decision aid was useful in decision making. Conclusion We developed a prolonged mechanical ventilation decision aid that is feasible, acceptable, and associated with both improved decision making quality and less resource utilization. Further evaluation using a randomized controlled trial design is needed to evaluate the decision aid's effect on long-term patient and surrogate outcomes. PMID:22635048

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

PubMed Central

2012-01-01

Background Blood pressure is considered to be a leading example of a valid surrogate endpoint. The aims of this study were to (i) formally evaluate systolic and diastolic blood pressure reduction as a surrogate endpoint for stroke prevention and (ii) determine what blood pressure reduction would predict a stroke benefit. Methods We identified randomised trials of at least six months duration comparing any pharmacologic anti-hypertensive treatment to placebo or no treatment, and reporting baseline blood pressure, on-trial blood pressure, and fatal and non-fatal stroke. Trials with fewer than five strokes in at least one arm were excluded. Errors-in-variables weighted least squares regression modelled the reduction in stroke as a function of systolic blood pressure reduction and diastolic blood pressure reduction respectively. The lower 95% prediction band was used to determine the minimum systolic blood pressure and diastolic blood pressure difference, the surrogate threshold effect (STE), below which there would be no predicted stroke benefit. The STE was used to generate the surrogate threshold effect proportion (STEP), a surrogacy metric, which with the R-squared trial-level association was used to evaluate blood pressure as a surrogate endpoint for stroke using the Biomarker-Surrogacy Evaluation Schema (BSES3). Results In 18 qualifying trials representing all pharmacologic drug classes of antihypertensives, assuming a reliability coefficient of 0.9, the surrogate threshold effect for a stroke benefit was 7.1 mmHg for systolic blood pressure and 2.4 mmHg for diastolic blood pressure. The trial-level association was 0.41 and 0.64 and the STEP was 66% and 78% for systolic and diastolic blood pressure respectively. The STE and STEP were more robust to measurement error in the independent variable than R-squared trial-level associations. Using the BSES3, assuming a reliability coefficient of 0.9, systolic blood pressure was a B + grade and diastolic blood pressure was an A grade surrogate endpoint for stroke prevention. In comparison, using the same stroke data sets, no STEs could be estimated for cardiovascular (CV) mortality or all-cause mortality reduction, although the STE for CV mortality approached 25 mmHg for systolic blood pressure. Conclusions In this report we provide the first surrogate threshold effect (STE) values for systolic and diastolic blood pressure. We suggest the STEs have face and content validity, evidenced by the inclusivity of trial populations, subject populations and pharmacologic intervention populations in their calculation. We propose that the STE and STEP metrics offer another method of evaluating the evidence supporting surrogate endpoints. We demonstrate how surrogacy evaluations are strengthened if formally evaluated within specific-context evaluation frameworks using the Biomarker- Surrogate Evaluation Schema (BSES3), and we discuss the implications of our evaluation of blood pressure on other biomarkers and patient-reported instruments in relation to surrogacy metrics and trial design. PMID:22409774

Deconstructing the surrogate species concept:a life history approach to the protection of ecosystem services.

USDA-ARS?s Scientific Manuscript database

The use of the surrogate species concept is widespread in environmental risk assessment and in particular the protection of species that provide ecosystem services, yet there are no standard protocols in place for the choice of surrogates. Surrogates are often chosen on the basis of convenience or v...

Deconstructing the surrogate species concept: a life history approach to the protection of ecosystem services

USDA-ARS?s Scientific Manuscript database

The use of the surrogate species concept is widespread in environmental risk assessment and in particular the protection of species that provide ecosystem services, yet there are no standard protocols in place for the choice of surrogates. Surrogates are often chosen on the basis of convenience or ...

Risk estimates for persistent high-risk human papillomavirus infections as surrogate endpoints of progressive cervical disease critically depend on reference category: analysis of the combined prospective cohort of the New Independent States of the Former Soviet Union and Latin American Screening studies.

PubMed

Syrjänen, K; Shabalova, I; Naud, P; Kozachenko, V; Derchain, S; Zakharchenko, S; Roteli-Martins, C; Nerovjna, R; Longatto-Filho, A; Kljukina, L; Tatti, S; Branovskaja, M; Hammes, L S; Branca, M; Grunjberga, V; Eržen, M; Juschenko, A; Costa, S; Sarian, L; Podistov, J; Syrjänen, S

2011-06-01

To make feasible future clinical trials with new-generation human papillomavirus (HPV) vaccines, novel virological surrogate endpoints of progressive disease have been proposed, including high-risk HPV (HR-HPV) persistence for six months (6M+) or 12 months (12M+). The risk estimates (relative risks [RRs]) of these 'virological endpoints' are influenced by several variables, not yet validated adequately. We compared the impact of three referent groups: (i) HPV-negative, (ii) HPV-transient, (iii) HPV-mixed outcome on the risk estimates for 6M+ or 12M+ HR-HPV persistence as predictors of progressive disease. Generalized estimating equation models were used to estimate the strength of 6M+ and 12M+ HR-HPV persistence with disease progression to squamous intraepithelial lesions (SILs), cervical intraepithelial neoplasia (CIN) grade 1+, CIN2+, CIN/SIL endpoints, comparing three optional reference categories (i)-(iii) in a prospective sub-cohort of 1865 women from the combined New Independent States of the Former Soviet Union (NIS) and Latin American Screening (LAMS) studies cohort (n = 15,301). The RRs of these viral endpoints as predictors of progressive disease are affected by the length of viral persistence (6M+ or 12M+) and the surrogate endpoint (SIL, CIN1, CIN2, CIN/SIL). Most dramatic is the effect of the referent group used in risk estimates, with the HPV-negative referent group giving the highest and most consistent RRs for both 6M+ and 12M+ viral persistence, irrespective of which surrogate is used. In addition to deciding on whether to use 6M+ or 12M+ persistence criteria, and cytological, histological or combined surrogate endpoints, one should adopt the HPV-negative referent group as the gold standard in all future studies using viral persistence as the surrogate endpoint of progressive disease.

Unexploded Ordnance Characterization And Detection in Muddy Estuarine Environments

NASA Astrophysics Data System (ADS)

Trembanis, A. C.; DuVal, C.

2017-12-01

There is recognized need for better quantitative understanding of the impact of coastal environments on UXO mobility, burial, and detection. Current efforts are underway to address aspects of UXO mobility and detection in sandy coastal areas. However, a significant data gap has been identified regarding UXO in shallow, muddy environments; 139 Formally Used Defense Sites (FUDS), in U.S. tidal waters alone, have been identified as containing muddy sediments. This study works to address this data gap. Using a shallow estuarine site in the Delaware Bay, this study 1) monitors the mobility and behavior of sensor-integrated surrogate munitions in muddy environments using a high-accuracy acoustic positioning system, 2) directly observes surrogate munition response to hydrodynamic forcing through instrumented bottom frame time-lapse hydrodynamic data and sonar imagery, and 3) monitors site changes through repetitive site surveying autonomous underwater vehicle (AUV) using both sonar and magnetometry. Surrogate UXO, modified with acoustic tracking devices and inertial motion units (IMU), are being deployed at a previously characterized muddy estuarine site. The surrogates are being monitored for changes in mobility and burial using the VEMCO positioning system, an off-the-shelf acoustic positioning system that is capable of tracking the position of multiple acoustic tags with accuracies down to 10 cm. Concurrently, time-series acoustic imagery and hydrodynamic sensors are being deployed to characterize UXO response to varied hydrodynamic conditions and compared to site-wide surrogate behavior. A series of repetitive surveys are being conducted using a magnetometer specifically designed for UXO detection on an autonomous underwater vehicle (AUV). Survey results will be compared to long-term acoustic positioning of the surrogate UXO to determine the effectiveness of the magnetometer for efficiently and effectively locating UXO in shallow, muddy environments. Additionally, this study will help inform parameters for UXO mobility and behavior in storms and muddy environments for integration into existing expert system models of UXO burial and mobility.

Surrogate markers for time-varying treatments and outcomes

PubMed Central

Hsu, Jesse Y; Kennedy, Edward H; Roy, Jason A; Stephens-Shields, Alisa J; Small, Dylan S; Joffe, Marshall M

2015-01-01

Background A surrogate marker is a variable commonly used in clinical trials to guide treatment decisions when the outcome of ultimate interest is not available. A good surrogate marker is one where the treatment effect on the surrogate is a strong predictor of the effect of treatment on the outcome. We review the situation when there is one treatment delivered at baseline, one surrogate measured at one later time point and one ultimate outcome of interest, and discuss new issues arising when variables are time-varying. Methods Most of the literature on surrogate markers has only considered simple settings with one treatment, one surrogate, and one outcome of interest at a fixed time point. However, more complicated time-varying settings are common in practice. In this paper, we describe the unique challenges in two settings, time-varying treatments and time-varying surrogates, while relating the ideas back to the causal-effects and causal-association paradigms. Conclusions In addition to discussing and extending popular notions of surrogacy to time-varying settings, we give examples illustrating that one can be misled by not taking into account time-varying information about the surrogate or treatment. We hope this paper has provided some motivation for future work on estimation and inference in such settings. PMID:25948621

Interpretations, perspectives and intentions in surrogate motherhood

PubMed Central

van Zyl, L.; van Niekerk, A.

2000-01-01

In this paper we examine the questions "What does it mean to be a surrogate mother?" and "What would be an appropriate perspective for a surrogate mother to have on her pregnancy?" In response to the objection that such contracts are alienating or dehumanising since they require women to suppress their evolving perspective on their pregnancies, liberal supporters of surrogate motherhood argue that the freedom to contract includes the freedom to enter a contract to bear a child for an infertile couple. After entering the contract the surrogate may not be free to interpret her pregnancy as that of a non-surrogate mother, but there is more than one appropriate way of interpreting one's pregnancy. To restrict or ban surrogacy contracts would be to prohibit women from making other particular interpretations of their pregnancies they may wish to make, requiring them to live up to a culturally constituted image of ideal motherhood. We examine three interpretations of a "surrogate pregnancy" that are implicit in the views and arguments put forward by ethicists, surrogacy agencies, and surrogate mothers themselves. We hope to show that our concern in this regard goes beyond the view that surrogacy contracts deny or suppress the natural, instinctive or conventional interpretation of pregnancy. Key Words: Surrogate motherhood • parental rights and responsibilities PMID:11055048

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

PubMed

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

2015-03-01

Understanding the behaviors of surrogate seekers (those who seek health information for others) may guide efforts to improve health information transmission. We used 2011-2012 data from the Health Information National Trends Survey to describe behaviors of online surrogate seekers. Respondents were asked about use of the Internet for surrogate-seeking over the prior 12 months. Data were weighted to calculate population estimates. Two thirds (66.6%) reported surrogate-seeking. Compared to those who sought health information online for only themselves, surrogate seekers were more likely to live in households with others (weighted percent 89.4 vs. 82.5% of self-seekers; p < 0.05); no significant differences in sex, race, income or education were observed. Surrogate seekers were more likely to report activities requiring user-generated content: email communication with healthcare providers; visits to social networking sites to read and share about medical topics and participation in online health support groups. On multivariate analysis, those who had looked online for healthcare providers were more likely to be surrogate seekers (OR 1.67, 95% CI 1.08-2.59). In addition to seeking health information, surrogate seekers create and pass along communications that may influence medical care decisions. Research is needed to identify ways to facilitate transmission of accurate health information.

Health information seeking on behalf of others: Characteristics of ‘surrogate seekers’

PubMed Central

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

2014-01-01

Understanding the behaviors of surrogate-seekers (those who seek health information for others) may guide efforts to improve health information transmission. We used 2011–2012 data from the Health Information National Trends Survey to describe behaviors of online surrogate-seekers. Respondents were asked about use of the Internet for surrogate-seeking over the prior 12 months. Data were weighted to calculate population estimates. Two-thirds (66.6%) reported surrogate-seeking. Compared to those who sought health information online for only themselves, surrogate-seekers were more likely to live in households with others (weighted percent 89.4% vs. 82.5% of self-seekers; p < 0.05); no significant differences in sex, race, income or education were observed. Surrogate-seekers were more likely to report activities requiring user-generated content: email communication with healthcare providers; visits to social networking sites to read and share about medical topics and participation in online health support groups. On multivariate analysis, those who had looked online for healthcare providers were more likely to be surrogate-seekers (OR 1.67, 95% CI 1.08–2.59). In addition to seeking health information, surrogate-seekers create and pass along communications that may influence medical care decisions. Research is needed to identify ways to facilitate transmission of accurate health information. PMID:24989816

Persistent high-risk human papillomavirus (HPV) infections as surrogate endpoints of progressive cervical disease. Potential new endpoint for efficacy studies with new-generation (non-HPV 16/18) prophylactic HPV vaccines.

PubMed

Syrjänen, K

2011-01-01

Recent data indicate that persistent HR-HPV infections represent a significantly increased risk of developing incident high-grade CIN and cervical cancer. Accordingly, 6-month (6M+) or 12-month (12M+) type-specific persistence of HR-HPV have been proposed as powerful surrogates of progressive disease. Because of substantial practical impact in future HPV vaccine trials using non-HPV 16/18 vaccines, studies on HR-HPV persistence as a surrogate endpoint of progressive CIN have been subject to a comprehensive meta-analyses recently. The present communication was solicited to bring this important and timely topic to the awareness of the readers, in a format consisting of a review of the recent literature, supplemented with the author's own experience from different studies. Based on a large number of relevant studies, there remains little doubt that persistence of HR-HPV for 6+ or 12+ months is associated with a significantly increased risk of developing incident high-grade CIN. However, some data also disclosed several important issues that need to be carefully considered and/or adequately resolved before adopting 6M+ or 12M+ HR-HPV persistence as a surrogate of progressive disease. These include i) definitions of HPV persistence, ii) HPV detection techniques and iii) testing intervals and iv) length of follow-up, as well as v) diagnosis of the surrogate endpoints, and vi) other study characteristics, including vii) the type of reference category used in calculating the risk estimates. All these issues are critically discussed in the present communication. Of major impact seems to be the reference category used to calculate these risk estimates, as evident from the NIS-LAMS cohort. Taken together, it is suggested that in all future studies using the 6M+ or 12M+ HR-HPV persistence as a surrogate endpoint of progressive disease, a "gold standard" should be used in calculating the risk estimates. In addition to deciding, 1) whether to use 6M+ or 12M+ persistence criteria, and 2) cytological, histological or combined surrogate endpoints (SIL, CIN1, CIN2, CIN/SIL), one should 3) use exclusively the HPV negative reference group in calculating the risk estimates for viral persistence endpoints. This is supported by the data from the recent meta-analysis as well as from the author's combined NIS-LAMS cohort, both implicating that the most consistent association to progressive disease is obtained when women with persistent HR-HPV are compared with HPV-negative women. It is the conviction of this author that the two other reference categories (HPV transient and HPV mixed outcome) are far too heterogeneous and subject to potential misclassifications to give consistent and reproducible risk estimates for HR-HPV persistence as a surrogate endpoint of progressive CIN.

[Selection of "surrogate" and "endpoints" evaluation of the efficacy of medical interventions].

PubMed

Lazebnik, L B; Gusein-Zade, M G; Efremov, L I

2011-01-01

With the advent of new medical technologies and medicines, as well as due to changes in disease patterns and demographic problems rises the need for continued increases in health spending. Increased costs can be totally inadequate, if it has been done without studying the effectiveness of medical interventions, based on the results of evidence-based medicine and economic of their feasibility. To evaluate the clinical effectiveness of medical interventions have been recently used specific criteria, so called points of clinical efficacy (surrogate and endpoints), that allow to conclude feasibility or harmfulness of the introduction or application of the intervention in clinical practice. The endpoint is reliable indicator the effectiveness of medical intervention. Surrogate point--is a biomarker that is intended to replace the endpoint and is a predictor of the effectiveness of medical intervention. The use of surrogate points has several advantages such as simple in identification and measurement, as well as more higher in compare with endpoints the vents frequency, that can significantly reduce the size of the selection and duration and cost of clinical trials, respectively. Finally, the surrogate points allow to evaluate treatment effect in situations where the use of endpoints is difficult or is unethical.

