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71.
Commonly used semiparametric estimators of causal effects specify parametric models for the propensity score (PS) and the conditional outcome. An example is an augmented inverse probability weighting (IPW) estimator, frequently referred to as a doubly robust estimator, because it is consistent if at least one of the two models is correctly specified. However, in many observational studies, the role of the parametric models is often not to provide a representation of the data-generating process but rather to facilitate the adjustment for confounding, making the assumption of at least one true model unlikely to hold. In this paper, we propose a crude analytical approach to study the large-sample bias of estimators when the models are assumed to be approximations of the data-generating process, namely, when all models are misspecified. We apply our approach to three prototypical estimators of the average causal effect, two IPW estimators, using a misspecified PS model, and an augmented IPW (AIPW) estimator, using misspecified models for the outcome regression (OR) and the PS. For the two IPW estimators, we show that normalization, in addition to having a smaller variance, also offers some protection against bias due to model misspecification. To analyze the question of when the use of two misspecified models is better than one we derive necessary and sufficient conditions for when the AIPW estimator has a smaller bias than a simple IPW estimator and when it has a smaller bias than an IPW estimator with normalized weights. If the misspecification of the outcome model is moderate, the comparisons of the biases of the IPW and AIPW estimators show that the AIPW estimator has a smaller bias than the IPW estimators. However, all biases include a scaling with the PS-model error and we suggest caution in modeling the PS whenever such a model is involved. For numerical and finite sample illustrations, we include three simulation studies and corresponding approximations of the large-sample biases. In a dataset from the National Health and Nutrition Examination Survey, we estimate the effect of smoking on blood lead levels. 相似文献
72.
Franco Alessandro Buoso Sara Zanin Laura Pinton Roberto Tomasi Nicola 《Journal of Plant Growth Regulation》2023,42(3):1567-1581
Journal of Plant Growth Regulation - The wide use of copper (Cu)-based fungicide has caused a stepwise accumulation of Cu in the environment increasing the occurrence of phytotoxicity in crops. To... 相似文献
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Paul G. Braunschweiger Vathsala S. Basrur Dayna Cameron Laura Sharpe Octavio Santos James P. Perras Bernd-Uwe Sevin Arnold M. Markoe 《Biotherapy》1997,10(2):129-137
The modulation of cisPlatin cytotoxicity by interleukin-1 (IL-1α) was studied in cultures of SCC-7 tumor cells with and without
tumor macrophages to examine potential mechanisms for the synergistic antitumor activity of cisPlatin and IL-1α in SCC-7 solid
tumors. Neither IL-1α nor tumor macrophages affected the survival of clonogenic tumor cells and IL-1α had no direct effect
on tumor cell growthin vitro. Macrophages had no direct effect on cisPlatin sensitivity (IC90=6.0 μM), but, the addition of IL-1α (500–2000U/ml) to co-cultures of cisPlatin pretreated tumor cells and resident tumor
macrophages increased cell killing (IC90=3.1 μM). Similar responses were seen in primary cultures treated with cisPlatin before IL-1α. The modulation of cisPlatin
cytotoxicity by IL-1α exhibited a biphasic dose response that paralleled the IL-1α dose dependent release of H2O2by resident tumor macrophages. Further, IL-1α modification of cisPlatin cytotoxicity was prompt and inhibited by catalase.
CisPlatin and exogenous H2O2 (50 μM) produced more than additive SCC-7 clonogenic cell kill and hydroxyl radicals played an important role in the response.
