BATE Curve in Assessment of Clinical Utility of Predictive Biomarkers

In this paper, for time-to-event data, we propose a new statistical framework for casual inference in evaluating clinical utility of predictive biomarkers and in selecting an optimal treatment for a particular patient. This new casual framework is based on a new concept, called Biomarker Adjusted Treatment Effect (BATE) curve, which can be used to represent the clinical utility of a predictive biomarker and select an optimal treatment for one particular patient. We then propose semi-parametric methods for estimating the BATE curves of biomarkers and establish asymptotic results of the proposed estimators for the BATE curves. We also conduct extensive simulation studies to evaluate finite-sample properties of the proposed estimation methods. Finally, we illustrate the application of the proposed method in a real-world data set

Semiparametric Two-Part Models with Proportionality Constraints: Analysis of the Multi-Ethnic Study of Atherosclerosis (MESA)

SUMMARY. In this article, we analyze the coronary artery calcium (CAC) score in the Multi-Ethnic Study of Atherosclerosis (MESA), where about half of the CAC scores are zero and the rest are continuously distributed. When the observed data has a mixture distribution, two-part models can be the natural choice. With a two-part model, there are two covariate effects, with one in each part of the model. Determination of whether the two covariate effects are proportional can provide more insights into the process underlying development and progression of CAC. In this study, we model the CAC score using a semiparametric two-part model, and investigate the determination of proportionality of the covariate effects. We propose penalized maximum likelihood estimation and using thin plate splines in practical data analysis, and establish asymptotic estimation properties. We propose a step-wise hypothesis testing based approach to determine proportionality. Simulation studies suggest satisfactory finite-sample performance of the proposed approach. Analysis of the MESA data suggests that proportionality holds for all covariates except the LDL and HDL

(2-{[2-(4-Chlorophenoxy)-1-oxido­ethyl­idene-κO 1]hydrazono­methyl}­phenol­ato-κ2 N 1,O)(1H-imidazole-κN 3)nickel(II)

In the title complex, [Ni(C15H11ClN2O3)(C3H4N2)], the NiII ion is coordinated by a phenolate O, hydrazine N and carbonyl O atom from the hydrazone ligand and by an N atom from the imidazole mol­ecule, forming a distorted square-planar geometry. Inter­molecular N—H⋯N hydrogen bonds link neighboring molecules into extended chains parallel to [100]

Development of an in situ polymeric hydrogel implant of methylprednisolone for spinal injuries

Purpose: To prepare and characterize in situ gel-forming implants of methylprednisolone for the treatment of spinal cord injuries.Methods: In situ hydrogels of methylprednisolone were prepared by dispersing polylactide glycolic acid (PLGA) polymer and methylprednisolone in N-methyl-pyrrolidone solvent, and subsequent membrane sterilization. Hydrogels were prepared using varying concentrations of PLGA polymer. The physicochemical properties of hydrogels, including visual appearance, clarity, pH, viscosity, drug content, and in vitro drug release, were characterized. In vivo studies were performed to examine antiinflammatory activity (paw edema test) and in vivo motor function activity in a rat spinal injury model after injecting the hydrogels into rats.Results: The physicochemical properties of the gels were satisfactory. F1, F2, F3, and F4 formulations showed 99.67, 95.29, 88.89 and 88.20 % drug release, respectively, at the end of 7 days. In vivo antiinflammatory activity was highest for F1 (62.85 %). Motor function activity scores (arbitrary scale) for the F1, F2, F3 and F4 formulations were 4.82 ± 0.12, 4.70 ± 0.12, 4.68 ± 0.02, and 4.60 ± 0.05, respectively, and were higher (p < 0.05) for F1, F2 and F3) than for the standard (methylprednisolone, 30 mg/kg body weight, iv; activity score, 4.59 ± 0.20).Conclusions: The in situ hydrogels of methylprednisolone developed may be useful for the effective management of spinal cord injuries in patients. However, further investigations are required to ascertain their suitability for clinical use.Keywords: Methylprednisolone, In situ hydrogel, Spinal injury, Motor activity, Implan

Poly[[[diaqua­sodium]-μ3-5-carb­oxy-2-ethyl-1H-imidazole-4-carboxyl­ato-κ4 N 3,O 4:O 5:O 5] monohydrate]

In the title complex, {[Na(C7H7N2O4)(H2O)2]·H2O}n, the NaI atom exhibits a distorted octa­hedral geometry and is six-coordinated in an NO5 environment. The equatorial plane is defined by three O atoms and one N atom from two distinct 5-carb­oxy-2-ethyl-1H-imidazole-4-carboxyl­ate (H2EIDC) ligands and one coordinated water mol­ecule, and the apical sites are occupied by one carboxyl O atom from one H2EIDC ligand and one O atom from the other coordinated water mol­ecule. The NaI atoms are linked by H2EIDC ligands, generating an infinite double chain along the a axis. These chains are further connected via O—H⋯O and N—H⋯O hydrogen bonds into a three-dimensional supra­molecular network