Ethical frameworks for surrogates’ end-of-life planning experiences: A qualitative systematic review

PubMed Central

Kim, Hyejin; Deatrick, Janet A; Ulrich, Connie M

2016-01-01

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. This systematic review of 30 qualitative research papers 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.. Seven papers explicitly identified ethical theories, principles, or concepts for their studies, such as autonomy, substituted judgment, and best interests. Themes identified about surrogate decision making included: responsibilities and goals, factors affecting surrogates’ decision making, and outcomes for surrogates. In fact, an overarching theme of “wanting to do the right thing” for incapacitated adults and/or themselves was prominent. Understanding the complexity of surrogates’ experiences of end-of-life care planning is beyond the scope of conventional ethical frameworks. 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. PMID:27005954

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

PubMed

Brudney, Daniel

2018-01-01

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

The Use of Surrogate Endpoints in Regulating Medicines for Cardio-Renal Disease: Opinions of Stakeholders

PubMed Central

Schievink, Bauke; Lambers Heerspink, Hiddo; Leufkens, Hubert; De Zeeuw, Dick; Hoekman, Jarno

2014-01-01

Aim There is discussion whether medicines can be authorized on the market based on evidence from surrogate endpoints. We assessed opinions of different stakeholders on this topic. Methods We conducted an online questionnaire that targeted various stakeholder groups (regulatory agencies, pharmaceutical industry, academia, relevant public sector organisations) and medical specialties (cardiology or nephrology vs. other). Participants were enrolled through purposeful sampling. We inquired for conditions under which surrogate endpoints can be used, the validity of various cardio-renal biomarkers and new approaches for biomarker use. Results Participants agreed that surrogate endpoints can be used when the surrogate is scientifically valid (5-point Likert response format, mean score: 4.3, SD: 0.9) or when there is an unmet clinical need (mean score: 3.8, SD: 1.2). Industry participants agreed to a greater extent than regulators and academics. However, out of four proposed surrogates (blood pressure (BP), HbA1c, albuminuria, CRP) for cardiovascular outcomes or end-stage renal disease, only use of BP for cardiovascular outcomes was deemed moderately accurate (mean: 3.6, SD: 1.1). Specialists in cardiology or nephrology tended to be more positive about the use of surrogate endpoints. Conclusion Stakeholders in drug development do not oppose to the use of surrogate endpoints in drug marketing authorization, but most surrogates are not considered valid. To solve this impasse, increased efforts are required to validate surrogate endpoints and to explore alternative ways to use them. PMID:25268242

The use of surrogate endpoints in regulating medicines for cardio-renal disease: opinions of stakeholders.

PubMed

Schievink, Bauke; Lambers Heerspink, Hiddo; Leufkens, Hubert; De Zeeuw, Dick; Hoekman, Jarno

2014-01-01

There is discussion whether medicines can be authorized on the market based on evidence from surrogate endpoints. We assessed opinions of different stakeholders on this topic. We conducted an online questionnaire that targeted various stakeholder groups (regulatory agencies, pharmaceutical industry, academia, relevant public sector organisations) and medical specialties (cardiology or nephrology vs. other). Participants were enrolled through purposeful sampling. We inquired for conditions under which surrogate endpoints can be used, the validity of various cardio-renal biomarkers and new approaches for biomarker use. Participants agreed that surrogate endpoints can be used when the surrogate is scientifically valid (5-point Likert response format, mean score: 4.3, SD: 0.9) or when there is an unmet clinical need (mean score: 3.8, SD: 1.2). Industry participants agreed to a greater extent than regulators and academics. However, out of four proposed surrogates (blood pressure (BP), HbA1c, albuminuria, CRP) for cardiovascular outcomes or end-stage renal disease, only use of BP for cardiovascular outcomes was deemed moderately accurate (mean: 3.6, SD: 1.1). Specialists in cardiology or nephrology tended to be more positive about the use of surrogate endpoints. Stakeholders in drug development do not oppose to the use of surrogate endpoints in drug marketing authorization, but most surrogates are not considered valid. To solve this impasse, increased efforts are required to validate surrogate endpoints and to explore alternative ways to use them.

Surrogate endpoints for overall survival in lung cancer trials: a review.

PubMed

Fiteni, Frédéric; Westeel, Virginie; Bonnetain, Franck

2017-05-01

Intermediate endpoints are often used as primary endpoints instead of overall survival (OS) in lung cancer trials but they are not systematically validated as surrogate endpoints for OS. Areas covered: The aim of the study was to review the studies which assessed potential surrogate endpoints for OS in lung cancer trials. Expert commentary: Twenty studies were identified. In operable non-small cell lung cancer (NSCLC) (adjuvant trials) and locally advanced NSCLC (radiotherapy trials), one individual-patient data meta-analysis found a high correlation of disease-free survival (DFS) and progression-free survival (PFS) with OS at patient and trial level. In trials of adjuvant chemotherapy, correlation between disease-free survival DFS and OS were 0.83 at the individual level (95% CI 0.83-0.83) and 0.92 at trial level (95% CI 0.88-0.95). In locally advanced disease, correlation between PFS and OS was 0.77 to 0.85 at the individual level, and 0.89 to 0.97 at trial level. This study provides a 'proof' of the surrogacy of PFS and DFS on OS according to the IQWiG framework and the surrogacy of PFS and DFS on OS was classified level 2 according to Fleming hierarchy. In all the other setting, no endpoint was judged to be valid surrogate for OS.

"We want to offer you peace of mind": Marketing of transnational commercial surrogacy services to intended parents.

PubMed

Gezinski, Lindsay B; Karandikar, Sharvari; Levitt, Alexis; Ghaffarian, Roxanne

2017-01-01

The purpose of this research study was to conduct a content analysis of commercial surrogacy websites to explore how surrogacy is marketed to intended parents. The researchers developed a template to code website data, and a total of 345 website pages were reviewed. Websites depicted surrogacy as a solution to a problem, privileged genetic parenthood, ignored the potential for exploitation, dismissed surrogates' capacity to bond with the fetuses they carry, emphasized that surrogacy arrangements are mutually beneficial, ignored structural inequalities, and depicted surrogates as conforming to strict gender roles. These framings introduce vulnerabilities to both intended parents and surrogate mothers.

Which factors influence the resort to surrogate consent in stroke trials, and what are the patient outcomes in this context?

PubMed

Mendyk, Anne-Marie; Labreuche, Julien; Henon, Hilde; Girot, Marie; Cordonnier, Charlotte; Duhamel, Alain; Leys, Didier; Bordet, Régis

2015-04-24

The provision of informed consent is a prerequisite for inclusion of a patient in a clinical research project. In some countries, the legislation on clinical research authorizes a third person to provide informed consent if the patient is unable to do so directly (i.e. surrogate consent). This is the case during acute stroke, when the symptoms may prevent the patient from providing informed consent and thus require a third party to be approached. Identification of factors associated with the medical team's decision to resort to surrogate consent may (i) help the care team during the inclusion process and (ii) enable the patient's family circle to be better informed (and thus feel less guilty) about providing surrogate consent. Patients included in the BIOSTROKE cohort (initially dedicated to the analysis of factors influencing stroke severity) were divided into two groups: those having provided informed consent directly and those for whom a third party (such as a family member) had provided surrogate consent. We compared the groups in terms of the initial clinical characteristics (age, gender, type of stroke, severity on the National Institutes of Health Stroke Scale (NIHSS), pre-stroke cognitive status according to the Informant Questionnaire on Cognitive Decline in the Elderly, and the stroke's aetiology) and the functional and cognitive impairments (according to the NIHSS, the modified Rankin score (mRS) and the Mini Mental State Examination) on post-stroke days 8 and 90. Three hundred and ninety five patients were included (mean ± SD age: 67 ± 15 years; 53% males). Surrogate consent had been obtained in 228 cases, and 167 patients had provided consent themselves. The patients included with surrogate consent were likely to be older and more aphasic, with a pre-existing cognitive disorder and more severe stroke (relative to the patients having provided consent). In terms of recovery, the patients included with surrogate consent had a worse functional prognosis (day 90 mRS ≥3: 57.6%, compared with 16.8% in patients having provided consent themselves; p < 0.0001) and a worse cognitive prognosis (day 90 MMS < 24: 15.4% and 4.8%, respectively; p < 0.002). The mortality rate was significantly higher in the surrogate consent group. We found that in addition to age, aphasia and stroke severity, pre-stroke cognitive status is a factor that should prompt the care team to consider requesting surrogate consent for participation in a clinical study. Given that the unfavourable outcome in patients with surrogate consent is often due to their initial clinical state (rather than inclusion in a trial per se), the issue of the family's feelings of guilt (and how to avoid these feelings) should be further addressed.

75 FR 3446 - Certain Frozen Warmwater Shrimp From the Socialist Republic of Vietnam: Preliminary Intent To...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-21

... Notice of Amended Final Determination of Sales at Less Than Fair Value and Antidumping Duty Order... FR 47190 (September 15, 2009). Surrogate Country and Surrogate Values On August 7, 2009, Nhat Duc submitted surrogate country comments, and on September 4, 2009, Nhat Duc submitted surrogate value data. No...

A computer-based education intervention to enhance surrogates' informed consent for genomics research.

PubMed

Shelton, Ann K; Freeman, Bradley D; Fish, Anne F; Bachman, Jean A; Richardson, Lloyd I

2015-03-01

Many research studies conducted today in critical care have a genomics component. Patients' surrogates asked to authorize participation in genomics research for a loved one in the intensive care unit may not be prepared to make informed decisions about a patient's participation in the research. To examine the effectiveness of a new, computer-based education module on surrogates' understanding of the process of informed consent for genomics research. A pilot study was conducted with visitors in the waiting rooms of 2 intensive care units in a Midwestern tertiary care medical center. Visitors were randomly assigned to the experimental (education module plus a sample genomics consent form; n = 65) or the control (sample genomics consent form only; n = 69) group. Participants later completed a test on informed genomics consent. Understanding the process of informed consent was greater (P = .001) in the experimental group than in the control group. Specifically, compared with the control group, the experimental group had a greater understanding of 8 of 13 elements of informed consent: intended benefits of research (P = .02), definition of surrogate consenter (P= .001), withdrawal from the study (P = .001), explanation of risk (P = .002), purpose of the institutional review board (P = .001), definition of substituted judgment (P = .03), compensation for harm (P = .001), and alternative treatments (P = .004). Computer-based education modules may be an important addition to conventional approaches for obtaining informed consent in the intensive care unit. Preparing patients' family members who may consider serving as surrogate consenters is critical to facilitating genomics research in critical care. ©2015 American Association of Critical-Care Nurses.

Endpoints and surrogate endpoints in colorectal cancer: a review of recent developments.

PubMed

Piedbois, Pascal; Buyse, Marc

2008-07-01

The purpose of this review is to discuss recently published work on endpoints for early and advanced colorectal cancer, as well as the statistical approaches used to validate surrogate endpoints. Most attempts to validate surrogate endpoints have estimated the correlation between the surrogate and the true endpoint, and between the treatment effects on these endpoints. The correlation approach has made it possible to validate disease-free survival and progression-free survival as acceptable surrogates for overall survival in early and advanced disease, respectively. The search for surrogate endpoints will intensify over the coming years. In parallel, efforts to either standardize or extend the endpoints or both will improve the reliability and relevance of clinical trial results.

Computer-Simulation Surrogates for Optimization: Application to Trapezoidal Ducts and Axisymmetric Bodies

NASA Technical Reports Server (NTRS)

Otto, John C.; Paraschivoiu, Marius; Yesilyurt, Serhat; Patera, Anthony T.

1995-01-01

Engineering design and optimization efforts using computational systems rapidly become resource intensive. The goal of the surrogate-based approach is to perform a complete optimization with limited resources. In this paper we present a Bayesian-validated approach that informs the designer as to how well the surrogate performs; in particular, our surrogate framework provides precise (albeit probabilistic) bounds on the errors incurred in the surrogate-for-simulation substitution. The theory and algorithms of our computer{simulation surrogate framework are first described. The utility of the framework is then demonstrated through two illustrative examples: maximization of the flowrate of fully developed ow in trapezoidal ducts; and design of an axisymmetric body that achieves a target Stokes drag.

Utilizing Adjoint-Based Error Estimates for Surrogate Models to Accurately Predict Probabilities of Events

DOE PAGES

Butler, Troy; Wildey, Timothy

2018-01-01

In thist study, we develop a procedure to utilize error estimates for samples of a surrogate model to compute robust upper and lower bounds on estimates of probabilities of events. We show that these error estimates can also be used in an adaptive algorithm to simultaneously reduce the computational cost and increase the accuracy in estimating probabilities of events using computationally expensive high-fidelity models. Specifically, we introduce the notion of reliability of a sample of a surrogate model, and we prove that utilizing the surrogate model for the reliable samples and the high-fidelity model for the unreliable samples gives preciselymore » the same estimate of the probability of the output event as would be obtained by evaluation of the original model for each sample. The adaptive algorithm uses the additional evaluations of the high-fidelity model for the unreliable samples to locally improve the surrogate model near the limit state, which significantly reduces the number of high-fidelity model evaluations as the limit state is resolved. Numerical results based on a recently developed adjoint-based approach for estimating the error in samples of a surrogate are provided to demonstrate (1) the robustness of the bounds on the probability of an event, and (2) that the adaptive enhancement algorithm provides a more accurate estimate of the probability of the QoI event than standard response surface approximation methods at a lower computational cost.« less

Utilizing Adjoint-Based Error Estimates for Surrogate Models to Accurately Predict Probabilities of Events

DOE Office of Scientific and Technical Information (OSTI.GOV)

Butler, Troy; Wildey, Timothy

In thist study, we develop a procedure to utilize error estimates for samples of a surrogate model to compute robust upper and lower bounds on estimates of probabilities of events. We show that these error estimates can also be used in an adaptive algorithm to simultaneously reduce the computational cost and increase the accuracy in estimating probabilities of events using computationally expensive high-fidelity models. Specifically, we introduce the notion of reliability of a sample of a surrogate model, and we prove that utilizing the surrogate model for the reliable samples and the high-fidelity model for the unreliable samples gives preciselymore » the same estimate of the probability of the output event as would be obtained by evaluation of the original model for each sample. The adaptive algorithm uses the additional evaluations of the high-fidelity model for the unreliable samples to locally improve the surrogate model near the limit state, which significantly reduces the number of high-fidelity model evaluations as the limit state is resolved. Numerical results based on a recently developed adjoint-based approach for estimating the error in samples of a surrogate are provided to demonstrate (1) the robustness of the bounds on the probability of an event, and (2) that the adaptive enhancement algorithm provides a more accurate estimate of the probability of the QoI event than standard response surface approximation methods at a lower computational cost.« less

Maintaining tumor targeting accuracy in real-time motion compensation systems for respiration-induced tumor motion

PubMed Central

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

2013-01-01

Purpose: To determine how best to time respiratory surrogate-based tumor motion model updates by comparing a novel technique based on external measurements alone to three direct measurement methods. Methods: Concurrently measured tumor and respiratory surrogate positions from 166 treatment fractions for lung or pancreas lesions were analyzed. Partial-least-squares regression models of tumor position from marker motion were created from the first six measurements in each dataset. Successive tumor localizations were obtained at a rate of once per minute on average. Model updates were timed according to four methods: never, respiratory surrogate-based (when metrics based on respiratory surrogate measurements exceeded confidence limits), error-based (when localization error ≥3 mm), and always (approximately once per minute). Results: Radial tumor displacement prediction errors (mean ± standard deviation) for the four schema described above were 2.4 ± 1.2, 1.9 ± 0.9, 1.9 ± 0.8, and 1.7 ± 0.8 mm, respectively. The never-update error was significantly larger than errors of the other methods. Mean update counts over 20 min were 0, 4, 9, and 24, respectively. Conclusions: The same improvement in tumor localization accuracy could be achieved through any of the three update methods, but significantly fewer updates were required when the respiratory surrogate method was utilized. This study establishes the feasibility of timing image acquisitions for updating respiratory surrogate models without direct tumor localization. PMID:23822413

Wildfire effects on lipid composition and hydrophobicity of bulk soil and soil size fractions under Quercus suber cover (SW-Spain).

