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Good Surrogate (good + surrogate)
Selected AbstractsUsing measured octanol-air partition coefficients to explain environmental partitioning of organochlorine pesticidesENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 5 2002Mahiba Shoeib Abstract Octanol-air partition coefficients (Koa) were measured directly for 19 organochlorine (OC) pesticides over the temperature range of 5 to 35°C. Values of log Koa at 25°C ranged over three orders of magnitude, from 7.4 for hexachlorobenzene to 10.1 for 1,1-dichloro-2,2-bis (p-chlorophenyl) ethane. Measured values were compared to values calculated as KowRT/H (where R is the ideal gas constant [8.314 J mol,1 K,1], T is absolute temperature, and H is Henry's law constant) were, in general, larger. Discrepancies of up to three orders of magnitude were observed, highlighting the need for direct measurements of Koa. Plots of Koa versus inverse absolute temperature exhibited a log-linear correlation. Enthalpies of phase transition between octanol and air (,Hoa) were determined from the temperature slopes and were in the range of 56 to 105 kJ mol,1 K,1. Activity coefficients in octanol (,o) were determined from Koa and reported supercooled liquid vapor pressures (p), and these were in the range of 0.3 to 12, indicating near-ideal solution behavior. Differences in Koa values for structural isomers of hexachlorocyclohexane were also explored. A Koa -based model was described for predicting the partitioning of OC pesticides to aerosols and used to calculate particulate fractions at 25 and ,10°C. The model also agreed well with experimental results for several OC pesticides that were equilibrated with urban aerosols in the laboratory. A log-log regression of the particle-gas partition coefficient versus Koa had a slope near unity, indicating that octanol is a good surrogate for the aerosol organic matter. [source] Use of turbidometry to characterize suspended sediment and phosphorus fluxes in the Lake Tahoe basin, California, USAHYDROLOGICAL PROCESSES, Issue 3 2007Andrew P. Stubblefield Abstract The efficacy of in-stream nephelometric turbidometry as a surrogate for total suspended solids (TSS) and total phosphorus (TP) concentrations was evaluated for use in low turbidity (<50 NTU) subalpine watersheds at Lake Tahoe, California,Nevada, USA. Continuous turbidity records for the 1999, 2000 and 2001 snowmelt seasons and data from water quality samples (1982,2000) were examined to determine watershed sediment delivery dynamics. Strong correlations were found between turbidity and both TSS and TP concentration. The strong correlation indicates that turbidity can serve as a good surrogate for direct measurement in these watersheds. The watersheds displayed clockwise hysteresis: sediment flushing and depletion, on daily, seasonal and decadal time-scales. The hysteresis curves had strong concave shapes, indicating a sensitive response to peak flow. A pronounced seasonal trend was observed for the ratio of suspended sediment concentration (SSC)/discharge over time, indicating early season flushing of available sediment. Significant linear relationships (p < 0·05) were found for 12 of 17 years. Comparison of annual sediment rating curve coefficients indicated smaller coefficients during high sediment loading years and in the years following. The smaller coefficients are evidence of sediment depletion during high flow years. The effect of hysteresis on monitoring methods was illustrated by comparing turbidity estimates of TSS load with sediment rating curve estimates of SSC. After accounting for differences in SSC/TSS methods of analysis, daily loads calculated with turbidity methods were 58,98% of rating curve estimates for the spring snowmelt seasons of 1999,2001. Copyright © 2006 John Wiley & Sons, Ltd. [source] Risk factors for prostate cancer incidence and progression in the health professionals follow-up studyINTERNATIONAL JOURNAL OF CANCER, Issue 7 2007Edward Giovannucci Abstract Risk factors for prostate cancer could differ for various sub-groups, such as for "aggressive" and "non-aggressive" cancers or by grade or stage. Determinants of mortality could differ from those for incidence. Using data from the Health Professionals Follow-Up Study, we re-examined 10 factors (cigarette smoking history, physical activity, BMI, family history of prostate cancer, race, height, total energy consumption, and intakes of calcium, tomato sauce and ,-linolenic acid) using multivariable Cox regression in relation to multiple subcategories for prostate cancer risk. These were factors that we previously found to be predictors of prostate cancer incidence or advanced prostate cancer in this cohort, and that have some support in the literature. In this analysis, only 4 factors had a clear statistically significant association with overall incident prostate cancer: African,American race, positive family history, higher tomato sauce intake (inversely) and ,-linolenic acid intake. In contrast, for fatal prostate cancer, recent smoking history, taller height, higher BMI, family history, and high intakes of total energy, calcium and ,-linolenic acid were associated with a statistically significant increased risk. Higher vigorous physical activity level was associated with lower risk. In relation to these risk factors, advanced stage at diagnosis was a good surrogate for fatal prostate cancer, but high-grade (Gleason , 7 or Gleason , 8) was not. Only for high calcium intake was there a close correspondence for associations among high-grade cancer, advanced and fatal prostate cancer. Tomato sauce (inversely) and ,-linolenic acid (positively) intakes were strong predictors of advanced cancer among those with low-grade cancers at diagnosis. Although the proportion of advanced stage cancers was much lower after PSA screening began, risk factors for advanced stage prostate cancers were similar in the pre-PSA and PSA era. The complexity of the clinical and pathologic manifestations of prostate cancer must be considered in the design and interpretation of studies. © 2007 Wiley-Liss, Inc. [source] In-vitro permeation of drugs into porcine hair follicles: is it quantitatively equivalent to permeation into human hair follicles?JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2008Yakov Frum It is already well-established that the general permeability properties of porcine skin are close to those of