On information fraction for Fleming-Harrington type weighted log-rank tests in a group-sequential clinical trial design.

When comparing survival times of treatment and control groups under a more realistic nonproportional hazards scenario, the standard log-rank (SLR) test may be replaced by a more efficient weighted log-rank (WLR) test, such as the Fleming-Harrington (FH) test. Designing a group-sequential clinical trial with one or more interim looks during which a FH test will be performed, necessitates correctly quantifying the information fraction (IF). For SLR test, IF is defined simply as the ratio of interim to final numbers of events; but for FH test, it can deviate substantially from this ratio. In this article, we separate the effect of weight function (of FH test) alone on IF from the effect of censoring. We have shown that, without considering the effect of censoring, IF can be derived analytically for FH test using information available at the design stage and the additional effect due to censoring is relatively smaller. This article intends to serve two major purposes: first, to emphasize and rationalize the deviation of IF in weighted log-rank test from that of SLR test which is often overlooked (Jiménez, Stalbovskaya, and Jones); second, although it is impossible to predict IF for a weighted log-rank test at the design stage, our decomposition of effects on IF provides a reasonable and practically feasible range of IF to work with. We illustrate our approach with an example and provide simulation results to evaluate operating characteristics.

Polymorphism in the ERCC2 codon 751 is associated with arsenic-induced premalignant hyperkeratosis and significant chromosome aberrations.

In West Bengal, India more than 6 million people are exposed to high levels of arsenic through drinking water. Since, only 15-20% of the exposed individuals show arsenic-induced skin lesions, it is assumed that genetic variation might play an important role in arsenic toxicity and carcinogenicity. Arsenic exposure often leads to the development of hyperkeratosis, the precursor of arsenic-induced skin cancer. ERCC2 (excision repair cross-complementing rodent repair deficiency, complementation group 2) is a nucleotide excision repair pathway gene, and its SNPs have been implicated in several types of epithelial cancers. We investigated the possible association of ERCC2 codon 751 A-->C polymorphism (lysine to glutamine) with arsenic-induced hyperkeratosis and correlated ERCC2 genotypes with increased frequencies of chromosomal aberration to ascertain whether any genotype leads to sub-optimal DNA repair. For this association study, 318 unrelated arsenic exposed subjects (165 with hyperkeratosis and 153 without any arsenic-induced skin lesions), drinking water contaminated with arsenic to a similar extent, were recruited. Genotyping was done through PCR-RFLP procedure. Lys/Lys genotype was significantly over-represented in the arsenic-induced hyperkeratosis-exhibiting group [odds ratio (OR) = 4.77, 95% confidence interval (CI) = 2.75-8.23]. A statistically significant increase in both CA/cell and percentage of aberrant cells was observed in the individuals with AA genotype compared to those with AC or CC genotype combined (P < 0.01) in each of the two study groups, as also, in the total study population. This study indicates that ERCC2 codon 751 Lys/Lys genotype is significantly associated with arsenic-induced premalignant hyperkeratosis and is possibly due to sub-optimal DNA repair capacity of the ERCC2 codon 751 Lys/Lys genotype.

Adsorption of 2-aminobenzothiazole on colloidal silver particles: an experimental and theoretical surface-enhanced Raman scattering study.

Surface-enhanced Raman scattering (SERS) spectra of the biologically important 2-aminobenzothiazole (2-ABT) molecule adsorbed on silver hydrosols are compared with its FTIR spectrum and normal Raman spectroscopy (NRS) spectrum in the bulk and in solution. The optimized structural parameters and the computed vibrational wavenumbers of the compound have been estimated from ab initio (Hatree-Fock) and density functional calculations. Some vibrational modes of the molecule have been reassigned. Concentration-dependent SERS spectra of the molecule reveal the existence of two types of vertically adsorbed species on colloidal silver particles, whose relative population varies with the adsorbate concentrations. The adsorption geometry and structural parameters of one type of adsorbed species are related to the NRS spectrum of the chemically prepared and theoretically modeled 2-ABT-Ag(I) coordination compound.

Experimental and theoretical surface enhanced Raman scattering study of 2-amino-4-methylbenzothiazole adsorbed on colloidal silver particles.

The adsorption of 2-amino-4-methylbenzothiazole (2-AMBT) on colloidal silver particles has been investigated by a surface enhanced Raman scattering (SERS) study. The SERS spectra of the 2-AMBT molecule at varied adsorbate concentrations recorded in different time domains are compared with its Fourier transform infrared (FTIR) spectrum and normal Raman spectrum (NRS) in the bulk and in solution. The experimentally observed SERS spectra are compared with the theoretically modeled surface complexes using ab initio restricted Hatree-Fock (RHF) and density functional theory (DFT) calculations. The most favorable adsorptive sites of the 2-AMBT molecule have been estimated by natural population analysis (NPA) using the above-mentioned high level of theories. The enhancement of the in-plane modes together with the appearance of Ag-N stretching frequency at 215 cm(-1) indicates that the 2-AMBT molecule is adsorbed on the silver surface through the lone pair electrons of both nitrogen atoms with the molecular plane nearly vertical to the surface.