PubMed

Jiménez-Morillo, Nicasio T; Spangenberg, Jorge E; Miller, Ana Z; Jordán, Antonio; Zavala, Lorena M; González-Vila, Francisco J; González-Pérez, José A

2017-11-01

Soil water repellency (hydrophobicity) prevents water from wetting or infiltrating soils, triggering changes in the ecosystems. Fire may develop, enhance or destroy hydrophobicity in previously wettable or water-repellent soils. Soil water repellency is mostly influenced by the quality and quantity of soil organic matter, particularly the lipid fraction. Here we report the results of a study on the effect of fire on the distribution of soil lipids and their role in the hydrophobicity grade of six particle size fractions (2-1, 1-0.5, 0.5-0.25, 0.25-0.1, 0.1-0.05 and <0.05mm) of an Arenosol under Quercus suber canopy at the Doñana National Park (SW-Spain). Hydrophobicity was determined using water drop penetration time test. Field emission scanning electron microscopy (FESEM) was used to assess the presence and morphology of the inorganic and organic soil components in the particle size fractions. Soil lipids were Soxhlet extracted with a dichloromethane-methanol mixture. Fatty acids (FAs) and neutral lipids were separated, derivatized, identified and quantified by gas chromatography/mass spectrometry and gas chromatography/flame ionization detection. The hydrophobicity values of soil samples and fractions were statistically different (P < 0.05), for both, the unburnt and burnt soils, and particle size fractions. All samples displayed a similar distribution of FAs, straight-chain saturated acids in the C 14 -C 32 range, and neutral lipids (n-alkan-1-ols, n-alkanes), only differing in their relative abundances. Among possible biogeochemical mechanisms responsible for the changes in soil lipids, the observed depletion of long chain FAs (C ≥24 ) in the coarse fraction is best explained by thermal cracking caused by the heat of the fire. The enrichment of long chain FAs observed in other fractions suggests possible exogenous additions of charred, lipid-rich, material, like cork suberin or other plant-derived macromolecules (cutins). Principal component analysis was used to study the relationships between hydrophobicity with soil organic matter and its different components. Extractable organic matter (EOM) and specifically long chain FAs content were positively correlated to soil hydrophobicity. Therefore, the latter could be used as biomarkers surrogated to hydrophobicity in sandy soils. Copyright © 2017 Elsevier Inc. All rights reserved.

Use of surrogate technologies to estimate suspended sediment in the Clearwater River, Idaho, and Snake River, Washington, 2008-10

USGS Publications Warehouse

Wood, Molly S.; Teasdale, Gregg N.

2013-01-01

Elevated levels of fluvial sediment can reduce the biological productivity of aquatic systems, impair freshwater quality, decrease reservoir storage capacity, and decrease the capacity of hydraulic structures. The need to measure fluvial sediment has led to the development of sediment surrogate technologies, particularly in locations where streamflow alone is not a good estimator of sediment load because of regulated flow, load hysteresis, episodic sediment sources, and non-equilibrium sediment transport. An effective surrogate technology is low maintenance and sturdy over a range of hydrologic conditions, and measured variables can be modeled to estimate suspended-sediment concentration (SSC), load, and duration of elevated levels on a real-time basis. Among the most promising techniques is the measurement of acoustic backscatter strength using acoustic Doppler velocity meters (ADVMs) deployed in rivers. The U.S. Geological Survey, in cooperation with the U.S. Army Corps of Engineers, Walla Walla District, evaluated the use of acoustic backscatter, turbidity, laser diffraction, and streamflow as surrogates for estimating real-time SSC and loads in the Clearwater and Snake Rivers, which adjoin in Lewiston, Idaho, and flow into Lower Granite Reservoir. The study was conducted from May 2008 to September 2010 and is part of the U.S. Army Corps of Engineers Lower Snake River Programmatic Sediment Management Plan to identify and manage sediment sources in basins draining into lower Snake River reservoirs. Commercially available acoustic instruments have shown great promise in sediment surrogate studies because they require little maintenance and measure profiles of the surrogate parameter across a sampling volume rather than at a single point. The strength of acoustic backscatter theoretically increases as more particles are suspended in the water to reflect the acoustic pulse emitted by the ADVM. ADVMs of different frequencies (0.5, 1.5, and 3 Megahertz) were tested to target various sediment grain sizes. Laser diffraction and turbidity also were tested as surrogate technologies. Models between SSC and surrogate variables were developed using ordinary least-squares regression. Acoustic backscatter using the high frequency ADVM at each site was the best predictor of sediment, explaining 93 and 92 percent of the variability in SSC and matching sediment sample data within +8.6 and +10 percent, on average, at the Clearwater River and Snake River study sites, respectively. Additional surrogate models were developed to estimate sand and fines fractions of suspended sediment based on acoustic backscatter. Acoustic backscatter generally appears to be a better estimator of suspended sediment concentration and load over short (storm event and monthly) and long (annual) time scales than transport curves derived solely from the regression of conventional sediment measurements and streamflow. Changing grain sizes, the presence of organic matter, and aggregation of sediments in the river likely introduce some variability in the model between acoustic backscatter and SSC.

Validation of surrogate endpoints in cancer clinical trials via principal stratification with an application to a prostate cancer trial.

PubMed

Tanaka, Shiro; Matsuyama, Yutaka; Ohashi, Yasuo

2017-08-30

Increasing attention has been focused on the use and validation of surrogate endpoints in cancer clinical trials. Previous literature on validation of surrogate endpoints are classified into four approaches: the proportion explained approach; the indirect effects approach; the meta-analytic approach; and the principal stratification approach. The mainstream in cancer research has seen the application of a meta-analytic approach. However, VanderWeele (2013) showed that all four of these approaches potentially suffer from the surrogate paradox. It was also shown that, if a principal surrogate satisfies additional criteria called one-sided average causal sufficiency, the surrogate cannot exhibit a surrogate paradox. Here, we propose a method for estimating principal effects under a monotonicity assumption. Specifically, we consider cancer clinical trials which compare a binary surrogate endpoint and a time-to-event clinical endpoint under two naturally ordered treatments (e.g. combined therapy vs. monotherapy). Estimation based on a mean score estimating equation will be implemented by the expectation-maximization algorithm. We will also apply the proposed method as well as other surrogacy criteria to evaluate the surrogacy of prostate-specific antigen using data from a phase III advanced prostate cancer trial, clarifying the complementary roles of both the principal stratification and meta-analytic approaches in the evaluation of surrogate endpoints in cancer. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woelfelschneider, J; Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, DE; Seregni, M

2015-06-15

Purpose: Tumor tracking is an advanced technique to treat intra-fractionally moving tumors. The aim of this study is to validate a surrogate-driven model based on four-dimensional computed tomography (4DCT) that is able to predict CT volumes corresponding to arbitrary respiratory states. Further, the comparison of three different driving surrogates is evaluated. Methods: This study is based on multiple 4DCTs of two patients treated for bronchial carcinoma and metastasis. Analyses for 18 additional patients are currently ongoing. The motion model was estimated from the planning 4DCT through deformable image registration. To predict a certain phase of a follow-up 4DCT, the modelmore » considers for inter-fractional variations (baseline correction) and intra-fractional respiratory parameters (amplitude and phase) derived from surrogates. In this evaluation, three different approaches were used to extract the motion surrogate: for each 4DCT phase, the 3D thoraco-abdominal surface motion, the body volume and the anterior-posterior motion of a virtual single external marker defined on the sternum were investigated. The estimated volumes resulting from the model were compared to the ground-truth clinical 4DCTs using absolute HU differences in the lung volume and landmarks localized using the Scale Invariant Feature Transform (SIFT). Results: The results show absolute HU differences between estimated and ground-truth images with median values limited to 55 HU and inter-quartile ranges (IQR) lower than 100 HU. Median 3D distances between about 1500 matching landmarks are below 2 mm for 3D surface motion and body volume methods. The single marker surrogates Result in increased median distances up to 0.6 mm. Analyses for the extended database incl. 20 patients are currently in progress. Conclusion: The results depend mainly on the image quality of the initial 4DCTs and the deformable image registration. All investigated surrogates can be used to estimate follow-up 4DCT phases, however uncertainties decrease for three-dimensional approaches. This work was funded in parts by the German Research Council (DFG) - KFO 214/2.« less

Anthropometric surrogates for screening of low birth weight newborns: a community-based study.

PubMed

Rustagi, Neeti; Prasuna, J G; Taneja, D K

2012-03-01

In developing countries, where about 75% of births occur at home or in the community, logistic problems prevent the weighing of every newborn child. This study compares various anthropometric surrogates for identification of low birth weight neonates. A longitudinal community based study was done in an urban resettlement colony and 283 singleton neonates within 7 days of birth were examined for the anthropometric measurements such as head, chest, mid upper arm circumference and foot length as a screening tool for low birth weight. Chest circumference measured within 7 days of birth appeared to be the most appropriate surrogate of low birth weight with highest sensitivity (75.4%), specificity (78.4%), and positive predictive value (48.9%) as compared with other anthropometric parameters. Low birth weight neonates in absence of weighing scales can be early identified by using simple anthropometric measurements for enhanced home-based care and timely referral.

Evaluating Candidate Principal Surrogate Endpoints

PubMed Central

Gilbert, Peter B.; Hudgens, Michael G.

2009-01-01

Summary Frangakis and Rubin (2002, Biometrics 58, 21–29) proposed a new definition of a surrogate endpoint (a “principal” surrogate) based on causal effects. We introduce an estimand for evaluating a principal surrogate, the causal effect predictiveness (CEP) surface, which quantifies how well causal treatment effects on the biomarker predict causal treatment effects on the clinical endpoint. Although the CEP surface is not identifiable due to missing potential outcomes, it can be identified by incorporating a baseline covariate(s) that predicts the biomarker. Given case–cohort sampling of such a baseline predictor and the biomarker in a large blinded randomized clinical trial, we develop an estimated likelihood method for estimating the CEP surface. This estimation assesses the “surrogate value” of the biomarker for reliably predicting clinical treatment effects for the same or similar setting as the trial. A CEP surface plot provides a way to compare the surrogate value of multiple biomarkers. The approach is illustrated by the problem of assessing an immune response to a vaccine as a surrogate endpoint for infection. PMID:18363776

Fast Prediction and Evaluation of Gravitational Waveforms Using Surrogate Models

NASA Astrophysics Data System (ADS)

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

2014-07-01

We propose a solution to the problem of quickly and accurately predicting gravitational waveforms within any given physical model. The method is relevant for both real-time applications and more traditional scenarios where the generation of waveforms using standard methods can be prohibitively expensive. Our approach is based on three offline steps resulting in an accurate reduced order model in both parameter and physical dimensions that can be used as a surrogate for the true or fiducial waveform family. First, a set of m parameter values is determined using a greedy algorithm from which a reduced basis representation is constructed. Second, these m parameters induce the selection of m time values for interpolating a waveform time series using an empirical interpolant that is built for the fiducial waveform family. Third, a fit in the parameter dimension is performed for the waveform's value at each of these m times. The cost of predicting L waveform time samples for a generic parameter choice is of order O(mL+mcfit) online operations, where cfit denotes the fitting function operation count and, typically, m ≪L. The result is a compact, computationally efficient, and accurate surrogate model that retains the original physics of the fiducial waveform family while also being fast to evaluate. We generate accurate surrogate models for effective-one-body waveforms of nonspinning binary black hole coalescences with durations as long as 105M, mass ratios from 1 to 10, and for multiple spherical harmonic modes. We find that these surrogates are more than 3 orders of magnitude faster to evaluate as compared to the cost of generating effective-one-body waveforms in standard ways. Surrogate model building for other waveform families and models follows the same steps and has the same low computational online scaling cost. For expensive numerical simulations of binary black hole coalescences, we thus anticipate extremely large speedups in generating new waveforms with a surrogate. As waveform generation is one of the dominant costs in parameter estimation algorithms and parameter space exploration, surrogate models offer a new and practical way to dramatically accelerate such studies without impacting accuracy. Surrogates built in this paper, as well as others, are available from GWSurrogate, a publicly available python package.

Predicting trace organic compound attenuation by ozone oxidation: Development of indicator and surrogate models.

PubMed

Park, Minkyu; Anumol, Tarun; Daniels, Kevin D; Wu, Shimin; Ziska, Austin D; Snyder, Shane A

2017-08-01

Ozone oxidation has been demonstrated to be an effective treatment process for the attenuation of trace organic compounds (TOrCs); however, predicting TOrC attenuation by ozone processes is challenging in wastewaters. Since ozone is rapidly consumed, determining the exposure times of ozone and hydroxyl radical proves to be difficult. As direct potable reuse schemes continue to gain traction, there is an increasing need for the development of real-time monitoring strategies for TOrC abatement in ozone oxidation processes. Hence, this study is primarily aimed at developing indicator and surrogate models for the prediction of TOrC attenuation by ozone oxidation. To this end, the second-order kinetic equations with a second-phase R ct value (ratio of hydroxyl radical exposure to molecular ozone exposure) were used to calculate comparative kinetics of TOrC attenuation and the reduction of indicator and spectroscopic surrogate parameters, including UV absorbance at 254 nm (UVA 254 ) and total fluorescence (TF). The developed indicator model using meprobamate as an indicator compound and the surrogate models with UVA 254 and TF exhibited good predictive power for the attenuation of 13 kinetically distinct TOrCs in five filtered and unfiltered wastewater effluents (R 2 values > 0.8). This study is intended to help provide a guideline for the implementation of indicator/surrogate models for real-time monitoring of TOrC abatement with ozone processes and integrate them into a regulatory framework in water reuse. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2013-08-01

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

Evaluation of bone surrogates for indirect and direct ballistic fractures.

PubMed

Bir, Cynthia; Andrecovich, Chris; DeMaio, Marlene; Dougherty, Paul J

2016-04-01

The mechanism of injury for fractures to long bones has been studied for both direct ballistic loading as well as indirect. However, the majority of these studies have been conducted on both post-mortem human subjects (PMHS) and animal surrogates which have constraints in terms of storage, preparation and testing. The identification of a validated bone surrogate for use in forensic, medical and engineering testing would provide the ability to investigate ballistic loading without these constraints. Two specific bone surrogates, Sawbones and Synbone, were evaluated in comparison to PMHS for both direct and indirect ballistic loading. For the direct loading, the mean velocity to produce fracture was 121 ± 19 m/s for the PMHS, which was statistically different from the Sawbones (140 ± 7 m/s) and Synbone (146 ± 3 m/s). The average distance to fracture in the indirect loading was .70 cm for the PMHS. The Synbone had a statistically similar average distance to fracture (.61 cm, p=0.54) however the Sawbones average distance to fracture was statistically different (.41 cm, p<0.05). Fractures patterns were found to be comparable to the PMHS for tests conducted with Synbones, however the input parameters were slightly varied to produce similar results. The fractures patterns with the Sawbones were not found to be as comparable to the PMHS. An ideal bone surrogate for ballistic testing was not identified and future work is warranted. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Surrogate endpoints for overall survival in advanced colorectal cancer: a clinician's perspective.

PubMed

Piedbois, Pascal; Miller Croswell, Jennifer

2008-10-01

Surrogate endpoints in oncology research and practice have garnered increasing attention over the past two decades. This activity has largely been driven by the promise surrogate endpoints appear to hold: the potential to get new therapies to seriously ill patients more rapidly. However, uncertainties abound. Even agreeing upon a definition of a "valid" surrogate endpoint has not been a straightforward exercise; this article begins by highlighting differences in how this term has been previously captured and applied, as well as laying out the basic criteria essential for its application in advanced colorectal cancer. Ideally, these elements include (but are not limited to) ease of measurement, rapid indication of treatment effect, and, most importantly, reliable and consistent prediction of the true impact of a treatment on the ultimate outcome of interest: overall survival. The strengths and weaknesses of current potential surrogate endpoints in advanced colorectal cancer, including performance status, carcinoembryonic antigen plasma level, overall response rate, time to progression, and disease-free survival, are each considered in turn. Finally, limitations of surrogate endpoints in the clinical setting, including challenges in extrapolation to new therapies, and the incomplete provision of information about potential adverse effects, are discussed. Work remains to be done between physicians and statisticians to bridge the gap between that which is statistically demonstrable and that which will be clinically useful.The term ;surrogate endpoint' was virtually unknown by most oncologists 15 years ago. A search in PubMed [http://www.ncbi.nlm.nih.gov] based on the words ;surrogate and cancer' shows that more than 2000 papers were published in medical journals in the last 20 years, with a dramatic increase of interest in the last five years. Interestingly, the same trend is observed when the words ;surrogate and heart' are entered into PubMed, suggesting that the issue of surrogate endpoints goes beyond the field of oncology, although the frequency of discussion varies (Figure 1; note different y-axis scales for oncology and cardiology).The goal of the present paper is to discuss the main issues surrounding surrogate endpoints from a clinician's point of view, using as an example surrogate endpoints of overall survival (OS) in advanced colorectal cancer (ACC).