human skin. However, very little is known with respect to drug absorption into hair follicles and the similarities if any between the two types of tissue. The aim of this study was to use the skin sandwich system to quantify follicular drug absorption into porcine hair follicles. To our knowledge, this is the first time that the skin sandwich has been extended to porcine tissue. For this purpose, seven different drugs , estradiol, corticosterone, hydrocortisone, aldosterone, cimetidine, deoxyadenosine and adenosine , exhibiting a wide range of log octanol-water partition coefficients (log Ko/w), but comparable molecular weights, were chosen as candidate solutes. The results showed a parabolic profile with maximal follicular contribution occurring at intermediate log Ko/w values. Linear regression analysis indicated that the follicular contributions in porcine skin correlated well with previously published follicular contributions in human skin (r2 = 0.87). The novelty of this research is that we show that porcine tissue is a good surrogate for modelling human skin permeability within the specific context of quantifying drug absorption into hair follicles. [source] RNA-dependent RNA polymerase activity encoded by GB virus-B non-structural protein 5BJOURNAL OF VIRAL HEPATITIS, Issue 5 2000Zhong Phylogenetic analysis and polyprotein organization comparison have shown that GB virus-B (GBV-B) is closely related to hepatitis C virus (HCV). In this study, the coding region for GBV-B non-structural protein 5B (NS5B) was isolated by reverse transcription,polymerase chain reaction (RT,PCR) from pooled serum of GBV-B-infected tamarins. Expression of soluble GBV-B NS5B protein in Escherichia coli was achieved by removal of a 19-amino acid hydrophobic domain at the C-terminus of the protein. The truncated GBV-B NS5B (NS5B,CT19) was purified to homogeneity and shown to possess an RNA-dependent RNA polymerase (RdRp) activity in both gel-based and scintillation proximity assays. NS5B,CT19 required the divalent cation Mn2+ for enzymatic activity, at an optimal concentration of 15 m M. Interestingly, Mg2+, at concentrations up to 20 m M, did not support the GBV-B NS5B activity. This differs from HCV NS5B where both Mn2+ and Mg2+ can support RdRp activity. Zn2+ was found to inhibit the activity of GBV-B NS5B, with a 50% inhibitory concentration (IC50) of 5,10 ,M. Higher concentrations of monovalent salts (NaCl or KCl > 100 m M) and glycerol (> 3%) were also inhibitory. NS5B,CT19 was able to bind to RNA homopolymers, but utilized most efficiently poly(C), the one with the lowest binding affinity for RNA synthesis. Mutational analysis of GBV-B NS5B demonstrated the importance of several conserved sequence motifs for enzymatic activity. Based on sequence homology (, 37% identity and 52% similarity) between GBV-B and HCV NS5B proteins, the active GBV-B RdRp provides a good surrogate assay system for HCV polymerase studies. [source] Related Causal Frameworks for Surrogate OutcomesBIOMETRICS, Issue 2 2009Marshall M. Joffe Summary Four major frameworks have been developed for evaluating surrogate markers in randomized trials: one based on conditional independence of observable variables, another based on direct and indirect effects, a third based on a meta-analysis, and a fourth based on principal stratification. The first two of these fit into a paradigm we call the causal-effects (CE) paradigm, in which, for a good surrogate, the effect of treatment on the surrogate, combined with the effect of the surrogate on the clinical outcome, allow prediction of the effect of the treatment on the clinical outcome. The last two approaches fall into the causal-association (CA) paradigm, in which the effect of the treatment on the surrogate is associated with its effect on the clinical outcome. We consider the CE paradigm first, and consider identifying assumptions and some simple estimation procedures; we then consider the CA paradigm. We examine the relationships among these approaches and associated estimators. We perform a small simulation study to illustrate properties of the various estimators under different scenarios, and conclude with a discussion of the applicability of both paradigms. [source] Surrogacy and persistence in reserve selection: landscape prioritization for multiple taxa in BritainJOURNAL OF APPLIED ECOLOGY, Issue 1 2009Aldina M. A. Franco Summary 1A principal goal of protected-area networks is to maintain viable populations of as many species as possible, particularly those that are vulnerable to environmental change outside reserves. Ideally, one wants to be able to protect all biodiversity when selecting priority areas for conservation. 2Using the area-prioritization algorithm ZONATION, we identified the locations where UK Biodiversity Action Plan (BAP) species of mammals, birds, herptiles, butterflies and plants occur in concentrated populations with high connectivity. Both these features are likely to be correlated with population persistence. The analyses were successful in maintaining a high proportion of the connectivity of narrow-range species, and large total amounts of the connectivity of wider-range species over 10% of the land surface of Great Britain. 3Biodiversity Action Plan (BAP , high priority) species of one taxonomic group were not particularly good surrogates (indicators) for BAP species of other taxonomic groups. Hence, maintaining population concentrations of one taxonomic group did not guarantee doing likewise for other taxa. 4Species with narrow geographic ranges were most effective at predicting conservation success for other species, probably because they represent the range of environmental conditions required by other species. 5Synthesis and applications. This study identifies landscape-scale priority areas for conservation of priority species from several taxonomic groups, using the Zonation software. ,Indicator groups' were only partially successful as predictors of priority areas for other taxonomic groups, and therefore, the identification of priority areas for biodiversity conservation should include information from all taxonomic groups available. Larger areas should be protected to account for species not included in the analyses. Conservation solutions based on data for many different species, and particularly those species with narrowly defined ranges, appear to be most effective at protecting other rare taxa. [source] | |||||||||||||