Improvements in the predictive accuracy of the hydrophobic subtraction model of reversed-phase selectivity.

The hydrophobic subtraction model (HSM) for characterizing the selectivity of reversed-phase liquid chromatography (LC) columns has been used extensively by the LC community since it was first developed in 2002. Continuing interest in the model is due in part to the large, publicly available set of column descriptors that has been assembled over the past 18 years. In the work described in this report, we sought to refine the HSM with the goal of improving the predictive accuracy of the model without compromising its physico-chemical interpretability. The approach taken here has the following facets. A set of retention measurements for 635 columns and the 16 probe solutes used to characterize new columns using the HSM was assembled. Principal components analysis (PCA) was used as a guide for the development of a refined version of the HSM. Several outlying columns (84) were eliminated from the analysis because they were either inconsistent with the PCA model or were outliers from the original HSM model. With the retention dataset for the 16 probe solutes on the remaining 551 columns, we determined that a six-component model is the most sophisticated form of the model that can be used without overfitting the data. In our refined version of the HSM, the S*σ term has been removed. Two new terms have been added, which more accurately account for the molecular volume of the solute (Vv), and the solute dipolarity (Dd), and the remaining terms have been adjusted to accommodate these changes. The refined model described here provides improved prediction of retention factors, with the model standard error being reduced from 1.0 for the original HSM to 0.35 for the refined model (16 solutes, 551 columns). Furthermore, the number of retention factors with errors greater than 10% are reduced from 231 to 25. A revised metric for column similarity, F, is also proposed as a part of this work.

Mortality in a cohort of Staffordshire pottery workers: follow-up to December 2008.

OBJECTIVES: To examine mortality from lung cancer, chronic obstructive pulmonary disease (COPD) and chronic non-malignant renal disease (cNMRD) in pottery workers exposed to silica. METHODS: A cohort of Stoke-on-Trent pottery workers (N=5115), previously followed to 1992, was traced for vital status and cause of death to December 2008. Standardised mortality ratio (SMR) analyses, comparing deaths to England and Wales and Stoke-on-Trent, examined underlying cause in 1985-1992 and 1993-2008 and mentioned cause for 1993-2008. Survival analysis considered exposure duration and concentration of respirable silica for lung cancer, COPD and cNMRD, using Cox regression. RESULTS: Excess risks of lung cancer, COPD and cNMRD were seen against both England and Wales and Stoke-on-Trent for 1985-2008. SMRs for lung cancer and COPD were lower in 1993-2008 and non-significant for lung cancer against Stoke-on-Trent in that period (SMR 1.07 95% CI 0.92 to 1.25). Exposure concentration, estimated for 1943 subjects, was related to lung cancer in smokers for early but not later deaths with mean silica concentration >200 µg/m(3) among deaths to June 1992 (HR 2.80 95% CI 1.21 to 6.50). For COPD an increasing trend with duration and (non-significantly) with mean concentration was seen for early but not later deaths in smokers. No relation was observed between estimated exposures and cNMRD. CONCLUSIONS: Excess rates of death from COPD and lung cancer were more marked in the period of the first follow-up (1985-1992) than in the second, with any relation to estimated exposure being limited to the earlier period. Conclusions about COPD and exposure were limited by an early selective destruction of files.

Sequence-based identification of aerobic actinomycetes.

We investigated the utility of 500-bp 16S rRNA gene sequencing for identifying clinically significant species of aerobic actinomycetes. A total of 28 reference strains and 71 clinical isolates that included members of the genera Streptomyces, Gordonia, and Tsukamurella and 10 taxa of Nocardia were studied. Methods of nonsequencing analyses included growth and biochemical analysis, PCR-restriction enzyme analysis of the 439-bp Telenti fragment of the 65 hsp gene, susceptibility testing, and, for selected isolates, high-performance liquid chromatography. Many of the isolates were included in prior taxonomic studies. Sequencing of Nocardia species revealed that members of the group were generally most closely related to the American Type Culture Collection (ATCC) type strains. However, the sequences of Nocardia transvalensis, N. otitidiscaviarum, and N. nova isolates were highly variable; and it is likely that each of these species contains multiple species. We propose that these three species be designated complexes until they are more taxonomically defined. The sequences of several taxa did not match any recognized species. Among other aerobic actinomycetes, each group most closely resembled the associated reference strain, but with some divergence. The study demonstrates the ability of partial 16S rRNA gene sequencing to identify members of the aerobic actinomycetes, but the study also shows that a high degree of sequence divergence exists within many species and that many taxa within the Nocardia spp. are unnamed at present. A major unresolved issue is the type strain of N. asteroides, as the present one (ATCC 19247), chosen before the availability of molecular analysis, does not represent any of the common taxa associated with clinical nocardiosis.