Estimating suspended sediment using acoustics in a fine-grained riverine system, Kickapoo Creek at Bloomington, Illinois

USGS Publications Warehouse

Manaster, Amanda D.; Domanski, Marian M.; Straub, Timothy D.; Boldt, Justin A.

2016-08-18

Acoustic technologies have the potential to be used as a surrogate for measuring suspended-sediment concentration (SSC). This potential was examined in a fine-grained (97-100 percent fines) riverine system in central Illinois by way of installation of an acoustic instrument. Acoustic data were collected continuously over the span of 5.5 years. Acoustic parameters were regressed against SSC data to determine the accuracy of using acoustic technology as a surrogate for measuring SSC in a fine-grained riverine system. The resulting regressions for SSC and sediment acoustic parameters had coefficients of determination ranging from 0.75 to 0.97 for various events and configurations. The overall Nash-Sutcliffe model-fit efficiency was 0.95 for the 132 observed and predicted SSC values determined using the sediment acoustic parameter regressions. The study of using acoustic technologies as a surrogate for measuring SSC in fine-grained riverine systems is ongoing. The results at this site are promising in the realm of surrogate technology.

Conceptualizing Surrogate Decision-Making at End of Life in the Intensive Care Unit using Cognitive Task Analysis

PubMed Central

Dionne-Odom, J. Nicholas; Willis, Danny G.; Bakitas, Marie; Crandall, Beth; Grace, Pamela J.

2014-01-01

Background Surrogate decision-makers (SDMs) face difficult decisions at end of life (EOL) for decisionally incapacitated intensive care unit (ICU) patients. Purpose Identify and describe the underlying psychological processes of surrogate decision-making for adults at EOL in the ICU. Method Qualitative case study design using a cognitive task analysis (CTA) interviewing approach. Participants were recruited from October 2012 to June 2013 from an academic tertiary medical center’s ICU located in the rural Northeastern United States. Nineteen SDMs for patients who had died in the ICU completed in-depth semi-structured CTA interviews. Discussion The conceptual framework formulated from data analysis reveals that three underlying, iterative, psychological dimensions: gist impressions, distressing emotions, and moral intuitions impact a SDM’s judgment about the acceptability of either the patient’s medical treatments or his or her condition. Conclusion The framework offers initial insights about the underlying psychological processes of surrogate decision-making and may facilitate enhanced decision support for SDMs. PMID:25982772

The potential investment impact of improved access to accelerated approval on the development of treatments for low prevalence rare diseases

PubMed Central

2011-01-01

Background Over 95% of rare diseases lack treatments despite many successful treatment studies in animal models. To improve access to treatments, the Accelerated Approval (AA) regulations were implemented allowing the use of surrogate endpoints to achieve drug approval and accelerate development of life-saving therapies. Many rare diseases have not utilized AA due to the difficulty in gaining acceptance of novel surrogate endpoints in untreated rare diseases. Methods To assess the potential impact of improved AA accessibility, we devised clinical development programs using proposed clinical or surrogate endpoints for fifteen rare disease treatments. Results We demonstrate that better AA access could reduce development costs by approximately 60%, increase investment value, and foster development of three times as many rare disease drugs for the same investment. Conclusion Our research brings attention to the need for well-defined and practical qualification criteria for the use of surrogate endpoints to allow more access to the AA approval pathway in clinical trials for rare diseases. PMID:21733145

Conceptualizing surrogate decision making at end of life in the intensive care unit using cognitive task analysis.

PubMed

Dionne-Odom, J Nicholas; Willis, Danny G; Bakitas, Marie; Crandall, Beth; Grace, Pamela J

2015-01-01

Surrogate decision makers (SDMs) face difficult decisions at end of life (EOL) for decisionally incapacitated intensive care unit (ICU) patients. To identify and describe the underlying psychological processes of surrogate decision making for adults at EOL in the ICU. Qualitative case study design using a cognitive task analysis interviewing approach. Participants were recruited from October 2012 to June 2013 from an academic tertiary medical center's ICU located in the rural Northeastern United States. Nineteen SDMs for patients who had died in the ICU completed in-depth semistructured cognitive task analysis interviews. The conceptual framework formulated from data analysis reveals that three underlying, iterative, psychological dimensions (gist impressions, distressing emotions, and moral intuitions) impact an SDM's judgment about the acceptability of either the patient's medical treatments or his or her condition. The framework offers initial insights about the underlying psychological processes of surrogate decision making and may facilitate enhanced decision support for SDMs. Copyright © 2015 Elsevier Inc. All rights reserved.

Physical Employment Standards for UK Firefighters

PubMed Central

Stevenson, Richard D.M.; Siddall, Andrew G.; Turner, Philip F.J.; Bilzon, James L.J.

2017-01-01

Objective: The aim of this study was to assess sensitivity and specificity of surrogate physical ability tests as predictors of criterion firefighting task performance and to identify corresponding minimum muscular strength and endurance standards. Methods: Fifty-one (26 male; 25 female) participants completed three criterion tasks (ladder lift, ladder lower, ladder extension) and three corresponding surrogate tests [one-repetition maximum (1RM) seated shoulder press; 1RM seated rope pull-down; repeated 28 kg seated rope pull-down]. Surrogate test standards were calculated that best identified individuals who passed (sensitivity; true positives) and failed (specificity; true negatives) criterion tasks. Results: Best sensitivity/specificity achieved were 1.00/1.00 for a 35 kg seated shoulder press, 0.79/0.92 for a 60 kg rope pull-down, and 0.83/0.93 for 23 repetitions of the 28 kg rope pull-down. Conclusions: These standards represent performance on surrogate tests commensurate with minimum acceptable performance of essential strength-based occupational tasks in UK firefighters. PMID:28045801

Runoff load estimation of particulate and dissolved nitrogen in Lake Inba watershed using continuous monitoring data on turbidity and electric conductivity.

PubMed

Kim, J; Nagano, Y; Furumai, H

2012-01-01

Easy-to-measure surrogate parameters for water quality indicators are needed for real time monitoring as well as for generating data for model calibration and validation. In this study, a novel linear regression model for estimating total nitrogen (TN) based on two surrogate parameters is proposed based on evaluation of pollutant loads flowing into a eutrophic lake. Based on their runoff characteristics during wet weather, electric conductivity (EC) and turbidity were selected as surrogates for particulate nitrogen (PN) and dissolved nitrogen (DN), respectively. Strong linear relationships were established between PN and turbidity and DN and EC, and both models subsequently combined for estimation of TN. This model was evaluated by comparison of estimated and observed TN runoff loads during rainfall events. This analysis showed that turbidity and EC are viable surrogates for PN and DN, respectively, and that the linear regression model for TN concentration was successful in estimating TN runoff loads during rainfall events and also under dry weather conditions.

Contrasting nest survival patterns for ducks and songbirds in northern mixed-grass prairie

USGS Publications Warehouse

Grant, Todd; Shaffer, Terry L.; Madden, Elizabeth M.; Nenneman, Melvin P.

2017-01-01

Management actions intended to protect or improve habitat for ducks may benefit grassland-nesting passerines, but scant information is available to explore this assumption. During 1998–2003, we examined nest survival of ducks and songbirds to determine whether effects of prescribed fire and other habitat features (e.g., shrub cover and distance to habitat edges) were similar for ducks and passerines breeding in North Dakota. We used the logistic-exposure method to estimate survival of duck and songbird nests (n = 3,171). We used an information-theoretic approach to identify factors that most influenced nest survival. Patterns of nest survival were markedly different between taxonomic groups. For ducks, nest survival was greater during the first postfire nesting season (daily survival rate [DSR] = 0.957, 85% CI = 0.951–0.963), relative to later postfire nesting seasons (DSR = 0.946, 85% CI = 0.942–0.950). Furthermore duck nest survival and nest densities were inversely related. Duck nest survival also was greater as shrub cover decreased and as distance from cropland and wetland edges increased. Passerines had lower nest survival during the first postfire nesting season (DSR = 0.934, 85% CI = 0.924–0.944), when densities also were low compared to subsequent postfire nesting seasons (DSR = 0.947, 85% CI = 0.944–0.950). Parasitism by brown-headed cowbirds (Molothrus ater) reduced passerine nest survival and this effect was more pronounced during the first postfire nesting season compared to subsequent nesting seasons. Passerine nest survival was greater as shrub cover decreased and perhaps for more concealed nests. Duck and songbird nest survival rates were not correlated during this study and for associated studies that examined additional variables using the same dataset, suggesting that different mechanisms influenced their survival. Based on our results, ducks should not be considered direct surrogates for passerines when predicting effects of prescribed fire, shrub cover, and habitat edges on nest survival.

A synopsis of short-term response to alternative restoration treatments in sagebrush-steppe: the SageSTEP project

USGS Publications Warehouse

McIver, James; Brunson, Mark; Bunting, Steve; Chambers, Jeanne; Doescher, Paul; Grace, James; Hulet, April; Johnson, Dale; Knick, Steven T.; Miller, Richard; Pellant, Mike; Pierson, Fred; Pyke, David; Rau, Benjamin; Rollins, Kim; Roundy, Bruce; Schupp, Eugene; Tausch, Robin; Williams, Jason

2014-01-01

The Sagebrush Steppe Treatment Evaluation Project (SageSTEP) is an integrated long-term study that evaluates ecological effects of alternative treatments designed to reduce woody fuels and to stimulate the herbaceous understory of sagebrush steppe communities of the Intermountain West. This synopsis summarizes results through 3 yr posttreatment. Woody vegetation reduction by prescribed fire, mechanical treatments, or herbicides initiated a cascade of effects, beginning with increased availability of nitrogen and soil water, followed by increased growth of herbaceous vegetation. Response of butterflies and magnitudes of runoff and erosion closely followed herbaceous vegetation recovery. Effects on shrubs, biological soil crust, tree cover, surface woody fuel loads, and sagebrush-obligate bird communities will take longer to be fully expressed. In the short term, cool wet sites were more resilient than warm dry sites, and resistance was mostly dependent on pretreatment herbaceous cover. At least 10 yr of posttreatment time will likely be necessary to determine outcomes for most sites. Mechanical treatments did not serve as surrogates for prescribed fire in how each influenced the fuel bed, the soil, erosion, and sage-obligate bird communities. Woody vegetation reduction by any means resulted in increased availability of soil water, higher herbaceous cover, and greater butterfly numbers. We identified several trade-offs (desirable outcomes for some variables, undesirable for others), involving most components of the study system. Trade-offs are inevitable when managing complex natural systems, and they underline the importance of asking questions about the whole system when developing management objectives. Substantial spatial and temporal heterogeneity in sagebrush steppe ecosystems emphasizes the point that there will rarely be a “recipe” for choosing management actions on any specific area. Use of a consistent evaluation process linked to monitoring may be the best chance managers have for arresting woodland expansion and cheatgrass invasion that may accelerate in a future warming climate.

Environmental diversity as a surrogate for species representation.

PubMed

Beier, Paul; de Albuquerque, Fábio Suzart

2015-10-01

Because many species have not been described and most species ranges have not been mapped, conservation planners often use surrogates for conservation planning, but evidence for surrogate effectiveness is weak. Surrogates are well-mapped features such as soil types, landforms, occurrences of an easily observed taxon (discrete surrogates), and well-mapped environmental conditions (continuous surrogate). In the context of reserve selection, the idea is that a set of sites selected to span diversity in the surrogate will efficiently represent most species. Environmental diversity (ED) is a rarely used surrogate that selects sites to efficiently span multivariate ordination space. Because it selects across continuous environmental space, ED should perform better than discrete surrogates (which necessarily ignore within-bin and between-bin heterogeneity). Despite this theoretical advantage, ED appears to have performed poorly in previous tests of its ability to identify 50 × 50 km cells that represented vertebrates in Western Europe. Using an improved implementation of ED, we retested ED on Western European birds, mammals, reptiles, amphibians, and combined terrestrial vertebrates. We also tested ED on data sets for plants of Zimbabwe, birds of Spain, and birds of Arizona (United States). Sites selected using ED represented European mammals no better than randomly selected cells, but they represented species in the other 7 data sets with 20% to 84% effectiveness. This far exceeds the performance in previous tests of ED, and exceeds the performance of most discrete surrogates. We believe ED performed poorly in previous tests because those tests considered only a few candidate explanatory variables and used suboptimal forms of ED's selection algorithm. We suggest future work on ED focus on analyses at finer grain sizes more relevant to conservation decisions, explore the effect of selecting the explanatory variables most associated with species turnover, and investigate whether nonclimate abiotic variables can provide useful surrogates in an ED framework. © 2015 Society for Conservation Biology.

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

PubMed Central

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

2014-01-01

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

Television the Surrogate Parent: Uses and Correlates of Television as Babysitter.

ERIC Educational Resources Information Center

Gantz, Walter

A study was conducted to determine (1) how often television was used as a surrogate parent, (2) the reasons leading to its use as such, and (3) the correlates of using television as a babysitter. Telephone interviews were conducted with 226 mothers who had children between the ages of 2 and 12. The respondents answered questions that addressed…

Evaluation of Viral Surrogate Markers for Study of Pathogen Dissemination During Simulations of Patient Care

PubMed Central

Alhmidi, Heba; John, Amrita; Mana, Thriveen C.; Koganti, Sreelatha; Cadnum, Jennifer L.; Shelton, Melissa B.

2017-01-01

Abstract During patient care simulations, cauliflower mosaic virus DNA and bacteriophage MS2 performed similarly as surrogate markers of pathogen dissemination. These markers disseminated to the environment in a manner similar to Clostridium difficile spores but were more frequently detected on skin and clothing of personnel after personal protective equipment removal. PMID:28752103

Uncertainty quantification of resonant ultrasound spectroscopy for material property and single crystal orientation estimation on a complex part

NASA Astrophysics Data System (ADS)

Aldrin, John C.; Mayes, Alexander; Jauriqui, Leanne; Biedermann, Eric; Heffernan, Julieanne; Livings, Richard; Goodlet, Brent; Mazdiyasni, Siamack

2018-04-01

A case study is presented evaluating uncertainty in Resonance Ultrasound Spectroscopy (RUS) inversion for a single crystal (SX) Ni-based superalloy Mar-M247 cylindrical dog-bone specimens. A number of surrogate models were developed with FEM model solutions, using different sampling schemes (regular grid, Monte Carlo sampling, Latin Hyper-cube sampling) and model approaches, N-dimensional cubic spline interpolation and Kriging. Repeated studies were used to quantify the well-posedness of the inversion problem, and the uncertainty was assessed in material property and crystallographic orientation estimates given typical geometric dimension variability in aerospace components. Surrogate model quality was found to be an important factor in inversion results when the model more closely represents the test data. One important discovery was when the model matches well with test data, a Kriging surrogate model using un-sorted Latin Hypercube sampled data performed as well as the best results from an N-dimensional interpolation model using sorted data. However, both surrogate model quality and mode sorting were found to be less critical when inverting properties from either experimental data or simulated test cases with uncontrolled geometric variation.

Isotope Inversion Experiment evaluating the suitability of calibration in surrogate matrix for quantification via LC-MS/MS-Exemplary application for a steroid multi-method.

