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Steroids are used to illustrate some of the significant advances that have been made in recent years in understanding the biological origin and geological fate of the organic compounds in sediments. The precursor sterols are transformed, initially by microbial activity and later by physicochemical constraints, into thermodynamically more stable saturated and aromatic hydrocarbons in mature sediments and petroleums. The steps in this transformation result in a complex web linking biogenesis, diagenesis, and catagenesis. Indeed, the complexity and variety of biological lipids such as the steroids are evidently matched in the corresponding geolipids. The extent of preservation of the biochemical imprint in the structures and stereochemistry of these geolipids, even over hundreds of millions of years, is startling, as is the systematic and sequential nature of the geochemical changes they evidently undergo. This new understanding of molecular organic geochemistry has applications in petroleum geochemistry, where biological marker compounds are valuable in the assessment of sediment maturity and in correlation work.

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Periods in Earth history characterized by extensive organic carbon deposition, so-called oceanic anoxic events (OAEs), are the subject of considerable scrutiny. Insight into the extent of anoxic conditions in the water column has been provided by the reported occurrence of derivatives of isorenieratene, a carotenoid found only in green sulphur bacteria and thus indicative of photic-zone euxinia (i.e. a water column containing free H 2 S), in North Atlantic deep-sea sediments deposited during the Cenomanian-Turonian boundary OAE2 (Bonarelli Event). In this study, we have used the distributions of chlorophyll and bacteriochlorophyll degradation products, maleimides (1-H-pyrrole-2,5-diones) and high molecular weight porphyrins, to examine further the Cenomanian-Turonian boundary OAE2 as well as other OAEs of the early Toarcian (Posidonienschiefer Event) and early Aptian (Selli Event). In particular, methyl isobutyl (Me,i-Bu) maleimide, on structural grounds, appears to be diagnostic of green sulphur bacteria. This compound occurs in five of seven examined marls that record the early Toarcian OAE (Marche-Umbria, Italy), further expanding the geographical range of Toarcian sediments where evidence for photic-zone euxinic conditions has been found. Me,i-Bu maleimide occurs in three of six black shales spanning the Livello Selli (Marche-Umbria, Italy), the type locality for the Aptian OAE1a, providing the first evidence for photic-zone euxinic conditions during this event. With respect to the Cenomanian-Turonian OAE, maleimide evidence for photic-zone euxinic conditions was found in all the North Atlantic sites investigated, including those characterized by relatively organic-lean sediments, several Tethyan sites and one site off western Australia. These data indicate that euxinic conditions were common in the water column during Mesozoic oceanic anoxic events.

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ObjectiveTo investigate whether antidrug antibodies and/or drug non‐trough levels predict the long‐term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.MethodsA total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme‐linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non‐trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.ResultsAmong patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels.ConclusionPharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months.

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Although there are some limitations to this study, our data suggest that alcohol consumption has an inverse and dose-related association with both risk and severity of RA.