Interleukin-1 modulation of cisPlatin cytotoxicity was schedule dependent. IL-1α treatment for 24 hrs, before cisPlatin, produced
drug resistance (IC90=11.1 μM). Our study shows that IL-1α can stimulate tumor macrophages to release pro-oxidants that modify cellular chemosensitivity
in a schedule and dose dependent fashion. Our findings may also provide a mechanistic explanation for the synergistic antitumor
activity of cisPlatin and IL-1αin vivo. 相似文献
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Stereoselectivity of the Chinese hamster ovary cell sialidase: sialoside hydrolysis with overall retention of configuration 总被引:1,自引:1,他引:0
The stereochemical course of enzymatic hydrolysis by the solublesialidase from Chinese hamster ovary cells, expressed as a recombinantprotein in insect Sf9 cells, was determined using proton nuclearmagnetic resonance spectroscopy. 4-Methyl umbelliferyl-N-acetylneuraminic acid was employed as substrate, and the stereoselectivityof the enzyme catalysis was ascertained by monitoring the H3axial and equatorial protons of the sialic acid product overthe reaction course. At both high (3 U) and low concentrations(1 U) of the enzyme, the alpha anomer of the sialic acid wasclearly observed as the initial reaction product. The correspondingbeta anomer of sialic acid appeared much later in the reaction,arising from mutarotation of the alpha anomer. Similar studieswere also carried out using the Salmonella typhimurium LT 2sialidase, a protein of similar size and substrate specificity.Both enzymes apparently cleave the alpha linked sialoside substratewith retention of configuration. Based on the observations ofa wide variety of other glycohydrolytic enzymes that have showna strong correlation of the stereoselectivity of catalysis withactive site topology (Gebler et al, J. Biol. Chem. 267, 1255912561,1992), the results obtained here suggest that the microbialand mammalian sialidases have a homologous active site architectureeven though the molecules do not share significant primary sequencesimilarities. sialidase NMR enzyme mechanism Chinese hamster 相似文献
79.
E. Regidor P. Navarro V. Dominguez C. Rodriguez 《BMJ (Clinical research ed.)》1997,315(7116):1130-1135
OBJECTIVE: To compare the relation between inequalities in long-term disability and income in the 17 regions of Spain. DESIGN: Data were taken from the survey on impairments, disabilities, and handicaps that was carried out in Spain in 1986. For each region the inequality in long-term disability associated with income was calculated as the odds ratio associated with reducing monthly household income by 10,000 pesetas (about Ponds 50) (estimate of effect of inequality of income) and the odds ratio for the inequality in long-term disability between those at the bottom and those at the top of the income hierarchy (relative index of inequality). MAIN OUTCOME MEASURE: Prevalence of long-term disability. RESULTS: Five of the eight regions where lowering income had a greater effect on long-term disability were among those with the lowest income per head, while six of the remaining nine regions where the effect was smaller were among those with the highest income per head. Three regions with the highest estimate of relative index of inequality had the highest estimate of effect, and another three regions with the lowest estimate of relative index of inequality had the lowest estimate of effect. In contrast, the relative position of the remaining 11 regions varied from one measure to another. CONCLUSIONS: These results support the theory that additional increments in material wellbeing have a negligible effect on health in countries with high socioeconomic development. However, inequality in income distribution did not determine inequality in health between those at the bottom and those at the top of the income hierarchy in many Spanish regions. 相似文献
80.
The selectins are a family of proteins that mediate leukocytetethering and rolling along the vascular endothelium. E-, P-,and L-selectin recognize various derivatives of the Lewisa andLewisx trisaccharides. The distribution of negative chargeson the Lewisa and Lewisx oligosaccharides appears to be an importantfactor in their binding by the selectins. Previous work exploringthis electrostatic dependence found that a series of syntheticanionic trisaccharides, 3'-sulfo, 3'-phospho, 6'-sulfo, and3',6'-disulfo Lewisa. (Glc), exhibited differing selectin inhibitoryefficacies. To explore the possibility that these differencesarise from conformational differences between the sugars, thesolution structures of these trisaccharides were determinedusing NMR and molecular dynamics simulations. Interproton distancesand interglycosidic torsion angles were determined at 37°Cusing NOESY buildup curves and 1D LRJ experiments, respectively.Data from both experiments agreed well with predictions madefrom 2000 picosecond unrestrained molecular dynamics simulations.We found that 3'-sulfation did not alter the core Lewisa conformation,a finding that reaffirms the results of previous study. In addition,we found that sulfation at the 6' position also leaves the trisaccharideconformation unperturbed. This is significant because the proximityof the 6'-sulfate group to the fucose ring might have alteredthe canonical Lewisa structure. The disulfate exhibited greaterflexibility than the other derivatives in dynamics simulations,but not so much as to affect NOE and heteronuclear couplingconstant measurements. Taken together, our findings supportthe use of Lewisa as a template onto which charged groups maybe added without significantly altering the trisaccharide'sstructure. oligosaccharides molecular dynamics simulations NMR sulfated Lewisa phosphorylated Lewisa 相似文献