PubMed

Suhr, Anna Catharina; Vogeser, Michael; Grimm, Stefanie H

2016-05-30

For quotable quantitative analysis of endogenous analytes in complex biological samples by isotope dilution LC-MS/MS, the creation of appropriate calibrators is a challenge, since analyte-free authentic material is in general not available. Thus, surrogate matrices are often used to prepare calibrators and controls. However, currently employed validation protocols do not include specific experiments to verify the suitability of a surrogate matrix calibration for quantification of authentic matrix samples. The aim of the study was the development of a novel validation experiment to test whether surrogate matrix based calibrators enable correct quantification of authentic matrix samples. The key element of the novel validation experiment is the inversion of nonlabelled analytes and their stable isotope labelled (SIL) counterparts in respect to their functions, i.e. SIL compound is the analyte and nonlabelled substance is employed as internal standard. As a consequence, both surrogate and authentic matrix are analyte-free regarding SIL analytes, which allows a comparison of both matrices. We called this approach Isotope Inversion Experiment. As figure of merit we defined the accuracy of inverse quality controls in authentic matrix quantified by means of a surrogate matrix calibration curve. As a proof-of-concept application a LC-MS/MS assay addressing six corticosteroids (cortisol, cortisone, corticosterone, 11-deoxycortisol, 11-deoxycorticosterone, and 17-OH-progesterone) was chosen. The integration of the Isotope Inversion Experiment in the validation protocol for the steroid assay was successfully realized. The accuracy results of the inverse quality controls were all in all very satisfying. As a consequence the suitability of a surrogate matrix calibration for quantification of the targeted steroids in human serum as authentic matrix could be successfully demonstrated. The Isotope Inversion Experiment fills a gap in the validation process for LC-MS/MS assays quantifying endogenous analytes. We consider it a valuable and convenient tool to evaluate the correct quantification of authentic matrix samples based on a calibration curve in surrogate matrix. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

Jovic, Olga S

2011-03-01

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

Advance Care Planning Beyond Advance Directives: Perspectives from Patients and Surrogates

PubMed Central

McMahan, Ryan; Knight, Sara J.; Fried, Terri R.; Sudore, Rebecca L.

2014-01-01

Context Advance care planning (ACP) has focused on documenting life-sustaining treatment preferences in advance directives (ADs). ADs alone may be insufficient to prepare diverse patients and surrogates for complex medical decisions. Objectives To understand what steps best prepare patients and surrogates for decision making. Methods We conducted 13 English/Spanish focus groups with participants from a Veterans Affairs and county hospital and the community. Seven groups included patients (n=38) aged ≥65 years, who reported making serious medical decisions. Six separate groups included surrogates (n=31), aged ≥18 years, who made decisions for others. Semi-structured focus groups asked what activities best prepared participants for decision making. Two investigators independently coded data and performed thematic content analysis. Disputes were resolved by consensus. Results Mean±SD patient age was 78±8 years and 61% were non-white. Mean±SD surrogate age was 57±10 years and 91% were non-white. Qualitative analysis identified four overarching themes about how to best prepare for decision making: 1) identify values based on past experiences and quality of life, 2) choose surrogates wisely and verify they understand their role, 3) decide whether to grant leeway in surrogate decision making, and 4) inform other family and friends of one's wishes to prevent conflict. Conclusion Beyond ADs, patients and surrogates recommend several additional steps to prepare for medical decision making including using past experiences to identify values, verifying the surrogate understands their role, deciding whether to grant surrogates leeway, and informing other family and friends of one's wishes. Future ACP interventions should consider incorporating these additional ACP activities. PMID:23200188

Multiscale registration algorithm for alignment of meshes

NASA Astrophysics Data System (ADS)

Vadde, Srikanth; Kamarthi, Sagar V.; Gupta, Surendra M.

2004-03-01

Taking a multi-resolution approach, this research work proposes an effective algorithm for aligning a pair of scans obtained by scanning an object's surface from two adjacent views. This algorithm first encases each scan in the pair with an array of cubes of equal and fixed size. For each scan in the pair a surrogate scan is created by the centroids of the cubes that encase the scan. The Gaussian curvatures of points across the surrogate scan pair are compared to find the surrogate corresponding points. If the difference between the Gaussian curvatures of any two points on the surrogate scan pair is less than a predetermined threshold, then those two points are accepted as a pair of surrogate corresponding points. The rotation and translation values between the surrogate scan pair are determined by using a set of surrogate corresponding points. Using the same rotation and translation values the original scan pairs are aligned. The resulting registration (or alignment) error is computed to check the accuracy of the scan alignment. When the registration error becomes acceptably small, the algorithm is terminated. Otherwise the above process is continued with cubes of smaller and smaller sizes until the algorithm is terminated. However at each finer resolution the search space for finding the surrogate corresponding points is restricted to the regions in the neighborhood of the surrogate points that were at found at the preceding coarser level. The surrogate corresponding points, as the resolution becomes finer and finer, converge to the true corresponding points on the original scans. This approach offers three main benefits: it improves the chances of finding the true corresponding points on the scans, minimize the adverse effects of noise in the scans, and reduce the computational load for finding the corresponding points.

The effect of prognostic data presentation format on perceived risk among surrogate decision makers of critically ill patients: a randomized comparative trial.

PubMed

Chapman, Andy R; Litton, Edward; Chamberlain, Jenny; Ho, Kwok M

2015-04-01

The purpose of this study is to determine whether varying the format used to present prognostic data alters the perception of risk among surrogate decision makers in the intensive care unit (ICU). This was a prospective randomized comparative trial conducted in a 23-bed adult tertiary ICU. Enrolled surrogate decision makers were randomized to 1 of 2 questionnaires, which presented hypothetical ICU scenarios, identical other than the format in which prognostic data were presented (eg, frequencies vs percentages). Participants were asked to rate the risk associated with each prognostic statement. We enrolled 141 surrogate decision makers. The perception of risk varied significantly dependent on the presentation format. For "quantitative data," risks were consistently perceived as higher, when presented as frequencies (eg, 1 in 50) compared with equivalent percentages (eg, 2%). Framing "qualitative data" in terms of chance of "death" rather than "survival" led to a statistically significant increase in perceived risks. Framing "quantitative" data in this way did not significantly affect risk perception. Data format had a significant effect on how surrogate decision makers interpreted risk. Qualitative statements are interpreted widely and affected by framing. Where possible, multiple quantitative formats should be used for presenting prognostic information. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Testing Surrogacy Assumptions: Can Threatened and Endangered Plants Be Grouped by Biological Similarity and Abundances?

PubMed Central

Che-Castaldo, Judy P.; Neel, Maile C.

2012-01-01

There is renewed interest in implementing surrogate species approaches in conservation planning due to the large number of species in need of management but limited resources and data. One type of surrogate approach involves selection of one or a few species to represent a larger group of species requiring similar management actions, so that protection and persistence of the selected species would result in conservation of the group of species. However, among the criticisms of surrogate approaches is the need to test underlying assumptions, which remain rarely examined. In this study, we tested one of the fundamental assumptions underlying use of surrogate species in recovery planning: that there exist groups of threatened and endangered species that are sufficiently similar to warrant similar management or recovery criteria. Using a comprehensive database of all plant species listed under the U.S. Endangered Species Act and tree-based random forest analysis, we found no evidence of species groups based on a set of distributional and biological traits or by abundances and patterns of decline. Our results suggested that application of surrogate approaches for endangered species recovery would be unjustified. Thus, conservation planning focused on individual species and their patterns of decline will likely be required to recover listed species. PMID:23240051

Testing surrogacy assumptions: can threatened and endangered plants be grouped by biological similarity and abundances?

PubMed

Che-Castaldo, Judy P; Neel, Maile C

2012-01-01

There is renewed interest in implementing surrogate species approaches in conservation planning due to the large number of species in need of management but limited resources and data. One type of surrogate approach involves selection of one or a few species to represent a larger group of species requiring similar management actions, so that protection and persistence of the selected species would result in conservation of the group of species. However, among the criticisms of surrogate approaches is the need to test underlying assumptions, which remain rarely examined. In this study, we tested one of the fundamental assumptions underlying use of surrogate species in recovery planning: that there exist groups of threatened and endangered species that are sufficiently similar to warrant similar management or recovery criteria. Using a comprehensive database of all plant species listed under the U.S. Endangered Species Act and tree-based random forest analysis, we found no evidence of species groups based on a set of distributional and biological traits or by abundances and patterns of decline. Our results suggested that application of surrogate approaches for endangered species recovery would be unjustified. Thus, conservation planning focused on individual species and their patterns of decline will likely be required to recover listed species.

An adaptive Gaussian process-based method for efficient Bayesian experimental design in groundwater contaminant source identification problems: ADAPTIVE GAUSSIAN PROCESS-BASED INVERSION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Jiangjiang; Li, Weixuan; Zeng, Lingzao

Surrogate models are commonly used in Bayesian approaches such as Markov Chain Monte Carlo (MCMC) to avoid repetitive CPU-demanding model evaluations. However, the approximation error of a surrogate may lead to biased estimations of the posterior distribution. This bias can be corrected by constructing a very accurate surrogate or implementing MCMC in a two-stage manner. Since the two-stage MCMC requires extra original model evaluations, the computational cost is still high. If the information of measurement is incorporated, a locally accurate approximation of the original model can be adaptively constructed with low computational cost. Based on this idea, we propose amore » Gaussian process (GP) surrogate-based Bayesian experimental design and parameter estimation approach for groundwater contaminant source identification problems. A major advantage of the GP surrogate is that it provides a convenient estimation of the approximation error, which can be incorporated in the Bayesian formula to avoid over-confident estimation of the posterior distribution. The proposed approach is tested with a numerical case study. Without sacrificing the estimation accuracy, the new approach achieves about 200 times of speed-up compared to our previous work using two-stage MCMC.« less

The Effect of Framing on Surrogate Optimism Bias: A Simulation Study

PubMed Central

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

2016-01-01

Purpose To explore the effect of emotion priming and physician communication behaviors on optimism bias. Materials and Methods We conducted a 5 × 2 between-subject randomized factorial experiment using a web-based interactive video designed to simulate a family meeting for a critically ill spouse/parent. Eligibility included age ≥ 35 and self-identifying as the surrogate for a spouse/parent. The primary outcome was the surrogate's election of code status. We defined optimism bias as the surrogate's estimate of prognosis with CPR > their recollection of the physician's estimate. Results 256/373 respondents (69%) logged-in and were randomized and 220 (86%) had non-missing data for prognosis. 67/220 (30%) overall, and 56/173 (32%) of those with an accurate recollection of the physician's estimate had optimism bias. Optimism bias correlated with choosing CPR (p<.001). Emotion priming (p=.397), physician attention to emotion (p=.537), and framing of CPR as the social norm (p=.884) did not affect optimism bias. Framing the decision as the patient's vs. the surrogate's (25% vs. 36%, p=.066) and describing the alternative to CPR as “allow natural death” instead of “do not resuscitate” (25% vs. 37%, p =.035) decreased optimism bias. Conclusions Framing of CPR choice during code status conversations may influence surrogates’ optimism bias. PMID:26796950

An Evaluation of Two Internal Surrogates for Determining the Three-Dimensional Position of Peripheral Lung Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spoelstra, Femke; Soernsen de Koste, John R. van; Vincent, Andrew

2009-06-01

Purpose: Both carina and diaphragm positions have been used as surrogates during respiratory-gated radiotherapy. We studied the correlation of both surrogates with three-dimensional (3D) tumor position. Methods and Materials: A total of 59 repeat artifact-free four-dimensional (4D) computed tomography (CT) scans, acquired during uncoached breathing, were identified in 23 patients with Stage I lung cancer. Repeat scans were co-registered to the initial 4D CT scan, and tumor, carina, and ipsilateral diaphragm were manually contoured in all phases of each 4D CT data set. Correlation between positions of carina and diaphragm with 3D tumor position was studied by use of log-likelihoodmore » ratio statistics. Models to predict 3D tumor position from internal surrogates at end inspiration (EI) and end expiration (EE) were developed, and model accuracy was tested by calculating SDs of differences between predicted and actual tumor positions. Results: Motion of both the carina and diaphragm significantly correlated with tumor motion, but log-likelihood ratios indicated that the carina was more predictive for tumor position. When craniocaudal tumor position was predicted by use of craniocaudal carina positions, the SDs of the differences between the predicted and observed positions were 2.2 mm and 2.4 mm at EI and EE, respectively. The corresponding SDs derived with the diaphragm positions were 3.7 mm and 3.9 mm at EI and EE, respectively. Prediction errors in the other directions were comparable. Prediction accuracy was similar at EI and EE. Conclusions: The carina is a better surrogate of 3D tumor position than diaphragm position. Because residual prediction errors were observed in this analysis, additional studies will be performed using audio-coached scans.« less

Early analysis of surrogate endpoints for metastatic melanoma in immune checkpoint inhibitor trials.

PubMed

Petrelli, Fausto; Coinu, Andrea; Cabiddu, Mary; Borgonovo, Karen; Ghilardi, Mara; Lonati, Veronica; Barni, Sandro

2016-06-01

Recent major phase III trials led to the approval of immune checkpoint inhibitors (ipilimumab, pembrolizumab, and nivolumab) in metastatic malignant melanoma (MM). We aim to assess whether median progression-free survival, and 1 and 2-year overall survival (OS) rates are reliable surrogate endpoints for median OS through a meta-analysis of published trials involving immunotherapy. A systematic literature search in PubMed, EMBASE, Web of Science, and SCOPUS of published phase II to III trials with immunotherapy as the treatment for MM was conducted. Adjusted weighted linear regression was used to calculate Pearson correlations (R) between surrogates and median OS, and between treatment effects on surrogates and median OS. A total of 13 studies involving 3373 patients with MM were identified. The correlation of progression-free survival with OS was not significant (R = 0.45, P = .11). Conversely, the correlation between 1-year OS and median OS was very strong (R = 0.93, 95% confidence interval [CI] 0.84-0.96, P < .00001), as was the correlation between 2-year OS and OS (R = 0.79, 95% CI 0.51-0.91, P = .0001). The correlation between the treatment effects on 1-year OS and OS was also significant (R = -0.86, 95% CI -0.3 to 0.97, P = .01). Similar results were obtained for 2-year OS. According to the available study data, 1-year OS rate could be regarded as a potential surrogate for median OS in novel immunotherapy trials of metastatic MM. Waiting for ongoing studies (e.g., pembrolizumab), we suggest that this intermediate endpoint could be considered as a potential primary endpoint in future clinical trials.

21 CFR 601.41 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Approval based on a surrogate endpoint or on an... Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or... uncertainty as to the relation of the surrogate endpoint to clinical benefit, or of the observed clinical...

21 CFR 314.510 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Approval based on a surrogate endpoint or on an... Serious or Life-Threatening Illnesses § 314.510 Approval based on a surrogate endpoint or on an effect on... the drug product has an effect on a surrogate endpoint that is reasonably likely, based on...

21 CFR 314.510 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Approval based on a surrogate endpoint or on an... Serious or Life-Threatening Illnesses § 314.510 Approval based on a surrogate endpoint or on an effect on... the drug product has an effect on a surrogate endpoint that is reasonably likely, based on...

21 CFR 601.41 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Approval based on a surrogate endpoint or on an... Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or... uncertainty as to the relation of the surrogate endpoint to clinical benefit, or of the observed clinical...

21 CFR 314.510 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Approval based on a surrogate endpoint or on an... Serious or Life-Threatening Illnesses § 314.510 Approval based on a surrogate endpoint or on an effect on... the drug product has an effect on a surrogate endpoint that is reasonably likely, based on...

21 CFR 601.41 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Approval based on a surrogate endpoint or on an... Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or... uncertainty as to the relation of the surrogate endpoint to clinical benefit, or of the observed clinical...

21 CFR 601.41 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Approval based on a surrogate endpoint or on an... Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or... uncertainty as to the relation of the surrogate endpoint to clinical benefit, or of the observed clinical...

21 CFR 314.510 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Approval based on a surrogate endpoint or on an... Serious or Life-Threatening Illnesses § 314.510 Approval based on a surrogate endpoint or on an effect on... the drug product has an effect on a surrogate endpoint that is reasonably likely, based on...

21 CFR 601.41 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Approval based on a surrogate endpoint or on an... Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or... uncertainty as to the relation of the surrogate endpoint to clinical benefit, or of the observed clinical...

Surrogate Poster Artist Concept

NASA Image and Video Library

2015-03-11

This artist's concept shows Surrogate, a robot that could one day assist in disasters or hazardous situations such as a dangerous chemical laboratory. Surrogate was designed and built at the Jet Propulsion Laboratory in Pasadena, California. Its components came from RoboSimian, another JPL-built robot designed for disaster relief and mitigation (see PIA19313). Surrogate rolls on a track rather than moving on its limbs. http://photojournal.jpl.nasa.gov/catalog/PIA19314

Identifying taxonomic and functional surrogates for spring biodiversity conservation.

PubMed

Jyväsjärvi, Jussi; Virtanen, Risto; Ilmonen, Jari; Paasivirta, Lauri; Muotka, Timo

2018-02-27

Surrogate approaches are widely used to estimate overall taxonomic diversity for conservation planning. Surrogate taxa are frequently selected based on rarity or charisma, whereas selection through statistical modeling has been applied rarely. We used boosted-regression-tree models (BRT) fitted to biological data from 165 springs to identify bryophyte and invertebrate surrogates for taxonomic and functional diversity of boreal springs. We focused on these 2 groups because they are well known and abundant in most boreal springs. The best indicators of taxonomic versus functional diversity differed. The bryophyte Bryum weigelii and the chironomid larva Paratrichocladius skirwithensis best indicated taxonomic diversity, whereas the isopod Asellus aquaticus and the chironomid Macropelopia spp. were the best surrogates of functional diversity. In a scoring algorithm for priority-site selection, taxonomic surrogates performed only slightly better than random selection for all spring-dwelling taxa, but they were very effective in representing spring specialists, providing a distinct improvement over random solutions. However, the surrogates for taxonomic diversity represented functional diversity poorly and vice versa. When combined with cross-taxon complementarity analyses, surrogate selection based on statistical modeling provides a promising approach for identifying groundwater-dependent ecosystems of special conservation value, a key requirement of the EU Water Framework Directive. © 2018 Society for Conservation Biology.

Program to Optimize Simulated Trajectories II (POST2) Surrogate Models for Mars Ascent Vehicle (MAV) Performance Assessment

NASA Technical Reports Server (NTRS)

Zwack, M. R.; Dees, P. D.; Thomas, H. D.; Polsgrove, T. P.; Holt, J. B.

2017-01-01

The primary purpose of the multiPOST tool is to enable the execution of much larger sets of vehicle cases to allow for broader trade space exploration. However, this exploration is not achieved solely with the increased case throughput. The multiPOST tool is applied to carry out a Design of Experiments (DOE), which is a set of cases that have been structured to capture a maximum amount of information about the design space with minimal computational effort. The results of the DOE are then used to fit a surrogate model, ultimately enabling parametric design space exploration. The approach used for the MAV study includes both DOE and surrogate modeling. First, the primary design considerations for the vehicle were used to develop the variables and ranges for the multiPOST DOE. The final set of DOE variables were carefully selected in order to capture the desired vehicle trades and take into account any special considerations for surrogate modeling. Next, the DOE sets were executed through multiPOST. Following successful completion of the DOE cases, a manual verification trial was performed. The trial involved randomly selecting cases from the DOE set and running them by hand. The results from the human analyst's run and multiPOST were then compared to ensure that the automated runs were being executed properly. Completion of the verification trials was then followed by surrogate model fitting. After fits to the multiPOST data were successfully created, the surrogate models were used as a stand-in for POST2 to carry out the desired MAV trades. Using the surrogate models in lieu of POST2 allowed for visualization of vehicle sensitivities to the input variables as well as rapid evaluation of vehicle performance. Although the models introduce some error into the output of the trade study, they were very effective at identifying areas of interest within the trade space for further refinement by human analysts. The next section will cover all of the ground rules and assumptions associated with DOE setup and multiPOST execution. Section 3.1 gives the final DOE variables and ranges, while section 3.2 addresses the POST2 specific assumptions. The results of the verification trials are given in section 4. Section 5 gives the surrogate model fitting results, including the goodness-of-fit metrics for each fit. Finally, the MAV specific results are discussed in section 6.

The Surgeon Volume-outcome Relationship: Not Yet Ready for Policy.

PubMed

Modrall, J Gregory; Minter, Rebecca M; Minhajuddin, Abu; Eslava-Schmalbach, Javier; Joshi, Girish P; Patel, Shivani; Rosero, Eric B

2018-05-01

Increasing surgeon volume may improve outcomes for index operations. We hypothesized that there may be surrogate operative experiences that yield similar outcomes for surgeons with a low-volume experience with a specific index operation, such as esophagectomy. The relationship between surgeon volume and outcomes has potential implications for credentialing of surgeons. Restrictions of privileges based on surgeon volume are only reasonable if there is no substitute for direct experience with the index operation. This study was aimed at determining whether there are valid surrogates for direct experience with a sample index operation-open esophagectomy. The Nationwide Inpatient Sample (2003-2009) was utilized. Surgeons were stratified into low and high-volume groups based on annual volume of esophagectomy. Surrogate volume was defined as the aggregate annual volume per surgeon of upper gastrointestinal operations including excision of esophageal diverticulum, gastrectomy, gastroduodenectomy, and repair of diaphragmatic hernia. In all, 26,795 esophagectomies were performed nationwide (2003-2009), with a crude inhospital mortality rate of 5.2%. Inhospital mortality decreased with increasing volume of esophagectomies performed annually: 7.7% and 3.8% for low and high-volume surgeons, respectively (P < 0.0001). Among surgeons with a low-volume esophagectomy experience, increasing volume of surrogate operations improved the outcomes observed for esophagectomy: 9.7%, 7.1%, and 4.3% for low, medium, and high-surrogate-volume surgeons, respectively (P = 0.016). Both operation-specific volume and surrogate volume are significant predictors of inhospital mortality for esophagectomy. Based on these observations, it would be premature to limit hospital privileges based solely on operation-specific surgeon volume criteria.

Enhancing autonomy in paid surrogacy.

PubMed

Damelio, Jennifer; Sorensen, Kelly

2008-06-01

The gestational surrogate--and her economic and educational vulnerability in particular--is the focus of many of the most persistent worries about paid surrogacy. Those who employ her, and those who broker and organize her services, usually have an advantage over her in resources and information. That asymmetry exposes her to the possibility of exploitation and abuse. Accordingly, some argue for banning paid surrogacy. Others defend legal permission on grounds of surrogate autonomy, but often retain concerns about the surrogate. In response to the dilemma of a ban versus bald permission, we propose a 'soft law' approach: states should require several hours of education of surrogates--education aimed at informing and enhancing surrogate autonomy.

Modeling of the radiation belt megnetosphere in decisional timeframes

DOEpatents

Koller, Josef; Reeves, Geoffrey D; Friedel, Reiner H.W.

2013-04-23

Systems and methods for calculating L* in the magnetosphere with essentially the same accuracy as with a physics based model at many times the speed by developing a surrogate trained to be a surrogate for the physics-based model. The trained model can then beneficially process input data falling within the training range of the surrogate model. The surrogate model can be a feedforward neural network and the physics-based model can be the TSK03 model. Operatively, the surrogate model can use parameters on which the physics-based model was based, and/or spatial data for the location where L* is to be calculated. Surrogate models should be provided for each of a plurality of pitch angles. Accordingly, a surrogate model having a closed drift shell can be used from the plurality of models. The feedforward neural network can have a plurality of input-layer units, there being at least one input-layer unit for each physics-based model parameter, a plurality of hidden layer units and at least one output unit for the value of L*.

Effects of a Mechanical Response-Contingent Surrogate on the Development of Behaviors in Nursery-Reared Rhesus Macaques (Macaca mulatta)

PubMed Central

Brunelli, Rebecca L; Blake, Jennifer; Willits, Neil; Rommeck, Ina; McCowan, Brenda

2014-01-01

Nursery-reared infants have several behavioral and physiologic differences from their mother-reared counterparts. We investigated whether a response-contingent surrogate mitigated some of those differences by decreasing fearfulness and partner-clinging and increasing environmental exploration in nursery-reared infants continuously paired with a peer. Six nursery-reared infant rhesus macaques (in pairs) were given a mechanical responsive surrogate (RS), and 6 (in pairs) were given an identical but nonresponsive surrogate (NRS). The 2 treatment groups were compared and then combined into a single group of all 12 of surrogate-exposed animals (CS) that was compared with a nonsurrogate control group (NS) of 10 nursery-reared infants. Results showed significant differences between CS and NS infants but no significant differences between the RS and NRS infants. As compared with NS infants, CS infants showed less partner-clinging, less affiliation directed toward only partner, and more foraging and tactile–oral exploration of the environment. These advantageous effects support additional research to develop improved surrogate and the implementation of surrogate programs for nursery-reared infants. PMID:25255068

Effects of a mechanical response-contingent surrogate on the development of behaviors in nursery-reared rhesus macaques (Macaca mulatta).

PubMed

Brunelli, Rebecca L; Blake, Jennifer; Willits, Neil; Rommeck, Ina; McCowan, Brenda

2014-09-01

Nursery-reared infants have several behavioral and physiologic differences from their mother-reared counterparts. We investigated whether a response-contingent surrogate mitigated some of those differences by decreasing fearfulness and partner-clinging and increasing environmental exploration in nursery-reared infants continuously paired with a peer. Six nursery-reared infant rhesus macaques (in pairs) were given a mechanical responsive surrogate (RS), and 6 (in pairs) were given an identical but nonresponsive surrogate (NRS). The 2 treatment groups were compared and then combined into a single group of all 12 of surrogate-exposed animals (CS) that was compared with a nonsurrogate control group (NS) of 10 nursery-reared infants. Results showed significant differences between CS and NS infants but no significant differences between the RS and NRS infants. As compared with NS infants, CS infants showed less partner-clinging, less affiliation directed toward only partner, and more foraging and tactile-oral exploration of the environment. These advantageous effects support additional research to develop improved surrogate and the implementation of surrogate programs for nursery-reared infants.

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

PubMed

Oultram, Stuart

2015-06-01

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

Biomarkers and Surrogate Markers: An FDA Perspective

PubMed Central

Katz, Russell

2004-01-01

Summary: Interest is increasing rapidly in the use of surrogate markers as primary measures of the effectiveness of investigational drugs in definitive drug trials. Many such surrogate markers have been proposed as potential candidates for use in definitive effectiveness trials of agents to treat neurologic or psychiatric disease, but as of this date, there are no such markers that have been adequately “validated,” that is, shown to predict the effect of the treatment on the clinical outcome of interest. While the current law and regulations permit the United States Food and Drug Administration to base the approval of a drug product on a determination the effect of the drug on an unvalidated surrogate marker (that is, one for which it is not known that an effect on the surrogate actually predicts the desired clinical benefit), there are a number of difficulties in interpreting trials that use surrogate markers as primary measures of drug effect. In this article, the relevant regulatory context will be discussed, as well as the epistemological problems related to the interpretation of clinical trials in which unvalidated surrogate markers are used as primary outcomes. PMID:15717019

Surrogate mother – praiseworthy or stigmatized: a qualitative study on perceptions of surrogacy in Assam, India

PubMed Central

Arvidsson, Anna; Vauquline, Polly; Johnsdotter, Sara; Essén, Birgitta

2017-01-01

ABSTRACT Background: Surrogacy is a reproductive practice that has been strongly marketed in India as a solution for childless couples. As a result, the number of surrogacy clinics is increasing. Meanwhile, a global discourse on surrogacy, originating from a Western perspective, has characterized surrogacy as being exploitative of women in low-income settings, where poverty drives them to become surrogate mothers. Objective: This study explored perspectives on surrogacy from men and women in Assam, an Indian state known to be a low-income setting. Surrogacy arrangements in Assam are still uncommon. It can be expected that the dominant global discourses on surrogacy will be unfamiliar to the general population, and the objective was also to position the results within the divergent global discourses of surrogacy. Methods: In order to explore local views on surrogacy, we conducted individual interviews and focus group discussions with people from various socioeconomic groups in Assam. Results: Our findings reveal that people in Assam perceive surrogacy as a good option for a childless couple, as it would result in a child who is a ‘blood’ relation – something highly desirable for sociocultural reasons. However, the part played by the surrogate mother complicates local views on surrogacy. Most people consider payment to the surrogate mother contrary to societal norms. A surrogate mother is also often judged in a moral light, either as a ‘bad mother’ for selling her child, or as a ‘noble woman’ who has helped a childless couple and deserves payment for her services. Conclusions: In order to decrease the stigmatization of women, a regulatory policy is needed that will take into account the complex understandings of surrogacy and perceptions of surrogate mothers in Indian society. In policy, the possible effect of the dominant exploitation discourse needs to be modulated by local understandings of this reproduction method. PMID:28604252

How Important Is ‘Accuracy’ of Surrogate Decision-Making for Research Participation?

PubMed Central

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

2013-01-01

Background There is a longstanding concern about the accuracy of surrogate consent in representing the health care and research preferences of those who lose their ability to decide for themselves. We sought informed, deliberative views of the older general public (≥50 years old) regarding their willingness to participate in dementia research and to grant leeway to future surrogates to choose an option contrary to their stated wishes. Methodology/Principal Findings 503 persons aged 50+ recruited by random digit dialing were randomly assigned to one of three groups: deliberation, education, or control. The deliberation group attended an all-day education/peer deliberation session; the education group received written information only. Participants were surveyed at baseline, after the deliberation session (or equivalent time), and one month after the session, regarding their willingness to participate in dementia research and to give leeway to surrogates, regarding studies of varying risk-benefit profiles (a lumbar puncture study, a drug randomized controlled trial, a vaccine randomized controlled trial, and an early phase gene transfer trial). At baseline, 48% (gene transfer scenario) to 92% (drug RCT) were willing to participate in future dementia research. A majority of respondents (57–71% depending on scenario) were willing to give leeway to future surrogate decision-makers. Democratic deliberation increased willingness to participate in all scenarios, to grant leeway in 3 of 4 scenarios (lumbar puncture, vaccine, and gene transfer), and to enroll loved ones in research in all scenarios. On average, respondents were more willing to volunteer themselves for research than to enroll their loved ones. Conclusions/Significance Most people were willing to grant leeway to their surrogates, and this willingness was either sustained or increased after democratic deliberation, suggesting that the attitude toward leeway is a reliable opinion. Eliciting a person’s current preferences about future research participation should also involve eliciting his or her leeway preferences. PMID:23382969

Stability of and Attachment to Lettuce by a Culturable Porcine Sapovirus Surrogate for Human Caliciviruses

PubMed Central

Zhang, Zhenwen

2012-01-01

Human noroviruses (HuNoVs) are the leading cause of food-borne illness, accounting for 58% of U.S. cases. Because HuNoVs are unculturable, surrogates are needed to investigate transmission routes and evaluate disinfection methods. However, the current surrogates, feline calicivirus (FCV) and murine NoV (MNV), are less tolerant than HuNoVs to acid and chlorine, respectively. Porcine sapovirus (SaV) is the only culturable enteropathogenic calicivirus. In this study, the resistance of SaV to physicochemical treatments was compared to that of HuNoVs (by reverse transcription-PCR), FCV, and MNV (by infectivity assays). Sapovirus and HuNoV (viral RNA) showed similar resistances to heat (56°C) and to different concentrations of chlorine. However, SaV was more resistant than HuNoVs to ethanol treatment (60% and 70%). Like HuNoVs, SaV was stable at pH 3.0 to 8.0, with a <1.0 log10 50% tissue culture infective dose (TCID50) reduction at pH 3.0 compared to the value for pH 4.0 to 8.0. SaV and MNV showed similar resistances, and both were more resistant than FCV to heat inactivation (56°C). FCV was more resistant than MNV and SaV to ethanol, and all three viruses showed similar resistances to treatment with low concentrations of chlorine for 1 min. Those results indicate that SaV is a promising surrogate for HuNoVs. Next, we used SaV as a surrogate to examine virus attachment to lettuce at different pHs. Sapovirus attached to lettuce leaves significantly at its capsid isoelectric point (pH 5.0), and the attached viral particles remained infectious on lettuce after 1 week of storage at 4°C. The culturable SaV is a good surrogate for studying HuNoV contamination and transmission in leafy greens and potential disinfectants. PMID:22447610

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paganelli, Chiara, E-mail: chiara.paganelli@polimi.it; Seregni, Matteo; Fattori, Giovanni

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zawisza, I; Yan, H; Yin, F

Purpose: To assure that tumor motion is within the radiation field during high-dose and high-precision radiosurgery, real-time imaging and surrogate monitoring are employed. These methods are useful in providing real-time tumor/surrogate motion but no future information is available. In order to anticipate future tumor/surrogate motion and track target location precisely, an algorithm is developed and investigated for estimating surrogate motion multiple-steps ahead. Methods: The study utilized a one-dimensional surrogate motion signal divided into three components: (a) training component containing the primary data including the first frame to the beginning of the input subsequence; (b) input subsequence component of the surrogatemore » signal used as input to the prediction algorithm: (c) output subsequence component is the remaining signal used as the known output of the prediction algorithm for validation. The prediction algorithm consists of three major steps: (1) extracting subsequences from training component which best-match the input subsequence according to given criterion; (2) calculating weighting factors from these best-matched subsequence; (3) collecting the proceeding parts of the subsequences and combining them together with assigned weighting factors to form output. The prediction algorithm was examined for several patients, and its performance is assessed based on the correlation between prediction and known output. Results: Respiratory motion data was collected for 20 patients using the RPM system. The output subsequence is the last 50 samples (∼2 seconds) of a surrogate signal, and the input subsequence was 100 (∼3 seconds) frames prior to the output subsequence. Based on the analysis of correlation coefficient between predicted and known output subsequence, the average correlation is 0.9644±0.0394 and 0.9789±0.0239 for equal-weighting and relative-weighting strategies, respectively. Conclusion: Preliminary results indicate that the prediction algorithm is effective in estimating surrogate motion multiple-steps in advance. Relative-weighting method shows better prediction accuracy than equal-weighting method. More parameters of this algorithm are under investigation.« less

Pathologic complete response and disease-free survival are not surrogate endpoints for 5-year survival in rectal cancer: an analysis of 22 randomized trials.

PubMed

Petrelli, Fausto; Borgonovo, Karen; Cabiddu, Mary; Ghilardi, Mara; Lonati, Veronica; Barni, Sandro

2017-02-01

We performed a literature-based analysis of randomized clinical trials to assess the pathologic complete response (pCR) (ypT0N0 after neoadjuvant therapy) and 3-year disease-free survival (DFS) as potential surrogate endpoints for 5-year overall survival (OS) in rectal cancer treated with neoadjuvant (chemo)radiotherapy (CT)RT. A systematic literature search of PubMed, EMBASE, the Web of Science, SCOPUS, CINAHL, and the Cochrane Library was performed. Treatment effects on 3-year DFS and 5-year OS were expressed as rates of patients alive (%), and those on pCR as differences in pCR rates (∆ pCR% ). A weighted regression analysis was performed at individual- and trial-level to test the association between treatment effects on surrogate (∆ pCR% and ∆ 3yDFS ) and the main clinical outcome (∆ 5yOS ). Twenty-two trials involving 10,050 patients, were included in the analysis. The individual level surrogacy showed that the pCR% and 3-year DFS were poorly correlated with 5-year OS (R=0.52; 95% CI, 0.31-0.91; P=0.002; and R=0.60; 95% CI, 0.36-1; P=0.002). The trial-level surrogacy analysis confirmed that the two treatment effects on surrogates (∆ pCR% and ∆ 3yDFS ) are not strong surrogates for treatment effects on 5-year OS % (R=0.2; 95% CI, -0.29-0.78; P=0.5 and R=0.64; 95% CI, 0.29-1; P=0.06). These findings were confirmed in neoadjuvant CTRT studies but not in phase III trials were 3-year DFS could still represent a valid surrogate. This analysis does not support the use of pCR and 3-year DFS% as appropriate surrogate endpoints for 5-year OS% in patients with rectal cancer treated with neoadjuvant therapy.

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

NASA Astrophysics Data System (ADS)

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

2018-01-01

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

Integrating surrogate models into subsurface simulation framework allows computation of complex reactive transport scenarios

NASA Astrophysics Data System (ADS)

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

2017-04-01

Reactive transport simulations - where geochemical reactions are coupled with hydrodynamic transport of reactants - are extremely time consuming and suffer from significant numerical issues. Given the high uncertainties inherently associated with the geochemical models, which also constitute the major computational bottleneck, such requirements may seem inappropriate and probably constitute the main limitation for their wide application. A promising way to ease and speed-up such coupled simulations is achievable employing statistical surrogates instead of "full-physics" geochemical models [1]. Data-driven surrogates are reduced models obtained on a set of pre-calculated "full physics" simulations, capturing their principal features while being extremely fast to compute. Model reduction of course comes at price of a precision loss; however, this appears justified in presence of large uncertainties regarding the parametrization of geochemical processes. This contribution illustrates the integration of surrogates into the flexible simulation framework currently being developed by the authors' research group [2]. The high level language of choice for obtaining and dealing with surrogate models is R, which profits from state-of-the-art methods for statistical analysis of large simulations ensembles. A stand-alone advective mass transport module was furthermore developed in order to add such capability to any multiphase finite volume hydrodynamic simulator within the simulation framework. We present 2D and 3D case studies benchmarking the performance of surrogates and "full physics" chemistry in scenarios pertaining the assessment of geological subsurface utilization. [1] Jatnieks, J., De Lucia, M., Dransch, D., Sips, M.: "Data-driven surrogate model approach for improving the performance of reactive transport simulations.", Energy Procedia 97, 2016, p. 447-453. [2] Kempka, T., Nakaten, B., De Lucia, M., Nakaten, N., Otto, C., Pohl, M., Chabab [Tillner], E., Kühn, M.: "Flexible Simulation Framework to Couple Processes in Complex 3D Models for Subsurface Utilization Assessment.", Energy Procedia, 97, 2016 p. 494-501.

Wildland fire as a self-regulating mechanism: the role of previous burns and weather in limiting fire progression.

PubMed

Parks, Sean A; Holsinger, Lisa M; Miller, Carol; Nelson, Cara R

2015-09-01

Theory suggests that natural fire regimes can result in landscapes that are both self-regulating and resilient to fire. For example, because fires consume fuel, they may create barriers to the spread of future fires, thereby regulating fire size. Top-down controls such as weather, however, can weaken this effect. While empirical examples demonstrating this pattern-process feedback between vegetation and fire exist, they have been geographically limited or did not consider the influence of time between fires and weather. The availability of remotely sensed data identifying fire activity over the last four decades provides an opportunity to explicitly quantify-the ability of wildland fire to limit the progression of subsequent fire. Furthermore, advances in fire progression mapping now allow an evaluation of how daily weather as a top-down control modifies this effect. In this study, we evaluated the ability of wildland fire to create barriers that limit the spread of subsequent fire along a gradient representing time between fires in four large study areas in the western United States. Using fire progression maps in conjunction with weather station data, we also evaluated the influence of daily weather. Results indicate that wildland fire does limit subsequent fire spread in all four study areas, but this effect decays over time; wildland fire no longer limits subsequent fire spread 6-18 years after fire, depending on the study area. We also found that the ability of fire to regulate, subsequent fire progression was substantially reduced under extreme conditions compared to moderate weather conditions in all four study areas. This study increases understanding of the spatial feedbacks that can lead to self-regulating landscapes as well as the effects of top-down controls, such as weather, on these feedbacks. Our results will be useful to managers who seek to restore natural fire regimes or to exploit recent burns when managing fire.

A Surrogate Technique for Investigating Deterministic Dynamics in Discrete Human Movement.

PubMed

Taylor, Paul G; Small, Michael; Lee, Kwee-Yum; Landeo, Raul; O'Meara, Damien M; Millett, Emma L

2016-10-01

Entropy is an effective tool for investigation of human movement variability. However, before applying entropy, it can be beneficial to employ analyses to confirm that observed data are not solely the result of stochastic processes. This can be achieved by contrasting observed data with that produced using surrogate methods. Unlike continuous movement, no appropriate method has been applied to discrete human movement. This article proposes a novel surrogate method for discrete movement data, outlining the processes for determining its critical values. The proposed technique reliably generated surrogates for discrete joint angle time series, destroying fine-scale dynamics of the observed signal, while maintaining macro structural characteristics. Comparison of entropy estimates indicated observed signals had greater regularity than surrogates and were not only the result of stochastic but also deterministic processes. The proposed surrogate method is both a valid and reliable technique to investigate determinism in other discrete human movement time series.

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

PubMed

Berend, Zsuzsa

2010-06-01

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

Responding to surrogate requests that seem inconsistent with a patient's living will.

PubMed

Vig, Elizabeth K; Sudore, Rebecca L; Berg, Karina M; Fromme, Erik K; Arnold, Robert M

2011-11-01

Clinicians may feel conflicted when a patient's legal decision maker is making decisions that seem inconsistent with a patient's living will. We provide evidence-based information to help clinicians consider whether a surrogate's inconsistent decisions are ethically appropriate. Surrogates are not flawless translators of their loved one's preferences; they are influenced by their own hopes and the current clinical context. Patients may be aware of this, are often concerned about burdening their loved ones, and often grant their surrogates leeway in interpreting their wishes. When appropriate, clinicians should respect surrogates' interpretations of patient values and take steps to decrease surrogate stress during the decision-making process. Finally, if clinicians are cognizant of their own values and preferences, they may recognize how these may affect their responses to certain clinical cases. Copyright © 2011 U.S. Cancer Pain Relief Committee. All rights reserved.

On Using Surrogates with Genetic Programming.

PubMed

Hildebrandt, Torsten; Branke, Jürgen

2015-01-01

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

Triglyceride glucose index as a surrogate measure of insulin sensitivity in obese adolescents with normoglycemia, prediabetes, and type 2 diabetes mellitus: Comparison with the hyperinsulinemic–euglycemic clamp

USDA-ARS?s Scientific Manuscript database

There is a need for simple surrogate estimates of insulin sensitivity in epidemiological studies of obese youth because the hyperinsulinemic-euglycemic clamp is not feasible on a large scale. Objectives: (i) To examine the triglyceride glucose (TyG) index (Ln[fasting triglycerides (mg/dL)'×'fasting ...

Evaluation of Enterococcus faecium NRRL B-2354 as a Surrogate for Salmonella During Extrusion of Low-Moisture Food.

PubMed

Verma, Tushar; Wei, Xinyao; Lau, Soon Kiat; Bianchini, Andreia; Eskridge, Kent M; Subbiah, Jeyamkondan

2018-04-01

Salmonella in low-moisture foods is an emerging challenge due to numerous food product recalls and foodborne illness outbreaks. Identification of suitable surrogate is critical for process validation at industry level due to implementation of new Food Safety Modernization Act of 2011. The objective of this study was to evaluate Enterococcus faecium NRRL B-2354 as a surrogate for Salmonella during the extrusion of low-moisture food. Oat flour, a low-moisture food, was adjusted to different moisture (14% to 26% wet basis) and fat (5% to 15% w/w) contents and was inoculated with E. faecium NRRL B-2354. Inoculated material was then extruded in a lab-scale single-screw extruder running at different screw speeds (75 to 225 rpm) and different temperatures (75, 85, and 95 °C). A split-plot central composite 2nd order response surface design was used, with the central point replicated six times. The data from the selective media (m-Enterococcus agar) was used to build the response surface model for inactivation of E. faecium NRRL B-2354. Results indicated that E. faecium NRRL B-2354 always had higher heat resistance compared to Salmonella at all conditions evaluated in this study. However, the patterns of contour plots showing the effect of various product and process parameters on inactivation of E. faecium NRRL B-2354 was different from that of Salmonella. Although E. faecium NRRL B-2354 may be an acceptable surrogate for extrusion of low-moisture products due to higher resistance than Salmonella, another surrogate with similar inactivation behavior may be preferred and needs to be identified. Food Safety Modernization Act requires the food industry to validate processing interventions. This study validated extrusion processing and demonstrated that E. faecium NRRL B-2354 is an acceptable surrogate for extrusion of low-moisture products. The developed response surface model allows the industry to identify process conditions to achieve a desired lethality for their products based on composition. © 2018 Institute of Food Technologists®.

Ictal high frequency oscillations distinguish two types of seizure territories in humans

PubMed Central

Weiss, Shennan A.; Banks, Garrett P.; McKhann, Guy M.; Goodman, Robert R.; Emerson, Ronald G.; Trevelyan, Andrew J.

2013-01-01

High frequency oscillations have been proposed as a clinically useful biomarker of seizure generating sites. We used a unique set of human microelectrode array recordings (four patients, 10 seizures), in which propagating seizure wavefronts could be readily identified, to investigate the basis of ictal high frequency activity at the cortical (subdural) surface. Sustained, repetitive transient increases in high gamma (80–150 Hz) amplitude, phase-locked to the low-frequency (1–25 Hz) ictal rhythm, correlated with strong multi-unit firing bursts synchronized across the core territory of the seizure. These repetitive high frequency oscillations were seen in recordings from subdural electrodes adjacent to the microelectrode array several seconds after seizure onset, following ictal wavefront passage. Conversely, microelectrode recordings demonstrating only low-level, heterogeneous neural firing correlated with a lack of high frequency oscillations in adjacent subdural recording sites, despite the presence of a strong low-frequency signature. Previously, we reported that this pattern indicates a failure of the seizure to invade the area, because of a feedforward inhibitory veto mechanism. Because multi-unit firing rate and high gamma amplitude are closely related, high frequency oscillations can be used as a surrogate marker to distinguish the core seizure territory from the surrounding penumbra. We developed an efficient measure to detect delayed-onset, sustained ictal high frequency oscillations based on cross-frequency coupling between high gamma amplitude and the low-frequency (1–25 Hz) ictal rhythm. When applied to the broader subdural recording, this measure consistently predicted the timing or failure of ictal invasion, and revealed a surprisingly small and slowly spreading seizure core surrounded by a far larger penumbral territory. Our findings thus establish an underlying neural mechanism for delayed-onset, sustained ictal high frequency oscillations, and provide a practical, efficient method for using them to identify the small ictal core regions. Our observations suggest that it may be possible to reduce substantially the extent of cortical resections in epilepsy surgery procedures without compromising seizure control. PMID:24176977

Pipe Overpack Container Fire Testing: Phase I II & III.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Figueroa, Victor G.; Ammerman, Douglas J.; Lopez, Carlos

The Pipe Overpack Container (POC) was developed at Rocky Flats to transport plutonium residues with higher levels of plutonium than standard transuranic (TRU) waste to the Waste Isolation Pilot Plant (WIPP) for disposal. In 1996 Sandia National Laboratories (SNL) conducted a series of tests to determine the degree of protection POCs provided during storage accident events. One of these tests exposed four of the POCs to a 30-minute engulfing pool fire, resulting in one of the 7A drum overpacks generating sufficient internal pressure to pop off its lid and expose the top of the pipe container (PC) to the firemore » environment. The initial contents of the POCs were inert materials, which would not generate large internal pressure within the PC if heated. POCs are now being used to store combustible TRU waste at Department of Energy (DOE) sites. At the request of DOE’s Office of Environmental Management (EM) and National Nuclear Security Administration (NNSA), starting in 2015 SNL conducted a series of fire tests to examine whether PCs with combustibles would reach a temperature that would result in (1) decomposition of inner contents and (2) subsequent generation of sufficient gas to cause the PC to over-pressurize and release its inner content. Tests conducted during 2015 and 2016 were done in three phases. The goal of the first phase was to see if the PC would reach high enough temperatures to decompose typical combustible materials inside the PC. The goal of the second test phase was to determine under what heating loads (i.e., incident heat fluxes) the 7A drum lid pops off from the POC drum. The goal of the third phase was to see if surrogate aerosol gets released from the PC when the drum lid is off. This report will describe the various tests conducted in phase I, II, and III, present preliminary results from these tests, and discuss implications for the POCs.« less

Attitudes toward surrogacy among doctors working in reproductive medicine and obstetric care in Sweden.

PubMed

Stenfelt, Camilla; Armuand, Gabriela; Wånggren, Kjell; Skoog Svanberg, Agneta; Sydsjö, Gunilla

2018-03-07

To investigate attitudes and opinions towards surrogacy among physicians working within obstetrics and reproductive medicine in Sweden. Physicians working within medically assisted reproduction (MAR), antenatal care and obstetrics were invited to participate in a cross-sectional nationwide survey study. The study-specific questionnaire measured attitudes and experiences in three domains: attitudes towards surrogacy, assessment of prospective surrogate mothers, and antenatal and obstetric care for surrogate mothers. Of the 103 physicians who participated (response rate 74%), 63% were positive or neutral towards altruistic surrogacy being introduced in Sweden. However, only 28% thought that it should be publicly financed. Physicians working at fertility clinics were more positive towards legalization as well as public financing of surrogacy compared than were those working within antenatal and delivery care. The majority of the physicians agreed that surrogacy involves the risk of exploitation of women's bodies (60%) and that there is a risk that the commissioning couple might pay the surrogate mother "under the table" (82%). They also expressed concerns about potential surrogate mothers not being able to understand fully the risks of entering pregnancy on behalf of someone else. There is a relatively strong support among physicians working within obstetrics and reproductive medicine for the introduction of surrogacy in Sweden. However, the physicians expressed concerns about the surrogate mothers' health as well as the risk of coercion. Further discussions about legalization of surrogacy should include views from individuals within a wide field of different medical professions and laymen. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

Use of aerobic spores as a surrogate for cryptosporidium oocysts in drinking water supplies.

PubMed

Headd, Brendan; Bradford, Scott A

2016-03-01

Waterborne illnesses are a growing concern among health and regulatory agencies worldwide. The United States Environmental Protection Agency has established several rules to combat the contamination of water supplies by cryptosporidium oocysts, however, the detection and study of cryptosporidium oocysts is hampered by methodological and financial constraints. As a result, numerous surrogates for cryptosporidium oocysts have been proposed by the scientific community and efforts are underway to evaluate many of the proposed surrogates. The purpose of this review is to evaluate the suitability of aerobic bacterial spores to serve as a surrogate for cryptosporidium oocysts in identifying contaminated drinking waters. To accomplish this we present a comparison of the biology and life cycles of aerobic spores and oocysts and compare their physical properties. An analysis of their surface properties is presented along with a review of the literature in regards to the transport, survival, and prevalence of aerobic spores and oocysts in the saturated subsurface environment. Aerobic spores and oocysts share many commonalities with regard to biology and survivability, and the environmental prevalence and ease of detection make aerobic spores a promising surrogate for cryptosporidium oocysts in surface and groundwater. However, the long-term transport and release of aerobic spores still needs to be further studied, and compared with available oocyst information. In addition, the surface properties and environmental interactions of spores are known to be highly dependent on the spore taxa and purification procedures, and additional research is needed to address these issues in the context of transport. Published by Elsevier Ltd.

Quantitative analysis of the growth of Salmonella stanley during alfalfa sprouting and evaluation of Enterobacter aerogenes as its surrogate.

PubMed

Liu, Bin; Schaffner, Donald W

2007-02-01

Raw seed sprouts have been implicated in several food poisoning outbreaks in the last 10 years. Few studies have included investigations of factors influencing the effectiveness of testing spent irrigation water, and in no studies to date has a nonpathogenic surrogate been identified as suitable for large-scale irrigation water testing trials. Alfalfa seeds were inoculated with Salmonella Stanley or its presumptive surrogate (nalidixic acid-resistant Enterobacter aerogenes) at three concentrations (-3, -30, and -300 CFU/g) and were then transferred into either flasks or a bench top-scale sprouting chamber. Microbial concentrations were determined in seeds, sprouts, and irrigation water at various times during a 4-day sprouting process. Data were fit to logistic regression models, and growth rates and maximum concentrations were compared using the generalized linear model procedure of SAS. No significant differences in growth rates were observed among samples taken from flasks or the chamber. Microbial concentrations in irrigation water were not significantly different from concentrations in sprout samples obtaihed at the same time. E. aerogenes concentrations were similar to those of Salmonella Stanley at corresponding time points for all three inoculum concentrations. Growth rates were also constant regardless of inoculum concentration or strain, except that lower inoculum concentrations resulted in lower final concentrations proportional to their initial concentrations. This research demonstrated that a nonpathogenic easy-to-isolate surrogate (nalidixic acid-resistant E. aerogenes) provides results similar to those obtained with Salmonella Stanley, supporting the use of this surrogate in future large-scale experiments.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rabiti, Cristian; Alfonsi, Andrea; Huang, Dongli

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

Will higher traffic flow lead to more traffic conflicts? A crash surrogate metric based analysis

PubMed Central

Kuang, Yan; Yan, Yadan

2017-01-01

In this paper, we aim to examine the relationship between traffic flow and potential conflict risks by using crash surrogate metrics. It has been widely recognized that one traffic flow corresponds to two distinct traffic states with different speeds and densities. In view of this, instead of simply aggregating traffic conditions with the same traffic volume, we represent potential conflict risks at a traffic flow fundamental diagram. Two crash surrogate metrics, namely, Aggregated Crash Index and Time to Collision, are used in this study to represent the potential conflict risks with respect to different traffic conditions. Furthermore, Beijing North Ring III and Next Generation SIMulation Interstate 80 datasets are utilized to carry out case studies. By using the proposed procedure, both datasets generate similar trends, which demonstrate the applicability of the proposed methodology and the transferability of our conclusions. PMID:28787022

Will higher traffic flow lead to more traffic conflicts? A crash surrogate metric based analysis.

PubMed

Kuang, Yan; Qu, Xiaobo; Yan, Yadan

2017-01-01

In this paper, we aim to examine the relationship between traffic flow and potential conflict risks by using crash surrogate metrics. It has been widely recognized that one traffic flow corresponds to two distinct traffic states with different speeds and densities. In view of this, instead of simply aggregating traffic conditions with the same traffic volume, we represent potential conflict risks at a traffic flow fundamental diagram. Two crash surrogate metrics, namely, Aggregated Crash Index and Time to Collision, are used in this study to represent the potential conflict risks with respect to different traffic conditions. Furthermore, Beijing North Ring III and Next Generation SIMulation Interstate 80 datasets are utilized to carry out case studies. By using the proposed procedure, both datasets generate similar trends, which demonstrate the applicability of the proposed methodology and the transferability of our conclusions.

Surrogacy, Compensation, and Legal Parentage: Against the Adoption Model.

PubMed

van Zyl, Liezl; Walker, Ruth

2015-09-01

Surrogate motherhood is treated as a form of adoption in many countries: the birth mother and her partner are presumed to be the parents of the child, while the intended parents have to adopt the baby once it is born. Other than compensation for expenses related to the pregnancy, payment to surrogates is not permitted. We believe that the failure to compensate surrogate mothers for their labour as well as the significant risks they undertake is both unfair and exploitative. We accept that introducing payment for surrogates would create a significant tension in the adoption model. However, we recommend rejecting the adoption model altogether rather than continuing to prohibit compensation to surrogates.

Development of a Contingency Gas Analyzer for the Orion Crew Exploration Vehicle

NASA Technical Reports Server (NTRS)

Niu, Bill; Carney, Kenneth; Steiner, George; OHarra, William; Lewis, John

2010-01-01

NASA's experience with electrochemical sensors in a hand-held toxic gas monitor serves as a basis for the development of a fixed on-board instrument, the Contingency Gas Analyzer (CGA), for monitoring selected toxic combustion products as well as oxygen and carbon dioxide on the Orion Crew Exploration Vehicle (CEV). Oxygen and carbon dioxide are major components of the cabin environment and accurate measurement of these compounds is critical to maintaining a safe working environment for the crew. Fire or thermal degradation events may produce harmful levels of toxic products, including carbon monoxide (CO), hydrogen cyanide (HCN), and hydrogen chloride (HCl) in the environment. These three components, besides being toxic in their own right, can serve as surrogates for a panoply of hazardous combustion products. On orbit monitoring of these surrogates provides for crew health and safety by indicating the presence of toxic combustion products in the environment before, during and after combustion or thermal degradation events. Issues identified in previous NASA experiences mandate hardening the instrument and components to endure the mechanical and operational stresses of the CEV environment while maintaining high analytical fidelity. Specific functional challenges involve protecting the sensors from various anticipated events- such as rapid pressure changes, low cabin pressures, and extreme vibration/shock exposures- and extending the sensor lifetime and calibration periods far beyond the current state of the art to avoid the need for on-orbit calibration. This paper focuses on lessons learned from the earlier NASA hardware, current testing results, and engineering solutions to the identified problems. Of particular focus will be the means for protecting the sensors, addressing well known cross-sensitivity issues and the efficacy of a novel self monitoring mechanism for extending sensor calibration periods.

Role of Volatility in the Development of JP-8 Surrogates for Diesel Engine Application

DTIC Science & Technology

2014-01-01

distillation curves of the surrogate fuels were calculated using the Aspen HYSYS [41] software package, and the Peng- Robinson model was chosen to...distillation curves for the surrogate fuels developed in this investigation, the accuracy of Aspen HYSYS software predictions were compared with...and SF3. The distillation curves calculated using Aspen HYSYS software for the five surrogate fuels of Table 1 are shown in Figure 7, along with the

Biomarkers and surrogate endpoints in glaucoma clinical trials

PubMed Central

Medeiros, Felipe A

2015-01-01

Surrogate endpoints are often used as replacements for true clinically relevant endpoints in several areas of medicine, as they enable faster and less expensive clinical trials. However, without proper validation, the use of surrogates may lead to incorrect conclusions about the efficacy and safety of treatments. This article reviews the general requirements for validating surrogate endpoints and provides a critical assessment of the use of intraocular pressure (IOP), visual fields, and structural measurements of the optic nerve as surrogate endpoints in glaucoma clinical trials. A valid surrogate endpoint must be able to predict the clinically relevant endpoint and fully capture the effect of an intervention on that endpoint. Despite its widespread use in clinical trials, no proper validation of IOP as a surrogate endpoint has ever been conducted for any class of IOP-lowering treatments. Evidence has accumulated with regard to the role of imaging measurements of optic nerve damage as surrogate endpoints in glaucoma. These measurements are predictive of functional losses in the disease and may explain, at least in part, treatment effects on clinically relevant endpoints. The use of composite endpoints in glaucoma trials may overcome weaknesses of the use of structural or functional endpoints in isolation. Unless research is dedicated to fully develop and validate suitable endpoints that can be used in glaucoma clinical trials, we run the risk of inappropriate judgments about the value of new therapies. PMID:25034049

Hypothesis test for synchronization: twin surrogates revisited.

PubMed

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

2009-03-01

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

Impact of a decision aid on surrogate decision-makers' perceptions of feeding options for patients with dementia.

PubMed

Snyder, E Amanda; Caprio, Anthony J; Wessell, Kathryn; Lin, Feng Chang; Hanson, Laura C

2013-02-01

In advanced dementia, feeding problems are nearly universal, and families face difficult decisions about feeding options. Initial interviews for a randomized trial were used to describe surrogates' perceptions of feeding options, and to determine whether a decision aid on feeding options in advanced dementia would improve knowledge, reduce expectation of benefit from tube feeding, and reduce conflict over treatment choices for persons with advanced dementia. Semistructured interview with prestudy and poststudy design for surrogates in the intervention group. Twenty-four skilled nursing facilities across North Carolina participating in a cluster randomized trial. Two hundred and fifty-five surrogate decision makers for nursing home residents with advanced dementia and feeding problems, in control (n = 129) and intervention (n = 126) groups. For intervention surrogates only, an audiovisual-print decision aid provided information on dementia, feeding problems in dementia, advantages and disadvantages of feeding tubes or assisted oral feeding options, and the role of surrogates in making these decisions. The interview included open-ended items asking surrogates to report advantages and disadvantages of tube feeding and assisted oral feeding. Knowledge of feeding options was measured with 19 true/false items and items measuring expectation of benefit from tube feeding. Surrogates reported which of these two feeding options they preferred for the person with dementia, and how confident they were in this choice; their level of conflict about the choice was measured using the decisional conflict scale. Before the decision aid, surrogates described advantages and disadvantages of assisted oral feeding and tube feeding in practical, ethical, and medical terms. After review of the decision aid, intervention surrogates had improved knowledge scores (15.5 vs 16.8; P < .001), decreased expectation of benefits from tube feeding (2.73 vs 2.32; P = .001), and reduced decisional conflict (2.24 vs 1.91; P < .001). Surrogates preferred assisted oral feeding initially and reported more certainty about this choice after the decision aid. A structured decision aid can be used to improve decision making about feeding options in dementia care. Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.

[Gestational surrogacy].

PubMed

Henrion, Roger; Bergoignan-Esper, Claudine

2009-03-01

After defining surrogate pregnancy and distinguishing cases in which the surrogate mother simply bears the child from those in which she is also the egg donor, the authors summarize foreign legislation in this area, together with the task force subs auditions and the literature. They list arguments for and against removing the current coup ban on surrogate motherhood. Arguments for include:--infertility due to the lack of a uterus, either congenitally or following hysterectomy, or to functional destruction of the uterus, repeated failure of in vitro fertilization, and the existence of a disorder that would threatening the future mother's life if she became pregnant;--perception of this infertility and the resulting suffering as an injustice;--the lack of alternative solutions;--the difficulties of adoption, and the fact that the adopted child does not carry the genes of the adopting parents;--the current recourse to surrogate mothers abroad, which is costly and discriminatory and leaves the child in a difficult legal situation on its return to France;--the generally satisfactory observed outcomes. Arguments against include:--the ban on financial exploitation of the human body;--possible exploitation of the surrogate mother;--the risk of undermining the symbolic value of maternity;--psychological and physical risks for the surrogate mother;--psychological and physical risks for the child;--risks for the surrogate mother's couple and her other children;--risks for the infertile couple;--the risk of abuse; and--financial issues. Two particular cases are envisaged: that in which the surrogate mother is also the biological mother, and that in which the surrogate mother is a member of the family. The French National Academy of Medicine considers that surrogate pregnancy is not only a medical matter but one that raises questions for society as a whole and should be dealt with principally by the legislator. In contrast, the Academy considers that it is within its remit to consider the possible complications that might ensue if this practice were to be legalized. The Academy points out that the long-term mental and physical risks are poorly assessed and recommends that, if surrogate pregnancy were to be legalized, the risks should be strictly evaluated, both objectively and transparently, and the practice should be strictly controlled.

Migration surrogates and their association with obesity among within-country migrants

PubMed Central

Bernabe-Ortiz, Antonio; Gilman, Robert H.; Smeeth, Liam; Miranda, J. Jaime

2010-01-01

Limited studies have evaluated the link between acculturation and health outcomes of within-country migrants. The objective of this study was to evaluate whether well-known acculturation surrogates were associated with obesity among Peruvian rural-to-urban migrants. We performed a cross sectional survey, the PERU MIGRANT study, using single-stage random sampling. Evaluation included weight, height, and waist circumference (WC) as well as acculturation surrogates. Obesity was assessed using body mass index (BMI) and WC. Length of residence, age at migration, language proficiency and language preferences (Spanish or Quechua) were assessed in logistic regression models to calculate odd ratios (OR) and 95% confidence intervals (CI) adjusting for potential confounders. A total of 589 rural-to-urban migrants were enrolled. The mean age was 47.8 (SD: 11.7, range: 30-92) and 280 (47.5%) were males. Obesity prevalence assessed by BMI was 30.4% among women and 10.7% among men (p<0.001), whereas abdominal obesity assessed by WC was 29.1% among women and 19.1% among men (p<0.01). Obesity was associated with older age at first migration, language speaking proficiency and language preferences. The association between obesity and acculturation surrogates is variable in this population. Thus, acculturation per se can explore positive channels associated with better health outcomes. The patterns shown in this report suggest a more complex association for these factors. PMID:20395946

Characterization of Non-Infectious Virus-Like Particle Surrogates for Viral Clearance Applications.

PubMed

Johnson, Sarah; Brorson, Kurt A; Frey, Douglas D; Dhar, Arun K; Cetlin, David A

2017-09-01

Viral clearance is a critical aspect of biopharmaceutical manufacturing process validation. To determine the viral clearance efficacy of downstream chromatography and filtration steps, live viral "spiking" studies are conducted with model mammalian viruses such as minute virus of mice (MVM). However, due to biosafety considerations, spiking studies are costly and typically conducted in specialized facilities. In this work, we introduce the concept of utilizing a non-infectious MVM virus-like particle (MVM-VLP) as an economical surrogate for live MVM during process development and characterization. Through transmission electron microscopy, size exclusion chromatography with multi-angle light scattering, chromatofocusing, and a novel solute surface hydrophobicity assay, we examined and compared the size, surface charge, and hydrophobic properties of MVM and MVM-VLP. The results revealed that MVM and MVM-VLP exhibited nearly identical physicochemical properties, indicating the potential utility of MVM-VLP as an accurate and economical surrogate to live MVM during chromatography and filtration process development and characterization studies.